{"source":"d1","version":"2026-11-08.54","coordinates":"pos = [x, y, z] in metres for an adult standing upright: origin on the floor between the feet, +x toward the person's left, +y up (top of head ~1.75), +z forward (front of the body).","columns":[{"id":"f","title":"Foods","sub":"what they contain","polarity":"good"},{"id":"c","title":"Compounds","sub":"how each one works","polarity":"good"},{"id":"vit","title":"Vitamins","sub":"what the body needs them for","polarity":"good"},{"id":"min","title":"Minerals","sub":"what the body needs them for","polarity":"good"},{"id":"aa","title":"Amino acids","sub":"building blocks and messengers","polarity":"good"},{"id":"eo","title":"Essential oils","sub":"what's in them and what they do","polarity":"good"},{"id":"h","title":"Habits & therapies","sub":"what doing them changes","polarity":"good"},{"id":"gb","title":"Helpful bacteria","sub":"what they make","polarity":"good"},{"id":"bb","title":"Harmful bacteria","sub":"what they disturb","polarity":"bad"},{"id":"v","title":"Viruses","sub":"what they are linked to","polarity":"bad"},{"id":"p","title":"Parasites","sub":"what they are linked to","polarity":"bad"},{"id":"al","title":"Allergens","sub":"what triggers allergies","polarity":"bad"},{"id":"tx","title":"Toxins & exposures","sub":"substances and habits that harm","polarity":"bad"},{"id":"wi","title":"Work injuries & exposures","sub":"how injuries happen on the job","polarity":"bad"},{"id":"sx","title":"Surgeries & procedures","sub":"what's removed or added, and what follows","polarity":"signal"},{"id":"hm","title":"Hormones","sub":"chemical messengers in the blood","polarity":"signal"},{"id":"m","title":"Body mechanisms","sub":"what everything acts through","polarity":"good"},{"id":"d","title":"Symptoms","sub":"how each works, what it feeds","polarity":"bad"},{"id":"br","title":"Brain regions","sub":"exactly where in the brain","polarity":"place"},{"id":"bp","title":"Body parts (claimed)","sub":"as named in workers' comp claims","polarity":"place"},{"id":"s","title":"Body systems","sub":"where it happens","polarity":"place"},{"id":"x","title":"Conditions","sub":"what they affect","polarity":"bad"}],"levels":{"proven":{"id":"proven","label":"Proven in human trials","rank":6,"weight":0.9,"dash":"","w":2.4},"established":{"id":"established","label":"Established physiology","rank":5,"weight":0.8,"dash":"","w":1.6},"association":{"id":"association","label":"Population association","rank":4,"weight":0.5,"dash":"7 5","w":1.8},"mixed":{"id":"mixed","label":"Mixed / conflicting trials","rank":3,"weight":0.3,"dash":"10 4 2 4","w":1.6},"lab":{"id":"lab","label":"Lab or animal only","rank":2,"weight":0.15,"dash":"2 4","w":1.9},"failed":{"id":"failed","label":"Tested in people, failed","rank":1,"weight":0,"dash":"4 4","w":1.6}},"nodes":[{"id":"sx_axillary_nodes","col":"sx","group":"Cancer surgery","name":"Armpit lymph-node removal","sub":"sentinel node biopsy or axillary dissection","how":"Surgery on the armpit lymph nodes, usually during breast cancer surgery such as a lumpectomy or mastectomy, to see whether the cancer has spread and to remove it. Sentinel node biopsy: a tracer injected near the tumour shows the first one to three nodes it drains to, and only those are removed and checked. Axillary dissection: most of the armpit nodes (often 10 to 20 or more) are removed. Taking nodes out cuts some of the lymph routes from the arm, so lymph can back up and the arm swell (lymphoedema), sometimes years later.","evidence":"About one in five women develop arm lymphoedema after breast cancer (DiSipio 2013); it is much less common after sentinel node biopsy alone than after full dissection (McLaughlin 2008). Radiotherapy to the armpit adds to the risk.","pos":[0.155,1.32,0]},{"id":"sx_cholecystectomy","col":"sx","group":"Removals","name":"Gallbladder removal","sub":"cholecystectomy","how":"The gallbladder, a small bag under the liver that stores bile, is taken out, usually by keyhole surgery through 3-4 small cuts in the belly. The liver still makes bile; it now trickles into the gut continuously instead of being squeezed out in a burst after a fatty meal.","evidence":"Most people live normally afterwards. About 1 in 6 notice looser, more urgent stools, often from bile reaching the large bowel (bile acid diarrhoea); younger people are more affected (Fisher 2008). Some feel discomfort after very fatty meals. Pain that continues after surgery happens in a minority (post-cholecystectomy syndrome).","pos":[-0.07,1.12,0.07]},{"id":"sx_appendectomy","col":"sx","group":"Removals","name":"Appendix removal","sub":"appendectomy","how":"The appendix, a finger-sized tube hanging off the start of the large bowel in the lower right belly, is removed, usually by keyhole surgery, most often because it is inflamed (appendicitis).","evidence":"People live normally without an appendix; there are no known long-term diet or bowel limits. Antibiotics alone can treat many uncomplicated cases, but in the CODA trial 29% of those people needed the operation within 90 days. Appendix removal and Parkinson's: a 2025 meta-analysis of 9 studies found no link (RR 1.01; Chin 2025, PMID 40761643).","pos":[-0.066,0.905,0.038]},{"id":"sx_colectomy","col":"sx","group":"Removals","name":"Bowel resection","sub":"partial colectomy, anterior resection","how":"A diseased length of the large bowel (colon or rectum) is cut out, for cancer, diverticulitis or inflammatory bowel disease, and the two ends are joined again; sometimes a temporary stoma protects the join while it heals.","evidence":"Most people recover normal eating. After removal of the right or left colon, stools may be looser or more frequent. After rectal surgery, about 4 in 10 have major low anterior resection syndrome: urgency, frequent small stools, clustering and leakage (Croese 2018, PMID 29936195); it often improves over 1-2 years.","pos":[0,1.06,0.08]},{"id":"sx_gastrectomy","col":"sx","group":"Removals","name":"Stomach removal","sub":"gastrectomy (partial or total)","how":"Part or all of the stomach is removed, mostly for stomach cancer; the gullet or stomach remnant is joined to the small intestine. The stomach normally stores food, grinds it and makes acid and intrinsic factor (needed to absorb vitamin B12).","evidence":"People eat small, frequent meals and many lose weight. Dumping (cramps, sweating, faintness after sugary food) is common. About half become low in vitamin B12 after total gastrectomy (Bahardoust 2024), and iron and calcium absorption fall, so lifelong vitamin B12 and blood checks are standard.","pos":[0.07,1.15,0.05]},{"id":"sx_splenectomy","col":"sx","group":"Removals","name":"Spleen removal","sub":"splenectomy","how":"The spleen, a fist-sized blood filter under the left ribs, is removed, most often after it ruptures in an injury (falls, vehicle crashes, crush) or for some blood disorders. The spleen clears certain bacteria with a sugar coat (pneumococcus, meningococcus, Hib) from the blood.","evidence":"Daily life is normal, but the risk of serious infection is raised for life: about 4-5 times the general population in the first year and still about 2.5 times after (Thomsen 2009). A rare but rapid blood infection (OPSI) is the main danger. Vaccines, sometimes antibiotics, and urgent care for any fever are the standard protection.","pos":[0.11,1.17,-0.03]},{"id":"sx_pancreatectomy","col":"sx","group":"Removals","name":"Pancreas removal","sub":"Whipple (pancreatoduodenectomy), distal or total pancreatectomy","how":"Part or all of the pancreas is removed, usually for cancer, cysts or chronic pancreatitis. In a Whipple operation the head of the pancreas, the first part of the small intestine, the gallbladder and the end of the bile duct are removed and the gut is re-plumbed; a distal pancreatectomy removes the tail (often with the spleen); a total pancreatectomy removes it all.","evidence":"The pancreas makes insulin and most digestive enzymes, so both can run short. New diabetes follows about 1 in 6 Whipple operations (Scholten 2018) and every total pancreatectomy; enzyme shortage (fatty stools, weight loss) follows about 4 in 10 Whipples (Moore 2021). After total removal, lifelong insulin and enzyme capsules are needed and quality of life is moderately lower (Scholten 2019).","pos":[0.03,1.12,0]},{"id":"sx_thyroidectomy","col":"sx","group":"Removals","name":"Thyroid removal","sub":"thyroidectomy (total or one lobe)","how":"All or half of the thyroid gland in the front of the neck is removed through a short low neck cut, for cancer, a large goitre or overactive thyroid. Two things lie close by: the tiny parathyroid glands that control blood calcium, and the nerves to the voice box.","evidence":"After total removal, thyroid hormone tablets are needed for life (after half, many people make enough). Low calcium (tingling, cramps) is common for days to weeks and permanent in about 0.5% in a high-volume centre and more in some series (Niu 2025). A hoarse or weak voice from nerve injury affects about 3-4%, mostly temporary (Higgins 2011).","pos":[0,1.44,0.05]},{"id":"sx_adrenalectomy","col":"sx","group":"Removals","name":"Adrenal removal","sub":"adrenalectomy","how":"One (rarely both) of the small glands on top of the kidneys is removed, usually by keyhole surgery, for a hormone-making tumour (for example making too much cortisol, aldosterone or adrenaline) or a suspicious lump.","evidence":"After one side is removed, the other gland usually takes over fully, although after a cortisol-making tumour the remaining gland may need months of steroid support to wake up. After both are removed, cortisol (and aldosterone) replacement is needed for life, with extra during illness, because sudden shortage (adrenal crisis) is dangerous.","pos":[0.06,1.17,-0.06]},{"id":"sx_nephrectomy","col":"sx","group":"Removals","name":"Kidney removal","sub":"nephrectomy (one kidney)","how":"One kidney is removed, for cancer, a badly damaged kidney, or to donate it to someone else. Partial nephrectomy removes only the diseased part. The remaining kidney grows and works harder to take up the load.","evidence":"People live normally with one healthy kidney. Long term, blood pressure and protein in the urine are checked. In living donors, the risk of kidney failure 15 years later was about 31 per 10,000 versus 4 per 10,000 in matched healthy non-donors: higher, but small (Muzaale 2014).","pos":[0.06,1.12,-0.06]},{"id":"sx_tonsillectomy","col":"sx","group":"Removals","name":"Tonsil removal","sub":"tonsillectomy (often with adenoids)","how":"The tonsils at the back of the throat (and often the adenoids behind the nose) are removed through the mouth, for repeated tonsillitis or for enlarged tonsils that block breathing in sleep.","evidence":"Sore throat for 1-2 weeks is normal. Bleeding occurs in roughly 3% early and up to about 9% later, and a few need a return to theatre (Söderman 2015). In children with sleep apnoea, it improves sleep, behaviour and quality of life (CHAT trial).","pos":[0,1.575,0.035]},{"id":"sx_lobectomy","col":"sx","group":"Removals","name":"Lung lobe removal","sub":"lobectomy (segmentectomy, pneumonectomy)","how":"One lobe of a lung (the right lung has three, the left two) is removed, usually for lung cancer, through keyhole or open chest surgery. Smaller cancers may need only a segment; rarely a whole lung is removed.","evidence":"Breathing capacity drops after surgery and most of the loss in exercise capacity recovers within a year (about 95% of the starting level; Nagamatsu 2007). Removing less lung keeps more function (JCOG0802). Pain at the chest wound can persist for months in some.","pos":[-0.07,1.33,0]},{"id":"sx_hysterectomy","col":"sx","group":"Removals","name":"Womb removal","sub":"hysterectomy (ovaries kept or removed)","how":"The uterus (womb), usually with the cervix, is removed through the belly, by keyhole or through the vagina, for fibroids, heavy bleeding, prolapse, endometriosis or cancer. The ovaries may be kept or removed at the same time (see ovary removal).","evidence":"Periods stop and pregnancy is no longer possible. If the ovaries are kept, they go on making hormones, so there is no immediate menopause, though natural menopause may come a little earlier. Most people recover in 4-8 weeks.","pos":[0,0.92,0.02]},{"id":"sx_oophorectomy","col":"sx","group":"Removals","name":"Ovary removal","sub":"bilateral oophorectomy (often with hysterectomy)","how":"Both ovaries (often with the fallopian tubes) are removed, for cancer, to prevent cancer in people with BRCA gene changes, or at the time of a hysterectomy.","evidence":"Before natural menopause this causes sudden surgical menopause: hot flushes, vaginal dryness, faster bone loss. Long-term studies link it, especially before age 45-50 and without hormone therapy, with more heart disease and death (Parker 2009) and more parkinsonism (Rocca 2008, 2022), while it lowers ovarian and breast cancer risk. For BRCA carriers the cancer benefit is large.","pos":[0.056,0.912,-0.012]},{"id":"sx_prostatectomy","col":"sx","group":"Removals","name":"Prostate removal","sub":"radical prostatectomy","how":"The whole prostate gland and seminal vesicles are removed, usually for prostate cancer, by keyhole or robotic surgery; the bladder is rejoined to the urethra. The nerves for erections run along the prostate and may be spared or removed depending on the cancer.","evidence":"No semen comes out at orgasm afterwards. In the ProtecT trial, surgery had the largest and most lasting effect on erections and urine leakage of the three options (Donovan 2016); both often improve over 1-2 years, and pelvic floor exercises help leakage.","pos":[0,0.84,0.02]},{"id":"sx_mastectomy","col":"sx","group":"Removals","name":"Breast removal","sub":"mastectomy (with or without armpit lymph nodes)","how":"All the breast tissue on one or both sides is removed, for breast cancer or to prevent it in people at very high risk; men can need it too. Some or all of the armpit lymph nodes may be removed to check or treat spread. Reconstruction can be done at the same time or later.","evidence":"Numbness of the chest wall and armpit is common; shoulder stiffness and body-image distress can follow. Arm swelling (lymphoedema) develops in about 1 in 5 after breast cancer treatment, more often when many armpit nodes are cleared (DiSipio 2013).","pos":[0.09,1.3,0.12]},{"id":"sx_amputation","col":"sx","group":"Removals","name":"Limb amputation","sub":"leg, foot, arm, hand or finger","how":"Part of a limb is removed, most often a toe, foot or lower leg because of poor circulation and diabetes, and in younger people after crush or other work and road injuries. The bone end is shaped and covered with muscle and skin to bear a prosthesis.","evidence":"Rehabilitation and a prosthetic limb restore walking for many, though energy cost is higher and falls more common. About 6 in 10 people feel pain in the missing part (phantom limb pain; Limakatso 2020), and pain in the stump is also common. Low mood and changed work are frequent after injury-related amputation.","pos":[0.1,0.35,0.02]},{"id":"sx_vagotomy","col":"sx","group":"Removals","name":"Vagotomy (cutting the vagus nerve)","sub":"truncal or (super)selective; mostly done for stomach ulcers before the 1990s","how":"The vagus nerve branches to the stomach are cut where they pass the lower gullet, to reduce stomach acid. Truncal vagotomy cuts the main trunks, removing vagus supply to the stomach and most of the gut; selective and superselective vagotomy cut only the branches to the acid-making part of the stomach. Since modern acid-reducing drugs and treatment of H. pylori arrived, it is rarely done.","evidence":"Established: truncal vagotomy slows stomach emptying (so a drainage operation was usually added) and causes diarrhoea in some people. Danish and Swedish register studies found a weak, inconsistent link between truncal vagotomy and fewer Parkinson's diagnoses decades later (Svensson 2015; Liu 2017).","pos":[0.025,1.22,0]},{"id":"sx_ostomy","col":"sx","group":"Additions & changes","name":"Stoma (colostomy or ileostomy)","sub":"bowel brought out through the belly wall","how":"The end of the bowel is brought out through the belly wall as a stoma and stool collects in a bag stuck to the skin. A colostomy (large bowel) usually sits low on the left and gives firmer stool; an ileostomy (small bowel) usually sits low on the right and gives liquid output. It may be temporary (to protect a join) or permanent.","evidence":"People can work, swim, exercise and travel with a stoma. Common problems: skin soreness around it, a bulge from a hernia beside it (about 1 in 3; Pilgrim 2010), and with an ileostomy, losing too much water and salt. Body image and confidence often take time.","pos":[0.07,1,0.12]},{"id":"sx_kidney_transplant","col":"sx","group":"Additions & changes","name":"Kidney transplant","sub":"new kidney from a living or deceased donor","how":"A donor kidney is placed low in the belly (usually the right side of the pelvis) and joined to the leg blood vessels and the bladder; the person's own kidneys are usually left in place. Anti-rejection drugs must be taken for life to stop the immune system attacking the new kidney.","evidence":"Most people can stop dialysis and live longer than if they stayed on dialysis (Wolfe 1999). The price is lifelong immune suppression: more infections (including unusual ones) and more cancer, especially skin cancer, which is many times more common (Krynitz 2013); sun protection and skin checks matter.","pos":[-0.08,0.95,0.05]},{"id":"sx_liver_transplant","col":"sx","group":"Additions & changes","name":"Liver transplant","sub":"whole or part liver from a donor","how":"The failing liver is removed and replaced with a whole liver from a deceased donor or part of a liver from a living donor (the liver regrows). Anti-rejection drugs are needed for life, usually at lower levels than for kidneys.","evidence":"Used for end-stage liver failure, some liver cancers and acute liver failure. Infections and cancers are more common afterwards because of immune suppression; skin cancer was about 32 times the general-population rate in Sweden (Krynitz 2013).","pos":[-0.08,1.17,0.03]},{"id":"sx_gastric_bypass","col":"sx","group":"Additions & changes","name":"Gastric bypass","sub":"Roux-en-Y bariatric surgery","how":"The stomach is stapled into a small pouch that is joined directly to a lower loop of small intestine, so food bypasses most of the stomach and the first part of the small intestine. Meals become small, and gut hormones that control hunger and blood sugar change.","evidence":"Large, lasting weight loss and often diabetes remission (STAMPEDE, SLEEVEPASS trials). Lifelong vitamins and blood checks are needed because B12, iron, calcium and vitamin D are absorbed less (ASMBS guideline). Alcohol reaches the blood much faster and higher, and alcohol problems become more common from the second year. Dumping, low blood sugar after meals and internal hernias can occur.","pos":[0.07,1.15,0.05]},{"id":"sx_sleeve_gastrectomy","col":"sx","group":"Additions & changes","name":"Sleeve gastrectomy","sub":"bariatric surgery","how":"About three-quarters of the stomach is cut away along its outer curve, leaving a narrow tube (sleeve). Food still follows the normal path, but meals are small and the hunger hormone ghrelin, made mostly in the removed part, falls.","evidence":"Lasting weight loss, slightly less than bypass at 10 years, and better diabetes control than medicines alone (SLEEVEPASS, STAMPEDE). Acid reflux and oesophagitis are more common than after bypass. Vitamin deficiencies are less common than after bypass but lifelong supplements are still advised.","pos":[0.07,1.15,0.05]},{"id":"sx_peg","col":"sx","group":"Additions & changes","name":"Feeding tube (PEG)","sub":"percutaneous endoscopic gastrostomy","how":"A soft tube is placed through the skin of the upper belly straight into the stomach, guided by a camera passed through the mouth. Liquid food, water and medicines go down the tube when swallowing is unsafe or too slow, for example after a stroke, in motor neurone disease, advanced Parkinson's, or head and neck cancer.","evidence":"Compared with a tube through the nose, a PEG fails or falls out less often (Gomes 2015). It does not stop saliva going the wrong way, so it does not clearly prevent aspiration pneumonia, and in advanced dementia it has not been shown to prolong life or improve nutrition (Sampson 2009). Skin infection or leakage at the site is common and usually minor.","pos":[0.06,1.15,0.11]},{"id":"sx_valve_replacement","col":"sx","group":"Additions & changes","name":"Heart valve replacement","sub":"surgical or catheter (TAVI) valve","how":"A narrowed or leaking heart valve, most often the aortic valve, is replaced with a mechanical valve or one made from animal tissue, either by open-heart surgery or, increasingly, by a valve folded inside a catheter passed up from the groin (TAVI).","evidence":"Breathlessness, chest pain and fainting from a tight aortic valve usually improve and survival is better (PARTNER). Mechanical valves last but need lifelong blood thinners; tissue valves avoid this but wear out after 10-20 years. Some need a pacemaker afterwards, and dental hygiene matters because valve infection is serious.","pos":[0.02,1.31,0.04]},{"id":"sx_stents","col":"sx","group":"Additions & changes","name":"Coronary stents","sub":"angioplasty, PCI","how":"A thin tube is passed from the wrist or groin artery to the heart; a balloon opens a narrowed coronary artery and a small metal mesh tube (stent), usually coated with a drug, is left to hold it open.","evidence":"In a heart attack, opening the artery fast saves heart muscle and lives (Keeley 2003). In stable chest pain, stents relieve angina in some people (ORBITA-2) but did not beat a placebo procedure when people were already on full medicines (ORBITA), and did not prevent heart attacks or deaths compared with medicines first (ISCHEMIA). Blood-thinning tablets are needed for months to stop clots in the stent.","pos":[0.03,1.31,0.06]},{"id":"sx_cabg","col":"sx","group":"Additions & changes","name":"Coronary bypass surgery","sub":"CABG","how":"Through a cut down the breastbone, veins from the leg or arteries from inside the chest or forearm are sewn on to carry blood around blocked coronary arteries.","evidence":"Relieves angina, and in people with many blocked arteries and a weak heart it lowers heart deaths over 10 years (STICH). Recovery of the breastbone takes about 6-12 weeks; memory and mood can dip for a while, and the leg wound can be slow to heal.","pos":[0.03,1.3,0.08]},{"id":"sx_hip_replacement","col":"sx","group":"Additions & changes","name":"Hip replacement","sub":"total hip arthroplasty","how":"The worn ball at the top of the thigh bone and the socket in the pelvis are replaced with a metal or ceramic ball on a stem in the thigh bone and a cup lined with plastic or ceramic.","evidence":"For severe arthritis it gives large improvements in pain and function, far more than exercise alone (Frydendal 2024). Most last 20 years or more. Risks: dislocation, blood clots, infection, leg-length difference; a broken hip in older people is also treated this way.","pos":[0.1,0.92,0]},{"id":"sx_knee_replacement","col":"sx","group":"Additions & changes","name":"Knee replacement","sub":"total knee arthroplasty","how":"The worn ends of the thigh and shin bones are capped with shaped metal parts with a plastic spacer between them; the back of the kneecap may also be resurfaced.","evidence":"Improves pain and function more than rehabilitation alone, but with more serious complications (Skou 2015). Recovery takes months and a minority remain dissatisfied with ongoing pain or stiffness. Kneeling can stay uncomfortable.","pos":[0.1,0.5,0.03]},{"id":"sx_spinal_fusion","col":"sx","group":"Additions & changes","name":"Spinal fusion","sub":"lumbar or cervical fusion","how":"Two or more vertebrae are joined into one solid bone using bone graft, often held with screws, rods or a cage between the bones, to stop painful movement, correct a slip or deformity, or stabilise the spine after removing a disc or bone pressing on nerves.","evidence":"Helps clearly for instability, fractures and deformity. For chronic low back pain alone, fusion beat usual care (Fritzell 2001) but did no better than intensive exercise and cognitive rehabilitation 11 years later (Mannion 2013). The levels next to the fusion carry more load and can wear faster.","pos":[0,1.02,-0.09]},{"id":"sx_cataract_surgery","col":"sx","group":"Additions & changes","name":"Cataract surgery","sub":"lens replacement","how":"The clouded natural lens is broken up with ultrasound through a tiny cut at the edge of the cornea and sucked out, and a folded plastic lens is placed inside the thin capsule that held the old lens.","evidence":"One of the most successful operations: vision clears within days. After first-eye surgery, older women fell about a third less (Harwood 2005); the effect of second-eye surgery on falls is uncertain (Foss 2006). The capsule behind the new lens clouds in many people over the following years (about 28% diagnosed within a year in one registry), fixed with a quick laser treatment.","pos":[0.032,1.629,0.0775]},{"id":"sx_pacemaker","col":"sx","group":"Additions & changes","name":"Pacemaker","sub":"implanted heart pacemaker","how":"A matchbox-sized battery and computer is placed under the skin below the left (sometimes right) collarbone, with one to three wires threaded through a vein into the right side of the heart. It senses the heartbeat and sends a small pulse whenever the heart's own wiring is too slow or pauses.","evidence":"Stops fainting and tiredness from a slow heart; life is largely normal. The battery is replaced every 7-12 years. Strong magnets and some machines should be kept away from it, and many newer models are MRI-safe. Wire displacement or pocket infection occur in a small minority.","pos":[0.08,1.42,0.09]},{"id":"sx_icd","col":"sx","group":"Additions & changes","name":"Implanted defibrillator (ICD)","sub":"implantable cardioverter-defibrillator","how":"Like a pacemaker, placed under the left collarbone with a wire into the heart (or a wire under the skin only), but it can also detect a dangerous fast rhythm and deliver a shock to reset it.","evidence":"In people with a weak heart pump it lowers the risk of sudden death (MADIT-II, SCD-HeFT). Shocks are painful and can be frightening; unneeded shocks and anxiety affect some people, and driving is restricted for a time after a shock.","pos":[0.08,1.42,0.09]},{"id":"sx_dbs","col":"sx","group":"Additions & changes","name":"Deep brain stimulation (DBS)","sub":"brain pacemaker","how":"Thin electrodes are passed through small holes in the skull into a deep movement-control centre: the subthalamic nucleus or globus pallidus for Parkinson's and dystonia, the thalamus for tremor. Wires run under the scalp and neck skin to a battery under the collarbone that sends steady pulses; settings are adjusted from outside.","evidence":"For Parkinson's with fluctuations, it adds hours of good ON time, cuts dyskinesia and lets medication be reduced (Deuschl 2006, Weaver 2009, EARLYSTIM 2013). It does not stop the disease and helps balance, freezing and thinking little. Downsides: surgical risks (bleeding, infection, about 1 in 6 serious device or surgery events in EARLYSTIM), speech often gets less clear (Tripoliti 2011), and mood changes and a higher suicide rate in the first year need watching (Voon 2008).","pos":[0.012,1.654,-0.013]},{"id":"sx_cochlear_implant","col":"sx","group":"Additions & changes","name":"Cochlear implant","sub":"bionic ear","how":"An electrode is threaded into the cochlea (the hearing snail of the inner ear) and a receiver is placed under the skin behind the ear. An outer microphone and processor clipped to the ear send sound to it, and the electrode stimulates the hearing nerve directly, bypassing the damaged hair cells.","evidence":"For severe to profound deafness where hearing aids are not enough. Speech understanding improves greatly in both younger and older adults (Schafer 2021), though it takes months of practice and sounds different at first; thinking-test scores improve slightly (Joyce 2026). Any natural hearing left in that ear may be lost, and some MRI scans need precautions.","pos":[0.042,1.62,0.005]},{"id":"sx_caesarean","col":"sx","group":"Additions & changes","name":"Caesarean birth","sub":"compared with vaginal birth","how":"A baby born vaginally is seeded with the mother's vaginal and gut bacteria; a baby born by caesarean is seeded more from skin and the hospital environment. The result is fewer bifidobacteria and more hospital-type bacteria in the first weeks, and the difference largely evens out over the first year.","evidence":"Shown in a large UK newborn study. Later health differences are associations only, and caesarean birth is often medically necessary."},{"id":"al_milk","col":"al","group":"Food allergens","name":"Cow's milk protein","sub":"casein and whey","how":"An immune reaction to milk proteins (casein, whey), not milk sugar. It is the most common food allergy in babies. Milk from goats and sheep usually cross-reacts. Many children can eat milk well-baked into foods before they tolerate fresh milk.","evidence":"Established: most children outgrow milk allergy by school age. Different from lactose intolerance, which is an enzyme shortage and never causes hives or anaphylaxis."},{"id":"al_egg","col":"al","group":"Food allergens","name":"Egg","sub":"ovomucoid, ovalbumin (mostly in the white)","how":"Egg-white proteins trigger IgE allergy, common in babies with eczema. Ovomucoid survives heating, so children who react to baked egg tend to have more lasting allergy; many tolerate egg well-baked into cakes before lightly cooked egg.","evidence":"Established: most children outgrow egg allergy. Early introduction is mixed: one large trial (EAT) missed its main goal, but pooled trials suggest egg at 4 to 6 months reduces egg allergy (Ierodiakonou 2016)."},{"id":"al_wheat","col":"al","group":"Food allergens","name":"Wheat","sub":"wheat proteins (e.g. omega-5 gliadin)","how":"An IgE reaction to wheat proteins causing hives, vomiting or anaphylaxis soon after eating. In some adults it only happens when wheat is followed by exercise (wheat-dependent exercise-induced anaphylaxis). Bakers can become allergic to breathed-in flour (baker's asthma).","evidence":"Established. Wheat allergy is not coeliac disease: coeliac is an autoimmune reaction to gluten that damages the gut lining over time."},{"id":"al_soy","col":"al","group":"Food allergens","name":"Soy","sub":"soybean proteins","how":"Soybean proteins trigger IgE allergy, mostly in young children, and usually mildly. Soy is a legume and can rarely cross-react with peanut.","evidence":"Established: most children outgrow soy allergy. Highly refined soy oil usually contains too little protein to cause reactions."},{"id":"al_fish","col":"al","group":"Food allergens","name":"Fish","sub":"parvalbumin","how":"Parvalbumin, a muscle protein shared by most bony fish, triggers IgE allergy; people allergic to one fish often react to others. Steam from cooking fish can trigger reactions in very sensitive people.","evidence":"Established: fish allergy usually lasts. It is unrelated to shellfish allergy, which involves a different protein. Some 'fish reactions' are actually scombroid poisoning from spoiled fish (histamine made by bacteria), not allergy."},{"id":"al_shellfish","col":"al","group":"Food allergens","name":"Shellfish (mainly crustaceans)","sub":"tropomyosin in shrimp, prawn, crab, lobster","how":"Tropomyosin, a muscle protein in crustaceans, causes most shellfish allergy; molluscs (mussels, clams, oysters, squid) cause it less often. Because dust mites and cockroaches carry a similar tropomyosin, people allergic to them can cross-react with shellfish.","evidence":"Established: shellfish allergy often starts in adulthood and usually lasts. Allergy to iodine is a myth: shellfish allergy does not mean allergy to iodine or X-ray contrast."},{"id":"al_peanut","col":"al","group":"Food allergens","name":"Peanut","sub":"Ara h 1, 2, 3, 6 storage proteins","how":"Peanut is a legume, not a tree nut. Its storage proteins are tough: roasting does not destroy them, and tiny amounts can trigger reactions in allergic people. It is one of the most common causes of severe and fatal food anaphylaxis, and usually lasts for life.","evidence":"Proven prevention: in the LEAP trial, regularly eating peanut foods from infancy cut peanut allergy at age 5 by more than 80% in high-risk babies (Du Toit 2015). Oral immunotherapy raises the amount tolerated (PALISADE 2018) but increases reactions and anaphylaxis during treatment (Chu 2019 meta-analysis)."},{"id":"al_tree_nuts","col":"al","group":"Food allergens","name":"Tree nuts","sub":"cashew, walnut, hazelnut, almond, pistachio, pecan, Brazil","how":"Seed-storage proteins in tree nuts trigger IgE allergy. Allergy to one nut often comes with allergy to related nuts (cashew with pistachio, walnut with pecan), but not always to all of them. Raw hazelnut can also cause mild mouth itching in birch-pollen allergy (pollen-food syndrome).","evidence":"Established. Like peanut, tree nut allergy usually lasts and can cause anaphylaxis. Coconut and nutmeg are not tree nuts for most allergic people."},{"id":"al_sesame","col":"al","group":"Food allergens","name":"Sesame","sub":"seeds, tahini, hummus, sesame oil","how":"Sesame seed proteins (and cold-pressed sesame oil) trigger IgE allergy, sometimes severe. It is hidden in many foods such as hummus, tahini, breads and spice mixes.","evidence":"Established. Sesame is now a labelled major allergen in the EU, UK, Australia and (since 2023) the US."},{"id":"al_alpha_gal","col":"al","group":"Food allergens","name":"Alpha-gal (red-meat allergy)","sub":"galactose-alpha-1,3-galactose; caused by tick bites","how":"Alpha-gal is a sugar found in the meat of non-primate mammals (beef, pork, lamb, venison) and in some gelatin, dairy and medicines. Bites from certain ticks (the lone star tick in the US, others in Europe and Australia) make some people produce IgE to alpha-gal. Unusually, reactions come 3 to 6 hours after eating red meat, often at night, as hives, gut symptoms or anaphylaxis.","evidence":"Association/clinical studies: case series linked delayed anaphylaxis after red meat to IgE against alpha-gal (Commins 2009), and IgE to alpha-gal rose sharply after tick bites (Commins 2011). The same IgE explained reactions to the cancer drug cetuximab (Chung 2008), and most red-meat-allergic people were also sensitised to gelatin, which carries alpha-gal (Mullins 2012). Poultry and fish do not contain alpha-gal. Avoiding further tick bites can let the allergy fade."},{"id":"al_nickel","col":"al","group":"Contact & other","name":"Nickel","sub":"jewellery, belt buckles, watch backs, buttons, phones","how":"The most common contact allergen. Nickel ions released by sweat from metal in contact with skin sensitise T cells; later contact causes an itchy eczema rash where the metal touches, one to three days afterwards. This is a delayed (type IV) T-cell allergy, not an IgE allergy, so it does not cause anaphylaxis. Ear piercing is a common start.","evidence":"Established: diagnosed by patch testing. Association: after EU limits on nickel release from jewellery and other items worn against the skin, nickel allergy fell in young women in Denmark, Germany, Italy and the UK (Garg 2013)."},{"id":"al_latex","col":"al","group":"Contact & other","name":"Natural rubber latex","sub":"gloves, balloons, catheters, condoms","how":"Proteins from the rubber tree in latex products can cause an immediate IgE allergy (hives, asthma, anaphylaxis), most often in health workers and people who have had many operations; rubber chemicals added in manufacture can also cause delayed contact dermatitis. Some latex-allergic people react to banana, avocado, kiwi and chestnut (latex-fruit syndrome).","evidence":"Established. Association: replacing powdered latex gloves with powder-free or latex-free gloves greatly reduced latex sensitisation and latex asthma in health workers (systematic review of mostly observational studies, LaMontagne 2006)."},{"id":"al_pollen","col":"al","group":"Airborne","name":"Pollen","sub":"grass, tree (birch, olive, cedar) and weed (ragweed, mugwort)","how":"Wind-carried pollen lands on the eyes and nose; in allergic people its proteins set off mast cells, giving seasonal hay fever. In northern temperate countries the seasons run roughly: alder and hazel in late winter; birch in spring (about March to May); grass from late spring to mid-summer; mugwort in mid to late summer; ragweed from late summer into autumn (about August to October, mainly North America and parts of Europe); olive and cypress in the Mediterranean spring. Timing shifts with region and weather and is getting longer as the climate warms. Each pollen has look-alike proteins in foods: birch with raw apple, pear, cherry, kiwi, hazelnut, carrot, celery and soy; mugwort with celery and spices; ragweed with melon and banana; grass with melon, tomato and orange. Most of these food reactions are an itchy mouth from the raw food, because cooking destroys the proteins involved (pollen-food syndrome), but mugwort-linked celery and birch-linked soy-drink reactions can be severe.","evidence":"Established. Thunderstorms can burst grass pollen into tiny particles that reach deep into the lungs and trigger 'thunderstorm asthma' outbreaks."},{"id":"al_dust_mite","col":"al","group":"Airborne","name":"House dust mites","sub":"Dermatophagoides; allergen in their droppings","how":"Microscopic mites living in bedding, mattresses, carpets and soft toys, feeding on skin flakes in warm, humid homes. Proteins in their droppings are the most common year-round indoor allergen and a major trigger of allergic asthma, hay fever and eczema flares. Their tropomyosin resembles shellfish tropomyosin.","evidence":"Established. Single measures such as mite-proof covers alone have not clearly improved asthma in trials; mite immunotherapy is used for mite-driven hay fever and asthma under specialists."},{"id":"al_pet_dander","col":"al","group":"Airborne","name":"Pet dander","sub":"cat (Fel d 1), dog, horse, rodents","how":"Tiny flakes of skin, saliva and urine proteins from furred animals stay airborne and stick to clothes and furniture, so they are found even in homes and schools without pets. Cat allergen is especially sticky and potent. No breed of cat or dog is truly 'hypoallergenic'.","evidence":"Established. Lab-animal allergy is a common cause of occupational asthma in researchers and animal technicians."},{"id":"al_mould","col":"al","group":"Airborne","name":"Mould spores","sub":"Alternaria, Aspergillus, Cladosporium, Penicillium","how":"Spores from moulds outdoors (late summer, damp leaves) and indoors (damp walls, bathrooms) are breathed in and trigger allergic reactions in sensitised people. Alternaria allergy is linked with severe asthma, and Aspergillus can cause a special allergic lung disease (ABPA) in some people with asthma.","evidence":"Established. Damp and mouldy homes are linked with more asthma and respiratory symptoms; fixing damp is the main measure."},{"id":"al_cockroach","col":"al","group":"Airborne","name":"Cockroach","sub":"proteins in droppings, saliva and body parts","how":"Cockroach proteins settle in house dust, especially in crowded city housing, and are a major year-round asthma trigger in sensitised children. Their tropomyosin resembles shellfish and dust-mite tropomyosin.","evidence":"Established: cockroach allergy is one of the strongest allergen links to asthma severity in inner-city children."},{"id":"al_venom","col":"al","group":"Drugs & stings","name":"Insect venom","sub":"bees, wasps, hornets, fire ants","how":"Venom proteins injected by a sting can sensitise the immune system; a later sting can then cause a large local swelling or, less often, a whole-body reaction with hives, swelling, wheeze or collapse (anaphylaxis).","evidence":"Established. Venom immunotherapy (a course of venom injections given by specialists over several years) greatly reduces the risk of severe reactions to later stings (Cochrane review, Boyle 2012). Large local swellings alone rarely progress to anaphylaxis."},{"id":"al_penicillin","col":"al","group":"Drugs & stings","name":"Penicillin & related antibiotics","sub":"penicillins, amoxicillin, cephalosporins","how":"Penicillin can cause an immediate IgE allergy (hives, swelling, anaphylaxis) or delayed rashes, which are usually T-cell reactions and occasionally severe skin reactions. Many 'penicillin allergy' labels come from childhood rashes that were actually caused by the infection.","evidence":"Established. About 1 in 10 people report penicillin allergy, but true allergy is uncommon and often fades with time; specialist testing removes the label safely in most people, which matters because wrong labels lead to broader antibiotics, more resistance and more C. difficile infection (Shenoy 2019)."},{"id":"al_other_drugs","col":"al","group":"Drugs & stings","name":"Other drug allergy","sub":"anaesthetic muscle relaxants, chlorhexidine, some biologics; aspirin/NSAID reactions","how":"Many medicines can cause allergic reactions. Some are true IgE allergies (such as muscle relaxants and the antiseptic chlorhexidine during surgery); others look allergic but are not IgE, such as reactions to aspirin and anti-inflammatory painkillers (NSAIDs) that worsen asthma, nasal polyps or hives by blocking an enzyme.","evidence":"Established. Drug reactions should be recorded precisely and assessed by an allergist, as many labels are wrong and some reactions (severe blistering rashes) mean the drug must never be given again."},{"id":"lipid_transfer_proteins","col":"al","group":"Allergen protein families","name":"Lipid transfer proteins (LTP)","sub":"peach Pru p 3; apple, cherry, hazelnut, walnut, peanut, tomato, grape, wheat, cannabis; mugwort and plane-tree pollen","how":"Lipid transfer proteins carry fats across plant cell walls and are concentrated in the skins of fruit (peach skin especially), in nuts and seeds. They are compact and tightly folded, so they survive cooking, processing and stomach acid, which lets them reach the gut intact; that is why LTP allergy, unlike birch pollen-food syndrome, can cause reactions to cooked foods, juices, beer and wine. People are often sensitised first to peach LTP (Pru p 3) and then react to LTPs in many unrelated plant foods (\"LTP syndrome\"), most common around the Mediterranean. How bad it gets: anything from an itchy mouth to hives and anaphylaxis; reactions are often worse when a cofactor is present, such as exercise, alcohol or anti-inflammatory painkillers.","evidence":"Association: in LTP-sensitised patients, anaphylaxis was reported by 37% (Ruano-Zaragoza 2021) to 76% (Pascal 2012). LTP food allergy is not driven by pollen the way PR-10 allergy is."},{"id":"seed_storage_proteins","col":"al","group":"Allergen protein families","name":"Seed storage proteins (2S albumins, vicilins, legumins)","sub":"peanut Ara h 1, 2, 3, 6; hazelnut Cor a 14; cashew Ana o 3; walnut Jug r 1; sesame Ses i 1; soy Gly m 5, 6; lupin","how":"Seeds pack protein away for the growing seedling in storage proteins: 2S albumins, vicilins (7S) and legumins (11S). They are the main cause of true, lasting peanut, tree-nut and sesame allergy. 2S albumins in particular are small and tightly folded, survive roasting and stomach digestion; dry roasting may even make peanut more allergenic than boiling does. Related storage proteins sit in other legumes (soy, lupin, chickpea, lentil). Peanut is a legume, not a nut, so allergy to peanut and to tree nuts often occurs together through separate sensitisations rather than only through shared proteins; cashew with pistachio and walnut with pecan are true close cross-reacting pairs. Lupin flour, used in some breads and gluten-free foods, sensitises about a third of peanut-allergic children but only a few react to it. How bad it gets: these are the allergies most often behind severe and fatal food anaphylaxis.","evidence":"Cohort: IgE to Ara h 2 and Ara h 6 best told peanut-allergic from peanut-tolerant children (Uotila 2018). Food challenges: 61% of children with one nut or sesame allergy had another (Brough 2020). Lupin: 34% sensitised, about 4% allergic among peanut-allergic children (Shaw 2008)."},{"id":"milk_caseins_whey","col":"al","group":"Allergen protein families","name":"Milk caseins and whey proteins","sub":"casein (heat-stable); whey beta-lactoglobulin and alpha-lactalbumin (heat-sensitive); shared by cow, goat, sheep and buffalo milk","how":"Milk protein is about four-fifths casein and one-fifth whey. Caseins are loose, flexible proteins that heat cannot unfold much further, so they keep their allergic punch through cooking. Whey proteins (beta-lactoglobulin, alpha-lactalbumin) are tightly folded and lose much of their allergenicity with long, high heating, which is why many children with cow's milk allergy can eat milk baked into cakes but not drink milk. The caseins of goat, sheep and buffalo milk are so similar to cow's that most people allergic to cow's milk also react to them; camel milk is more distant. Rarely, someone is allergic only to goat and sheep milk. How bad it gets: usually skin and gut symptoms in babies, often outgrown, but anaphylaxis can happen; high casein IgE marks a more persistent and severe allergy.","evidence":"Lab: cow's-milk-allergic IgE recognised goat, ewe and buffalo milk proteins but not camel (Restani 1999). Cohort with food challenges: 68 of 100 milk-allergic children tolerated baked milk (Nowak-Wegrzyn 2008)."},{"id":"ovomucoid","col":"al","group":"Allergen protein families","name":"Ovomucoid (egg white Gal d 1)","sub":"the heat- and digestion-resistant egg-white allergen","how":"Ovomucoid makes up about a tenth of egg-white protein. Unlike ovalbumin, the most plentiful egg-white protein, it survives heating and stomach enzymes, so it can still trigger reactions in well-baked egg. Many egg-allergic children react to scrambled or lightly cooked egg but not to egg baked into cakes or muffins; those with high ovomucoid IgE are the ones more likely to react even to baked egg and to keep the allergy longer. Egg yolk carries less of these allergens. How bad it gets: egg allergy is usually outgrown in childhood, but reactions can be severe in some.","evidence":"Double-blind food challenges: most egg-allergic people who reacted to heated egg white tolerated it once ovomucoid was removed (Urisu 1997). Cohort: 64 of 117 egg-allergic children tolerated baked egg, and higher ovomucoid IgE marked those who did not (Lemon-Mule 2008)."},{"id":"profilins","col":"al","group":"Allergen protein families","name":"Profilins","sub":"pan-allergen in all pollens, latex and many plant foods (banana, melon, tomato, citrus, celery)","how":"Profilins are small proteins that every plant cell uses to build its internal scaffolding, and they look alike across plants. Once someone is sensitised to profilin through grass, birch, mugwort or ragweed pollen (or latex), they may react to many unrelated plant foods, especially melon and watermelon, banana, tomato, citrus, pineapple and celery. Profilins are easily destroyed by heat and digestion. How bad it gets: almost always mild, an itchy mouth or throat from raw fruit, with cooked or processed food tolerated; a few people, mainly in places with very high grass pollen exposure, have stronger reactions.","evidence":"Association: about 30% of pollen-allergic patients in one Italian series were profilin-sensitised, and most had mouth-only symptoms (Asero 2008)."},{"id":"pr10_proteins","col":"al","group":"Allergen protein families","name":"PR-10 proteins (birch Bet v 1 family)","sub":"birch Bet v 1; look-alikes in apple, cherry, hazelnut, carrot, celery, soy, peanut, kiwi","how":"PR-10 proteins are plant defence proteins. The birch-pollen allergen Bet v 1 is one, and very similar ones sit in raw apple (Mal d 1), cherry and other stone fruit, hazelnut (Cor a 1), carrot, celery, soy (Gly m 4), peanut (Ara h 8) and kiwi. Someone first sensitised by breathing birch pollen can then react to these foods because the immune system mistakes them for birch (pollen-food syndrome, also called oral allergy syndrome). PR-10 proteins are fragile: cooking, canning, pasteurising and stomach digestion break them down, which is why cooked apple or roasted hazelnut is often fine. How bad it gets: usually mild and quick, itching or tingling of the lips, mouth and throat within minutes of eating the raw food. Rare exceptions are more serious, such as reactions to soy protein drinks and some celery reactions.","evidence":"Established food composition. Association: guideline and clinical series link birch sensitisation to raw-food mouth reactions (Skypala 2022, BSACI). Being sensitised to PR-10 does not by itself mean true peanut or tree-nut allergy (Uotila 2018)."},{"id":"hevein_chitinases","col":"al","group":"Allergen protein families","name":"Latex Hev b proteins and hevein-like chitinases","sub":"latex Hev b 1, 3, 5, 6.02 (hevein); class I chitinases in avocado, banana, chestnut","how":"Natural rubber latex holds more than a dozen allergenic proteins, named Hev b 1 to 15. Hev b 1 and 3 matter most for people with many operations (such as spina bifida), Hev b 5 and 6.02 (hevein) for health workers. Hevein is a small chitin-binding piece that plants use to defend against fungi, and the same piece sits at the end of class I chitinase enzymes in avocado, banana and chestnut; this shared shape helps explain the latex-fruit syndrome. Fruit chitinases rise when fruit is ripened with ethylene gas and are inactivated by heating, so cooked fruit is less of a problem. Latex proteins stick to glove powder and become airborne, which made powdered gloves a major cause of latex asthma. Hidden latex sources include gloves, balloons, catheters, condoms, elastic, dental dams and some adhesive tapes. How bad it gets: latex allergy and latex-fruit reactions are often systemic, including anaphylaxis.","evidence":"Lab: hevein-domain chitinases from chestnut and avocado gave positive skin tests in about 7 in 10 latex-fruit-allergic patients (Blanco 1999). Review: latex-fruit syndrome in 4 to 88% of latex-allergic people (Gromek 2024)."},{"id":"tropomyosin","col":"al","group":"Allergen protein families","name":"Tropomyosin (invertebrate)","sub":"shrimp, crab, lobster, molluscs; house dust mite (Der p 10); cockroach (Bla g 7)","how":"Tropomyosin is a muscle protein. The versions in invertebrates (shrimp, prawn, crab, lobster, squid, snails, and also house dust mites, cockroaches and edible insects) are so alike that IgE against one often binds the others; tropomyosin from fish, meat and other vertebrates is not allergenic. It survives boiling and cooking, so cooked shellfish and the steam from cooking it can trigger reactions. How bad it gets: shellfish allergy is usually lifelong and can cause anaphylaxis; people sensitised only through dust mites are often sensitised to shrimp on testing without always reacting when they eat it.","evidence":"Established: tropomyosin is the major heat-stable shellfish allergen (Leung 1994; Reese 1999). Lab/association: dust-mite-allergic people who never ate shellfish can be shrimp-sensitised (Fernandes 2003)."},{"id":"parvalbumin","col":"al","group":"Allergen protein families","name":"Parvalbumin (fish)","sub":"beta-parvalbumin in the muscle of bony fish; most in white fish, least in tuna and mackerel","how":"Parvalbumin is a small calcium-binding protein in fish muscle, and it is the main fish allergen. Versions in cod, salmon, herring and most bony fish are similar enough that people allergic to one fish usually react to several; dark-fleshed fish such as tuna and mackerel have less of it and cross-react less, but which fish an individual tolerates can only be found out with an allergist. It is fairly heat-stable, so cooked fish still causes reactions (heavy processing such as canning lowers it somewhat), and vapour from cooking fish can cause reactions in very sensitive people. Shark and ray (cartilaginous fish) have a different parvalbumin, and shellfish allergy involves a different protein altogether. How bad it gets: fish allergy is usually lifelong and can cause anaphylaxis.","evidence":"Lab: carp parvalbumin bound IgE from all 60 fish-allergic patients tested (Swoboda 2002); cross-reactivity was strongest among cod, salmon, pollack, herring and wolffish and weakest for tuna and mackerel (Van Do 2005)."},{"id":"eo_lemon","col":"eo","group":"Citrus","name":"Lemon oil","sub":"cold-pressed peel; limonene, citral","how":"Pressed from the peel; mostly limonene with some citral. Inhaled it gives a bright citrus smell signal. Cold-pressed lemon oil also carries small amounts of light-sensitising furocoumarins, so skin covered in it can burn in strong sun.","evidence":"No reliable trials for health claims beyond mood in small aroma studies. Lemon scent is one of the four classic smell-training odours."},{"id":"eo_sweet_orange","col":"eo","group":"Citrus","name":"Sweet orange oil","sub":"Citrus sinensis peel; limonene","how":"Pressed from the peel and over 90% limonene. Inhaled it reaches the emotional brain through the smell pathway.","evidence":"Mixed: in small unblinded studies, orange scent in waiting rooms lowered anxiety. Old oil oxidises and can cause skin allergy."},{"id":"eo_bergamot","col":"eo","group":"Citrus","name":"Bergamot oil","sub":"Citrus bergamia peel; limonene, linalyl acetate, bergapten","how":"Pressed from the peel of a bitter Italian citrus (the flavour of Earl Grey tea). Contains limonene, linalyl acetate and linalool, plus bergapten, which makes skin burn in sunlight.","evidence":"Established harm: blistering burns when skin with bergamot oil meets sun or tanning lamps. Calming claims rest on small aroma studies."},{"id":"eo_spearmint","col":"eo","group":"Mint family","name":"Spearmint oil","sub":"Mentha spicata; carvone, limonene","how":"Mostly carvone (the spearmint smell) with limonene, and much less menthol than peppermint, so it cools less.","evidence":"No reliable trials of the oil for health outcomes."},{"id":"eo_peppermint","col":"eo","group":"Mint family","name":"Peppermint oil","sub":"Mentha × piperita; menthol, menthone","how":"Mostly menthol and menthone. Swallowed in enteric-coated capsules (which open past the stomach) it relaxes gut muscle and calms spasm; rubbed on the forehead it cools the skin; inhaled it gives a sharp 'fresh' smell signal. It also relaxes the valve at the top of the stomach, which is why it can cause heartburn.","evidence":"Proven: enteric-coated capsules eased IBS symptoms and belly pain in pooled trials, though trial quality was low and the largest trial missed its main endpoint. Mixed: rubbed on for tension headache (one small trial). Failed: smelling peppermint did not reduce nausea after surgery (Cochrane 2018). Neat oil should not be put on or near the faces of babies and young children."},{"id":"eo_lavender","col":"eo","group":"Flowers","name":"Lavender oil","sub":"Lavandula angustifolia; linalool, linalyl acetate","how":"Mostly linalool and linalyl acetate. Swallowed as a standardised capsule (Silexan) it reaches the brain and in lab work damps calcium entry into nerve cells, a calming action partly like the drug pregabalin; inhaled, its smell reaches the emotional (limbic) brain through the olfactory bulb; on skin it can sensitise once oxidised.","evidence":"Proven: Silexan capsules reduced anxiety more than placebo in pooled trials (largely run by the maker); burping and mild stomach upset are its common side effects. Mixed: inhaled lavender for sleep and situational anxiety (small, unblinded trials). In one experiment lavender scent slightly worsened working memory. Lab only: Parkinson's and brain-protection claims. Case reports link repeated skin use to breast growth in children."},{"id":"eo_clary_sage","col":"eo","group":"Flowers","name":"Clary sage oil","sub":"Salvia sclarea; linalyl acetate, linalool","how":"A sage relative whose oil is mostly linalyl acetate and linalool, similar to lavender; it also contains sclareol. Usually inhaled or used in massage oils.","evidence":"Claims for hormones, periods and menopause rest on very small or uncontrolled studies; no reliable trials. It is a different plant from culinary sage, whose oil contains seizure-provoking thujone."},{"id":"eo_ylang_ylang","col":"eo","group":"Flowers","name":"Ylang-ylang oil","sub":"Cananga odorata; linalool, benzyl esters, germacrene","how":"A sweet, heavy floral oil rich in linalool, benzyl benzoate and other esters. Inhaled it is used for relaxation; on skin it is a well-known fragrance allergen.","evidence":"Calming claims rest on tiny, unblinded studies. Association: one of the commonest essential oils to cause positive allergy patch tests."},{"id":"eo_chamomile","col":"eo","group":"Flowers","name":"Chamomile oil","sub":"German (Matricaria) and Roman (Chamaemelum); bisabolol, chamazulene, esters","how":"German chamomile oil is blue from chamazulene and contains bisabolol; Roman chamomile oil is mostly esters. The calming apigenin in chamomile tea barely distils into the oil.","evidence":"No reliable trials of the oil itself; chamomile tea evidence is listed under the parsley & celery food. Chamomile is in the daisy family, and people allergic to daisy-family plants can react to it on the skin."},{"id":"eo_wintergreen","col":"eo","group":"Trees & resins","name":"Wintergreen oil","sub":"Gaultheria; about 98% methyl salicylate","how":"Distilled from wintergreen leaves (or sweet birch bark) and almost entirely methyl salicylate. Used in muscle rubs and liniments for a warming, counter-irritant effect.","evidence":"Mixed: salicylate rubs give little or no pain relief in better trials. Established harms: very small swallowed amounts have killed young children; skin use can boost the blood thinner warfarin and cause bleeding."},{"id":"eo_eucalyptus","col":"eo","group":"Trees & resins","name":"Eucalyptus oil","sub":"Eucalyptus globulus; 1,8-cineole","how":"Mostly 1,8-cineole. Inhaled as steam or rub it gives a strong cooling, 'opening' sensation in the nose (it stimulates cold-sensing nerves rather than actually widening airways).","evidence":"Purified cineole capsules have some trial evidence for COPD and bronchitis; the oil itself has little. Harms: should not be swallowed; poisoning causes drowsiness, vomiting and sometimes seizures, though most children who swallow small amounts stay well. Do not put it on or near the faces of babies and young children."},{"id":"eo_camphor","col":"eo","group":"Trees & resins","name":"Camphor oil","sub":"Cinnamomum camphora; camphor, cineole","how":"White camphor oil from the camphor laurel; contains camphor and 1,8-cineole, and is found in many chest rubs and Asian balms.","evidence":"No good trials for any benefit. Established harm: swallowing camphor products, or rubbing them repeatedly on small children, can cause seizures."},{"id":"eo_tea_tree","col":"eo","group":"Trees & resins","name":"Tea tree oil","sub":"Melaleuca alternifolia; terpinen-4-ol","how":"Mostly terpinen-4-ol with gamma-terpinene and a little 1,8-cineole. Used on skin as a diluted gel or solution, where it kills bacteria and fungi in lab tests. Oxidised (old) oil is a stronger skin allergen.","evidence":"Mixed: small trials for acne and athlete's foot; equal to a weak antifungal for toenails. Association: a frequent cause of allergic skin rash. Should not be swallowed; poisoning has been reported in children. Case reports link repeated skin use to breast growth in boys."},{"id":"eo_frankincense","col":"eo","group":"Trees & resins","name":"Frankincense oil","sub":"Boswellia resin; alpha-pinene, limonene","how":"Steam-distilled from Boswellia resin; mostly alpha-pinene and other light terpenes. The boswellic acids studied for arthritis stay behind in the resin and are taken as swallowed extracts, not as the oil.","evidence":"The oil itself has no good human trials. Arthritis evidence belongs to Boswellia resin extracts (mixed)."},{"id":"eo_sandalwood","col":"eo","group":"Trees & resins","name":"Sandalwood oil","sub":"Santalum album; alpha- and beta-santalol","how":"A woody oil mostly made of santalols. Inhaled or worn as perfume; a known skin allergen.","evidence":"No reliable trials for health benefits. Association: about 1.5% of patients tested in European allergy clinics react to it."},{"id":"eo_cedarwood","col":"eo","group":"Trees & resins","name":"Cedarwood oil","sub":"Virginia or Atlas cedarwood; cedrol, thujopsene, himachalenes","how":"A woody oil of heavier terpenes (cedrol, thujopsene, himachalenes). Not the same as cedar-leaf (thuja) oil, which contains seizure-provoking thujone.","evidence":"No human trials for health outcomes; claims rest on animal or lab work."},{"id":"eo_smell_kit","col":"eo","group":"Kits & blends","name":"Smell-training oils","sub":"rose, lemon, eucalyptus, clove (olfactory training)","how":"A set of four strong, distinct odours (rose, lemon, eucalyptus and clove: the flowery, fruity, resinous and spicy families) sniffed deliberately, twice a day for months. The repeated practice is thought to help the olfactory bulb and smell cortex relearn and to encourage regrowth of smell nerve cells, which renew throughout life.","evidence":"Mixed: meta-analyses and trials suggest more people regain smell after viral infections (including COVID-19) when they train, especially if started early, but trials can't be blinded and a large post-COVID trial was inconclusive. In Parkinson's, one unblinded study found modest gains. The oils themselves are not a medicine; it is the practice that matters."},{"id":"eo_rosemary","col":"eo","group":"Herbs & spices","name":"Rosemary oil","sub":"Rosmarinus officinalis (now Salvia rosmarinus); cineole, camphor, alpha-pinene","how":"Mostly 1,8-cineole, camphor and alpha-pinene. Inhaled, some cineole is absorbed into the blood. The rosemary herb's rosmarinic and carnosic acids hardly distil into the oil.","evidence":"Mixed: rosemary aroma improved memory quality but slowed memory speed in one randomised experiment. Harm: its camphor and cineole can provoke seizures in people with epilepsy; it is listed among oils to avoid in epilepsy."},{"id":"eo_oregano","col":"eo","group":"Herbs & spices","name":"Oregano oil","sub":"Origanum vulgare; carvacrol, thymol","how":"Mostly carvacrol with some thymol; strong and irritating on skin and in the mouth unless well diluted.","evidence":"Lab only: kills bacteria and fungi in dishes. No reliable human trials for infections or gut problems."},{"id":"eo_thyme","col":"eo","group":"Herbs & spices","name":"Thyme oil","sub":"Thymus vulgaris; thymol, p-cymene","how":"Mostly thymol (in the common type) with p-cymene; antiseptic and skin-irritating when concentrated.","evidence":"Thymol's benefit is shown only as part of essential-oil mouthwashes; the oil alone lacks human trials."},{"id":"eo_clove","col":"eo","group":"Herbs & spices","name":"Clove oil","sub":"Syzygium aromaticum; eugenol","how":"Mostly eugenol. Dabbed on the gum it numbs; dentists use eugenol in temporary fillings and dry-socket dressings. Neat oil can burn the mouth lining.","evidence":"Mixed: clove gel matched benzocaine for needle pain in one small trial. Association: a common essential-oil skin allergen."},{"id":"eo_cinnamon","col":"eo","group":"Herbs & spices","name":"Cinnamon oil","sub":"bark oil (cinnamaldehyde) or leaf oil (eugenol)","how":"Cinnamon bark oil is mostly cinnamaldehyde; leaf oil is mostly eugenol. Both are strong irritants and sensitisers on skin and in the mouth.","evidence":"No reliable human trials for health benefits of the oil (cinnamon as a food is listed separately). Association: cinnamon flavour is a recognised cause of mouth and skin allergy."},{"id":"eo_lemongrass","col":"eo","group":"Herbs & spices","name":"Lemongrass oil","sub":"Cymbopogon; citral, geraniol","how":"Mostly citral (a lemon-scented aldehyde) with geraniol and myrcene; citral is a known skin sensitiser.","evidence":"No reliable human trials. Association: one of the commonest essential oils to cause positive allergy patch tests."},{"id":"eo_ginger","col":"eo","group":"Herbs & spices","name":"Ginger oil","sub":"Zingiber officinale; zingiberene, beta-sesquiphellandrene","how":"Steam-distilled from the root; mostly zingiberene and other light terpenes. The pungent gingerols that give ginger root its effects mostly stay behind and are not in the oil.","evidence":"No oil-specific trials of note; aromatherapy in general did not clearly reduce nausea after surgery (Cochrane 2018). Ginger root as food is listed separately."},{"id":"eo_black_pepper","col":"eo","group":"Herbs & spices","name":"Black pepper oil","sub":"Piper nigrum; beta-caryophyllene, limonene, pinenes","how":"Distilled from peppercorns; mostly beta-caryophyllene and light terpenes, with almost none of the piperine that gives pepper its bite. Sniffed, it stimulates the smell and taste areas of the brain (insula), which help trigger swallowing.","evidence":"Mixed: sniffing it sped up the swallow reflex in one trial in older stroke survivors."},{"id":"tx_tce","col":"tx","group":"Solvents","name":"Trichloroethylene (TCE)","sub":"degreaser, dry cleaning, contaminated groundwater","how":"A chlorinated solvent used to degrease metal and once in dry cleaning and decaffeination. It is breathed as vapour, absorbed through skin, or drunk in contaminated water; it is fat-soluble so it enters the brain, and is processed in the liver into toxic breakdown products.","evidence":"Association: linked with Parkinson's in a twin study (about 6 times the odds; Goldman 2012) and in Marines exposed through contaminated water at Camp Lejeune (about 70% higher risk; Goldman 2023). Established: classed by the WHO cancer agency as a known cause of kidney cancer (Guha 2012). The US EPA moved to ban most uses in 2024."},{"id":"tx_perc","col":"tx","group":"Solvents","name":"Perchloroethylene (PERC)","sub":"dry-cleaning solvent","how":"The main dry-cleaning solvent, breathed as vapour by workers and people living above dry cleaners. Like TCE it is fat-soluble, reaches the brain and is broken down in the liver.","evidence":"Established: classed as a probable cause of bladder cancer (Guha 2012). Parkinson's: a twin study showed a similar trend to TCE (OR 10.5) but too few exposed people to be certain (Goldman 2012), so no link is drawn yet."},{"id":"tx_hexane","col":"tx","group":"Solvents","name":"n-Hexane","sub":"glues, cleaners, solvent sniffing","how":"A petroleum solvent in glues, cleaners and extraction work, breathed as vapour. The liver turns it into 2,5-hexanedione, which cross-links the internal scaffolding of long nerve fibres so they swell and die back from the toes and fingers.","evidence":"Established: heavy work exposure or glue sniffing causes a nerve damage starting in the feet and hands, which usually improves slowly after exposure stops."},{"id":"tx_toluene","col":"tx","group":"Solvents","name":"Toluene","sub":"paints, thinners, glue sniffing","how":"A solvent in paints, thinners and glues, breathed as vapour. It dissolves into the fatty white matter of the brain, acting like an anaesthetic short term and damaging white matter with years of heavy exposure.","evidence":"Established: chronic solvent abuse causes cerebellar damage (unsteadiness, tremor), dementia-like thinking problems and hearing loss. Effects of lower work exposure are milder and less certain."},{"id":"tx_tobacco","col":"tx","group":"Habits","name":"Tobacco smoke","sub":"cigarettes, cigars, second-hand smoke","how":"Burning tobacco makes thousands of chemicals that are breathed deep into the lungs: tar, carbon monoxide, oxidising gases and cancer-causing compounds, plus addictive nicotine. They irritate and scar the airways, damage the lining of blood vessels, and keep the immune system inflamed.","evidence":"Established: the leading preventable cause of lung disease, heart attack and stroke. Proven: in a randomised quit-smoking trial, stopping slowed lung function loss and lowered deaths (Lung Health Study 1994, 2005). Association: more dementia and MS. The Parkinson's paradox: smokers get Parkinson's less often, but easier quitting may itself be an early sign of the disease (Ritz 2014), and nicotine patches did not slow Parkinson's (NIC-PD 2023), so this is not a reason to smoke."},{"id":"tx_vaping","col":"tx","group":"Habits","name":"Vaping (e-cigarettes)","sub":"nicotine or THC aerosol","how":"A battery heats a liquid (usually nicotine, flavourings, propylene glycol and glycerol) into an aerosol that is breathed into the lungs. It avoids burning, so it carries far fewer of the tar and combustion chemicals of smoke, but still delivers addictive nicotine and other irritants.","evidence":"Association: the 2019 outbreak of vaping lung injury (EVALI) was tied mostly to illicit THC vapes containing vitamin E acetate (Blount 2020). Proven: for smokers trying to quit with support, e-cigarettes helped more people stop smoking than nicotine replacement (Hajek 2019). Long-term effects of years of nicotine vaping are not yet known."},{"id":"tx_alcohol","col":"tx","group":"Habits","name":"Alcohol","sub":"beer, wine, spirits","how":"Ethanol is absorbed from the stomach and gut and broken down mainly in the liver into acetaldehyde, a toxic chemical. Heavy drinking inflames and scars the liver, poisons nerves directly, crowds out food and blocks thiamine (vitamin B1) absorption, and over years shrinks the brain.","evidence":"Established: heavy drinking damages the liver, nerves and cerebellum and causes Wernicke–Korsakoff syndrome through thiamine deficiency. Proven: stopping drinking reduced atrial fibrillation in a randomised trial. Association: brain shrinkage is seen even at moderate intake, and genetic studies find dementia risk rising with drinking; the old idea that light drinking protects the brain does not hold up in better-controlled studies. Parkinson's: no consistent link."},{"id":"tx_bpa","col":"tx","group":"Plastics & industrial chemicals","name":"Bisphenol A (BPA)","sub":"polycarbonate plastic, can linings, receipts","how":"BPA leaches from hard plastics, food-can linings and till receipts into food and skin. It is cleared within hours, but exposure is near-constant. Its shape lets it bind oestrogen receptors and act as a weak oestrogen.","evidence":"Lab: acts like oestrogen in cells and harms development in animals. Association: human studies link it to reproductive, metabolic and child behaviour outcomes, but causation is not established (Rochester 2013)."},{"id":"tx_phthalates","col":"tx","group":"Plastics & industrial chemicals","name":"Phthalates","sub":"soft PVC, fragrances, cosmetics","how":"Chemicals that make plastic soft and carry fragrances; they leach into food and are absorbed through skin. Some, such as DEHP, block testosterone production in the testes of animals.","evidence":"Association: higher levels go with lower testosterone in men, women and children (Meeker 2014, cross-sectional) and, before birth, with signs of lower testosterone action in baby boys (Swan 2005). Lab: anti-testosterone effects are clear in animals."},{"id":"tx_pfas","col":"tx","group":"Plastics & industrial chemicals","name":"PFAS (\"forever chemicals\")","sub":"non-stick, waterproofing, firefighting foam","how":"Fluorinated chemicals that repel water and grease. They enter through drinking water and food, bind to blood proteins and stay in the body for years because the kidneys reabsorb them.","evidence":"Association: in children, higher PFAS went with weaker vaccine responses (Grandjean 2012); in adults, higher PFOA with more kidney cancer (Shearer 2021). Other links (cholesterol, thyroid, pregnancy) are being studied; most evidence is observational."},{"id":"tx_pbde","col":"tx","group":"Plastics & industrial chemicals","name":"PBDE flame retardants","sub":"older foam furniture, electronics","how":"Brominated flame retardants added to foam and electronics shed into house dust and are swallowed, especially by toddlers. They build up in body fat and resemble thyroid hormone, which the developing brain needs.","evidence":"Association: children with higher levels before birth scored lower on development tests (Herbstman 2010). Most uses are now phased out, but they persist in old products and dust."},{"id":"tx_microplastics","col":"tx","group":"Plastics & industrial chemicals","name":"Micro- and nanoplastics","sub":"fragments from plastic breakdown","how":"Tiny plastic fragments from breaking-down packaging, textiles and tyres are swallowed and breathed in. The smallest can cross into blood and lodge in tissues, including artery plaque and brain.","evidence":"Emerging. Association: plastic in artery plaque was linked with more heart attacks, strokes and deaths (Marfella 2024); plastic levels in brains rose from 2016 to 2024 and were higher in people with dementia (Nihart 2025). Whether they cause harm, or just collect in damaged tissue, is not known."},{"id":"tx_paraquat","col":"tx","group":"Pesticides","name":"Paraquat","sub":"weed killer","how":"A widely used weed killer, absorbed mainly by breathing spray or through the skin while mixing and spraying. Inside cells it cycles back and forth making reactive oxygen, overwhelming antioxidant defences; swallowed, it severely scars the lungs.","evidence":"Established: poisoning destroys the lungs. Association: farmers who used it have about 1.6 to 2.5 times the odds of Parkinson's (Tanner 2011; Tangamornsuksan 2019). It is banned in the EU and many other countries."},{"id":"tx_rotenone","col":"tx","group":"Pesticides","name":"Rotenone","sub":"plant-derived insecticide, fish poison","how":"A plant-derived insecticide and fish poison that blocks complex I, the first step of energy production in mitochondria, starving cells of energy and producing reactive oxygen.","evidence":"Established: complex I blocker. Lab: it reproduces Parkinson's-like damage in animals. Association: users had about 2.5 times the odds of Parkinson's in the Agricultural Health Study (Tanner 2011). Now withdrawn from most farm uses in the US and EU."},{"id":"tx_organophosphates","col":"tx","group":"Pesticides","name":"Organophosphate insecticides","sub":"chlorpyrifos, malathion and others","how":"Absorbed through skin, lungs or gut, they block the enzyme that clears acetylcholine, so nerve signals to muscles, glands and the gut fire non-stop. Some types later damage long nerves weeks after poisoning.","evidence":"Established: acute poisoning causes sweating, drooling, cramps, weakness and breathing failure; some cause delayed nerve damage. Long-term low-level effects, including on Parkinson's risk, are less consistent."},{"id":"tx_organochlorines","col":"tx","group":"Pesticides","name":"Organochlorine pesticides","sub":"DDT, dieldrin and similar","how":"Older insecticides that dissolve in fat and persist for decades in soil, food chains and body fat. They disturb nerve-cell ion channels and some act like weak hormones.","evidence":"Association: higher dieldrin in blood stored decades earlier was linked with later Parkinson's in never smokers, though the overall trend was borderline (Weisskopf 2010). Most are banned but still found in people today."},{"id":"tx_pm25","col":"tx","group":"Air","name":"Fine particle pollution (PM2.5)","sub":"traffic, burning, industry, wildfire smoke","how":"Particles smaller than 2.5 thousandths of a millimetre are breathed deep into the air sacs; the finest pass into the blood. They inflame the lungs and blood vessels, thicken the blood and stiffen arteries, and some reach the brain.","evidence":"Association, from large cohorts: more heart attacks and strokes (Miller 2007; Shah 2015) and more dementia, though the pooled dementia estimate is modest and depends on study quality (Wilker 2023). A leading environmental cause of death worldwide."},{"id":"tx_co","col":"tx","group":"Air","name":"Carbon monoxide","sub":"faulty heaters, engines, fires","how":"A colourless, odourless gas from incomplete burning. It binds haemoglobin over 200 times more tightly than oxygen, so blood carries less oxygen, and it poisons cell energy production; the brain and heart suffer first.","evidence":"Established: poisoning causes headache, confusion, collapse and death; some survivors develop delayed memory loss and Parkinson-like stiffness and gait days to weeks later, which often recovers within a year (Choi 1983)."},{"id":"tx_diesel","col":"tx","group":"Air","name":"Diesel exhaust","sub":"engines, mines, trucks, generators","how":"A mix of soot particles coated with cancer-causing chemicals and irritant gases. The soot is fine enough to reach deep lung tissue.","evidence":"Association: in miners, lung cancer deaths rose with diesel exposure after accounting for smoking (DEMS, Silverman 2012); the WHO cancer agency classes it as a known human carcinogen."},{"id":"tx_silica","col":"tx","group":"Dusts & fibres","name":"Crystalline silica dust","sub":"stone, sand, concrete, engineered stone","how":"Cutting, grinding or blasting stone, concrete and engineered stone makes fine quartz dust that is breathed deep into the lungs. Immune cells that swallow the sharp particles die and release scarring signals, so hard nodules of scar tissue build up.","evidence":"Established: causes silicosis, a permanent, often progressive lung scarring, and raises tuberculosis risk. Association: higher lung cancer risk in exposed workers (Poinen-Rughooputh 2016)."},{"id":"tx_asbestos","col":"tx","group":"Dusts & fibres","name":"Asbestos","sub":"old insulation, boards, brake linings","how":"Long, thin mineral fibres released when old insulation, boards or linings are disturbed. Breathed in, they lodge in the lungs and the lining around them, where the body cannot break them down, causing scarring and, decades later, cancer.","evidence":"Established: causes asbestosis (lung scarring), pleural plaques, mesothelioma and lung cancer, typically 20 to 40 years after exposure; smoking multiplies the lung-cancer risk."},{"id":"tx_lead","col":"tx","group":"Heavy metals","name":"Lead","sub":"old paint, pipes, soil, some jobs","how":"Lead is swallowed (dust from old paint, soil, water from lead pipes) or breathed as fumes at work. The body mistakes it for calcium and zinc, so it stores in bone for decades and disrupts nerve signalling, brain development and the kidneys, and raises blood pressure.","evidence":"Established: no safe level in children; it lowers IQ even at low blood levels (Lanphear 2005). Association, judged causal by reviewers: higher blood pressure, and more cardiovascular deaths at low adult levels (Navas-Acien 2007; Lanphear 2018)."},{"id":"tx_mercury","col":"tx","group":"Heavy metals","name":"Mercury","sub":"methylmercury in fish, mercury vapour","how":"Methylmercury builds up in large predatory fish and is absorbed from the gut; it crosses into the brain and the unborn baby's brain. Mercury vapour (from gold mining, broken instruments, some industries) is breathed in. Both poison nerve cells; inorganic mercury also damages the kidneys.","evidence":"Established: high methylmercury exposure (Minamata disease) causes numbness, poor coordination, narrowed vision and hearing loss, and severe brain damage in babies exposed before birth. The low levels in ordinary fish eating are a different, much smaller question."},{"id":"tx_arsenic","col":"tx","group":"Heavy metals","name":"Arsenic","sub":"contaminated well water, rice","how":"Inorganic arsenic dissolves naturally into groundwater in some regions and is swallowed in water and food. It interferes with cell energy enzymes and DNA repair, building up in skin, hair and nails.","evidence":"Established: long-term high exposure causes skin thickening and dark spots, and cancers of the skin, bladder and lung (Hughes 2011). Association: skin lesions rise with dose even at moderate levels and improve when exposure falls (Argos 2011; Seow 2012). High exposure also damages nerves."},{"id":"tx_cadmium","col":"tx","group":"Heavy metals","name":"Cadmium","sub":"tobacco smoke, some foods, batteries","how":"Cadmium enters through tobacco smoke, food grown in contaminated soil, and some jobs (batteries, smelting). It is stored in the kidneys for 10 to 30 years, damaging the tubules that reclaim minerals, and weakens bone.","evidence":"Established: kidney tubule damage and bone loss (itai-itai disease at high exposure; Järup 2009). Low iron stores increase absorption."},{"id":"aa_phenylalanine","col":"aa","group":"Essential","name":"Phenylalanine","sub":"essential; made into tyrosine","how":"An essential amino acid (the body cannot make it, so it must come from food). It is built into proteins, and the liver turns the spare into tyrosine. Absorbed in the small intestine and carried into the brain by the same large-neutral-amino-acid carrier (LAT1) that levodopa uses. Aspartame sweetener is also a source.","evidence":"Needed by everyone. People with the inherited condition PKU cannot convert it, and it builds up and harms the developing brain, which is why foods with aspartame carry a warning. Phenylalanine supplements have no good evidence of benefit."},{"id":"aa_tryptophan","col":"aa","group":"Essential","name":"Tryptophan","sub":"essential; made into serotonin and melatonin","how":"An essential amino acid. Built into proteins; a small share is turned into 5-HTP and then serotonin (in the gut and the brain) and, at night in the pineal gland, into melatonin. Most is broken down along the kynurenine pathway, which also makes niacin (vitamin B3). Enters the brain on the LAT1 carrier, competing with the other large neutral amino acids and levodopa.","evidence":"Needed for serotonin and melatonin; extra beyond a normal diet isn't shown to do more for most people. Supplements for depression: the few good trials were small and inconclusive (Cochrane 2002). In 1989 contaminated tryptophan supplements from one maker caused an epidemic of eosinophilia-myalgia syndrome (Kilbourne 1996)."},{"id":"aa_bcaa","col":"aa","group":"Essential","name":"Leucine, isoleucine & valine","sub":"the branched-chain amino acids (BCAAs)","how":"Three essential amino acids with a branched shape. Unlike most amino acids they are burned mainly in muscle rather than the liver. Leucine also acts as a signal (through mTOR) that switches on muscle-protein building after a meal. All three enter the brain on the LAT1 carrier that levodopa uses.","evidence":"Needed for building muscle. Leucine supplements on their own did not add muscle or strength in older adults across 17 trials (Guo 2022); combined with vitamin D and protein, small gains in grip and walking speed appeared, on low-quality evidence (Huang 2025). Leucine and isoleucine drinks switched off the effect of a levodopa drip in Parkinson's (Nutt 1984)."},{"id":"aa_lysine","col":"aa","group":"Essential","name":"Lysine","sub":"essential; low in grains","how":"An essential amino acid. Built into proteins, and needed for the cross-links that make collagen strong and to make carnitine. Cereals are low in it and legumes rich, which is why grains and beans complement each other. It is not a large neutral amino acid and does not compete with levodopa.","evidence":"Needed for collagen and protein. Lysine was tested directly and did not blunt levodopa (Nutt 1984). Supplement claims (for example, against cold sores) are outside this map and not well supported."},{"id":"aa_histidine","col":"aa","group":"Essential","name":"Histidine","sub":"essential; made into histamine","how":"An essential amino acid. Built into proteins (including haemoglobin), and turned into histamine, the messenger of allergy, stomach acid and wakefulness, and into carnosine in muscle. Enters the brain on the LAT1 carrier.","evidence":"Needed; extra beyond a normal diet isn't shown to do more. No good evidence for supplements in brain conditions."},{"id":"aa_threonine","col":"aa","group":"Essential","name":"Threonine","sub":"essential; gut mucus","how":"An essential amino acid. Built into proteins and used heavily for the mucus (mucin) proteins that coat the gut lining. Can use the LAT1 carrier, though more weakly than leucine or phenylalanine.","evidence":"Needed; extra beyond a normal diet isn't shown to do more."},{"id":"aa_methionine","col":"aa","group":"Essential","name":"Methionine","sub":"essential; the source of the body's methyl groups","how":"An essential amino acid and the first one in every new protein. Turned into SAM, the body's main donor of methyl groups (used to make creatine, adrenaline and to break down levodopa via COMT); what is left is homocysteine, which B12 and folate recycle back, or B6 turns into cysteine. Enters the brain on the LAT1 carrier.","evidence":"Needed. Levodopa's breakdown uses up methyl groups and tends to raise homocysteine; B vitamins lower it, and whether everyone on levodopa needs them is debated (Ahlskog 2023). Methionine supplements are not shown to help."},{"id":"aa_tyrosine","col":"aa","group":"Conditionally essential","name":"Tyrosine","sub":"made from phenylalanine; makes L-DOPA","how":"Made in the liver from phenylalanine, or taken in from protein. Nerve cells turn it into L-DOPA with the enzyme tyrosine hydroxylase, then into dopamine and noradrenaline; the thyroid builds it into thyroid hormone and skin cells into melanin. Reaches the brain on the same LAT1 carrier as levodopa.","evidence":"Normally there is plenty, and the slow step in making dopamine is the enzyme, not the supply. In Parkinson's, oral tyrosine raised a dopamine breakdown marker in spinal fluid (Growdon 1982), but symptom benefit has not been shown. In healthy people, tyrosine seems to help thinking only under short bursts of stress or heavy demand (Jongkees 2015). Not a substitute for levodopa."},{"id":"aa_glutamine","col":"aa","group":"Conditionally essential","name":"Glutamine","sub":"fuel for the gut and immune cells","how":"The most plentiful amino acid in the blood. Made mainly by muscle; the main fuel of gut-lining and immune cells; carries nitrogen safely between organs; and, in the brain, is the raw material nerve cells use to remake glutamate and GABA after support cells (astrocytes) clear them.","evidence":"Needed; can become short in severe illness. Supplements have no good evidence in brain conditions."},{"id":"aa_glycine","col":"aa","group":"Conditionally essential","name":"Glycine","sub":"smallest amino acid; collagen; a calming messenger","how":"The simplest amino acid, a third of collagen. Made from serine. In the spinal cord and brainstem it is a calming (inhibitory) messenger, and in the brain it is a co-activator needed for NMDA glutamate receptors. Also used to make glutathione, creatine and haem.","evidence":"Small trials found glycine before bed improved sleep and next-day tiredness in healthy people, with high risk of bias (Soh 2024). Glycine did not blunt levodopa in a direct test (Nutt 1984)."},{"id":"aa_serine","col":"aa","group":"Conditionally essential","name":"Serine","sub":"made from glucose; makes glycine and D-serine","how":"Made in the body from glucose. Used to make glycine, cell-membrane fats, and, in the brain, D-serine (its mirror-image form), which helps switch on NMDA glutamate receptors.","evidence":"Needed. A 10-person pilot crossover trial of D-serine in Parkinson's lowered movement and behaviour scores (Gelfin 2012); not repeated in a larger trial."},{"id":"aa_cysteine","col":"aa","group":"Conditionally essential","name":"Cysteine","sub":"made from methionine; builds glutathione","how":"Made from methionine (with vitamin B6) or taken in from protein. It supplies the sulfur for glutathione, the cell's main antioxidant, and for taurine; its pairs (cystine) hold keratin and many proteins in shape. N-acetylcysteine (NAC) is a supplement form that the body turns into cysteine.","evidence":"Needed for glutathione; extra beyond a normal diet isn't shown to protect brain cells in people. NAC trials are covered on the NAC card."},{"id":"aa_arginine","col":"aa","group":"Conditionally essential","name":"Arginine","sub":"makes nitric oxide and creatine","how":"Taken in from protein and made in the kidneys from citrulline. Blood-vessel linings turn it into nitric oxide, which relaxes vessels; it also feeds the urea cycle that clears ammonia, and starts the making of creatine.","evidence":"Needed. Small trials found arginine supplements lowered blood pressure a little (about 4 mmHg over 24 hours across 5 trials; Shi 2026), relevant for anyone whose pressure drops on standing. No Parkinson's trials."},{"id":"aa_5htp","col":"aa","group":"Neurotransmitters & derivatives","name":"5-HTP","sub":"5-hydroxytryptophan; the step between tryptophan and serotonin","how":"Made from tryptophan in the body; sold as a supplement extracted from Griffonia seeds. It skips the slow step in serotonin making and is turned into serotonin by AADC, the same enzyme that turns levodopa into dopamine, so carbidopa (which blocks AADC outside the brain) changes how much reaches the brain. Crosses into the brain on amino-acid carriers.","evidence":"In Parkinson's, one 25-person crossover trial found better depression scores but no change in apathy (Meloni 2020), and an 18-person trial found more REM sleep without more dream enactment (Meloni 2022). Small, short, unreplicated. It adds to serotonin-raising medicines, which carries a risk of serotonin excess."},{"id":"aa_glutamate","col":"aa","group":"Neurotransmitters & derivatives","name":"Glutamate","sub":"the main 'go' messenger; umami taste","how":"The most common amino acid in protein and the brain's main excitatory messenger. Free glutamate gives umami taste (tomatoes, aged cheese, mushrooms, MSG). Almost all glutamate eaten is used as fuel by the gut wall and very little reaches the blood; the brain makes its own from glutamine and blood glucose, behind the blood-brain barrier. Turned into GABA by an enzyme that needs vitamin B6.","evidence":"Needed. Too much glutamate signalling (excitotoxicity) damages nerve cells in lab models, but dietary glutamate does not meaningfully reach the brain."},{"id":"aa_gaba","col":"aa","group":"Neurotransmitters & derivatives","name":"GABA","sub":"the main 'stop' messenger; also sold as a supplement","how":"The brain's main inhibitory messenger, made inside nerve cells from glutamate (with vitamin B6). It is not built into proteins. Some is made by gut bacteria and present in fermented foods; sold as a calming supplement.","evidence":"The brain's own GABA is essential to calm circuits. Whether swallowed GABA reaches the brain is unclear, and evidence for a calming effect is thin and partly conflicted (Boonstra 2015). Not tested in Parkinson's."},{"id":"aa_aspartate","col":"aa","group":"Neurotransmitters & derivatives","name":"Aspartate","sub":"energy cycle; weak excitatory messenger","how":"A non-essential amino acid made from the energy cycle in mitochondria. Shuttles energy (the malate-aspartate shuttle), feeds the urea cycle, and is a weaker excitatory messenger at NMDA receptors. Part of aspartame.","evidence":"Needed; the body makes plenty. No good evidence for supplements."},{"id":"aa_taurine","col":"aa","group":"Other","name":"Taurine","sub":"made from cysteine; bile and cell water balance","how":"Not built into proteins. Made from cysteine and plentiful in meat and seafood (almost absent from plants). The liver attaches it to bile acids to make bile salts; cells in the heart, muscle, eye and brain use it to balance water and calcium. Added to energy drinks.","evidence":"Needed; the body makes enough on most diets. Taurine loss was recently proposed, from animal studies, as a driver of ageing, but in 137 men aged 20-93 blood taurine was unrelated to age, muscle or fitness (Marcangeli 2025). No Parkinson's trials."},{"id":"aa_citrulline","col":"aa","group":"Other","name":"Citrulline","sub":"watermelon; turned into arginine","how":"Not built into proteins. Made in the gut and liver, and found in watermelon. Unlike arginine it is not broken down by the gut and liver on the way in, so the kidneys turn swallowed citrulline into arginine.","evidence":"Needed for the urea and arginine cycles; supplements raise blood arginine, but no good evidence for brain conditions."},{"id":"aa_creatine","col":"aa","group":"Other","name":"Creatine","sub":"energy buffer in muscle and brain","how":"Made in the kidney and liver from arginine, glycine and methionine (using a lot of the body's methyl groups), and eaten in meat and fish. Muscle and brain store it as phosphocreatine, a quick-release energy reserve that recharges ATP in seconds.","evidence":"Proven to add a little strength when taken with resistance training in older adults (meta-analyses 2025-2026). Failed in Parkinson's: the NET-PD Long-term Study 1 gave 1741 people creatine for at least 5 years, and it did not slow decline; stopped early for futility (2015). Earlier small trials also showed no clear benefit (Cochrane 2014)."},{"id":"aa_carnitine","col":"aa","group":"Other","name":"Carnitine","sub":"ferries fats into mitochondria","how":"Made in the liver and kidneys from lysine and methionine, and eaten mainly in red meat. It carries long fatty acids into mitochondria to be burned for energy, especially in muscle and heart.","evidence":"Needed; healthy people make enough. Supplements are used for rare inherited carnitine deficiency and in some dialysis patients; benefit for brain conditions is not established, and there are no meaningful Parkinson's trials."},{"id":"wi_lifting","col":"wi","group":"Sudden & heavy loads","name":"Lifting & overexertion","sub":"lifting, pushing, pulling, carrying, twisting","how":"Heavy or frequent loads squeeze the low-back discs and pull on back muscles and ligaments; a sudden heavy lift or lift-and-twist can strain muscle or crack the tough outer ring of a disc. Shoulders, knees and the groin wall also take the load.","evidence":"Overexertion is the most common cause of lost-time work injuries. Long-term studies show low back pain rises with heavier and more frequent lifting."},{"id":"wi_vehicle","col":"wi","group":"Sudden & heavy loads","name":"Motor-vehicle crashes","sub":"driving for work","how":"In a crash the body is held by the seat belt while the head keeps moving, whipping the neck (whiplash); the head and chest can strike the vehicle. Crashes are a leading cause of work deaths.","evidence":"Textbook injury mechanics."},{"id":"wi_slip_trip_fall","col":"wi","group":"Sudden & heavy loads","name":"Slips, trips & same-level falls","sub":"wet floors, clutter, ice, uneven ground","how":"The feet lose grip or catch, and the body lands on an outstretched hand, a knee, a hip, or the back of the head. Sprains and fractures of wrist, ankle and hip are typical; the head can strike the floor.","evidence":"Textbook injury mechanics; a leading cause of work injuries."},{"id":"wi_fall_height","col":"wi","group":"Sudden & heavy loads","name":"Falls from height","sub":"ladders, roofs, scaffolds","how":"Landing energy rises with height: heel and ankle fractures, spinal compression fractures, pelvic and rib fractures, and serious head injury. The leading cause of deaths in construction.","evidence":"Textbook injury mechanics."},{"id":"wi_struck_caught","col":"wi","group":"Sudden & heavy loads","name":"Struck by or caught in objects","sub":"falling objects, vehicles, machinery","how":"Being hit by falling or moving objects, or having a hand or limb pulled into machinery, causes crush injuries, fractures, cuts, amputations and head injury.","evidence":"Textbook injury mechanics."},{"id":"wi_head_impacts","col":"wi","group":"Sudden & heavy loads","name":"Head impacts","sub":"blows, blasts, repeated knocks","how":"A blow or blast accelerates the head so the brain moves inside the skull, stretching nerve fibres and disturbing brain chemistry. Repeated hits add up.","evidence":"Textbook injury mechanics."},{"id":"wi_assault","col":"wi","group":"Sudden & heavy loads","name":"Assault & workplace violence","sub":"health care, police, retail, transit, social work","how":"Physical attacks cause head, face, teeth and hand injuries; threats and attacks also cause psychological injury.","evidence":"Workplace violence is linked with post-traumatic stress in a dose-response pattern."},{"id":"wi_wbv","col":"wi","group":"Cumulative strain","name":"Whole-body vibration","sub":"trucks, tractors, forklifts, heavy equipment","how":"Sitting for hours on a vibrating seat shakes the spine at frequencies the low back resonates with, adding repeated loading to the discs and tiring the back muscles, usually on top of long sitting and jolts.","evidence":"Pooled studies link it with more low back pain and sciatica."},{"id":"wi_prolonged_posture","col":"wi","group":"Cumulative strain","name":"Prolonged standing or sitting","sub":"","how":"Standing for hours loads the feet, legs and low back and pools blood in the leg veins; sitting for hours keeps the spine and hips in one position with little muscle activity.","evidence":"Long standing/walking is linked with more groin hernia repairs; links with back pain are weaker and less consistent."},{"id":"wi_repetitive","col":"wi","group":"Cumulative strain","name":"Repetitive & forceful hand-arm work","sub":"assembly, meat and fish processing, keyboard, tools","how":"The same small movements thousands of times a day, often with a forceful grip, give tendons and their sheaths too little recovery time, and swelling in tight spaces such as the carpal tunnel squeezes the nerve.","evidence":"Repetition and hand force are linked with carpal tunnel syndrome, shoulder tendon disorders and epicondylitis in systematic reviews."},{"id":"wi_awkward_posture","col":"wi","group":"Cumulative strain","name":"Awkward & static postures","sub":"overhead work, kneeling, bending, neck flexion","how":"Holding arms above shoulder height pinches the rotator cuff tendons; long kneeling and squatting load the knee cartilage; bending and neck flexion load the spine. Static holding starves working muscles of blood flow.","evidence":"Arm elevation and awkward postures are linked with shoulder disorders; kneeling and squatting with knee osteoarthritis."},{"id":"wi_hav","col":"wi","group":"Cumulative strain","name":"Hand-arm vibration","sub":"grinders, jackhammers, chainsaws, impact drills","how":"Vibration from power tools travels into the fingers and damages small blood vessels (fingers go white in the cold), touch nerves (numbness, tingling, clumsiness), and the median nerve at the wrist.","evidence":"Strong, dose-related association with vascular and nerve damage in the hands."},{"id":"wi_traumatic_events","col":"wi","group":"Psychological & schedule","name":"Traumatic events at work","sub":"witnessing death, serious injury, disasters, threats","how":"Facing death, serious injury or threat switches on the brain's fear system (amygdala, adrenaline, cortisol). Usually this settles, but in some people the fear memory stays 'live', with flashbacks, avoidance and constant alertness.","evidence":"Exposed rescue and disaster workers develop more acute stress, depression and PTSD than unexposed workers."},{"id":"wi_job_strain","col":"wi","group":"Psychological & schedule","name":"Job strain","sub":"high demands with little control","how":"Long-running pressure with little say over how work is done keeps stress hormones and blood pressure raised and disturbs sleep and mood.","evidence":"Linked with clinical depression and, modestly, with coronary heart disease in large pooled cohorts."},{"id":"wi_shift_work","col":"wi","group":"Psychological & schedule","name":"Shift work & night work","sub":"","how":"Working at night and sleeping by day fights the body clock: light at night suppresses melatonin, daytime sleep is short and broken, and eating at the 'wrong' clock time worsens blood-sugar control.","evidence":"Causes sleep loss around night and early shifts; linked with accidents, type 2 diabetes, weight gain and heart disease (associations, modest in size)."},{"id":"wi_welding_fumes","col":"wi","group":"Chemical exposures","name":"Welding & smelting fumes (manganese)","sub":"welding, steel making, manganese mining","how":"Welding rod and steel fumes contain fine manganese particles that are breathed in and reach the brain, partly directly along the smell nerve; manganese builds up in the basal ganglia (especially the globus pallidus) and disturbs movement circuits (shown mainly in animal studies).","evidence":"Established toxicology: high exposure causes manganism. Welders show more parkinsonism, worsening with cumulative dose."},{"id":"wi_solvent_degreasing","col":"wi","group":"Chemical exposures","name":"Solvent work & degreasing (trichloroethylene)","sub":"metal degreasing, dry cleaning, paints, glues","how":"Organic solvents are breathed in and absorbed through skin; they dissolve in fatty tissue such as the brain, causing dizziness and headache short-term. Trichloroethylene (TCE) and its breakdown products damage mitochondria in dopamine neurons in animal studies, and harm the liver and kidneys.","evidence":"TCE is linked with Parkinson's in human studies (association); it is a recognised carcinogen."},{"id":"wi_pesticide_application","col":"wi","group":"Chemical exposures","name":"Pesticide application (paraquat and others)","sub":"farm work, mixing and spraying","how":"Pesticides enter through skin and lungs during mixing and spraying. Paraquat makes damaging oxygen radicals; rotenone blocks mitochondria. Both kill dopamine neurons in animals.","evidence":"Pesticide exposure is linked with Parkinson's in many studies; for paraquat specifically the human evidence is mixed. Chemical-resistant gloves appeared protective in one large farm cohort."},{"id":"wi_lead_work","col":"wi","group":"Chemical exposures","name":"Lead work","sub":"battery making and recycling, smelting, old-paint removal, firing ranges","how":"Lead dust and fume are breathed or swallowed and stored in bone for decades. Lead blocks enzymes and mimics calcium in nerves, harming the brain, peripheral nerves, kidneys and blood formation.","evidence":"High exposure causes established lead poisoning; lifelong lower exposure is linked with poorer thinking and with Parkinson's (association)."},{"id":"wi_carbon_monoxide","col":"wi","group":"Chemical exposures","name":"Carbon monoxide at work","sub":"engines and forklifts indoors, furnaces, fires","how":"Carbon monoxide binds haemoglobin over 200 times more tightly than oxygen, starving the brain and heart of oxygen; it also directly injures brain cells. Days to weeks after poisoning, memory and thinking problems or parkinsonism can appear.","evidence":"Established toxicology. Hyperbaric oxygen reduced later thinking problems in a randomised trial."},{"id":"wi_wet_work","col":"wi","group":"Chemical exposures","name":"Wet work & skin irritants","sub":"hand washing, gloves, cleaning products, hairdressing, food work","how":"Hours of wet hands or occlusive gloves strip the skin's oily barrier, letting irritants and allergens (rubber chemicals, epoxy, hair dyes) in, which inflames the skin.","evidence":"Two or more hours of wet work a day is linked with 2 to 3.5 times the odds of hand eczema."},{"id":"wi_noise","col":"wi","group":"Noise, heat & dust","name":"Loud noise","sub":"machinery, construction, music, firearms","how":"Loud sound over-drives the hair cells of the inner ear; with years of exposure (or one blast) they die and do not regrow, and the nerve connections to them are lost first.","evidence":"Established: one of the commonest occupational diseases."},{"id":"wi_heat","col":"wi","group":"Noise, heat & dust","name":"Heat exposure","sub":"outdoor work, foundries, kitchens, protective clothing","how":"Hard work in heat makes the body pour blood to the skin and lose water and salt in sweat. When cooling can't keep up, core temperature rises; repeated dehydration also strains the kidneys.","evidence":"Workers under heat strain have more heat illness and kidney injury in pooled studies."},{"id":"wi_silica_dust","col":"wi","group":"Noise, heat & dust","name":"Silica dust","sub":"cutting stone, engineered stone, concrete, sandblasting, mining","how":"Fine crystalline silica particles reach the deepest air sacs; immune cells that swallow them die and release scar-promoting signals, so nodules of scar tissue build up in the lungs.","evidence":"Established cause of silicosis; also raises tuberculosis and lung cancer risk."},{"id":"wi_asbestos_work","col":"wi","group":"Noise, heat & dust","name":"Asbestos work","sub":"old-building renovation, demolition, shipyards, insulation, brakes","how":"Asbestos fibres are long and thin; breathed in, they lodge in the lungs and lining of the chest and can't be cleared, driving scarring and, decades later, cancer.","evidence":"Established cause of asbestosis, mesothelioma and lung cancer; disease appears 20 to 50 years after exposure."},{"id":"wi_isocyanates","col":"wi","group":"Noise, heat & dust","name":"Isocyanates & other sensitisers","sub":"spray paints, foams, glues; also flour, latex, animals","how":"Some workplace chemicals and proteins train the immune system to react to them; afterwards even tiny amounts trigger airway narrowing (asthma). Isocyanates are a leading chemical cause.","evidence":"Established cause of occupational asthma; outcome is best when exposure stops early."},{"id":"wi_bloodborne","col":"wi","group":"Biological exposures","name":"Bloodborne pathogens (needlesticks, splashes)","sub":"health care, cleaning, waste handling, first responders","how":"A needlestick, cut or splash of infected blood into the eye or mouth can transmit hepatitis B, hepatitis C or HIV.","evidence":"Established transmission route; hepatitis B vaccination and post-exposure treatment greatly reduce risk."},{"id":"wi_covid19","col":"wi","group":"Biological exposures","name":"COVID-19 exposure at work","sub":"health care, care homes, transport, food processing","how":"Close contact with infected people or crowded indoor work raises the chance of breathing in SARS-CoV-2.","evidence":"Front-line health-care workers had several times the community infection rate early in the pandemic."},{"id":"bp_cervical_spine","col":"bp","group":"Musculoskeletal","name":"Neck (cervical spine)","sub":"7 neck vertebrae, discs, nerve roots","how":"The seven neck bones stack on cushioning discs and protect the top of the spinal cord; nerve roots leave here for the arms. Work injuries: whiplash strains in vehicle crashes, sprains from falls or lifting, and disc wear or herniation that pinches a nerve root and sends pain, tingling or weakness down an arm.","evidence":"Textbook anatomy and occupational medicine.","pos":[0,1.5,-0.04]},{"id":"bp_thoracic_spine","col":"bp","group":"Musculoskeletal","name":"Mid back (thoracic spine)","sub":"12 vertebrae joined to the ribs","how":"The twelve mid-back bones anchor the ribs, so this part of the spine moves less and is injured less often. Work injuries: compression fractures from falls from height or heavy impacts, and muscle strains.","evidence":"Textbook anatomy and occupational medicine.","pos":[0,1.3,-0.1]},{"id":"bp_lumbar_spine","col":"bp","group":"Musculoskeletal","name":"Low back (lumbar spine)","sub":"5 vertebrae, discs, sciatic nerve roots","how":"The five low-back bones carry most of the upper body's weight; the discs between them and the nerve roots leaving for the legs are under the most load. Work injuries: strains and sprains from lifting and twisting (the most common claimed injury), disc herniation pressing on a nerve root (sciatica), and wear from whole-body vibration.","evidence":"Textbook anatomy and occupational medicine. California law (education, not advice): for police, sheriffs, Highway Patrol and UC peace officers with at least 5 years' full-time service who must wear a duty belt, low-back impairment is presumed work-related (rebuttable; Cal. Labor Code § 3213.2). In general, permanent disability is apportioned by cause: doctors estimate what share came from the work injury versus other factors such as age-related wear or earlier injuries, and the employer pays only the work-caused share (§§ 4663, 4664); that causation apportionment does not apply to the § 3213.2 and § 3212-series presumptions (§ 4663(e)). Lifetime awards for 'the spine' are capped at 100% (§ 4664(c)). Each claim turns on its facts and current law.","pos":[0,1.02,-0.09]},{"id":"bp_shoulders","col":"bp","group":"Musculoskeletal","name":"Shoulders","sub":"both sides: rotator cuff, joint, collarbone, thoracic outlet","how":"Both sides. A shallow ball-and-socket joint held in place by four rotator cuff muscles and their tendons, which makes it very mobile but easy to overload. The nerves (brachial plexus) and blood vessels to the arm pass over the first rib, between the neck's scalene muscles and under the collarbone: the thoracic outlet, where they can be squeezed (thoracic outlet syndrome: arm and hand tingling, worse with arms raised). Work injuries: rotator cuff tendon irritation and tears from overhead and repetitive work, dislocation and fractures from falls.","evidence":"Textbook anatomy and occupational medicine.","pos":[0.19,1.44,0]},{"id":"bp_elbows","col":"bp","group":"Musculoskeletal","name":"Elbows","sub":"both sides: tendons, ulnar nerve (cubital tunnel)","how":"Both sides. A hinge joint where forearm muscles that grip and twist attach by tendons; the ulnar nerve ('funny bone') runs behind it through the cubital tunnel, a groove behind the inner knob of the elbow. Work injuries: tennis and golfer's elbow (tendon overload from forceful gripping and tool use), ulnar nerve compression in the cubital tunnel from leaning on the elbow or keeping it bent for long periods (numb, tingling ring and little fingers, weak grip), fractures from falls.","evidence":"Textbook anatomy and occupational medicine.","pos":[0.265,1.135,-0.012]},{"id":"bp_wrists_hands","col":"bp","group":"Musculoskeletal","name":"Wrists & hands","sub":"both sides: carpal tunnel, tendons, small bones","how":"Both sides. Eight small wrist bones, tendons that bend the fingers, and the median nerve passing through the narrow carpal tunnel. Work injuries: carpal tunnel syndrome and tendon inflammation from forceful, repetitive or vibrating work; fractures and sprains from catching a fall; crush and cut injuries.","evidence":"Textbook anatomy and occupational medicine. California law (education, not advice): a work injury is either 'specific' (one incident, such as a fall onto the hand) or 'cumulative' (repeated physical or mental strain over time, such as carpal tunnel from years of forceful hand work) (Cal. Labor Code § 3208.1). For a cumulative injury, the legal date of injury is when the worker first had disability from it and knew, or reasonably should have known, that work caused it (§ 5412). Each claim turns on its facts and current law.","pos":[0.35,0.865,0.033]},{"id":"bp_fingers","col":"bp","group":"Musculoskeletal","name":"Fingers & thumbs","sub":"both sides","how":"Both sides. Small jointed bones moved by long tendons, with fine nerves and blood vessels for touch. Work injuries: crush, cut and amputation injuries in machinery, trigger finger, and white, numb fingers from vibrating tools (hand-arm vibration syndrome).","evidence":"Textbook anatomy and occupational medicine.","pos":[0.38,0.775,0.05]},{"id":"bp_hips","col":"bp","group":"Musculoskeletal","name":"Hips","sub":"both sides: ball-and-socket joint, pelvis","how":"Both sides. The deep ball-and-socket joint joining leg to pelvis, carrying body weight with every step. Work injuries: fractures from falls (especially in older workers), bursitis and strains, and arthritis linked to years of heavy lifting.","evidence":"Textbook anatomy and occupational medicine.","pos":[0.1,0.92,0]},{"id":"bp_knees","col":"bp","group":"Musculoskeletal","name":"Knees","sub":"both sides: meniscus, ligaments, cartilage, fibular nerve","how":"Both sides. A hinge joint cushioned by two cartilage pads (menisci) and held by ligaments. Just below the outer side of the knee, the common fibular (peroneal) nerve wraps around the head of the fibula close under the skin, where pressure from crossed legs, long squatting or kneeling, or a tight cast or brace can pinch it and cause foot drop (weak lifting of the foot and toes) and numbness on the top of the foot. Work injuries: meniscus and ligament tears from twisting or falls, and osteoarthritis from years of kneeling, squatting, climbing and heavy lifting.","evidence":"Textbook anatomy and occupational medicine. California law (education, not advice): a knee injury can be claimed as 'specific' (one twist or fall) or 'cumulative' (years of kneeling, squatting and lifting) (Cal. Labor Code § 3208.1); for a cumulative injury the date of injury is when disability began and the worker knew or reasonably should have known work caused it (§ 5412). Lifetime permanent disability awards are capped at 100% per body region, and the legs including the hips form one region (§ 4664(c)). Each claim turns on its facts and current law.","pos":[0.1,0.5,0.03]},{"id":"bp_ankles_feet","col":"bp","group":"Musculoskeletal","name":"Ankles & feet","sub":"both sides: bones, ligaments, tarsal tunnel","how":"Both sides. Twenty-six bones per foot plus ankle ligaments that take full body weight. The tibial nerve runs behind the inner ankle bone through the tarsal tunnel, under a band of tissue, where it can be squeezed (tarsal tunnel syndrome: burning or tingling in the sole). Work injuries: sprains and fractures from slips, trips and falls, crush injuries from dropped loads, and heel and arch pain from prolonged standing on hard floors.","evidence":"Textbook anatomy and occupational medicine.","pos":[0.1,0.06,0.03]},{"id":"bp_chest_ribs","col":"bp","group":"Musculoskeletal","name":"Chest wall & ribs","sub":"","how":"The ribs, breastbone and chest-wall muscles that protect the heart and lungs and move with breathing. Work injuries: rib fractures and bruising from falls, crush and being struck, which make breathing painful.","evidence":"Textbook anatomy and occupational medicine.","pos":[0,1.3,0.1]},{"id":"bp_abdomen","col":"bp","group":"Musculoskeletal","name":"Abdomen & groin (hernia)","sub":"abdominal wall, inguinal canal","how":"The muscle wall of the belly and the groin canal (inguinal canal) where it has a natural weak spot. Work injuries: hernias, where gut or fat pushes through a weak spot, and abdominal-wall strains.","evidence":"Textbook anatomy and occupational medicine. California law (education, not advice): a hernia that develops or shows up during service is presumed work-related for listed police, sheriffs, Highway Patrol, DA investigators, firefighters (including CAL FIRE, UC and, from 1 Jan 2026, certain Defense Department, NASA and airport fire departments), Fish and Wildlife wardens, county peace officers and Justice Department safety staff (Cal. Labor Code §§ 3212, 3212.4, 3212.7). The presumption can be rebutted with other evidence and cannot be blamed on an earlier disease. Each claim turns on its facts and current law.","pos":[0.05,0.95,0.11]},{"id":"bp_head_brain","col":"bp","group":"Head, senses, organs & mind","name":"Head & brain","sub":"skull, scalp, brain","how":"The skull protects the brain, which floats in fluid. Work injuries: concussion and other traumatic brain injury from falls, being struck, vehicle crashes and assaults (the brain is jolted against the skull), plus damage from toxic exposures such as carbon monoxide, lead and manganese.","evidence":"Textbook anatomy and occupational medicine.","pos":[0,1.68,0]},{"id":"bp_face_jaw","col":"bp","group":"Head, senses, organs & mind","name":"Face & jaw (TMJ)","sub":"both sides: jaw joint, facial bones","how":"Both sides. The facial bones and the jaw joint (temporomandibular joint, TMJ) in front of each ear. Work injuries: facial fractures from blows and falls, and jaw-joint pain from direct trauma or clenching under stress.","evidence":"Textbook anatomy and occupational medicine.","pos":[0.05,1.58,0.03]},{"id":"bp_eyes","col":"bp","group":"Head, senses, organs & mind","name":"Eyes","sub":"both sides","how":"Both sides. Work injuries: flying particles and metal fragments, chemical splashes, welding arc flash (a burn of the eye's surface), and blunt blows.","evidence":"Textbook anatomy and occupational medicine.","pos":[0.032,1.63,0.085]},{"id":"bp_ears","col":"bp","group":"Head, senses, organs & mind","name":"Ears & hearing","sub":"both sides: hearing, ringing, balance","how":"Both sides. Work injuries: permanent hearing loss and ringing (tinnitus) from years of loud noise or a single blast, burst eardrum from blasts or blows, and dizziness after head injury.","evidence":"Textbook anatomy and occupational medicine.","pos":[0.075,1.62,0]},{"id":"bp_teeth","col":"bp","group":"Head, senses, organs & mind","name":"Teeth","sub":"","how":"Teeth set in the jaw bones. Work injuries: broken or knocked-out teeth from falls, blows and assaults.","evidence":"Textbook anatomy and occupational medicine.","pos":[0,1.56,0.08]},{"id":"bp_internal_organs","col":"bp","group":"Head, senses, organs & mind","name":"Internal organs","sub":"liver, spleen, kidneys, gut","how":"The organs of the belly. Work injuries: tears and bleeding from crush injuries, falls and vehicle crashes; organ damage from chemicals (some solvents harm the liver; heat stress and some metals harm the kidneys).","evidence":"Textbook anatomy and occupational medicine.","pos":[0,1.12,0.03]},{"id":"bp_psyche","col":"bp","group":"Head, senses, organs & mind","name":"Psyche (mental health)","sub":"claimed as a psychiatric injury","how":"How the mind copes, claimed when work causes a mental-health condition. Work causes: violence and threats, witnessing death or serious injury, long-term job strain, and the stress of a painful physical injury, leading to post-traumatic stress, depression or anxiety.","evidence":"Textbook anatomy and occupational medicine. California law (education, not advice): a psychiatric work injury must be a diagnosed mental disorder that causes disability or need for treatment, and actual work events must outweigh all other causes combined; if the worker was the victim of, or directly exposed to, a significant violent act, work need only be a 'substantial cause' (at least 35–40%) (Cal. Labor Code § 3208.3). It also requires at least 6 months with that employer unless a sudden and extraordinary event caused it, adds hurdles for claims filed after a layoff or termination notice, and bars claims substantially caused by lawful, good-faith personnel actions. For listed firefighters, peace officers in active law enforcement and Office of Emergency Services fire and rescue coordinators, PTSD is presumed work-related (§ 3212.15, injuries from 1 Jan 2020; repealed 1 Jan 2029 unless extended). 'Mental and behavioral disorders' is its own body region for lifetime disability caps (§ 4664). For injuries from 1 Jan 2013, a physical injury's permanent rating may not be raised for a psychiatric disorder that follows from it, unless the psychiatric injury came from a violent act or a catastrophic injury such as paralysis or a severe burn or head injury; treatment is still allowed (§ 4660.1(c)). Each claim turns on its facts and current law.","pos":[0,1.69,0.03]},{"id":"bp_sleep","col":"bp","group":"Head, senses, organs & mind","name":"Sleep","sub":"claimed as a sleep disorder","how":"Sleep is driven by the brain's body clock and sleep switches. Work causes: night and rotating shifts that fight the body clock, chronic pain, post-traumatic stress, and some brain injuries.","evidence":"Textbook anatomy and occupational medicine. California law (education, not advice): sleep problems are often claimed as a consequence of a physical work injury (for example pain keeping someone awake). For injuries on or after 1 Jan 2013, a physical injury's permanent impairment rating may not be increased for sleep dysfunction, though treatment for sleep problems caused by the work injury is still allowed (Cal. Labor Code § 4660.1(c)). Each claim turns on its facts and current law.","pos":[0,1.645,0.012]},{"id":"bp_sexual_function","col":"bp","group":"Head, senses, organs & mind","name":"Sexual function","sub":"","how":"Depends on intact nerves from the low spine and pelvis, blood flow, hormones and mood. Work causes: spinal and pelvic injuries, nerve damage, pain medicines, and depression after injury.","evidence":"Textbook anatomy and occupational medicine. California law (education, not advice): sexual dysfunction is often claimed as a consequence of a physical work injury (for example after a spinal injury or from pain medicines). For injuries on or after 1 Jan 2013, a physical injury's permanent impairment rating may not be increased for sexual dysfunction, though treatment for it when caused by the work injury is still allowed (Cal. Labor Code § 4660.1(c)). Each claim turns on its facts and current law.","pos":[0,0.84,0.06]},{"id":"bp_skin","col":"bp","group":"Head, senses, organs & mind","name":"Skin","sub":"the body's surface","how":"The body's outer barrier. Work injuries: cuts, burns and chemical burns, and contact dermatitis (an itchy, cracked rash) from wet work, irritants such as solvents and cleaning products, and allergens such as rubber or epoxy.","evidence":"Textbook anatomy and occupational medicine. California law (education, not advice): skin cancer is presumed work-related for public lifeguards employed more than three consecutive months a year (Cal. Labor Code § 3212.11), and MRSA skin infection for police, sheriffs, peace officers and firefighters (§ 3212.8, lasting 90 days after service). Both are rebuttable. Each claim turns on its facts and current law.","pos":[0.02,1.2,0.13]},{"id":"bp_lungs","col":"bp","group":"Head, senses, organs & mind","name":"Lungs","sub":"both sides","how":"Both sides. Work injuries and diseases: occupational asthma from sensitisers such as isocyanates and flour dust, scarring (silicosis, asbestosis) from mineral dust, mesothelioma from asbestos, and infections caught at work.","evidence":"Textbook anatomy and occupational medicine. California law (education, not advice): for listed police, firefighters and correctional officers, pneumonia (§§ 3212, 3212.3, 3212.4, 3212.5, 3212.7, 3212.10, 3213) and tuberculosis (§§ 3212.6, 3212.7, 3212.10) are presumed work-related. Separately, for firefighters, certain peace officers and OES fire and rescue coordinators who show exposure in service to a known carcinogen, cancer of any site, including leukemia, is presumed work-related, extending up to 120 months after service (§ 3212.1). All are rebuttable. Each claim turns on its facts and current law.","pos":[0.08,1.33,0]},{"id":"bp_heart_circulation","col":"bp","group":"Head, senses, organs & mind","name":"Heart & circulation","sub":"heart, blood vessels, blood pressure","how":"The heart and blood vessels. Work causes argued in claims: heat strain, sudden heavy exertion, long-term job strain, carbon monoxide, and shift work.","evidence":"Textbook anatomy and occupational medicine. California law (education, not advice): for listed police, sheriffs, Highway Patrol, DA investigators, firefighters and correctional and Justice Department safety officers, heart trouble that develops during service is presumed work-related; some police sections need 5 years' service first; rebuttable, and it continues after leaving service 3 months per year served, up to 60 months (Cal. Labor Code §§ 3212, 3212.2, 3212.3, 3212.4, 3212.5, 3212.7, 3212.10, 3213). Each claim turns on its facts and current law.","pos":[0.03,1.3,0.05]},{"id":"hm_cortisol","col":"hm","group":"Stress hormones","name":"Cortisol","sub":"the slow stress hormone","how":"Made by the adrenal glands on orders from the brain (hypothalamus, then pituitary). It peaks soon after waking and falls through the day. It raises blood sugar, calms inflammation and helps the body cope with strain; kept high for months it thins bone and muscle and wears on the memory centre (hippocampus).","evidence":"Established physiology. Long-term high cortisol and poorer memory: population association."},{"id":"hm_adrenaline","col":"hm","group":"Stress hormones","name":"Adrenaline & noradrenaline","sub":"the fast stress hormones","how":"Released by the adrenal core within seconds of a fright or effort (noradrenaline is mainly a nerve messenger, but some also enters the blood this way). They speed the heart, tighten blood vessels, open the airways, release sugar and make muscles tremble more.","evidence":"Established physiology."},{"id":"hm_thyroid","col":"hm","group":"Metabolism","name":"Thyroid hormone","sub":"T4 and T3","how":"The thyroid gland makes T4 from iodine, on orders from the pituitary (TSH); body tissues convert it to the active form T3. It sets the pace of almost every cell: energy use, heart rate, body heat, gut speed and brain function. Too little slows everything down; too much speeds it up and thins bone.","evidence":"Established physiology. Needed at a normal level; extra beyond normal does not help and causes its own problems."},{"id":"hm_insulin","col":"hm","group":"Metabolism","name":"Insulin","sub":"and how well the body responds to it","how":"Released by the pancreas after eating. It lets muscle, liver and fat take sugar out of the blood and store it. When cells stop responding well (insulin resistance), the pancreas pushes out more and more insulin, so a persistently high level usually means the system is struggling.","evidence":"Established physiology. Exercise improves insulin sensitivity in trials; insulin resistance is linked to Alzheimer's changes in population studies."},{"id":"hm_glucagon","col":"hm","group":"Metabolism","name":"Glucagon","sub":"","how":"Released by the pancreas when blood sugar falls, for example between meals. It tells the liver to release stored sugar. It works as insulin's opposite to keep blood sugar steady.","evidence":"Established physiology."},{"id":"hm_leptin","col":"hm","group":"Metabolism","name":"Leptin","sub":"the fullness signal from fat","how":"Made by fat cells in proportion to how much fat there is. It tells the hypothalamus that the body has enough energy stored, reducing hunger. People with obesity often have high leptin but respond to it poorly.","evidence":"Established physiology."},{"id":"hm_ghrelin","col":"hm","group":"Metabolism","name":"Ghrelin","sub":"the hunger signal","how":"Made mainly by the stomach lining when it is empty; levels rise before meals and fall after eating. It makes us feel hungry, triggers growth hormone release and speeds stomach emptying.","evidence":"Established physiology."},{"id":"hm_oestrogen","col":"hm","group":"Sex hormones","name":"Oestrogen","sub":"estradiol","how":"Made mainly by the ovaries before menopause (and in smaller amounts by fat tissue and, from testosterone, in men). It drives female development and the monthly cycle and helps keep bone strong; its fall at menopause speeds bone loss and brings hot flushes.","evidence":"Established for bone. Hormone therapy to protect thinking failed in a large trial of older women."},{"id":"hm_progesterone","col":"hm","group":"Sex hormones","name":"Progesterone","sub":"","how":"Made by the ovary after an egg is released, and in large amounts by the placenta in pregnancy. It prepares and holds the womb lining; when it falls, a period starts. A breakdown product acts as a mild calming signal in the brain.","evidence":"Established physiology."},{"id":"hm_testosterone","col":"hm","group":"Sex hormones","name":"Testosterone","sub":"","how":"Made mainly by the testes (and in small amounts by the ovaries and adrenal glands), on orders from the pituitary's luteinising hormone; rising levels signal the brain to slow production. It builds muscle, bone and red blood cells, drives male development and sex drive, and is partly turned into oestrogen. Levels drift down with age and are often low with illness, obesity and lack of sleep.","evidence":"Established for muscle, bone density and red blood cells. In large trials of men with low levels, treatment improved sex drive and anaemia and lifted mood slightly, but did not improve memory or prevent fractures, and did not raise heart attacks or strokes over about 3 years (Lincoff 2023). A small Parkinson's trial found no benefit."},{"id":"hm_melatonin","col":"hm","group":"Sleep & growth","name":"Melatonin (the body's own)","sub":"the darkness signal","how":"The pineal gland makes melatonin in the evening and night; light reaching the eyes switches it off. It tells the whole body that it is night and helps time sleep. The night-time rise shrinks with age and is flatter in Parkinson's.","evidence":"Established physiology. Lower melatonin rhythm in Parkinson's goes with daytime sleepiness (small study)."},{"id":"hm_gh","col":"hm","group":"Sleep & growth","name":"Growth hormone","sub":"","how":"Released by the pituitary in pulses, mostly in the first deep sleep of the night. It makes the liver release IGF-1, which builds bone and muscle in children and helps maintain them in adults. Levels fall with age.","evidence":"Established physiology."},{"id":"hm_oxytocin","col":"hm","group":"Bonding & water","name":"Oxytocin","sub":"","how":"Made in the hypothalamus and released from the back of the pituitary. It contracts the womb in labour, lets milk flow in breastfeeding, and acts in the brain on trust and bonding. Popularly called the love hormone, but its effects in adults are less clear than that suggests.","evidence":"Established for birth and breastfeeding. Links to everyday social contact are inconsistent."},{"id":"hm_vasopressin","col":"hm","group":"Bonding & water","name":"Vasopressin","sub":"antidiuretic hormone (ADH)","how":"Made in the hypothalamus and released from the back of the pituitary when the blood gets too concentrated or blood pressure falls. It tells the kidneys to keep water, so less urine is made, and it squeezes blood vessels. It normally rises at night, which is why we make less urine while asleep.","evidence":"Established physiology.","pos":[0,1.637,0.009]},{"id":"hm_prolactin","col":"hm","group":"Bonding & water","name":"Prolactin","sub":"","how":"Released by the pituitary to make breast milk. Dopamine from the hypothalamus constantly holds it down, so medicines that raise dopamine (levodopa, agonists) lower it and medicines that block dopamine raise it. Too much prolactin switches off the sex hormones.","evidence":"Established physiology."},{"id":"hm_calcitriol","col":"hm","group":"Bone & minerals","name":"Calcitriol","sub":"active vitamin D","how":"Vitamin D from sunlight or food is changed first in the liver and then in the kidneys into calcitriol, a true hormone. It switches on genes that make the gut absorb calcium and phosphate, keeping bone mineralised and muscles working. The kidneys make more when calcium runs low.","evidence":"Established physiology."},{"id":"br_snc","col":"br","group":"Basal ganglia","name":"Substantia nigra (pars compacta)","sub":"dopamine source; both sides","how":"A thin dark band in the midbrain whose neurons make dopamine and send it up to the striatum. That dopamine lets wanted movements start smoothly and on time. The dark colour is neuromelanin, a by-product of making dopamine.","evidence":"","pos":[0.012,1.648,-0.018]},{"id":"br_putamen","col":"br","group":"Basal ganglia","name":"Putamen","sub":"motor part of the striatum; both sides","how":"The outer part of the striatum, wired to the movement areas of the cortex. It receives most of the dopamine from the substantia nigra and uses it to let practised, automatic movements (walking, writing) run smoothly.","evidence":"","pos":[0.025,1.662,0.003]},{"id":"br_gp","col":"br","group":"Basal ganglia","name":"Globus pallidus","sub":"main output of the basal ganglia; both sides","how":"A pale wedge inside the putamen. Its inner part is the main output of the basal ganglia: it keeps the thalamus held back by default and releases it when a movement is chosen. A common deep-brain-stimulation target.","evidence":"","pos":[0.019,1.66,-0.004]},{"id":"br_caudate","col":"br","group":"Basal ganglia","name":"Caudate nucleus","sub":"part of the striatum; both sides","how":"A C-shaped part of the striatum curling beside each lateral ventricle. It takes in signals from the front of the brain and helps choose plans, switch between tasks and stop unwanted thoughts or habits.","evidence":"","pos":[0.012,1.67,0.012]},{"id":"br_accumbens","col":"br","group":"Basal ganglia","name":"Nucleus accumbens","sub":"ventral striatum, reward; both sides","how":"The lower front part of the striatum, where the caudate and putamen meet. It receives dopamine from the midbrain and links wanting a reward to the effort of getting it, so it drives motivation.","evidence":"","pos":[0.01,1.652,0.01]},{"id":"br_stn","col":"br","group":"Basal ganglia","name":"Subthalamic nucleus","sub":"the brake; both sides","how":"A small lens-shaped nucleus under the thalamus that drives the globus pallidus to hold movement back, acting like a brake. In Parkinson's it fires too much; damage to it causes wild flinging movements. A common deep-brain-stimulation target.","evidence":"","pos":[0.012,1.654,-0.013]},{"id":"br_lc","col":"br","group":"Brainstem","name":"Locus coeruleus","sub":"noradrenaline, alertness; both sides","how":"A small blue-tinged nucleus in the upper pons. It makes almost all of the brain's noradrenaline, which raises alertness, focuses attention and fires up the stress response.","evidence":"","pos":[0.005,1.637,-0.037]},{"id":"br_raphe","col":"br","group":"Brainstem","name":"Raphe nuclei","sub":"serotonin source; midline","how":"A chain of nuclei along the midline of the brainstem. They make the brain's serotonin, which helps set mood, sleep and appetite, and the lower ones turn down pain signals in the spinal cord.","evidence":"","pos":[0,1.64,-0.03]},{"id":"br_dmnv","col":"br","group":"Brainstem","name":"Dorsal motor nucleus of the vagus","sub":"drives the gut; both sides","how":"A nucleus in the lower brainstem (medulla) that sends signals down the vagus nerve to the stomach and intestines to keep them moving. One of the first brain sites where Parkinson's changes appear.","evidence":"","pos":[0.004,1.622,-0.037]},{"id":"br_ppn","col":"br","group":"Brainstem","name":"Pedunculopontine nucleus","sub":"gait and posture; both sides","how":"A nucleus at the midbrain-pons junction, linked to the basal ganglia, that helps start and keep walking, keep posture and stay awake.","evidence":"","pos":[0.008,1.642,-0.03]},{"id":"br_sld","col":"br","group":"Brainstem","name":"Sublaterodorsal nucleus","sub":"REM-sleep muscle switch-off; both sides","how":"A small area beside the locus coeruleus (called subcoeruleus in people) that, during dream (REM) sleep, signals down to the spinal cord to relax the muscles so dreams are not acted out.","evidence":"","pos":[0.006,1.635,-0.035]},{"id":"br_red_nucleus","col":"br","group":"Brainstem","name":"Red nucleus","sub":"midbrain","how":"A pair of nuclei in the midbrain that help coordinate arm and hand movement. It sits in a loop with the cerebellum and thalamus, a loop that is involved in some kinds of tremor.","evidence":"Established anatomy.","pos":[0,1.657,-0.01]},{"id":"br_pag","col":"br","group":"Brainstem","name":"Periaqueductal grey","sub":"PAG, midbrain","how":"Grey matter around the fluid channel of the midbrain. It is a control centre for the body's own pain-damping system and for fear, freeze-or-flee responses and breathing changes.","evidence":"Established anatomy and physiology.","pos":[0,1.657,-0.021]},{"id":"br_vta","col":"br","group":"Brainstem","name":"Ventral tegmental area (VTA)","sub":"midbrain reward dopamine; both sides","how":"A small group of dopamine-making nerve cells in the midbrain, just inside the substantia nigra. They send dopamine to the nucleus accumbens and the front of the brain, the pathway that links wanting something to going after it.","evidence":"Textbook anatomy. In Parkinson's, post-mortem counts show the VTA loses dopamine cells too, but fewer than the substantia nigra next to it.","pos":[0,1.652,-0.006]},{"id":"br_hippocampus","col":"br","group":"Limbic","name":"Hippocampus","sub":"new memories; both sides","how":"A curled ridge on the inner side of each temporal lobe. It turns today's events into lasting memories and helps you find your way. It is one of the first places hit in Alzheimer's disease.","evidence":"Its role in forming new memories and finding your way is established physiology. Shrinkage in Alzheimer's, depression, PTSD and Parkinson's with memory decline comes from imaging and autopsy studies (association). Whether exercise enlarges it in people is mixed.","pos":[0.028,1.648,-0.022]},{"id":"br_amygdala","col":"br","group":"Limbic","name":"Amygdala","sub":"threat and emotion; both sides","how":"An almond-shaped cluster in front of the hippocampus. It spots threats and emotional meaning, triggers fear and the stress response, and tags memories with emotion.","evidence":"","pos":[0.022,1.642,-0.004]},{"id":"br_acc","col":"br","group":"Limbic","name":"Anterior cingulate cortex","sub":"effort, conflict, emotion; both sides","how":"Cortex wrapping the front of the corpus callosum on the inner surface of each half. It notices conflict and errors, decides whether something is worth the effort, and carries the unpleasant part of pain. Its lower (subgenual) part is linked to mood.","evidence":"","pos":[0.005,1.68,0.03]},{"id":"br_entorhinal","col":"br","group":"Limbic","name":"Entorhinal cortex","sub":"gateway to the hippocampus; both sides","how":"A strip of cortex on the inner underside of each temporal lobe, in front of and beside the hippocampus. It gathers information from across the cortex (sights, sounds, smells, places) and passes it into the hippocampus, and carries the hippocampus's output back out. Its grid cells help map where you are.","evidence":"Anatomy and its gateway role are established. That Alzheimer's tau tangles start here comes from large autopsy staging studies.","pos":[0.022,1.632,-0.008]},{"id":"br_cerebellum","col":"br","group":"Cerebellum","name":"Cerebellum","sub":"timing and smoothing of movement; both sides","how":"The 'little brain' at the back, under the cortex. It compares the movement you meant with the one happening and corrects it on the fly, keeping movement smooth, timed and balanced.","evidence":"","pos":[0.025,1.625,-0.065]},{"id":"br_dentate","col":"br","group":"Cerebellum","name":"Dentate nucleus","sub":"cerebellum's main output; both sides","how":"The largest nucleus deep inside each cerebellar half. It sends the cerebellum's corrections to the thalamus and on to the motor cortex.","evidence":"","pos":[0.015,1.625,-0.057]},{"id":"br_olfactory_bulb","col":"br","group":"Smell","name":"Olfactory bulb","sub":"first relay for smell; both sides","how":"A small bulb on the underside of the front of the brain, just above the nose. Smell nerves from the nose end here and it passes smell signals on to the brain. One of the first places Parkinson's changes appear.","evidence":"","pos":[0.008,1.635,0.04]},{"id":"br_m1","col":"br","group":"Cortex","name":"Primary motor cortex","sub":"sends movement commands; both sides","how":"A strip of cortex just in front of the central groove at the top of the brain. Each part controls a body part and sends the final command for a movement down the spinal cord.","evidence":"","pos":[0.035,1.72,-0.02]},{"id":"br_sma","col":"br","group":"Cortex","name":"Supplementary motor area","sub":"plans self-started movements; both sides","how":"Cortex on the inner top surface of each half, in front of the motor strip. It prepares movements you start yourself, and sequences, and depends on input from the basal ganglia via the thalamus.","evidence":"","pos":[0.005,1.725,-0.005]},{"id":"br_dlpfc","col":"br","group":"Cortex","name":"Dorsolateral prefrontal cortex","sub":"working memory, planning; both sides","how":"The upper side of the front of the brain. It holds information in mind while you use it, plans steps, and shifts attention. It is part of a loop with the caudate.","evidence":"","pos":[0.04,1.69,0.04]},{"id":"br_ofc","col":"br","group":"Cortex","name":"Orbitofrontal cortex","sub":"weighs reward, checks behaviour; both sides","how":"The underside of the front of the brain, above the eyes. It weighs how good or bad an outcome will be, updates when things change, and helps stop behaviour that no longer fits.","evidence":"","pos":[0.025,1.645,0.045]},{"id":"br_insula","col":"br","group":"Cortex","name":"Insula","sub":"feels the body from inside; both sides","how":"A fold of cortex hidden deep in the side groove of each half. It reads signals from inside the body (heartbeat, gut, pain, urges) and turns them into feelings.","evidence":"","pos":[0.038,1.665,0.005]},{"id":"br_visual","col":"br","group":"Cortex","name":"Visual cortex","sub":"builds what we see; both sides","how":"Cortex at the back of the brain (occipital lobe) that receives signals from the eyes via the thalamus and builds the image we see; nearby areas recognise shapes, faces and motion.","evidence":"","pos":[0.01,1.665,-0.07]},{"id":"br_thalamus","col":"br","group":"Deep forebrain","name":"Thalamus","sub":"relay to the cortex; both sides","how":"An egg-shaped pair of relay stations in the middle of the brain. Almost every signal to the cortex passes through it: senses, and the movement loops from the basal ganglia and cerebellum. Its tremor relay (ventral intermediate nucleus) is a surgical target for tremor.","evidence":"","pos":[0.01,1.668,-0.018]},{"id":"br_hypothalamus","col":"br","group":"Deep forebrain","name":"Hypothalamus","sub":"sleep, appetite, thirst, hormones; midline, both sides","how":"A small region under the thalamus around the bottom of the third ventricle. It keeps the body in balance: sleep and wake (its orexin cells keep you awake), hunger, thirst, temperature, and the stress and other hormones via the pituitary.","evidence":"","pos":[0.004,1.65,-0.002]},{"id":"br_scn","col":"br","group":"Deep forebrain","name":"Suprachiasmatic nucleus","sub":"the body's 24-hour clock; both sides","how":"A tiny pair of nuclei in the hypothalamus just above where the optic nerves cross. They get light signals from the eyes and set the 24-hour rhythm of sleep, hormones and body temperature.","evidence":"","pos":[0.002,1.646,0.004]},{"id":"br_nbm","col":"br","group":"Deep forebrain","name":"Nucleus basalis of Meynert","sub":"acetylcholine for the cortex; both sides","how":"A band of large neurons in the basal forebrain, under the globus pallidus. They supply most of the cortex's acetylcholine, which sharpens attention and helps memory.","evidence":"","pos":[0.018,1.65,-0.002]},{"id":"levodopa","col":"c","group":"Plant compounds","name":"Levodopa","sub":"velvet bean (Mucuna), fava beans","how":"An amino acid that is the direct building block of dopamine. It is absorbed in the small intestine by the large-neutral-amino-acid transporter, crosses into the brain on the LAT1 transporter, and is turned into dopamine by the enzyme AADC inside surviving nerve terminals. In the gut and blood the same enzyme wastes it, which is why the medicine is paired with carbidopa.","evidence":"Proven: the most effective Parkinson's medicine. Food sources hold uncontrolled, variable amounts; Mucuna has small trials, but the dose can't be standardised and it stacks with prescribed levodopa. Not a substitute."},{"id":"caffeine","col":"c","group":"Plant compounds","name":"Caffeine","sub":"coffee, tea","how":"Its shape mimics adenosine, so it sits in adenosine receptors without switching them on. In the striatum, A2A receptors sit on the same \"stop-path\" neurons as dopamine D2 receptors and push the opposite way, so blocking A2A eases a brake on movement. It also blocks A1 receptors that carry sleep pressure, which is why it keeps you awake.","evidence":"Association: coffee drinkers have a lower rate of Parkinson's in large cohorts, one of the most consistent findings in the field. Treatment: a 2017 trial of caffeine for motor symptoms showed no lasting benefit. A prescription A2A blocker (istradefylline) is approved as an add-on in some countries."},{"id":"sulforaphane","col":"c","group":"Plant compounds","name":"Sulforaphane","sub":"broccoli sprouts","how":"Sprouts store glucoraphanin, which is inert. Crushing or chewing releases the plant enzyme myrosinase, which cuts it into sulforaphane (heavy cooking destroys myrosinase; gut bacteria do a little of the conversion). Sulforaphane reacts with sensor cysteines on the protein Keap1, which normally tags Nrf2 for destruction. Freed Nrf2 enters the nucleus and switches on protective genes: glutathione synthesis, NQO1, heme oxygenase-1.","evidence":"In humans the results conflict: small trials found Nrf2 target genes rose after sprouts or extract, but the largest placebo-controlled trial (Wise 2016) found no rise. Protection of dopamine neurons is shown only in cells and animals; there is no Parkinson's trial result."},{"id":"quercetin","col":"c","group":"Plant compounds","name":"Quercetin","sub":"onions, apples, capers","how":"A flavonol. In the gut and liver it is mostly converted to glucuronide and sulfate conjugates, so free quercetin in blood is very low. In dishes and cells it scavenges radicals, weakly activates Nrf2 and inhibits several inflammatory kinases.","evidence":"Lab and animal only for Parkinson's. Poor bioavailability is the main gap between the dish and the brain."},{"id":"anthocyanins","col":"c","group":"Plant compounds","name":"Anthocyanins","sub":"berries, red cabbage","how":"The red-blue pigments. Little is absorbed intact; most reach the colon, where bacteria break them into smaller phenolic acids (such as protocatechuic acid) that are absorbed and circulate. They also shift which microbes grow.","evidence":"Association: higher flavonoid and berry intake is linked to lower Parkinson's risk in men (Gao 2012) and to lower mortality in people with Parkinson's. Mechanisms (anti-inflammatory, microbiome) are shown in the lab."},{"id":"fibre","col":"c","group":"Plant compounds","name":"Fibre","sub":"legumes, oats, vegetables, psyllium; gut bacteria turn it into butyrate","how":"Humans can't digest fibre; colon bacteria ferment it into short-chain fatty acids: acetate, propionate, butyrate. Butyrate is the main fuel of the cells lining the colon, helps them keep their tight junctions sealed, and calms immune cells (through the GPR43/GPR109A receptors and by inhibiting HDAC enzymes). Fibre also holds water, which softens and bulks stool.","evidence":"People with Parkinson's have fewer butyrate-producing bacteria (replicated in many studies). Fibre improves constipation in trials, including with probiotics in Parkinson's (Barichella 2016)."},{"id":"kiwi","col":"c","group":"Plant compounds","name":"Sorbitol & actinidin","sub":"prune sugar alcohol, kiwi enzyme","how":"Prunes carry fibre plus sorbitol, a sugar alcohol the gut doesn't absorb, so it pulls water into the bowel. Kiwifruit fibre holds a lot of water and the fruit carries the enzyme actinidin.","evidence":"Proven for chronic constipation in general-population trials, not tested specifically in Parkinson's."},{"id":"omega3","col":"c","group":"Plant compounds","name":"Omega-3 DHA/EPA","sub":"algae oil, oily fish; ALA in flax and walnuts","how":"DHA is built into nerve-cell membranes and synapses. DHA and EPA are converted into resolvins and protectins, molecules that actively switch inflammation off. In lab experiments DHA binds the Nurr1 receptor's pocket. Plant ALA converts to DHA only a few percent.","evidence":"Lab for Nurr1 and neuroprotection. One small trial in Parkinson's depression was positive; depression trials overall are mixed."},{"id":"ergothioneine","col":"c","group":"Plant compounds","name":"Ergothioneine","sub":"mushrooms","how":"An antioxidant made only by fungi and some bacteria. Humans have a dedicated transporter for it, OCTN1 (gene SLC22A4), and concentrate it in tissues under stress, which suggests the body actively wants it. In lab studies it neutralises reactive oxygen species and protects mitochondria.","evidence":"Association: blood ergothioneine is lower in people with Parkinson's (Hatano 2016). Protection: lab only."},{"id":"egcg","col":"c","group":"Plant compounds","name":"EGCG","sub":"green tea","how":"The main catechin in green tea. In test tubes it binds α-synuclein and redirects it into harmless off-pathway clumps. It is poorly absorbed and quickly broken down.","evidence":"Failed: the PROMESA trial in multiple system atrophy (a related synuclein disease) showed no benefit, and high-dose extracts have caused liver injury. Drinking tea is a different matter (see caffeine)."},{"id":"curcumin","col":"c","group":"Plant compounds","name":"Curcumin","sub":"turmeric","how":"The yellow pigment. In the lab it binds amyloid-like clumps and dampens NF-κB inflammatory signalling. Very little reaches the blood, and it is essentially undetected in spinal fluid.","evidence":"For Parkinson's: helpful in lab and animal studies, but the one small human trial (9 months, add-on) found no benefit. Outside Parkinson's, supplement trials lowered blood inflammation markers and modestly eased knee osteoarthritis pain."},{"id":"resveratrol","col":"c","group":"Plant compounds","name":"Resveratrol","sub":"grapes, peanuts","how":"A stilbene. In cells it activates the energy sensors SIRT1 and AMPK and acts as an antioxidant. The liver conjugates it quickly, so free resveratrol in blood is tiny.","evidence":"Lab and animal only for Parkinson's."},{"id":"olive","col":"c","group":"Plant compounds","name":"Olive polyphenols","sub":"extra-virgin olive oil","how":"Hydroxytyrosol is a strong radical scavenger. Oleocanthal, the throat sting of fresh oil, weakly blocks COX enzymes the way ibuprofen does. Part of the Mediterranean eating pattern.","evidence":"Association: closer adherence to Mediterranean/MIND diets is linked to later onset and lower risk (Metcalfe-Roach 2021 and others). Specific compounds: lab."},{"id":"nightshade","col":"c","group":"Plant compounds","name":"Nightshade nicotine","sub":"peppers, tomatoes","how":"Peppers, tomatoes and potatoes carry trace nicotine. Nicotine acts on nicotinic acetylcholine receptors that sit on dopamine terminals and boost dopamine release.","evidence":"Association: eating peppers is linked to lower risk (Nain 2013). Failed: nicotine patches did not slow Parkinson's in the NIC-PD trial (2023)."},{"id":"cannabinoids","col":"c","group":"Plant compounds","name":"Cannabinoids","sub":"THC, CBD","how":"THC activates CB1 receptors, which sit densely in the basal ganglia and act as a brake on transmitter release at synapses. CBD works on several other targets and barely activates CB1.","evidence":"Tourette: small early THC trials suggested fewer tics; the larger CANNA-TICS trial (nabiximols, 2023) missed its main goal. Parkinson's: no proven motor benefit. Side effects and legal status matter."},{"id":"flavanols","col":"c","group":"Plant compounds","name":"Flavan-3-ols (flavanols)","sub":"cocoa, tea, apples, grapes","how":"A family of plant compounds: epicatechin and catechin, tea catechins such as EGCG, and their chains, the procyanidins. Epicatechin is partly absorbed in the small intestine; the longer chains reach the colon, where bacteria break them into smaller molecules that are absorbed. In blood vessels they appear to help the inner lining make nitric oxide, which lets arteries relax.","evidence":"Proven for modest improvements in blood pressure, cholesterol and blood-sugar markers across many short trials (guideline from 157 trials, Crowe-White 2022). The large COSMOS trial of cocoa extract did not significantly cut total heart and stroke events, though heart deaths were fewer (a secondary result). The guideline is about foods, not supplements."},{"id":"theanine","col":"c","group":"Plant compounds","name":"L-theanine","sub":"tea","how":"An amino acid almost unique to tea. Well absorbed, it reaches the brain through amino-acid carriers, where it is structurally similar to glutamate and modestly shifts glutamate and GABA signalling and brain alpha waves (a relaxed-alert pattern). Whether it competes with levodopa for those carriers at tea amounts is untested.","evidence":"Small randomised trials suggest better sleep quality and lower stress. With caffeine, it improves short-term attention more than caffeine alone."},{"id":"chlorogenic_acid","col":"c","group":"Plant compounds","name":"Chlorogenic acid","sub":"coffee","how":"The main polyphenol of coffee (also in apples and potatoes). About a third is absorbed in the small intestine; the rest reaches the colon, where bacteria break it down into caffeic, ferulic and other phenolic acids that are then absorbed. Lab work shows antioxidant effects and slower sugar uptake. Light roasts keep more; dark roasting destroys much of it.","evidence":"Small manufacturer-funded trials found lower blood pressure; independent confirmation is lacking."},{"id":"rosmarinic_acid","col":"c","group":"Plant compounds","name":"Rosmarinic acid","sub":"rosemary, oregano, sage, lemon balm","how":"A caffeic-acid ester common in mint-family herbs. Antioxidant and anti-inflammatory in cells (it damps the HMGB1-TLR4-NF-kB alarm pathway in microglia). Poorly absorbed; much is broken down by gut bacteria into smaller phenolic acids.","evidence":"Lab and animal only for the brain."},{"id":"hericenones","col":"c","group":"Plant compounds","name":"Lion's mane compounds","sub":"hericenones, erinacines","how":"Hericenones (in the mushroom body) and erinacines (mostly in the grown mycelium) are small molecules reported to trigger nerve growth factor production in lab cells. Erinacines cross into the brain in rodents; human absorption and brain levels are unknown.","evidence":"One small trial in mild cognitive impairment was positive; a single-dose trial in young adults was not. Parkinson's evidence is animal-only."},{"id":"piperine","col":"c","group":"Plant compounds","name":"Piperine","sub":"black pepper","how":"Piperine is the pungent alkaloid in black pepper. In the gut wall and liver it slows the enzymes (glucuronidation, CYP3A4) and the pump (P-glycoprotein) that normally tag and throw out many foreign molecules, so other compounds eaten with it stay in the blood longer. That is how it raised curcumin and EGCG levels in early studies (newer human trials did not confirm the curcumin boost), and it also slows the breakdown of some medicines (shown for phenytoin, propranolol and theophylline in volunteers). Piperine itself is reasonably well absorbed.","evidence":"Human evidence is about absorption only, and it conflicts: one early study found much higher blood curcumin with piperine, newer randomised crossover trials did not. No trial shows piperine on its own improves a health outcome. The amounts studied were supplement-sized, larger than a sprinkle of pepper on food."},{"id":"gingerols","col":"c","group":"Plant compounds","name":"Gingerols & shogaols","sub":"ginger","how":"Gingerols are the pungent compounds of fresh ginger; drying or cooking turns some into shogaols. They act on gut nerve receptors (including serotonin 5-HT3 and TRPV1 receptors) that control nausea and stomach contractions, and dampen inflammatory enzymes in cells. They are absorbed quickly but mostly converted by the gut and liver, so blood levels of the free compounds are low.","evidence":"Ginger reduces nausea in pregnancy and after surgery in many small trials, and sped stomach emptying in two small randomised crossover studies. Not tested in Parkinson's."},{"id":"thymoquinone","col":"c","group":"Plant compounds","name":"Thymoquinone","sub":"black seed","how":"A small quinone molecule that can accept and pass on electrons, so it acts as an antioxidant and switches on Nrf2 defence genes in cells, while damping the NF-kB inflammation switch. It is fat-soluble and poorly water-soluble, so absorption is limited and much is bound to blood proteins; how much reaches the brain in people is unknown.","evidence":"Trials of the whole seed or oil (not pure thymoquinone) lowered blood markers of inflammation, blood pressure and blood sugar in many small trials. Parkinson's evidence is animal-only. Rare allergic skin reactions are reported."},{"id":"allicin","col":"c","group":"Plant compounds","name":"Garlic sulfur compounds","sub":"allicin, S-allylcysteine","how":"Allicin forms within seconds when raw garlic is crushed. It is unstable and breaks down in the gut into other sulfur compounds (diallyl sulfides, ajoene); little or no allicin itself reaches the blood. These sulfur compounds feed the body's hydrogen sulfide and nitric oxide signals that relax blood vessels. S-allylcysteine, from aged garlic, is stable and well absorbed.","evidence":"Garlic supplements lower blood pressure modestly in people with high blood pressure (meta-analyses of randomised trials). Garlic can add to the effect of blood thinners."},{"id":"cinnamaldehyde","col":"c","group":"Plant compounds","name":"Cinnamaldehyde","sub":"cinnamon","how":"The flavour molecule of cinnamon. It reacts with sulfur groups on proteins, which nudges the Nrf2 defence switch and calms inflammatory signalling in cells. In the body it is quickly turned into cinnamic acid and then into benzoate, so little cinnamaldehyde circulates as such.","evidence":"Cinnamon trials for blood sugar give mixed results. Parkinson's evidence is from mice only."},{"id":"isoflavones","col":"c","group":"Plant compounds","name":"Soy isoflavones","sub":"genistein, daidzein","how":"Plant molecules shaped enough like oestrogen to bind oestrogen receptors weakly, preferring the beta type, so they act as mild oestrogen-like or oestrogen-blocking signals depending on the tissue. They are eaten with a sugar attached; gut bacteria remove it before absorption. Some people's gut bacteria further turn daidzein into equol, a more active form, and only a minority of Western adults can.","evidence":"Bone results are mixed across meta-analyses. Human brain effects are unproven."},{"id":"ellagitannins","col":"c","group":"Plant compounds","name":"Ellagitannins","sub":"pomegranate, walnuts, strawberries, raspberries","how":"Large tannin molecules that are hardly absorbed. In the gut they release ellagic acid, which colon bacteria (such as Gordonibacter and Ellagibacter) gradually convert into urolithins, which are absorbed. People differ: some make lots of urolithin A, some make other urolithins, and some make almost none.","evidence":"Mainly a precursor; effects in people depend on gut bacteria."},{"id":"urolithin_a","col":"c","group":"Plant compounds","name":"Urolithin A","sub":"made by gut bacteria from ellagitannins","how":"Not in food itself: gut bacteria make it from ellagitannins. Urolithin A switches on mitophagy, the cell's system for recycling worn-out mitochondria (the cell's power units), so healthier mitochondria replace damaged ones. It is well absorbed and is tagged by the liver before circulating.","evidence":"Purified urolithin A improved muscle mitochondrial markers in randomised trials, with mixed effects on strength and endurance. Parkinson's evidence is animal-only. Whether eating pomegranate or walnuts makes enough depends on a person's gut bacteria."},{"id":"fisetin","col":"c","group":"Plant compounds","name":"Fisetin","sub":"strawberries, apples","how":"A flavonol close to quercetin. In the lab it helps clear senescent ('zombie') cells that release inflammatory signals, and boosts memory-related signalling (ERK, CREB) in neurons. Absorption is poor and it is quickly tagged by the liver; food amounts are far below those used in animal work.","evidence":"Lab and animal only; human trials of high-dose fisetin are under way. In one rat Parkinson's model it did not protect dopamine neurons."},{"id":"proanthocyanidins","col":"c","group":"Plant compounds","name":"Cranberry proanthocyanidins","sub":"type-A PACs","how":"Chains of flavanol units. The type-A form in cranberries stops E. coli from gripping the bladder lining using its finger-like fimbriae, so bacteria are washed out with urine. Mostly not absorbed intact; small breakdown products reach the urine.","evidence":"Cranberry products reduce repeat urinary infections in some groups (Cochrane 2023), but not in care-home residents or people with nerve-related bladder emptying problems."},{"id":"lycopene","col":"c","group":"Plant compounds","name":"Lycopene","sub":"tomatoes","how":"The red carotenoid pigment of tomatoes, watermelon and pink grapefruit. A long chain of alternating double bonds lets it quench singlet oxygen, a reactive form of oxygen. It dissolves only in fat: absorption from raw tomato is low and rises when tomatoes are cooked (heat frees it from the cell walls) and eaten with fat.","evidence":"Population studies link tomato-rich diets with some health benefits; trials of lycopene pills are small and inconsistent. Parkinson's evidence is animal-only."},{"id":"beta_carotene","col":"c","group":"Plant compounds","name":"Beta-carotene","sub":"carrots, sweet potato, greens","how":"An orange carotenoid that the gut wall cuts in half to make vitamin A when the body needs it (the enzyme BCO1, which slows down when vitamin A is sufficient, so food beta-carotene cannot cause vitamin A overdose). Fat-soluble: absorption from raw vegetables can be under 10% and rises a lot with cooking and fat.","evidence":"Needed as a vitamin A source in plant-based diets. High-dose beta-carotene pills raised lung cancer in smokers in two large trials; food sources are not linked to this harm."},{"id":"lutein","col":"c","group":"Plant compounds","name":"Lutein & zeaxanthin","sub":"greens, egg yolk, corn","how":"Yellow carotenoids that the body moves selectively into the centre of the retina (the macula), where they form a yellow filter that absorbs blue light and quench reactive oxygen. They also collect in the brain. Fat-soluble: absorbed best with fat in the meal.","evidence":"Supplements raise macular pigment reliably. Effects on thinking are mixed: some small trials positive, the large AREDS2 trial found no slowing of cognitive decline."},{"id":"citrus_flavanones","col":"c","group":"Plant compounds","name":"Hesperidin & naringenin","sub":"citrus flavanones","how":"Flavanones carried on a sugar. Gut bacteria in the colon must cut off the sugar before they can be absorbed, so absorption is slow, varies a lot between people and is often under 10%. In blood vessels they help the lining release nitric oxide, which relaxes the vessel; in cells they act on inflammatory and antioxidant signalling.","evidence":"Orange juice and hesperidin lowered blood pressure modestly in randomised trials. Parkinson's evidence is from rats only."},{"id":"apigenin_luteolin","col":"c","group":"Plant compounds","name":"Apigenin & luteolin","sub":"parsley, celery, chamomile","how":"Two closely related flavones. Apigenin binds the benzodiazepine site of GABA-A receptors (the brain's calming receptors) in lab studies; luteolin calms activated microglia, the brain's immune cells. Both are absorbed poorly and quickly tagged by the liver for removal, so brain levels after food are probably low.","evidence":"Chamomile (an apigenin source) improved self-rated sleep quality in a meta-analysis, but did not improve insomnia in the one trial that tested it. Brain effects of the pure compounds are lab-only."},{"id":"nitrate","col":"c","group":"Plant compounds","name":"Dietary nitrate","sub":"beetroot, rocket, spinach","how":"Plants store nitrate from the soil. After it is absorbed, the salivary glands pump it back into the mouth, where bacteria on the tongue turn it into nitrite; nitrite is swallowed and changed into nitric oxide, which relaxes blood vessels. This needs the mouth bacteria: strong antiseptic mouthwash blocks it. Absorption of nitrate itself is nearly complete.","evidence":"Lowers blood pressure in pooled crossover trials. Plant nitrate is distinct from the nitrites added to processed meat. Not studied in Parkinson's dizziness on standing."},{"id":"betalains","col":"c","group":"Plant compounds","name":"Betalains","sub":"beetroot","how":"Red-violet (betacyanin, such as betanin) and yellow pigments found in beetroot, chard stems and prickly pear. They donate electrons to neutralise reactive oxygen and damp inflammatory signalling in cells. Fairly unstable and absorbed only in small amounts.","evidence":"Lab and animal evidence; human studies are small and mostly about exercise."},{"id":"capsaicin","col":"c","group":"Plant compounds","name":"Capsaicin","sub":"hot chilli peppers","how":"The heat of chillies. It opens the TRPV1 receptor on pain and heat nerve endings, causing burning; with repeated or strong exposure those endings stop firing for a while (desensitisation), which is the basis of capsaicin pain patches. In the throat, TRPV1 activation triggers release of substance P, which speeds up the swallow and cough reflexes. Swallowed capsaicin is well absorbed and broken down by the liver.","evidence":"Capsaicin lozenges sharpened the swallowing reflex in small trials in older people; high-strength skin patches help some nerve pain. Not tested for swallowing in Parkinson's."},{"id":"boswellic_acids","col":"c","group":"Plant compounds","name":"Boswellic acids","sub":"frankincense resin (Boswellia), taken as extracts","how":"Resin acids from frankincense gum that block 5-lipoxygenase, an enzyme that makes inflammatory leukotrienes. They are heavy molecules that stay in the resin and barely distil into frankincense essential oil.","evidence":"Mixed: swallowed Boswellia extracts eased knee osteoarthritis pain in several small trials, but pooled results disagree."},{"id":"protein","col":"c","group":"Nutrients & supplements","name":"Dietary protein","sub":"amino acids; timing matters with levodopa","how":"Dietary protein breaks down into large neutral amino acids (leucine, phenylalanine, tyrosine…) that use the same transporters in the gut wall and the blood-brain barrier as levodopa. A protein-heavy meal near a dose means competition at the door.","evidence":"Small trials: protein redistribution reduces fluctuations in some people. Must not cut total protein; worth planning with the care team or a dietitian."},{"id":"melatonin","col":"c","group":"Nutrients & supplements","name":"Melatonin","sub":"hormone; small amounts in tart cherries","how":"Made by the pineal gland in darkness. Acts on MT1 receptors (dampens the clock's alerting signal, sleepiness) and MT2 (shifts the clock). It is a timing signal, not a sedative.","evidence":"Mixed: modest help with falling asleep. For dream enactment, small trials conflict; a Parkinson's trial (Gilat 2020) found no difference from placebo."},{"id":"magnesium","col":"min","group":"Major minerals","name":"Magnesium","sub":"oxide/citrate","how":"Poorly absorbed forms stay in the bowel and pull water in (an osmotic laxative). It is also a cofactor for hundreds of enzymes and steadies nerve and muscle excitability.","evidence":"Proven as a laxative in general constipation. Not safe for everyone with kidney disease."},{"id":"b12","col":"vit","group":"Water-soluble","name":"Vitamin B12","sub":"","how":"B12 works with folate to recycle homocysteine back into methionine. Levodopa is broken down by COMT, which takes a methyl group from SAM, so every dose produces homocysteine. B12 also maintains the myelin insulation on nerves and is needed to make red blood cells. It comes only from animal foods and fortified foods, and absorption falls with age, long-term stomach-acid medicines and metformin.","evidence":"Established: homocysteine rises on levodopa, and low B12 causes neuropathy and anaemia. A reason to have levels checked, not to self-dose; extra above a normal level isn't shown to help."},{"id":"vitd","col":"vit","group":"Fat-soluble","name":"Vitamin D","sub":"sunlight; supplements","how":"Made in skin by sunlight, converted by liver and kidney into calcitriol, which binds the vitamin D receptor (a gene switch) to raise calcium absorption and support bone and muscle. Many people with Parkinson's run low.","evidence":"Established for bone when deficient. For Parkinson's symptoms or falls, trials are mixed."},{"id":"probiotics","col":"c","group":"Nutrients & supplements","name":"Probiotics","sub":"multi-strain","how":"Live bacteria (Lactobacillus, Bifidobacterium strains) that pass through and temporarily shift the gut community, make lactate and short-chain fatty acids, and speed transit.","evidence":"Proven for constipation in Parkinson's in two randomised trials (Barichella 2016, Tan 2021). The shift in microbes is temporary."},{"id":"b6","col":"vit","group":"Water-soluble","name":"Vitamin B6","sub":"","how":"As pyridoxal phosphate it is the cofactor for the enzymes that make GABA, serotonin and dopamine, including AADC, which turns levodopa into dopamine. Taken in high doses with levodopa but without carbidopa, it speeds levodopa's breakdown before it reaches the brain.","evidence":"Tics: one small trial of magnesium plus B6 in children was positive (2009) and has not been replicated. Very high doses over long periods damage nerves."},{"id":"nac","col":"c","group":"Nutrients & supplements","name":"N-acetylcysteine","sub":"NAC","how":"Supplies cysteine for glutathione and adjusts glutamate release through the cystine-glutamate exchanger, which is why it was tried in compulsive and tic disorders.","evidence":"Failed for tics: a trial in children and teens with Tourette found no difference from placebo (Bloch 2016)."},{"id":"sugar","col":"c","group":"Nutrients & supplements","name":"Added sugar","sub":"","how":"Sugars absorbed quickly raise blood glucose and insulin. Popularly blamed for hyperactivity.","evidence":"Failed as a cause of hyperactivity: blinded trials, combined in a meta-analysis, found no effect on behaviour or thinking in children (Wolraich 1995)."},{"id":"colours","col":"c","group":"Nutrients & supplements","name":"Artificial food colours","sub":"and sodium benzoate","how":"Synthetic dyes (such as tartrazine and sunset yellow) used in sweets and drinks; how they might affect behaviour is unknown.","evidence":"Mixed: a blinded trial found a small increase in hyperactivity in some children (McCann 2007), which led to warning labels in Europe; effects are small and vary between children."},{"id":"exercise","col":"h","group":"Habits & therapies","name":"Exercise","sub":"aerobic, strength, balance, dance, tai chi","how":"Working muscle releases BDNF and other signalling molecules; aerobic training improves how efficiently remaining dopamine is released and used (seen on imaging); balance practice retrains posture circuits; movement stimulates the gut; leg muscles pump blood back up; daytime effort builds sleep pressure.","evidence":"Proven for movement, balance and mood. Whether it slows the disease is being tested (SPARX3)."},{"id":"fluids","col":"h","group":"Habits & therapies","name":"Water & salt","sub":"","how":"Water raises blood volume, and drinking water quickly triggers a reflex that raises standing blood pressure for about an hour in people with autonomic failure. Salt holds water in the blood. More water also softens stool.","evidence":"Proven first-line for low blood pressure on standing (Jordan 2000). Salt isn't suitable for everyone with heart or kidney disease."},{"id":"light","col":"h","group":"Habits & therapies","name":"Morning light & schedule","sub":"","how":"Bright light at the eye reaches the body clock (SCN) through special retinal cells (melanopsin), resetting it and suppressing daytime melatonin. Regular sleep and meal times keep the clock strong.","evidence":"Small Parkinson's trial: bright light therapy improved daytime sleepiness and sleep quality (Videnovic 2017)."},{"id":"voice","col":"h","group":"Habits & therapies","name":"Voice & swallow therapy","sub":"e.g. LSVT LOUD","how":"High-effort, repeated practice (\"think loud\") recalibrates the brain's sense of how loud and big movements should be: motor learning in the remaining circuits.","evidence":"Proven for voice loudness in randomised trials; swallowing therapy evidence is smaller."},{"id":"social","col":"h","group":"Habits & therapies","name":"Social contact","sub":"","how":"Conversation is speech practice; company drives activity and engages reward and mood circuits.","evidence":"Association: social engagement goes with better mood and quality of life."},{"id":"cbit","col":"h","group":"Habits & therapies","name":"Tic training (CBIT)","sub":"behavioural therapy","how":"Awareness training teaches noticing the urge before a tic; competing-response training means doing a movement that physically blocks the tic until the urge fades. The urge shrinks as the brain learns it passes without the tic (habituation), and situations that drive tics are adjusted.","evidence":"Proven: randomised trials in children (Piacentini 2010) and adults (Wilhelm 2012); a first-line treatment. Holding tics back this way does not cause a rebound."},{"id":"m_dopa","col":"m","group":"Movement chemistry","name":"Dopamine supply in the striatum","sub":"","how":"Dopamine from the substantia nigra tunes the striatum: D1 receptors drive the \"go\" path, D2 receptors quiet the \"stop\" path. Anything that raises dopamine at these receptors (levodopa, release boosters) shifts the balance back toward movement.","evidence":""},{"id":"m_absorb","col":"m","group":"Movement chemistry","name":"Levodopa absorption","sub":"gastric emptying, transporter competition","how":"Levodopa must leave the stomach, be carried across the small-intestine wall by the amino-acid transporter, and then cross the blood-brain barrier on LAT1. A slow stomach delays it; protein amino acids and iron compete or bind; constipation slows the whole tract.","evidence":""},{"id":"m_aden","col":"m","group":"Movement chemistry","name":"Adenosine blocking (caffeine's target)","sub":"blocks the A2A movement brake and A1 sleep pressure","how":"Adenosine builds up with activity and wakefulness. A1 receptors carry sleep pressure. A2A receptors on striatal stop-path neurons oppose D2 dopamine receptors. Blocking them lifts sleepiness and lightens the movement brake.","evidence":""},{"id":"m_nrf2","col":"m","group":"Cell defences","name":"Nrf2 protective genes","sub":"","how":"A master switch for about 200 defence genes: glutathione production, detoxifying enzymes, heme oxygenase-1. Normally held back by Keap1; electrophiles like sulforaphane release it.","evidence":""},{"id":"m_oxid","col":"m","group":"Cell defences","name":"Mitochondria & antioxidant defence","sub":"","how":"Dopamine neurons are unusually exposed: dopamine itself oxidises, they fire constantly with heavy calcium load, and their huge branching axons need lots of energy. Mitochondrial damage (complex I) and reactive oxygen species are found in Parkinson's brains.","evidence":""},{"id":"m_asyn","col":"m","group":"Cell defences","name":"Keeping α-synuclein unclumped","sub":"","how":"α-Synuclein is a normal synapse protein. In Parkinson's it misfolds and stacks into clumps (Lewy bodies), and the misfolded form can template others. Shown here only at the level of \"a compound changed clumping in a dish\", never more.","evidence":""},{"id":"m_inflam","col":"m","group":"Cell defences","name":"Inflammation control","sub":"microglia, gut immune cells","how":"Microglia (the brain's immune cells) and gut immune cells become activated in Parkinson's, releasing cytokines that stress neurons. Inflammation also feeds fatigue and low mood through cytokine signalling to the brain.","evidence":""},{"id":"m_nurr1","col":"m","group":"Cell defences","name":"Nurr1","sub":"dopamine-neuron identity gene","how":"A nuclear receptor that keeps dopamine neurons making tyrosine hydroxylase and the dopamine transporter. Low Nurr1 lets neurons go \"silent\". Activating it protects neurons in animal models.","evidence":""},{"id":"m_micro","col":"m","group":"Gut","name":"Butyrate & short-chain fatty acids","sub":"","how":"Bacteria ferment fibre into acetate, propionate and butyrate. Butyrate fuels the cells lining the colon, keeps oxygen low at the gut wall (which favours helpful anaerobes over E. coli-type bacteria), and calms immune cells. In Parkinson's, butyrate producers are reduced in many studies.","evidence":""},{"id":"m_barrier","col":"m","group":"Gut","name":"Gut barrier","sub":"tight junctions","how":"A single layer of cells sealed by tight-junction proteins and a mucus coat. When it leaks, bacterial products reach immune cells and drive inflammation. Increased permeability is reported in Parkinson's.","evidence":""},{"id":"m_motility","col":"m","group":"Gut","name":"Gut motility & stool water","sub":"","how":"The gut's own nervous system (enteric) plus the vagus nerve drive the muscle waves that move contents along. The longer stool sits, the more water the colon pulls out. Fibre, osmotic agents and water keep it soft; movement and transit time set the pace.","evidence":""},{"id":"m_clock","col":"m","group":"Sleep & energy","name":"Body clock (24-hour rhythm)","sub":"SCN; melatonin is its night signal","how":"The suprachiasmatic nucleus sets a 24-hour rhythm from light, and signals sleep through night-time melatonin. In Parkinson's the rhythm flattens (lower melatonin amplitude), which weakens both night sleep and daytime alertness.","evidence":""},{"id":"m_methyl","col":"m","group":"Sleep & energy","name":"Methylation & homocysteine","sub":"","how":"Methyl groups from SAM run many reactions; when used, homocysteine is left. B12 and folate recycle it. High homocysteine is toxic to blood vessels and nerves.","evidence":""},{"id":"m_bp","col":"m","group":"Circulation & body","name":"Blood volume & vessel tone","sub":"","how":"Standing blood pressure depends on how much blood there is (volume), how tight the vessels can squeeze (sympathetic noradrenaline), and the leg muscle pump.","evidence":""},{"id":"m_plastic","col":"m","group":"Circulation & body","name":"Neuroplasticity & motor learning","sub":"BDNF","how":"Practice strengthens the circuits that remain, helped by growth factors such as BDNF. This is how training improves walking, balance and voice even as neurons are lost.","evidence":""},{"id":"m_reward","col":"m","group":"Circulation & body","name":"Mood & reward circuits","sub":"dopamine, serotonin, noradrenaline","how":"The ventral striatum, prefrontal cortex and brainstem nuclei (raphe, locus coeruleus) set motivation and mood. Activity, achievement and company engage them.","evidence":""},{"id":"m_bone","col":"m","group":"Circulation & body","name":"Bone & muscle strength","sub":"","how":"Bone is rebuilt constantly in response to load; it needs calcium (absorbed with vitamin D) and use. Muscle mass keeps posture and protects in a fall.","evidence":""},{"id":"m_cstc","col":"m","group":"Control circuits","name":"Habit loops & inhibitory control","sub":"cortex–striatum–thalamus","how":"Loops from cortex through the striatum and thalamus back to cortex pick one movement and hold competing ones back. Inhibitory interneurons in the striatum and the prefrontal cortex supply the \"no\". Training can strengthen that control.","evidence":""},{"id":"m_excit","col":"m","group":"Control circuits","name":"Nerve excitability","sub":"glutamate, GABA, magnesium","how":"The balance of excitatory (glutamate) and inhibitory (GABA) signalling sets how easily circuits fire. Magnesium sits in NMDA glutamate channels and blocks them at rest.","evidence":""},{"id":"m_cb","col":"m","group":"Control circuits","name":"Endocannabinoid system","sub":"CB1 receptors","how":"The body makes its own cannabinoids (anandamide, 2-AG) that act on CB1 receptors to turn down transmitter release; CB1 is especially dense in the basal ganglia.","evidence":""},{"id":"m_catechol","col":"m","group":"Control circuits","name":"Prefrontal dopamine & noradrenaline","sub":"attention, waiting, planning","how":"The prefrontal cortex holds a goal in mind and stops impulses using dopamine and noradrenaline. Too little signalling there makes focus drift and waiting hard; ADHD medicines work by raising these signals.","evidence":""},{"id":"m_stress","col":"m","group":"Control circuits","name":"Stress & fear circuits","sub":"amygdala, adrenaline, cortisol","how":"The amygdala flags threats and triggers adrenaline and cortisol. When this system is over-sensitive, worry, tension, poor sleep and outbursts follow; adrenaline also makes tremor and tics worse.","evidence":""},{"id":"m_bladderctl","col":"m","group":"Control circuits","name":"Bladder reflex control","sub":"","how":"Brain centres hold back the bladder's emptying reflex until it is convenient. Training, pelvic-floor muscles and avoiding bladder irritants help that control.","evidence":""},{"id":"m_painproc","col":"m","group":"Control circuits","name":"Pain processing","sub":"spinal and brain pain gates","how":"Pain signals are turned up or down in the spinal cord and brain. Movement, sleep and mood all change how loud the same signal feels.","evidence":""},{"id":"progression","col":"d","group":"Neurons","name":"Parkinson's progression","sub":"dopamine-neuron loss and wider spread","how":"Dopamine neurons in the substantia nigra die slowly; by diagnosis a large share of striatal dopamine terminals are already gone, and nerve endings fail before cell bodies (dying-back). Clumped α-synuclein also appears in the brainstem, gut and smell pathways, which is why many non-movement symptoms come first.","evidence":""},{"id":"movement","col":"d","group":"Movement","name":"Slowness & stiffness","sub":"bradykinesia, rigidity","how":"With dopamine low, the striatum's \"stop\" path dominates: the globus pallidus over-inhibits the thalamus, and the cortex gets too little drive, so movements get small and slow and muscles co-contract (rigidity).","evidence":""},{"id":"off","col":"d","group":"Movement","name":"OFF periods","sub":"wearing off, fluctuations","how":"Early on, surviving terminals store dopamine and release it smoothly, buffering levodopa's ~90-minute half-life. As terminals are lost, brain dopamine tracks blood levodopa directly, so every late or poorly absorbed dose becomes an OFF period, and peaks can cause dyskinesia.","evidence":""},{"id":"falls","col":"d","group":"Movement","name":"Balance & falls","sub":"","how":"Automatic posture reflexes run partly through the cholinergic pedunculopontine nucleus in the brainstem, which degenerates and responds poorly to levodopa. Freezing of gait, low standing blood pressure and slowed attention add up to falls.","evidence":""},{"id":"speech","col":"d","group":"Movement","name":"Soft voice","sub":"hypophonia","how":"Movements shrink, including breath support and vocal-fold closure, so the voice gets soft and flat. The brain's own sense of loudness recalibrates, so the person feels they are speaking normally.","evidence":""},{"id":"swallow","col":"d","group":"Movement","name":"Swallowing & drooling","sub":"","how":"Swallowing is a fast, sequenced movement run by brainstem pattern generators; it slows and weakens like other movements. People swallow saliva less often: drooling comes from too little swallowing, not too much saliva.","evidence":""},{"id":"tics","col":"d","group":"Tics","name":"Motor & vocal tics","sub":"","how":"Sudden, repeated movements or sounds. The basal ganglia normally let one wanted movement through and hold the rest back; in Tourette that gating is leaky, so fragments of movement or sound escape. Tics can be held back for a while with effort; they rise with stress, excitement and tiredness and fall during focused activity.","evidence":""},{"id":"urge","col":"d","group":"Tics","name":"Premonitory urge","sub":"the feeling before a tic","how":"Most people with tics feel an itch, pressure or tension before a tic, linked to the insula and supplementary motor area. Doing the tic relieves it briefly, which reinforces the tic: the loop that tic training targets.","evidence":""},{"id":"constipation","col":"d","group":"Gut","name":"Constipation","sub":"","how":"α-Synuclein pathology appears in the gut's own nervous system and in the vagus nerve's motor nucleus, often years before movement signs. Slower muscle waves mean stool stays longer, loses more water and hardens. Pelvic-floor muscles may fail to relax on straining (a form of dystonia).","evidence":""},{"id":"stomach","col":"d","group":"Gut","name":"Slow stomach emptying","sub":"gastroparesis","how":"The same vagal and enteric slowing delays stomach emptying. Levodopa is absorbed in the small intestine, not the stomach, so a dose sitting in a slow stomach arrives late or in bursts: \"delayed ON\" and \"no ON\".","evidence":""},{"id":"nausea","col":"d","group":"Gut","name":"Nausea & vomiting","sub":"feeling sick","how":"A vomiting centre in the brainstem collects signals from a trigger zone (area postrema) that sits outside the blood-brain barrier and samples the blood for drugs and toxins, from the gut through the vagus nerve, and from the balance organs of the inner ear (motion sickness). Levodopa turned into dopamine in the blood stimulates that trigger zone, which is why nausea is common when starting it; a stomach that empties slowly also causes fullness and nausea.","evidence":"Textbook physiology."},{"id":"d_abdominal_pain","col":"d","group":"Gut","name":"Belly pain & cramps","sub":"abdominal pain","how":"Pain from the gut comes from stretching, spasm, inflammation or poor blood supply of its wall, sensed by nerves that are poor at pinpointing location, so it is often felt vaguely in the middle of the belly. Inflamed organs that touch the belly lining (like the appendix or gallbladder) give sharper, better-localised pain.","evidence":"Established physiology. Sudden severe, constant pain, pain with fever, vomiting blood or black stools needs urgent medical assessment."},{"id":"d_bloating","col":"d","group":"Gut","name":"Bloating & wind","sub":"abdominal distension, gas","how":"Gut bacteria ferment carbohydrates that were not absorbed higher up, making gas. Bloating is felt when there is more gas than usual, when it moves slowly, or when the gut is over-sensitive to normal amounts; the belly wall can also relax and push out by reflex.","evidence":"Established physiology. Common in IBS, lactose intolerance, coeliac disease and constipation."},{"id":"d_diarrhoea","col":"d","group":"Gut","name":"Diarrhoea","sub":"loose or frequent stools","how":"Stool becomes loose when the gut secretes more water than it absorbs (toxins from infections), when unabsorbed substances hold water in the bowel (lactose in lactase shortage), when an inflamed lining leaks and cannot absorb (inflammatory bowel disease, coeliac disease), or when contents move too fast.","evidence":"Established physiology. Severe or bloody diarrhoea, or diarrhoea lasting more than a few weeks, needs medical assessment; dehydration is the main danger."},{"id":"d_jaundice","col":"d","group":"Gut","name":"Jaundice","sub":"yellow skin and eyes","how":"Old red blood cells are broken down into yellow bilirubin, which the liver clears into bile. If the liver is damaged, the bile ducts are blocked (stone, tumour), or red cells break down too fast, bilirubin builds up in the blood and stains the skin and whites of the eyes yellow; urine darkens and stool may turn pale.","evidence":"Established physiology. New jaundice in an adult always needs medical assessment."},{"id":"heartburn","col":"d","group":"Gut","name":"Heartburn & acid regurgitation","sub":"burning behind the breastbone, sour taste","how":"Acid in the lower oesophagus stimulates pain nerves in its lining, felt as burning behind the breastbone that rises toward the throat, often after meals, on bending or lying down. Regurgitation is the feeling of sour fluid coming up into the mouth.","evidence":"Established: the typical symptoms of reflux. Chest pain can also be from the heart, so new chest pain needs assessment."},{"id":"insomnia","col":"d","group":"Sleep","name":"Broken night sleep","sub":"","how":"Nights break up from being unable to turn over (low night-time levodopa), cramps and dystonia, needing to urinate, restless legs, low mood, and degeneration of brainstem and hypothalamic sleep nuclei.","evidence":""},{"id":"rbd","col":"d","group":"Sleep","name":"Dream enactment (RBD)","sub":"","how":"In normal REM sleep a brainstem circuit (sublaterodorsal nucleus to a medullary relay) paralyses the muscles. Damage there removes the paralysis, so people act out dreams. It often comes years before Parkinson's.","evidence":""},{"id":"sleepy","col":"d","group":"Sleep","name":"Daytime sleepiness","sub":"","how":"Wakefulness is held up by arousal systems: orexin, noradrenaline (locus coeruleus), histamine, serotonin, dopamine. Several degenerate; dopamine-agonist medicines add sedation and sudden sleep attacks; a bad night adds pressure.","evidence":""},{"id":"fatigue","col":"d","group":"Sleep","name":"Fatigue","sub":"","how":"Exhaustion out of proportion to effort, different from sleepiness. Partly central (altered effort signalling in basal-ganglia–frontal circuits), partly from poor sleep, depression, deconditioning, low blood pressure and inflammation.","evidence":""},{"id":"depression","col":"d","group":"Mood & thinking","name":"Depression","sub":"","how":"Part of the disease, not only a reaction: serotonin (raphe), noradrenaline (locus coeruleus) and mesolimbic dopamine systems all degenerate. Mood often dips during OFF periods.","evidence":""},{"id":"anxiety","col":"d","group":"Mood & thinking","name":"Anxiety","sub":"","how":"The same transmitter systems as depression, plus unpredictable OFF periods. Adrenaline and stress worsen tremor and freezing, closing a loop.","evidence":""},{"id":"apathy","col":"d","group":"Mood & thinking","name":"Apathy","sub":"","how":"Loss of motivation from mesolimbic dopamine and frontal-striatal circuit dysfunction. Different from sadness, and sometimes improves with dopamine treatment.","evidence":""},{"id":"cognition","col":"d","group":"Mood & thinking","name":"Thinking & attention","sub":"","how":"Early: slow processing, attention and planning problems from frontal-striatal dopamine loss. Later: cholinergic loss (nucleus basalis) and Lewy pathology in cortex. Low blood pressure and poor sleep worsen it day to day.","evidence":""},{"id":"adhd","col":"d","group":"Mood & thinking","name":"Attention & impulsivity","sub":"ADHD","how":"Present in about half of people with Tourette. Frontal-striatal circuits that hold attention and stop impulses run on dopamine and noradrenaline; under-signalling there makes focus and waiting hard. Often more disabling than the tics.","evidence":""},{"id":"ocd","col":"d","group":"Mood & thinking","name":"Obsessions & compulsions","sub":"OCD","how":"In roughly a third to half of people with Tourette. Overactive loops between the orbitofrontal cortex, striatum and thalamus produce intrusive thoughts and the urge to repeat actions until they feel \"just right\".","evidence":""},{"id":"rage","col":"d","group":"Mood & thinking","name":"Anger outbursts","sub":"rage attacks","how":"Sudden, out-of-proportion explosions, more common when ADHD or OCD come with Tourette; weak prefrontal brakes on emotional responses.","evidence":""},{"id":"oh","col":"d","group":"Autonomic","name":"Dizziness on standing","sub":"orthostatic hypotension","how":"Standing pools around half a litre of blood in the legs. Normally baroreceptors sense the drop and sympathetic nerves release noradrenaline to tighten vessels. In Parkinson's those nerves (including the heart's, visible on MIBG scans) degenerate, so pressure falls: dizziness, blurred vision, fatigue, falls. Several medicines lower it further.","evidence":""},{"id":"bladder","col":"d","group":"Autonomic","name":"Urgency & night urination","sub":"","how":"The basal ganglia normally help hold back the bladder reflex. With dopamine low, the bladder muscle contracts before it's full: urgency and frequency. At night, lying flat returns pooled fluid to the circulation and raises urine output.","evidence":"","pos":[0,0.89,0.05]},{"id":"smell","col":"d","group":"Senses & pain","name":"Loss of smell","sub":"","how":"The olfactory bulb is one of the first places Lewy pathology appears; smell loss often comes years before movement symptoms and makes food less appealing.","evidence":""},{"id":"pain","col":"d","group":"Senses & pain","name":"Pain","sub":"","how":"Dystonia (sustained cramping postures, often during OFF), rigidity loading joints and muscles, and altered pain processing in the basal ganglia.","evidence":""},{"id":"neuropathy","col":"d","group":"Senses & pain","name":"Numb feet","sub":"peripheral neuropathy","how":"Damage to peripheral nerves: numbness, tingling, poor position sense in the feet. More common with long-term levodopa, linked to low B12 and high homocysteine, and it worsens balance. Typically starts in both feet evenly (longest nerves first); numbness confined to one nerve's patch, such as the thumb to middle finger or the top of one foot, usually points instead to a nerve pinched at a single site (carpal tunnel, fibular head).","evidence":""},{"id":"headache","col":"d","group":"Senses & pain","name":"Headache","sub":"","how":"Pain from the head and neck: tension in scalp and neck muscles, irritated pain nerves of the head after injury, or migraine circuits in the brainstem.","evidence":""},{"id":"tinnitus","col":"d","group":"Senses & pain","name":"Ringing in the ears (tinnitus)","sub":"","how":"Sound heard with no outside source, usually after hearing damage: the brain's hearing pathways turn up their gain when input from the ear is lost.","evidence":""},{"id":"vertigo","col":"d","group":"Senses & pain","name":"Spinning dizziness (vertigo)","sub":"false sense of movement","how":"A false feeling that you or the room is spinning or moving, often with nausea and unsteadiness. It usually comes from the inner ear's balance organs or their brain connections, unlike light-headedness on standing, which comes from blood pressure.","evidence":"Established. Common causes are BPPV, inner-ear nerve inflammation, Ménière's disease and vestibular migraine; stroke is a rare but important cause."},{"id":"vision_pd","col":"d","group":"Senses & pain","name":"Faded contrast & colour vision","sub":"sharp eyesight but a washed-out picture","how":"Seeing outlines and shades less clearly (low contrast), with colours, especially blues and greens, harder to tell apart, even when the letter chart is normal. In Parkinson's this starts partly in the retina, where dopamine cells that sharpen contrast are lost, and partly further along the visual pathway. It makes reading, dim light, stairs and kerbs harder.","evidence":"Association: found consistently in Parkinson's in many studies. Small before-and-after studies suggest dopamine medicine can partly improve it, but there are no good trials."},{"id":"dry_eye","col":"d","group":"Senses & pain","name":"Dry, gritty eyes","sub":"tear film breaks up","how":"Burning, gritty or tired eyes, blurred vision that clears with blinking, and paradoxically watery eyes, because the tear film breaks up too fast. Common with age, screens (we blink less while staring), some medicines and lid-gland problems. In Parkinson's, blinking slows and the cornea becomes less sensitive, so the surface can dry without much warning.","evidence":"Association: more common in Parkinson's than in controls in several studies. Eye-surface care is standard; fish-oil omega-3 failed in a large trial."},{"id":"diplopia","col":"d","group":"Senses & pain","name":"Double vision","sub":"two images instead of one","how":"Seeing two images of one object, when the two eyes are not pointing exactly at the same target. In Parkinson's it most often comes from weak convergence (turning both eyes in for reading), and it tends to come and go with medication timing.","evidence":"Association: reported by roughly one in ten to one in three people with Parkinson's; linked to longer disease, motor fluctuations, hallucinations and cognitive decline."},{"id":"inactivity","col":"d","group":"Life factors","name":"Moving less","sub":"","how":"When moving is effortful, tiring or frightening, people move less, which deconditions muscle, heart, bowel and bone.","evidence":""},{"id":"dehydration","col":"d","group":"Life factors","name":"Drinking less","sub":"","how":"People drink less to avoid urgency, and thirst blunts with age. Lower blood volume worsens standing blood pressure; drier stool worsens constipation.","evidence":""},{"id":"isolation","col":"d","group":"Life factors","name":"Social withdrawal","sub":"","how":"A soft voice, reduced facial expression, mobility and embarrassment reduce contact, which removes a major source of activity, speech practice and mood support.","evidence":""},{"id":"nutrition","col":"d","group":"Life factors","name":"Weight & nutrition","sub":"","how":"Smell loss, swallowing trouble, constipation, low mood and the energy cost of tremor or dyskinesia lead to weight loss and poor intake.","evidence":""},{"id":"fracture","col":"d","group":"Life factors","name":"Fractures","sub":"","how":"Falls plus low vitamin D, inactivity and weight loss lower bone density; hip fractures are much more common in Parkinson's.","evidence":""},{"id":"pneumonia","col":"d","group":"Life factors","name":"Aspiration pneumonia","sub":"","how":"Food or saliva entering the airway, often silently and with a weak cough, causes pneumonia: a leading cause of hospital stays in advanced Parkinson's.","evidence":""},{"id":"parkinsons","col":"x","group":"Conditions","name":"Parkinson's disease","sub":"","how":"A slowly progressive brain disease: dopamine neurons in the substantia nigra die, and α-synuclein clumps spread through the brainstem, gut, smell pathways and later the cortex. Too little dopamine in the striatum gives slowness, stiffness and tremor; damage elsewhere gives the long list of non-movement problems.","evidence":"Proven: levodopa and other dopamine medicines, exercise, physiotherapy and speech therapy, deep brain stimulation for selected people. Nothing is yet proven to slow the disease.","timeline":[{"label":"Prodromal: smell and gut (Braak 1)","from":-20,"to":-3,"affects":["smell","s_smell","br_olfactory_bulb","constipation","s_gut","br_dmnv","s_autonomic"],"note":"Years before any tremor, many people slowly lose their sense of smell and become constipated, which fits Braak's idea that Lewy changes start in the smell bulb and the vagus nerve centre; this is a strong population link, but most people with these common symptoms never get Parkinson's.","sources":[{"id":"pmid:12498954","citation":"Braak H et al., Neurobiol Aging","year":2003,"design":"lab","finding":"Autopsy staging: Lewy pathology starts in the vagus nucleus and olfactory region, climbs the brainstem, then reaches the temporal mesocortex and finally the neocortex."},{"id":"pmid:31111143","citation":"Fereshtehnejad SM et al., Brain","year":2019,"design":"cohort","finding":"In people with RBD followed until they developed Parkinson's or Lewy body dementia, smell loss began over 20 years before, constipation 10–16 years before, and subtle motor signs 5–7 years before."},{"id":"pmid:19933976","citation":"Savica R et al., Neurology","year":2009,"design":"case-control","finding":"Constipation recorded 20 or more years before movement symptoms was still linked to later Parkinson's disease."},{"id":"pmid:11502913","citation":"Abbott RD et al., Neurology","year":2001,"design":"cohort","finding":"Men with fewer than one bowel movement a day had about 2.7 times the risk of Parkinson's over 24 years of follow-up."},{"id":"pmid:18067173","citation":"Ross GW et al., Ann Neurol","year":2008,"design":"cohort","finding":"Older men with the poorest sense of smell were about 5 times more likely to be diagnosed with Parkinson's within the next 4 years."}]},{"label":"Prodromal: dream enactment and mood (Braak 2)","from":-12,"to":0,"affects":["rbd","br_sld","br_lc","br_raphe","s_brainstem","depression","anxiety"],"note":"Higher brainstem centres for sleep and mood (locus coeruleus, raphe, the REM-sleep switch) are involved next, so acting out dreams, low mood and anxiety often appear several years before diagnosis; dream enactment is the strongest single warning sign, but it is more typical of the \"body-first\" route and many people with Parkinson's never have it.","sources":[{"id":"pmid:30789229","citation":"Postuma RB et al., Brain","year":2019,"design":"cohort","finding":"Of 1280 people with isolated RBD, about 6% a year developed Parkinson's, Lewy body dementia or MSA, and about 74% had converted after 12 years."},{"id":"pmid:25435387","citation":"Schrag A et al., Lancet Neurol","year":2015,"design":"case-control","finding":"In UK primary care, tremor and constipation were more common 10 years before a Parkinson's diagnosis, and depression, anxiety, dizziness and fatigue by 5 years before."},{"id":"pmid:32830221","citation":"Horsager J et al., Brain","year":2020,"design":"case-control","finding":"Imaging supports two routes: a body-first type (with RBD, gut and heart nerves affected first) and a brain-first type (dopamine loss first, body nerves later)."}]},{"label":"Substantia nigra and the movement diagnosis (Braak 3)","from":-6,"to":3,"affects":["br_snc","br_putamen","s_bg","tremor","movement","br_amygdala"],"note":"Once enough dopamine cells in the substantia nigra are lost, slowness, stiffness and often a resting tremor appear and the diagnosis is made; subtle movement changes can be measured 5–7 years earlier, and in \"brain-first\" cases this may be the very first stage rather than the third.","sources":[{"id":"pmid:12498954","citation":"Braak H et al., Neurobiol Aging","year":2003,"design":"lab","finding":"Autopsy staging: Lewy pathology starts in the vagus nucleus and olfactory region, climbs the brainstem, then reaches the temporal mesocortex and finally the neocortex."},{"id":"pmid:31111143","citation":"Fereshtehnejad SM et al., Brain","year":2019,"design":"cohort","finding":"In people with RBD followed until they developed Parkinson's or Lewy body dementia, smell loss began over 20 years before, constipation 10–16 years before, and subtle motor signs 5–7 years before."},{"id":"pmid:25435387","citation":"Schrag A et al., Lancet Neurol","year":2015,"design":"case-control","finding":"In UK primary care, tremor and constipation were more common 10 years before a Parkinson's diagnosis, and depression, anxiety, dizziness and fatigue by 5 years before."},{"id":"pmid:32830221","citation":"Horsager J et al., Brain","year":2020,"design":"case-control","finding":"Imaging supports two routes: a body-first type (with RBD, gut and heart nerves affected first) and a brain-first type (dopamine loss first, body nerves later)."}]},{"label":"Temporal mesocortex (Braak 4)","from":0,"to":10,"affects":["br_entorhinal","br_hippocampus","s_limbic","cognition"],"note":"In Braak's autopsy scheme the deep temporal cortex near the memory circuits is involved next, which may relate to early thinking changes, but no study has pinned a Braak stage to a number of years and stage does not match how severe symptoms are.","sources":[{"id":"pmid:12498954","citation":"Braak H et al., Neurobiol Aging","year":2003,"design":"lab","finding":"Autopsy staging: Lewy pathology starts in the vagus nucleus and olfactory region, climbs the brainstem, then reaches the temporal mesocortex and finally the neocortex."},{"id":"pmid:19067353","citation":"Burke RE et al., Ann Neurol","year":2008,"design":"review","finding":"Many older people without symptoms have Braak stage 4–6 pathology, the pattern often fails in dementia with Lewy bodies, and Braak stage does not track clinical severity."}]},{"label":"Levodopa years: wearing-off and dyskinesia","from":3,"to":15,"affects":["off","chorea","movement","br_putamen","s_bg"],"note":"After some years of treatment the benefit of each dose can wear off early (OFF periods) and extra writhing movements (dyskinesia) may appear; in a population cohort about a third developed dyskinesia, usually about 4 years after starting levodopa and usually mild, while specialist cohorts report higher figures.","sources":[{"id":"pmid:30404780","citation":"Turcano P et al., Neurology","year":2018,"design":"cohort","finding":"In a population cohort, about 30% of people on levodopa developed dyskinesia, typically about 4 years after starting it, and most cases were mild."},{"id":"pmid:15551331","citation":"Hely MA et al., Mov Disord","year":2005,"design":"cohort","finding":"At 15 years, most had had wearing-off and dyskinesia, but the disabling problems were falls (81%), choking (50%), hallucinations (50%) and dementia (48%), which levodopa does not help."}]},{"label":"Later: falls, swallowing, blood pressure and bladder","from":8,"to":20,"affects":["falls","fracture","swallow","pneumonia","speech","oh","bladder","s_throat","br_ppn"],"note":"Problems that do not respond well to levodopa come to dominate later: falls, choking and swallowing trouble, a soft voice, dizziness on standing and bladder urgency were each reported by roughly a third to over four fifths of 15–20-year survivors, though timing varies a lot with age at onset.","sources":[{"id":"pmid:15551331","citation":"Hely MA et al., Mov Disord","year":2005,"design":"cohort","finding":"At 15 years, most had had wearing-off and dyskinesia, but the disabling problems were falls (81%), choking (50%), hallucinations (50%) and dementia (48%), which levodopa does not help."},{"id":"pmid:18307261","citation":"Hely MA et al., Mov Disord","year":2008,"design":"cohort","finding":"At 20 years from diagnosis, 83% of survivors had dementia, 87% had fallen, 74% had hallucinations and 48% had choking episodes."},{"id":"pmid:20371510","citation":"Kempster PA et al., Brain","year":2010,"design":"cohort","finding":"Falls, hallucinations, dementia and needing residential care arrive at a similar time before death whatever the age, and link to Lewy pathology in the cortex."}]},{"label":"Neocortex: dementia and hallucinations (Braak 5–6)","from":10,"to":20,"affects":["cognition","memory","hallucinations","s_cortex","br_dlpfc","br_visual","br_nbm"],"note":"When Lewy changes reach the outer cortex, dementia and seeing things that are not there become common: most people living 15–20 years with Parkinson's develop dementia, and hallucinations usually progress over time; Alzheimer-type changes often add to this.","sources":[{"id":"pmid:12498954","citation":"Braak H et al., Neurobiol Aging","year":2003,"design":"lab","finding":"Autopsy staging: Lewy pathology starts in the vagus nucleus and olfactory region, climbs the brainstem, then reaches the temporal mesocortex and finally the neocortex."},{"id":"pmid:12633150","citation":"Aarsland D et al., Arch Neurol","year":2003,"design":"cohort","finding":"Over 8 years, about 78% of a population-based Parkinson's group developed dementia; early hallucinations predicted it."},{"id":"pmid:18307261","citation":"Hely MA et al., Mov Disord","year":2008,"design":"cohort","finding":"At 20 years from diagnosis, 83% of survivors had dementia, 87% had fallen, 74% had hallucinations and 48% had choking episodes."},{"id":"pmid:20371510","citation":"Kempster PA et al., Brain","year":2010,"design":"cohort","finding":"Falls, hallucinations, dementia and needing residential care arrive at a similar time before death whatever the age, and link to Lewy pathology in the cortex."},{"id":"pmid:16682540","citation":"Goetz CG et al., Arch Neurol","year":2006,"design":"cohort","finding":"Hallucinations in Parkinson's where insight was kept usually progressed over 3 years to loss of insight or delusions."}]}]},{"id":"tourette","col":"x","group":"Conditions","name":"Tourette syndrome","sub":"","how":"A neurodevelopmental condition: several motor tics and at least one vocal tic for more than a year, starting in childhood (usually age 5–7), peaking around 10–12 and easing in many by adulthood. The circuits that select and suppress movements let unwanted programs through; post-mortem studies find fewer inhibitory interneurons in the striatum, and dopamine signalling there seems overactive: roughly the opposite direction from Parkinson's, which is why dopamine-blocking medicines reduce tics. Strongly genetic, through many genes of small effect. Not degenerative.","evidence":"Proven: tic training (CBIT), and medicines (α2-agonists, dopamine blockers) for more severe tics. Foods and supplements: nothing proven. Omega-3 did not reduce tics (Gabbay 2012); N-acetylcysteine failed (Bloch 2016); magnesium + B6 had one small positive trial; cannabinoids mixed (CANNA-TICS 2023 missed its main goal). Low vitamin D has been linked with worse tics (association only).","timeline":[{"label":"Onset: simple motor tics (about age 5–7)","from":0,"to":2,"affects":["tics","br_sma","br_putamen","br_caudate","s_bg"],"note":"Years are counted from the first tic, which on average starts around age 5–6, usually as blinking or facial tics that come and go; vocal tics typically follow later.","sources":[{"id":"pmid:9651407","citation":"Leckman JF et al., Pediatrics","year":1998,"design":"cohort","finding":"Tics began at about 5.6 years, were worst at about 10, then steadily declined; by 18 nearly half were virtually tic-free."}]},{"label":"Comorbid ADHD, OCD and anxiety emerge","from":0,"to":6,"affects":["adhd","ocd","anxiety","rage","s_prefrontal"],"note":"Most children with Tourette also develop ADHD, OCD or anxiety, with the highest risk of these starting between about 4 and 10 years old, and they often cause more trouble than the tics.","sources":[{"id":"pmid:25671412","citation":"Hirschtritt ME et al., JAMA Psychiatry","year":2015,"design":"cross-sectional","finding":"About 86% of people with Tourette had another psychiatric condition, mostly ADHD or OCD, with highest-risk onset between ages 4 and 10."}]},{"label":"Peak tic years (about age 10–12)","from":3,"to":7,"affects":["tics","urge","insomnia","isolation","br_sma","s_bg"],"note":"Tics usually build to their worst around age 10–11, and at this age children start to notice and describe the uncomfortable urge that comes before a tic.","sources":[{"id":"pmid:9651407","citation":"Leckman JF et al., Pediatrics","year":1998,"design":"cohort","finding":"Tics began at about 5.6 years, were worst at about 10, then steadily declined; by 18 nearly half were virtually tic-free."},{"id":"pmid:16389213","citation":"Bloch MH et al., Arch Pediatr Adolesc Med","year":2006,"design":"cohort","finding":"Most (85%) reported fewer tics during adolescence; worst tics averaged age 10.6 and worst OCD symptoms came about 2 years later and persisted more."},{"id":"pmid:16344654","citation":"Woods DW et al., J Dev Behav Pediatr","year":2005,"design":"cross-sectional","finding":"Older youths report a premonitory urge before tics; the urge scale did not work reliably in children aged 10 and under."}]},{"label":"Adolescent improvement; OCD peaks later","from":6,"to":13,"affects":["tics","ocd","adhd"],"note":"Through the teenage years tics fade for most (85% in one cohort), while obsessive-compulsive symptoms tend to peak about 2 years after the tics and linger longer.","sources":[{"id":"pmid:16389213","citation":"Bloch MH et al., Arch Pediatr Adolesc Med","year":2006,"design":"cohort","finding":"Most (85%) reported fewer tics during adolescence; worst tics averaged age 10.6 and worst OCD symptoms came about 2 years later and persisted more."},{"id":"pmid:28335874","citation":"Groth C et al., J Am Acad Child Adolesc Psychiatry","year":2017,"design":"cohort","finding":"Tic, OCD and ADHD severity fell yearly through adolescence; after 16, 18% had no tics, 60% mild tics and 23% moderate or severe."}]},{"label":"Adulthood: most improve, some persist","from":12,"to":25,"affects":["tics","ocd","anxiety","depression"],"note":"By the late teens nearly half are almost tic-free and most of the rest have mild tics, but around one in five still has moderate or severe tics and other conditions often persist.","sources":[{"id":"pmid:9651407","citation":"Leckman JF et al., Pediatrics","year":1998,"design":"cohort","finding":"Tics began at about 5.6 years, were worst at about 10, then steadily declined; by 18 nearly half were virtually tic-free."},{"id":"pmid:28335874","citation":"Groth C et al., J Am Acad Child Adolesc Psychiatry","year":2017,"design":"cohort","finding":"Tic, OCD and ADHD severity fell yearly through adolescence; after 16, 18% had no tics, 60% mild tics and 23% moderate or severe."}]}]},{"id":"broccsprouts","col":"f","group":"Vegetables","name":"Broccoli sprouts","sub":"","how":"Young broccoli shoots.","evidence":""},{"id":"brassicas","col":"f","group":"Vegetables","name":"Broccoli, kale, cabbage","sub":"","how":"Cruciferous vegetables.","evidence":""},{"id":"redcabbage","col":"f","group":"Vegetables","name":"Red cabbage","sub":"","how":"A crucifer with red-purple pigment.","evidence":""},{"id":"onions","col":"f","group":"Vegetables","name":"Onions, capers","sub":"","how":"","evidence":""},{"id":"greens","col":"f","group":"Vegetables","name":"Leafy greens","sub":"spinach, chard","how":"","evidence":""},{"id":"mushrooms","col":"f","group":"Vegetables","name":"Mushrooms","sub":"","how":"Fungi, not plants, but eaten as vegetables.","evidence":""},{"id":"peppers","col":"f","group":"Vegetables","name":"Peppers","sub":"","how":"A nightshade.","evidence":""},{"id":"tomatoes","col":"f","group":"Vegetables","name":"Tomatoes","sub":"","how":"A nightshade.","evidence":""},{"id":"potatoes","col":"f","group":"Vegetables","name":"Potatoes","sub":"","how":"A nightshade.","evidence":""},{"id":"eggplant","col":"f","group":"Vegetables","name":"Eggplant","sub":"","how":"A nightshade.","evidence":""},{"id":"lions_mane","col":"f","group":"Vegetables","name":"Lion's mane mushroom","sub":"Hericium erinaceus","how":"An edible white, shaggy mushroom, eaten as food in East Asia and sold as powders and extracts.","evidence":""},{"id":"garlic","col":"f","group":"Vegetables","name":"Garlic","sub":"","how":"A bulb of the onion family. Crushing or chopping mixes the stored compound alliin with the enzyme alliinase, making allicin; aged garlic extract instead contains S-allylcysteine. Also rich in inulin-type fibre.","evidence":""},{"id":"carrots","col":"f","group":"Vegetables","name":"Carrots","sub":"","how":"Orange root vegetable; one of the richest sources of beta-carotene and alpha-carotene. Cooking and a little fat release far more of the carotene than eating raw carrot alone.","evidence":""},{"id":"sweet_potato","col":"f","group":"Vegetables","name":"Sweet potato","sub":"orange-fleshed","how":"Orange-fleshed sweet potato is very rich in beta-carotene and also supplies fibre and potassium. Not a nightshade, unlike ordinary potato.","evidence":""},{"id":"beetroot","col":"f","group":"Vegetables","name":"Beetroot","sub":"and beet juice","how":"A root vegetable very rich in nitrate and in red-purple betalain pigments; also supplies folate and fibre. Beet juice can turn urine and stool pink or red (harmless, but can be mistaken for blood).","evidence":""},{"id":"berries","col":"f","group":"Fruit","name":"Blueberries, blackberries","sub":"","how":"","evidence":""},{"id":"cherries","col":"f","group":"Fruit","name":"Tart cherries","sub":"","how":"","evidence":""},{"id":"grapes","col":"f","group":"Fruit","name":"Red grapes","sub":"","how":"","evidence":""},{"id":"apples","col":"f","group":"Fruit","name":"Apples","sub":"pectin, flavonoids in the skin","how":"Apples carry soluble fibre (pectin) and several plant compounds: quercetin, epicatechin and procyanidins (flavan-3-ols), chlorogenic acid and phloridzin. Most of these, except chlorogenic acid, sit in or just under the skin. They also contain sorbitol and more fructose than glucose, which some people do not fully absorb, so apples can cause wind or loose stools in sensitive guts. Clear apple juice keeps the sugar but loses the pectin.","evidence":"Small trials show whole apples modestly lower LDL cholesterol in some people; pooled results are borderline (see the link to blood vessels). In large US cohorts apples were linked with a slightly lower risk of type 2 diabetes (association). For Parkinson's, the same cohorts found no specific link for apples; the flavonoid-rich food that stood out was berries (Gao 2012; Zhang 2022)."},{"id":"prunes","col":"f","group":"Fruit","name":"Prunes","sub":"","how":"Dried plums.","evidence":""},{"id":"kiwifruit","col":"f","group":"Fruit","name":"Kiwifruit","sub":"","how":"","evidence":""},{"id":"bananas","col":"f","group":"Fruit","name":"Bananas","sub":"","how":"","evidence":""},{"id":"olives","col":"f","group":"Fruit","name":"Olives & olive oil","sub":"extra-virgin","how":"","evidence":""},{"id":"pomegranate","col":"f","group":"Fruit","name":"Pomegranate","sub":"","how":"Seeds (arils) and juice rich in ellagitannins, especially punicalagin, which is concentrated in the peel and pressed into whole-fruit juice.","evidence":""},{"id":"strawberries","col":"f","group":"Fruit","name":"Strawberries","sub":"","how":"Supply vitamin C, anthocyanins (the red colour), ellagitannins and fisetin, one of the few foods with measurable fisetin.","evidence":""},{"id":"cranberries","col":"f","group":"Fruit","name":"Cranberries","sub":"","how":"Tart red berries rich in type-A proanthocyanidins, anthocyanins and quercetin. Most cranberry juice drinks are heavily sweetened.","evidence":""},{"id":"avocado","col":"f","group":"Fruit","name":"Avocado","sub":"","how":"A fatty fruit (mostly monounsaturated fat) with fibre, potassium and some lutein. Its fat helps carry fat-soluble plant pigments from other foods in the same meal into the body.","evidence":""},{"id":"citrus","col":"f","group":"Fruit","name":"Citrus fruit","sub":"oranges, lemons, grapefruit","how":"Oranges, lemons, limes and grapefruit. Rich in vitamin C, pectin fibre and flavanones (hesperidin, naringenin), which sit mostly in the white pith and membranes, so whole fruit and juice with pulp carry more. Grapefruit also contains furanocoumarins that block the gut enzyme CYP3A4 and can raise blood levels of many medicines.","evidence":""},{"id":"fava","col":"f","group":"Beans, nuts & grains","name":"Fava beans","sub":"","how":"Can cause a dangerous reaction in people with G6PD deficiency (favism).","evidence":""},{"id":"mucuna","col":"f","group":"Beans, nuts & grains","name":"Velvet bean","sub":"Mucuna pruriens","how":"Sold as a supplement; concentrated levodopa.","evidence":""},{"id":"legumes","col":"f","group":"Beans, nuts & grains","name":"Lentils, beans, chickpeas","sub":"","how":"","evidence":""},{"id":"oats","col":"f","group":"Beans, nuts & grains","name":"Oats & whole grains","sub":"","how":"","evidence":""},{"id":"nuts","col":"f","group":"Beans, nuts & grains","name":"Nuts & seeds","sub":"walnuts, almonds, hazelnuts, pumpkin seeds (flax has its own entry)","how":"","evidence":""},{"id":"peanuts","col":"f","group":"Beans, nuts & grains","name":"Peanuts","sub":"","how":"","evidence":""},{"id":"soy","col":"f","group":"Beans, nuts & grains","name":"Soy foods","sub":"tofu, tempeh, edamame, soy milk","how":"Soybeans and foods made from them. A complete plant protein, rich in isoflavones; fermented forms (tempeh, miso, natto) are partly broken down by microbes.","evidence":""},{"id":"flaxseed","col":"f","group":"Beans, nuts & grains","name":"Flaxseed","sub":"linseed","how":"Small brown or golden seeds rich in ALA omega-3 fat, sticky soluble fibre and lignans (the richest dietary lignan source). Whole seeds often pass through undigested; ground seed releases more.","evidence":""},{"id":"chia","col":"f","group":"Beans, nuts & grains","name":"Chia seeds","sub":"","how":"Seeds of Salvia hispanica; rich in ALA omega-3 and in soluble fibre that forms a gel in water.","evidence":"Dry seeds swell greatly in liquid, so they are usually eaten soaked; worth bearing in mind for anyone with swallowing difficulty."},{"id":"coffee","col":"f","group":"Drinks","name":"Coffee","sub":"","how":"","evidence":""},{"id":"greentea","col":"f","group":"Drinks","name":"Green tea","sub":"","how":"","evidence":""},{"id":"cocoa","col":"f","group":"Drinks","name":"Cocoa & dark chocolate","sub":"","how":"","evidence":""},{"id":"sweets","col":"f","group":"Drinks","name":"Sweets & sugary drinks","sub":"","how":"","evidence":""},{"id":"turmeric","col":"f","group":"Herbs & other","name":"Turmeric","sub":"","how":"The dried, ground root of Curcuma longa. Its yellow colour comes from curcumin, a few percent of the spice, which is poorly absorbed; supplements use extracts, fat-based or 'nano' forms, or add black pepper extract (piperine) to raise blood levels.","evidence":"Supplement trials (not the spice in food) lowered blood inflammation markers and eased knee osteoarthritis pain a little. A small trial in Parkinson's found no benefit. Rarely, turmeric supplements have caused liver injury. Combined with black seed it has been compared with each alone in only two small trials, with no clear extra benefit from the pair."},{"id":"algae","col":"f","group":"Herbs & other","name":"Seaweed & algal oil","sub":"","how":"","evidence":""},{"id":"fermented","col":"f","group":"Herbs & other","name":"Fermented foods","sub":"sauerkraut, kimchi, kefir","how":"","evidence":""},{"id":"cannabis","col":"f","group":"Herbs & other","name":"Cannabis","sub":"","how":"","evidence":""},{"id":"fortified","col":"f","group":"Herbs & other","name":"Fortified foods","sub":"nutritional yeast, plant milks","how":"","evidence":""},{"id":"herbs_mint","col":"f","group":"Herbs & other","name":"Rosemary, oregano & sage","sub":"mint-family herbs","how":"Culinary herbs of the mint family, rich in rosmarinic acid; rosemary also contains carnosic acid, and oregano carvacrol. Usually eaten in small amounts.","evidence":""},{"id":"black_pepper","col":"f","group":"Herbs & other","name":"Black pepper","sub":"","how":"The dried fruit of Piper nigrum; its bite comes from piperine. Usually eaten in small amounts as a seasoning.","evidence":""},{"id":"ginger","col":"f","group":"Herbs & other","name":"Ginger","sub":"fresh or dried root","how":"A root used fresh, dried or as tea. Its pungent compounds are gingerols (fresh) and shogaols (formed when ginger is dried or cooked).","evidence":""},{"id":"black_seed","col":"f","group":"Herbs & other","name":"Black seed","sub":"Nigella sativa, kalonji","how":"Small black seeds used as a spice and pressed for oil across the Middle East and South Asia. Main active compound: thymoquinone.","evidence":"Not the same plant as black cumin (Bunium) or onion seed, though often sold under those names. Trials of the seed or oil (as capsules) show modest drops in blood pressure, cholesterol, blood sugar and blood inflammation markers. Taken together with turmeric it has been tested in only two small human trials against each alone: one suggested the pair at lower doses did slightly more, the other found the pair no better than either alone; no trial of the pair exists for Parkinson's or any brain outcome. Rare reports of skin reactions from oil on the skin, and single cases of kidney and liver injury and of bleeding in a patient on blood-thinning drugs."},{"id":"cinnamon","col":"f","group":"Herbs & other","name":"Cinnamon","sub":"Ceylon and cassia","how":"The inner bark of Cinnamomum trees; its flavour is cinnamaldehyde. Cassia cinnamon (the common supermarket kind) also contains coumarin, which can harm the liver in people who eat a lot of it; Ceylon cinnamon has very little.","evidence":""},{"id":"parsley_celery","col":"f","group":"Herbs & other","name":"Parsley & celery","sub":"also chamomile tea","how":"Parsley is one of the richest dietary sources of apigenin; celery and its seeds supply apigenin and luteolin. Chamomile tea is another apigenin source.","evidence":""},{"id":"dairy","col":"f","group":"Dairy & eggs","name":"Milk, yoghurt & cheese","sub":"","how":"Milk and its products: protein, calcium, B12, iodine and phosphorus. Yoghurt and kefir can also carry live bacteria.","evidence":"Several large studies link high dairy intake, especially low-fat milk, to a somewhat higher chance of getting Parkinson's; others found no link, and the reason is unknown. The protein in it can compete with levodopa."},{"id":"eggs","col":"f","group":"Dairy & eggs","name":"Eggs","sub":"","how":"Yolk holds most of the choline, vitamin D, B12, biotin and selenium; the white is mostly protein. Raw egg white contains avidin, which locks up biotin; cooking destroys it.","evidence":""},{"id":"oilyfish","col":"f","group":"Fish & seafood","name":"Oily fish","sub":"salmon, sardines, mackerel, herring","how":"The main food source of the long-chain omega-3s DHA and EPA, and one of the few natural foods with real vitamin D. Also protein, B12, selenium and iodine; sardines eaten with bones add calcium.","evidence":""},{"id":"whitefish","col":"f","group":"Fish & seafood","name":"White fish","sub":"cod, haddock, pollock","how":"Lean protein; sea fish are a good source of iodine and selenium.","evidence":""},{"id":"shellfish","col":"f","group":"Fish & seafood","name":"Shellfish","sub":"oysters, mussels, clams, shrimp","how":"Oysters and mussels are among the richest sources of zinc, copper, B12 and selenium, plus iron and iodine.","evidence":""},{"id":"redmeat","col":"f","group":"Meat","name":"Red meat","sub":"beef, lamb, pork; ham and sausages","how":"Protein, haem iron (absorbed much better than plant iron), zinc and B12. Processed meats add a lot of salt.","evidence":""},{"id":"poultry","col":"f","group":"Meat","name":"Chicken & turkey","sub":"","how":"Lean protein, niacin (B3), B6 and selenium.","evidence":""},{"id":"liver","col":"f","group":"Meat","name":"Liver & organ meats","sub":"liver, kidney, pâté","how":"Very concentrated vitamin A, B12, folate, copper and iron.","evidence":"Because its vitamin A is so concentrated, eating liver often can push vitamin A to harmful levels, especially in pregnancy."},{"id":"tremor","col":"d","group":"Movement","name":"Tremor","sub":"","how":"Rhythmic shaking. Parkinson's tremor is mostly at rest and comes from abnormal rhythmic loops between the basal ganglia and the cerebellum–thalamus circuit. Essential tremor is mostly during action (holding a cup) and comes from the cerebellum and its loops. Stress and adrenaline make every tremor larger.","evidence":""},{"id":"chorea","col":"d","group":"Movement","name":"Involuntary writhing movements","sub":"chorea, dyskinesia","how":"Flowing, dance-like movements that aren't chosen. In Huntington's the striatal \"stop\" neurons die first, so movement gets through too easily. In Parkinson's the same pattern appears at levodopa peaks (dyskinesia), when a damaged system gets too much dopamine at once.","evidence":""},{"id":"rls","col":"d","group":"Movement","name":"Restless legs","sub":"","how":"An uncomfortable urge to move the legs, worse at rest and in the evening, relieved by moving. Linked to low iron inside the brain (iron is needed to make dopamine and myelin) and to dopamine signalling that follows a daily rhythm.","evidence":""},{"id":"seizures","col":"d","group":"Movement","name":"Seizures","sub":"","how":"A burst of abnormal, synchronised firing in the cortex. Whether a seizure starts depends on the balance of excitation (glutamate) and inhibition (GABA); scars, cysts and tumours create irritable spots; sleep loss lowers the threshold.","evidence":""},{"id":"memory","col":"d","group":"Mood & thinking","name":"Memory loss","sub":"","how":"New memories are laid down by the hippocampus and stored across the cortex. In Alzheimer's, amyloid plaques and tau tangles build up and the hippocampus is hit early, so recent events are lost first while old memories last.","evidence":""},{"id":"hallucinations","col":"d","group":"Mood & thinking","name":"Hallucinations","sub":"","how":"Seeing (more rarely hearing) things that aren't there. In Lewy body disease and Parkinson's they come from damaged visual-processing and attention networks plus cholinergic loss; dopamine medicines can trigger or worsen them.","evidence":""},{"id":"breathless","col":"d","group":"Breathing","name":"Breathlessness","sub":"","how":"Feeling unable to get enough air, when lungs are stiff, airways narrowed, or the heart can't keep up.","evidence":""},{"id":"wheeze","col":"d","group":"Breathing","name":"Wheeze & tight chest","sub":"","how":"A whistling sound when breathing out, from air squeezing through airways narrowed by tightened muscle, swelling and mucus.","evidence":"Established. Common in asthma and in severe allergic reactions."},{"id":"d_cough","col":"d","group":"Breathing","name":"Cough & phlegm","sub":"long-lasting cough, mucus","how":"Coughing is a reflex that clears mucus, dust and anything inhaled from the airways. A cough lasting more than a few weeks, especially with phlegm, usually means the airways are irritated or inflamed: smoking, asthma, COPD, infection, reflux or post-nasal drip are common causes.","evidence":"Textbook clinical medicine."},{"id":"hives","col":"d","group":"Allergic reactions","name":"Hives","sub":"urticaria rash, wheals","how":"Raised, itchy, pale-centred red bumps (wheals) that come and go within hours, caused by histamine making small skin blood vessels leak fluid.","evidence":"Established. Hives within minutes to two hours of a food, sting or drug suggests an IgE allergy; hives that keep coming back for weeks usually have no allergic trigger."},{"id":"angioedema","col":"d","group":"Allergic reactions","name":"Swelling of lips, eyes or tongue","sub":"angioedema","how":"Deeper swelling under the skin or lining of the mouth and throat, from the same histamine leak as hives but in deeper tissue. Swelling of the tongue or throat can block the airway.","evidence":"Established. Some angioedema is not allergic (for example from certain blood-pressure tablets or a rare inherited condition) and does not respond to allergy treatment."},{"id":"itchy_nose_eyes","col":"d","group":"Allergic reactions","name":"Sneezing, runny nose & itchy eyes","sub":"allergic rhinitis and conjunctivitis","how":"Histamine from mast cells in the nose and eye lining causes sneezing, a runny or blocked nose, and red, itchy, watery eyes.","evidence":"Established. Seasonal symptoms point to pollen; year-round symptoms point to dust mites, pets, mould or cockroaches."},{"id":"d_itch","col":"d","group":"Allergic reactions","name":"Itchy skin","sub":"pruritus","how":"Itch is a separate nerve signal from pain: thin nerve fibres in the top layers of skin fire when histamine (from mast cells) or other itch chemicals (IL-31, IL-4 and IL-13 in eczema, proteases, bile salts in liver disease) touch them. Scratching briefly overrides the signal but damages the skin barrier, which releases more alarm signals and more itch: the itch-scratch cycle. In hives the itch is histamine-driven and antihistamines help; in eczema it is mostly not histamine-driven, which is why antihistamines help it little.","evidence":"Established physiology. Itch from eczema is a leading cause of broken sleep in children. Itch can also come from dry skin, liver and kidney disease, iron deficiency, some medicines and nerve damage, so long-lasting itch without a rash needs a doctor's check."},{"id":"lymphoedema","col":"d","group":"Swelling","name":"Lymphoedema","sub":"swelling from blocked lymph drainage","how":"When lymph vessels or nodes are damaged or missing, protein-rich fluid collects under the skin and a limb (or other area) swells, feels heavy, and over time the skin thickens and infections become more likely. Common causes: lymph nodes removed or irradiated in cancer treatment (arm after breast cancer, leg after pelvic cancers), and in the tropics a mosquito-spread worm (lymphatic filariasis) that lives in lymph vessels. Some people are born with weak lymph vessels.","evidence":"Exercise, including progressive weight lifting, does not worsen it and eases symptoms in trials; whether it prevents it is uncertain (see links). Compression sleeves after breast cancer surgery reduced how often lymphoedema developed and arm volume in a 2025 meta-analysis (Cheng, PMID 41389304). Manual lymphatic drainage (a gentle massage) gives mixed results: one meta-analysis found less new lymphoedema and pain but no change in volume (Lin 2022, PMID 35370085); another found no significant reduction (Liang 2020, PMID 33285693). Usually treated with combined care from a lymphoedema therapist."},{"id":"swollen_nodes","col":"d","group":"Swelling","name":"Swollen lymph nodes","sub":"\"swollen glands\"","how":"Lymph nodes enlarge when immune cells inside them multiply to fight an infection nearby (a sore throat swells the neck nodes). Most go down within weeks. Nodes that are hard, painless, keep growing or last more than a few weeks need a doctor's check, as they can rarely be a sign of cancer.","evidence":"Textbook medicine."},{"id":"period_pain","col":"d","group":"Women's health","name":"Period pain","sub":"dysmenorrhoea","how":"Cramping pain low in the belly just before and during a period, sometimes spreading to the back and thighs. The shedding womb lining releases prostaglandins that make the womb muscle squeeze hard and briefly cut its blood flow. Painful periods from the teenage years are common and usually not a sign of disease; pain that starts later in life or keeps getting worse can point to endometriosis, adenomyosis or fibroids.","evidence":"Established mechanism. Anti-inflammatory painkillers are the best-tested treatment; regular exercise helped in low-quality trials (Armour 2019)."},{"id":"heavy_periods","col":"d","group":"Women's health","name":"Heavy periods","sub":"heavy menstrual bleeding","how":"Bleeding heavy enough to get in the way of daily life: flooding, large clots, or soaking through protection quickly. Common causes are fibroids, polyps, irregular ovulation (around puberty, perimenopause and in PCOS) and inherited bleeding disorders. The blood lost each month drains iron stores.","evidence":"Established: a leading cause of iron deficiency and anaemia in women of reproductive age (Munro 2023)."},{"id":"hot_flushes","col":"d","group":"Women's health","name":"Hot flushes & night sweats","sub":"vasomotor symptoms","how":"Sudden waves of heat over the face, neck and chest with flushing and sweating, often followed by a chill; at night they are night sweats. Falling oestrogen over-excites a group of temperature-control nerve cells in the hypothalamus (using the signal neurokinin B), so the body dumps heat at small temperature changes.","evidence":"Established: the commonest menopause symptom, lasting several years in many women. Hormone therapy is the most effective treatment in trials; newer non-hormonal medicines block the neurokinin B signal (Anderson 2019)."},{"id":"stress_incontinence","col":"d","group":"Women's health","name":"Leaking urine on effort","sub":"stress urinary incontinence","how":"Urine leaks when coughing, sneezing, laughing, lifting or exercising because the pelvic-floor muscles and the tissues that support the urethra are weak or stretched, so they cannot hold the urethra shut against a sudden rise in belly pressure. Pregnancy and vaginal birth are the main causes in women; menopause, ageing, obesity and chronic cough add to it. In men it mostly follows prostate surgery.","evidence":"Established. Pelvic-floor muscle training cures or improves it in women in many trials (Dumoulin 2018)."},{"id":"dry_mouth","col":"d","group":"Mouth","name":"Dry mouth","sub":"xerostomia, low saliva","how":"Too little saliva, or the feeling of it. Without saliva's washing and acid-buffering, teeth decay faster, gums and the tongue get sore, dentures rub, and chewing, swallowing, taste and speech get harder. Common causes are medicines (especially those that block acetylcholine, such as some bladder medicines, older antidepressants and the anticholinergic drugs sometimes used for Parkinson's tremor), dehydration, mouth-breathing, radiotherapy to the head and neck, and Sjögren's syndrome.","evidence":"Association: medicine use, and the number of medicines, is strongly linked with dry mouth in older people; bladder (urinary) medicines, antidepressants and psycholeptics carry the highest odds (meta-analysis Tan 2018). In Parkinson's, resting saliva flow is lower and dry mouth is common, often alongside drooling (Baram 2026; van Dijk 2026)."},{"id":"d_weak_stream","col":"d","group":"Urinary & sexual","name":"Weak stream & poor emptying","sub":"hesitancy, dribbling, retention","how":"Trouble starting, a weak or stop-start stream, dribbling at the end and a feeling of not having emptied. Usually from a narrowed outlet (enlarged prostate, scarring of the urethra) or a weak bladder muscle (nerve damage, some medicines such as anticholinergics). Urine left behind raises the risk of infection, and a complete blockage (retention) is painful and urgent.","evidence":"Established clinical physiology."},{"id":"ed","col":"d","group":"Urinary & sexual","name":"Erectile dysfunction","sub":"trouble getting or keeping an erection","how":"An erection needs healthy arteries, intact nerves from the low spine and pelvis, enough testosterone and a willing mind. Most ED in older men is a blood-vessel problem from the same artery disease that affects the heart: smoking, diabetes, high blood pressure and high cholesterol. Nerve causes include Parkinson's, multiple system atrophy, MS, diabetes, spinal injury and pelvic surgery or radiotherapy (including prostate cancer treatment). Many medicines contribute, among them some blood-pressure pills, many antidepressants, prostate drugs that block DHT, opioids and anti-androgens. Depression and anxiety both cause and follow it.","evidence":"Established: common and rising with age; diabetes is one of its strongest risk factors. Phosphodiesterase-5 inhibitor medicines are proven in large trials to help most men. ED often appears a few years before heart disease, so it is treated as a reason to check heart risk."},{"id":"d_incontinence","col":"d","group":"Urinary & sexual","name":"Urine leakage","sub":"urinary incontinence","how":"Leaking urine. Urge leakage: the bladder squeezes before reaching the toilet (common in Parkinson's, MS, stroke). Stress leakage: a cough or lift overcomes a weak sphincter or pelvic floor (after childbirth in women; after prostate removal or radiotherapy in men). Overflow: a bladder that cannot empty, behind an enlarged prostate or with nerve damage, dribbles constantly. Slow movement and difficulty with clothing make any type worse.","evidence":"Established. Treatments depend on the type: bladder and pelvic-floor training, medicines that calm the bladder, devices and surgery.","pos":[0,0.86,0.04]},{"id":"d_chest_pain","col":"d","group":"Heart & circulation","name":"Chest pain or pressure","sub":"angina and other causes","how":"Heart muscle short of oxygen (because a coronary artery is narrowed or blocked) signals through the same nerves as the chest wall, arm, neck and jaw, so it is felt as a pressing, tight or heavy pain there, typically brought on by effort and eased by rest (angina). Pain that comes at rest or lasts more than a few minutes can be a heart attack and is an emergency. Many chest pains come from muscles, the gullet or the lungs instead.","evidence":"Textbook cardiology.","pos":[0,1.3,0.1]},{"id":"d_palpitations","col":"d","group":"Heart & circulation","name":"Palpitations","sub":"feeling the heartbeat","how":"Becoming aware of the heartbeat as racing, pounding, fluttering or skipping. Often harmless (extra beats, anxiety, caffeine, fever), but it can be an arrhythmia such as atrial fibrillation, which is checked with an ECG while it is happening.","evidence":"Textbook cardiology.","pos":[0.03,1.3,0.05]},{"id":"d_leg_swelling","col":"d","group":"Heart & circulation","name":"Leg & ankle swelling","sub":"oedema","how":"Fluid leaks out of the small vessels into the tissues and gathers low down with gravity. Both legs swelling points to the heart (failure), kidneys, liver, some medicines, or long sitting; one leg swelling, especially a painful calf, can be a clot in a deep vein. In Parkinson's, sitting a lot and some medicines (dopamine agonists, amantadine) are common causes.","evidence":"Textbook medicine.","pos":[0.09,0.12,0.03]},{"id":"d_fever","col":"d","group":"Infection signs","name":"Fever","sub":"raised temperature, chills","how":"The brain's thermostat (hypothalamus) is turned up by immune messengers released during infection, so the body shivers and conserves heat until it reaches a higher set point. Fever helps immune cells work but raises heart rate and fluid loss. In older people, infection may cause little fever and show as confusion instead.","evidence":"Established physiology."},{"id":"d_sore_throat","col":"d","group":"Infection signs","name":"Sore throat","sub":"pharyngitis","how":"Inflammation of the throat lining, most often from cold viruses; about one in ten adult sore throats (more in children) is due to group A streptococcus.","evidence":"Established (textbook)."},{"id":"d_rash","col":"d","group":"Skin","name":"Rash","sub":"spots, blotches or blisters","how":"Infections cause rashes when the germ infects the skin directly (chickenpox, herpes) or when immune reactions inflame small skin vessels (measles, rubella). A rash that does not fade when a glass is pressed on it can mean bleeding into the skin, as in meningococcal sepsis, and is an emergency.","evidence":"Established (textbook)."},{"id":"s_bg","col":"s","group":"Brain","name":"Basal ganglia","sub":"movement selection, dopamine","how":"Deep brain nuclei (striatum, globus pallidus, substantia nigra, subthalamic nucleus) that pick which movement or thought goes ahead and hold the rest back. Dopamine from the substantia nigra tunes them.","evidence":"","pos":[0,1.66,0.01]},{"id":"s_cortex","col":"s","group":"Brain","name":"Cerebral cortex","sub":"thinking, perception, memory store","how":"The folded outer layer: planning, language, perception, and long-term storage of memories.","evidence":"","pos":[0,1.71,0.01]},{"id":"s_prefrontal","col":"s","group":"Brain","name":"Prefrontal cortex","sub":"attention, self-control","how":"The front of the brain: holds goals in mind, directs attention and puts the brakes on impulses, using dopamine and noradrenaline.","evidence":"","pos":[0,1.68,0.07]},{"id":"s_limbic","col":"s","group":"Brain","name":"Limbic & reward circuits","sub":"mood, motivation, hippocampus","how":"Amygdala, hippocampus, ventral striatum and their connections: emotion, motivation, reward and laying down new memories.","evidence":"","pos":[0,1.64,0.01]},{"id":"s_hypo","col":"s","group":"Brain","name":"Hypothalamus & body clock","sub":"sleep, appetite, hormones","how":"Sets the 24-hour clock (SCN), sleep and wake switches (orexin), appetite, temperature and stress hormones.","evidence":"","pos":[0,1.635,0.02]},{"id":"s_brainstem","col":"s","group":"Brain","name":"Brainstem","sub":"sleep switches, swallowing, arousal","how":"Connects brain and spinal cord; holds REM-sleep paralysis circuits, arousal centres (locus coeruleus, raphe), swallowing and breathing centres, and the vagus nerve's nuclei.","evidence":"","pos":[0,1.6,-0.02]},{"id":"s_cerebellum","col":"s","group":"Brain","name":"Cerebellum","sub":"timing, coordination","how":"Fine-tunes the timing and smoothness of movement by comparing intended and actual movement.","evidence":"","pos":[0,1.6,-0.06]},{"id":"s_smell","col":"s","group":"Brain","name":"Smell system","sub":"olfactory bulb","how":"The olfactory bulb and its connections; one of the first places Lewy pathology appears.","evidence":"","pos":[0,1.63,0.065]},{"id":"s_spinal","col":"s","group":"Nerves","name":"Spinal cord","sub":"","how":"The cable of nerve tissue inside the spinal canal that carries signals between the brain and the body and runs its own reflexes. It has 31 segments: 8 neck (cervical), 12 chest (thoracic), 5 lower back (lumbar), 5 sacral and 1 tailbone (coccygeal), and each segment sends out a pair of nerves. In cross-section, a butterfly of grey matter (nerve cell bodies: movement cells at the front, sensory relay cells at the back) is surrounded by white matter (myelinated tracts running up and down). It is thicker where the arm and leg nerves leave and ends at about the first or second lumbar vertebra in a tapered tip (the conus); below that, the nerve roots carry on as the cauda equina. Damage depends on the level: an injury in the neck can weaken all four limbs and breathing, lower down the legs, bladder and bowel. Myelinated tracts are damaged in multiple sclerosis, and low B12 or copper damages the back columns that carry position sense.","evidence":"Textbook neuroanatomy.","pos":[0,1.33,-0.08]},{"id":"s_peripheral","col":"s","group":"Nerves","name":"Peripheral nerves","sub":"sensation, reflexes","how":"Nerves to skin and muscle; need B12 and good blood supply to keep their myelin. Where a nerve passes through a tight space it can be pinched: the median nerve in the carpal tunnel at the wrist; the ulnar nerve in the cubital tunnel behind the inner elbow (the 'funny bone'); the nerves and vessels to the arm (brachial plexus) between the collarbone, first rib and neck muscles (thoracic outlet); the common fibular (peroneal) nerve where it wraps around the head of the fibula just below the outer knee; and the tibial nerve in the tarsal tunnel behind the inner ankle bone.","evidence":"Textbook anatomy.","pos":[0.1,0.72,-0.03]},{"id":"s_autonomic","col":"s","group":"Nerves","name":"Autonomic nerves & circulation","sub":"blood pressure, heart","how":"Automatic control of blood pressure, heart rate, sweating and gut: the sympathetic and parasympathetic (vagus) nerves.","evidence":"","pos":[0.03,1.3,-0.06]},{"id":"s_vagus","col":"s","group":"Nerves","name":"Vagus nerve","sub":"cranial nerve X; both sides, neck to belly","how":"The longest nerve leaving the brain. It starts in the lower brainstem, runs down each side of the neck beside the big neck arteries, through the chest along the gullet, and spreads over the heart, lungs, stomach and most of the intestines. It is the main 'rest and digest' (parasympathetic) nerve: it slows the heart, drives stomach acid and the muscle waves of the gut, and works the throat and voice-box muscles. Most of its fibres carry messages the other way, from the organs up to the brain, telling it about stretch, nutrients, irritation and inflammation in the gut.","evidence":"Textbook anatomy and physiology. Its role in Parkinson's, in inflammation and in mood is an active research area: see the links.","pos":[0.022,1.45,0.005]},{"id":"n_spinal_roots","col":"s","group":"Nerves","name":"Spinal nerve roots & dorsal root ganglia","sub":"where each spinal nerve joins the cord","how":"At every spinal segment a front (ventral) root carries movement signals out and a back (dorsal) root carries sensation in; the back root has a swelling, the dorsal root ganglion, holding the cell bodies of the sensory nerves. The two roots join into a spinal nerve that leaves through a gap between two vertebrae. A slipped disc or bony spur in that gap presses on a root (radiculopathy): pain, tingling or numbness in that root's strip of skin and weakness of its muscles. The chickenpox virus sleeps in the dorsal root ganglia and can wake up as shingles.","evidence":"Textbook neuroanatomy.","pos":[0.015,1.25,-0.085]},{"id":"n_cauda_equina","col":"s","group":"Nerves","name":"Cauda equina","sub":"the \"horse's tail\" of nerve roots below the cord","how":"Below the end of the spinal cord (around the first lumbar vertebra) the lower back and sacral nerve roots run down the spinal canal as a bundle that looks like a horse's tail, before leaving at their own levels. They supply the legs, the bladder, the bowel, the genitals and the skin of the saddle area. A large central disc, tumour, infection or bleed can squash the whole bundle (cauda equina syndrome): numbness in the saddle area, new trouble passing or holding urine or stool, and leg weakness. This is a surgical emergency.","evidence":"Textbook neuroanatomy.","pos":[0,0.98,-0.085]},{"id":"n_dermatomes","col":"s","group":"Nerves","name":"Dermatomes","sub":"the strip of skin fed by each nerve root","how":"Each spinal nerve root carries feeling from its own band of skin, a dermatome, in an orderly pattern: C6 to the thumb, C8 to the little finger, T4 around the nipples, T10 around the navel, L4 to the inner shin, L5 to the top of the foot and big toe, S1 to the outer foot and sole. Doctors use them to work out which root a slipped disc is pressing on, and shingles appears as a rash in one or two dermatomes on one side.","evidence":"Maps differ between textbooks. A systematic review (Lee 2008) found most were based on flawed studies and built an evidence-based map, stressing that neighbouring dermatomes overlap and vary between people, so a single numb patch rarely pins down one root exactly."},{"id":"s_gut","col":"s","group":"Digestive","name":"Gut & its nervous system","sub":"enteric nervous system","how":"A tube with its own nervous system (about 500 million neurons) that moves food along, linked to the brain by the vagus nerve and home to the microbiome.","evidence":"","pos":[0,1.05,0.06]},{"id":"s_mouth","col":"s","group":"Digestive","name":"Mouth & teeth","sub":"chewing, saliva","how":"Teeth cut and grind food, the tongue mixes it with saliva, which starts digesting starch and makes food easy to swallow.","evidence":"Textbook anatomy.","pos":[0,1.555,0.07]},{"id":"s_oesophagus","col":"s","group":"Digestive","name":"Oesophagus","sub":"food pipe","how":"A muscular tube behind the windpipe and heart that squeezes swallowed food down into the stomach in a wave.","evidence":"Textbook anatomy.","pos":[0,1.36,-0.03]},{"id":"s_stomach","col":"s","group":"Digestive","name":"Stomach","sub":"acid, churning","how":"A muscular bag that stores a meal, mixes it with acid and enzymes to break down protein, and lets it out into the small intestine a little at a time.","evidence":"Textbook anatomy.","pos":[0.07,1.15,0.05]},{"id":"s_small_intestine","col":"s","group":"Digestive","name":"Small intestine","sub":"absorbs nutrients","how":"About 6 metres of folded tube where food is finished off by enzymes and bile and almost all nutrients (and many medicines) are absorbed into the blood.","evidence":"Textbook anatomy.","pos":[-0.01,1,0.06]},{"id":"s_colon","col":"s","group":"Digestive","name":"Large intestine (colon)","sub":"water, stool, microbiome","how":"The last part of the gut: it takes water back out of what is left, forms stool, and is home to most of the gut bacteria, which ferment fibre.","evidence":"Textbook anatomy.","pos":[0,1.08,0.08]},{"id":"s_liver","col":"s","group":"Digestive","name":"Liver","sub":"chemical factory","how":"The largest internal organ: it processes nutrients from the gut, stores energy, makes bile and blood proteins, and breaks down medicines and toxins.","evidence":"Textbook anatomy.","pos":[-0.08,1.17,0.03]},{"id":"s_gallbladder","col":"s","group":"Digestive","name":"Gallbladder","sub":"stores bile","how":"A small pouch under the liver that stores bile and squeezes it into the small intestine after a fatty meal to help digest fat.","evidence":"Textbook anatomy.","pos":[-0.07,1.12,0.07]},{"id":"s_appendix","col":"s","group":"Digestive","name":"Appendix","sub":"worm-shaped tube of gut lymph tissue","how":"A narrow, blind-ended tube, usually 6 to 10 cm long, hanging from the caecum (the first part of the large intestine) in the lower right belly. Its wall is packed with lymph follicles, especially in childhood, so it is part of the gut's immune tissue. It may also act as a safe house for normal gut bacteria that can recolonise the colon after a bout of diarrhoea, an idea supported by indirect evidence. Blockage of its narrow opening causes appendicitis.","evidence":"Textbook anatomy; the \"safe house\" role is a hypothesis.","pos":[-0.066,0.902,0.038]},{"id":"s_les","col":"s","group":"Digestive","name":"Lower oesophageal sphincter","sub":"the valve between gullet and stomach","how":"A ring of muscle at the bottom of the oesophagus, helped by the diaphragm wrapped around it. It stays shut between swallows so stomach acid cannot rise, and relaxes for a few seconds to let food through. When it relaxes too often or the stomach top slides up through the diaphragm (hiatus hernia), acid refluxes into the gullet.","evidence":"Established anatomy and physiology. Weak or too-frequent relaxations of this valve are the main mechanism of reflux disease.","pos":[0.025,1.215,-0.005]},{"id":"s_duodenum","col":"s","group":"Digestive","name":"Duodenum","sub":"first part of the small intestine","how":"A C-shaped first loop of small intestine, curling round the head of the pancreas just after the stomach outlet. Bile from the liver and digestive juice from the pancreas pour in here through a small opening (the ampulla), and acid from the stomach is neutralised. Iron and calcium are mostly absorbed here.","evidence":"Established anatomy. Most peptic ulcers are in the first part of the duodenum.","pos":[-0.035,1.1,0.01]},{"id":"s_ileum","col":"s","group":"Digestive","name":"Ileum (end of the small intestine)","sub":"terminal ileum, joins the colon at the caecum","how":"The last stretch of the small intestine, in the lower right belly, ending at a valve into the large intestine. It is the only place vitamin B12 and bile salts are taken back into the blood, and it is rich in gut lymph tissue (Peyer's patches).","evidence":"Established anatomy and physiology. It is the commonest site of Crohn's disease.","pos":[-0.05,0.97,0.05]},{"id":"s_rectum_anus","col":"s","group":"Digestive","name":"Rectum & anus","sub":"stool store, anal sphincters, pelvic floor","how":"The rectum is the last part of the large intestine, lying in the back of the pelvis in front of the tailbone. It stores stool until it stretches enough to signal the urge to go. Opening the bowels needs the inner and outer anal sphincters and the pelvic-floor muscles to relax together while the belly pushes; the anal cushions (normal blood vessel pads) help seal it.","evidence":"Established anatomy and physiology. In Parkinson's, the pelvic floor and sphincter often tighten instead of relaxing on straining, one cause of constipation.","pos":[0,0.85,-0.06]},{"id":"s_bile_ducts","col":"s","group":"Digestive","name":"Bile ducts","sub":"tubes from liver and gallbladder to the duodenum","how":"Small tubes collect bile inside the liver and join into one common bile duct, which the gallbladder's duct also joins. It runs behind the duodenum through the head of the pancreas and usually shares its opening with the pancreatic duct. A stone or tumour blocking it backs bile up into the blood, causing jaundice, and can inflame the pancreas.","evidence":"Established anatomy.","pos":[-0.04,1.12,0.02]},{"id":"s_portal_vein","col":"s","group":"Digestive","name":"Hepatic portal vein","sub":"carries blood from the gut to the liver","how":"A large vein formed behind the pancreas from the veins of the intestines, stomach, pancreas and spleen. It brings nutrient-rich blood (and anything swallowed, including many medicines) to the liver first, before the rest of the body. Scarring of the liver raises the pressure in it (portal hypertension), which swells the spleen and opens fragile bypass veins in the gullet.","evidence":"Established anatomy and physiology.","pos":[-0.025,1.13,0]},{"id":"s_liver_segment_1","col":"s","group":"Digestive","name":"Liver segment 1 (caudate lobe)","sub":"the small lobe at the back of the liver","how":"Wraps round the front of the inferior vena cava at the back of the liver and drains straight into it through its own small veins. Because of that separate drainage it often swells when the main hepatic veins are blocked (Budd-Chiari syndrome). Each of the liver's eight Couinaud segments has its own branch of the portal vein, hepatic artery and bile duct at its centre, with hepatic veins running between segments, so a surgeon can remove one segment and leave the rest working; this is how liver tumours and living-donor grafts are cut out.","evidence":"Textbook anatomy","pos":[-0.003,1.168,-0.02]},{"id":"s_liver_segment_2","col":"s","group":"Digestive","name":"Liver segment 2","sub":"upper part of the left lateral liver","how":"The upper back part of the left lateral section, to the left of the falciform ligament. With segment 3 it forms the left lateral section, the part most often taken from a living adult donor for a child's liver transplant. Each of the liver's eight Couinaud segments has its own branch of the portal vein, hepatic artery and bile duct at its centre, with hepatic veins running between segments, so a surgeon can remove one segment and leave the rest working; this is how liver tumours and living-donor grafts are cut out.","evidence":"Textbook anatomy","pos":[0.043,1.234,0.011]},{"id":"s_liver_segment_3","col":"s","group":"Digestive","name":"Liver segment 3","sub":"lower part of the left lateral liver","how":"The lower front part of the left lateral section, left of the falciform ligament and the ligamentum teres. Each of the liver's eight Couinaud segments has its own branch of the portal vein, hepatic artery and bile duct at its centre, with hepatic veins running between segments, so a surgeon can remove one segment and leave the rest working; this is how liver tumours and living-donor grafts are cut out.","evidence":"Textbook anatomy","pos":[0.036,1.175,0.044]},{"id":"s_liver_segment_4","col":"s","group":"Digestive","name":"Liver segment 4 (quadrate area)","sub":"the left medial section, next to the gallbladder","how":"Lies between the falciform ligament and the line from the gallbladder to the inferior vena cava; its lower part (4b) is the quadrate lobe beside the gallbladder bed. Gallbladder cancer spreads into it first. Each of the liver's eight Couinaud segments has its own branch of the portal vein, hepatic artery and bile duct at its centre, with hepatic veins running between segments, so a surgeon can remove one segment and leave the rest working; this is how liver tumours and living-donor grafts are cut out.","evidence":"Textbook anatomy","pos":[-0.028,1.192,0.071]},{"id":"s_liver_segment_5","col":"s","group":"Digestive","name":"Liver segment 5","sub":"front lower part of the right liver","how":"The lower front part of the right liver, under the gallbladder bed. Each of the liver's eight Couinaud segments has its own branch of the portal vein, hepatic artery and bile duct at its centre, with hepatic veins running between segments, so a surgeon can remove one segment and leave the rest working; this is how liver tumours and living-donor grafts are cut out.","evidence":"Textbook anatomy","pos":[-0.069,1.133,0.029]},{"id":"s_liver_segment_6","col":"s","group":"Digestive","name":"Liver segment 6","sub":"back lower part of the right liver","how":"The lower back part of the right liver, resting on the right kidney; a needle liver biopsy from the side often goes through it. Each of the liver's eight Couinaud segments has its own branch of the portal vein, hepatic artery and bile duct at its centre, with hepatic veins running between segments, so a surgeon can remove one segment and leave the rest working; this is how liver tumours and living-donor grafts are cut out.","evidence":"Textbook anatomy","pos":[-0.079,1.144,-0.031]},{"id":"s_liver_segment_7","col":"s","group":"Digestive","name":"Liver segment 7","sub":"back upper part of the right liver","how":"The upper back part of the right liver, under the right dome of the diaphragm, behind segment 8. Each of the liver's eight Couinaud segments has its own branch of the portal vein, hepatic artery and bile duct at its centre, with hepatic veins running between segments, so a surgeon can remove one segment and leave the rest working; this is how liver tumours and living-donor grafts are cut out.","evidence":"Textbook anatomy","pos":[-0.09,1.234,-0.054]},{"id":"s_liver_segment_8","col":"s","group":"Digestive","name":"Liver segment 8","sub":"front upper part of the right liver","how":"The upper front part of the right liver, under the diaphragm, between the right and middle hepatic veins. Each of the liver's eight Couinaud segments has its own branch of the portal vein, hepatic artery and bile duct at its centre, with hepatic veins running between segments, so a surgeon can remove one segment and leave the rest working; this is how liver tumours and living-donor grafts are cut out.","evidence":"Textbook anatomy","pos":[-0.096,1.232,0.046]},{"id":"s_ligamentum_teres","col":"s","group":"Digestive","name":"Ligamentum teres (round ligament of the liver)","sub":"the remnant of the umbilical vein","how":"A fibrous cord in the free edge of the falciform ligament, running from the navel to the underside of the liver between segments 3 and 4. Before birth it was the umbilical vein carrying oxygen-rich blood from the placenta; it closes soon after birth. In portal hypertension a small vein beside it can reopen, giving swollen veins around the navel.","evidence":"Textbook anatomy","pos":[0.006,1.117,0.081]},{"id":"s_hepatic_lobules","col":"s","group":"Digestive","name":"Hepatic lobules (liver cell plates)","sub":"the liver's repeating working units","how":"The liver is built from about a million six-sided lobules, each about a millimetre or two across: plates of liver cells (hepatocytes) radiate out from a central vein, with a portal vein branch, arteriole and bile ductule at each corner. Blood flows inward past the cells, which take up nutrients, drugs and toxins, store sugar, make proteins and bile, and send bile outward the other way. In cirrhosis, scar tissue breaks up this layout.","evidence":"Textbook anatomy","pos":[-0.068,1.159,0.054]},{"id":"s_sinusoids","col":"s","group":"Digestive","name":"Hepatic sinusoids","sub":"the leaky capillaries between the liver cell plates","how":"Wide, leaky capillaries that carry mixed portal and arterial blood from the corners of each lobule to its central vein. Their walls have large pores and no proper floor, so blood plasma reaches the liver cells directly, and resident immune cells (Kupffer cells) line them to clear bacteria and debris arriving from the gut. Scarring around them raises the pressure in the portal vein.","evidence":"Textbook anatomy","pos":[-0.069,1.159,0.056]},{"id":"s_gallbladder_fundus","col":"s","group":"Digestive","name":"Gallbladder fundus","sub":"the rounded tip of the gallbladder","how":"The blind end that sticks out below the edge of the liver, touching the front belly wall where the right rib margin meets the edge of the rectus muscle; this is where a doctor presses to check for gallbladder pain (Murphy's sign). It is also the commonest site of a localised wall thickening (adenomyomatosis).","evidence":"Textbook anatomy","pos":[-0.063,1.118,0.045]},{"id":"s_gallbladder_body","col":"s","group":"Digestive","name":"Gallbladder body","sub":"the main sac of the gallbladder","how":"The middle part of the sac, lying in a shallow bed on the underside of the liver and touching the duodenum and colon. It stores and concentrates bile between meals and squeezes it out after fatty food. Gallstones form and lie here; an inflamed gallbladder can stick to and even erode into the bowel next to it.","evidence":"Textbook anatomy","pos":[-0.054,1.13,0.026]},{"id":"s_gallbladder_neck","col":"s","group":"Digestive","name":"Gallbladder neck (Hartmann's pouch)","sub":"the narrow end leading into the cystic duct","how":"The narrowing end of the sac, with a small bulge (Hartmann's pouch) where stones often get stuck, blocking the outflow and causing gallbladder attacks (biliary colic) or inflammation (cholecystitis).","evidence":"Textbook anatomy","pos":[-0.046,1.137,0.006]},{"id":"s_gallbladder_mucosa","col":"s","group":"Digestive","name":"Gallbladder lining (mucosa)","sub":"the honeycomb-folded inner lining","how":"A lining of tall cells folded into a honeycomb pattern that soaks up water and salt from the stored bile, concentrating it several times over. Long-standing irritation from stones inflames it; most gallbladder cancers start in this lining.","evidence":"Textbook anatomy","pos":[-0.054,1.128,0.024]},{"id":"s_cystic_duct","col":"s","group":"Digestive","name":"Cystic duct","sub":"joins the gallbladder to the main bile duct","how":"A short duct from the gallbladder neck to the common hepatic duct; together they form the common bile duct. Its lining is folded in a spiral (the spiral valve of Heister) that keeps it open. A stone stuck here causes gallbladder pain and inflammation; surgeons clip and divide it, with the cystic artery, when removing the gallbladder.","evidence":"Textbook anatomy","pos":[-0.037,1.122,0.008]},{"id":"s_common_hepatic_duct","col":"s","group":"Digestive","name":"Common hepatic duct","sub":"the bile duct leaving the liver","how":"Formed at the porta hepatis by the right and left hepatic ducts, it carries bile out of the liver until the cystic duct joins it. A large stone in the gallbladder neck can press on it and cause jaundice (Mirizzi syndrome).","evidence":"Textbook anatomy","pos":[-0.031,1.125,0.014]},{"id":"s_common_bile_duct","col":"s","group":"Digestive","name":"Common bile duct","sub":"carries bile to the duodenum","how":"Formed by the common hepatic and cystic ducts, it runs down behind the duodenum and through the head of the pancreas to the ampulla of Vater, joining the pancreatic duct. A stone stuck in it, or a tumour of the pancreatic head pressing on it, blocks bile and causes jaundice; a stone at its lower end can also trigger pancreatitis.","evidence":"Textbook anatomy","pos":[-0.036,1.088,0.009]},{"id":"s_pancreas_head","col":"s","group":"Digestive","name":"Head of the pancreas","sub":"the part nestled in the curve of the duodenum","how":"The widest part of the pancreas, cradled in the C-shaped curve of the duodenum, with the common bile duct running through it. Most pancreatic cancers start here and press on the bile duct, so painless jaundice is often the first sign; the Whipple operation removes it with the duodenum.","evidence":"Textbook anatomy","pos":[-0.028,1.066,0.026]},{"id":"s_pancreas_uncinate","col":"s","group":"Digestive","name":"Uncinate process","sub":"the hook of the pancreatic head","how":"A hook-shaped extension of the head that curls behind the superior mesenteric vein and artery. Tumours here can wrap around these vessels, which can make surgery impossible.","evidence":"Textbook anatomy","pos":[-0.02,1.047,-0.001]},{"id":"s_pancreas_neck","col":"s","group":"Digestive","name":"Neck of the pancreas","sub":"the narrow part in front of the portal vein","how":"A short narrow part joining head and body, lying in front of the place where the splenic and superior mesenteric veins join to form the portal vein. Surgeons divide the pancreas here in the Whipple operation.","evidence":"Textbook anatomy","pos":[-0.009,1.078,0.024]},{"id":"s_pancreas_body","col":"s","group":"Digestive","name":"Body of the pancreas","sub":"the middle of the pancreas across the spine","how":"Runs to the left across the aorta and the spine behind the stomach, with the splenic artery along its upper edge and the splenic vein behind it. Being pressed against the spine, it is where a hard blow to the upper belly (such as from bicycle handlebars) can split the pancreas.","evidence":"Textbook anatomy","pos":[0.025,1.09,-0.003]},{"id":"s_pancreas_tail","col":"s","group":"Digestive","name":"Tail of the pancreas","sub":"the end of the pancreas at the spleen","how":"The narrow end that reaches the hilum of the spleen; it has the highest density of insulin-making islets. It can be injured when the spleen is removed, leaking pancreatic juice.","evidence":"Textbook anatomy","pos":[0.071,1.109,-0.03]},{"id":"s_pancreatic_duct","col":"s","group":"Digestive","name":"Main pancreatic duct (duct of Wirsung)","sub":"carries digestive juice out of the pancreas","how":"Runs the length of the pancreas from tail to head, collecting enzyme-rich juice from side branches, and joins the common bile duct at the ampulla of Vater to empty into the duodenum. A blockage (stone, tumour, scarring) backs juice up and can cause pancreatitis; a widened duct on a scan is a warning sign.","evidence":"Textbook anatomy","pos":[0.026,1.089,0.003]},{"id":"s_accessory_pancreatic_duct","col":"s","group":"Digestive","name":"Accessory pancreatic duct (duct of Santorini)","sub":"a second, smaller drain from the pancreas","how":"A smaller duct draining the upper head of the pancreas into the duodenum through its own small (minor) papilla, a little above the ampulla of Vater. In some people (pancreas divisum) most of the pancreas drains through it.","evidence":"Textbook anatomy","pos":[-0.021,1.079,0.02]},{"id":"s_ampulla_of_vater","col":"s","group":"Digestive","name":"Ampulla of Vater and sphincter of Oddi","sub":"where bile and pancreatic juice enter the duodenum","how":"The small chamber where the common bile duct and the main pancreatic duct join and open into the second part of the duodenum through the major papilla, guarded by a ring of muscle (sphincter of Oddi) that relaxes after meals. A stone lodged here can block both ducts and cause jaundice and pancreatitis; doctors reach it with a camera (ERCP) to remove stones.","evidence":"Textbook anatomy","pos":[-0.042,1.063,0.015]},{"id":"s_bladder","col":"s","group":"Body","name":"Bladder","sub":"","how":"A muscular bag whose emptying reflex is held back by brain centres including the basal ganglia.","evidence":"","pos":[0,0.88,0.05]},{"id":"s_throat","col":"s","group":"Body","name":"Throat & voice","sub":"swallowing, speech muscles","how":"Tongue, throat, larynx and oesophagus: quick, sequenced movements for swallowing and voice.","evidence":"","pos":[0,1.48,0.03]},{"id":"s_muscle","col":"s","group":"Body","name":"Muscles","sub":"strength, muscle mass","how":"Skeletal muscles pull on bones to move the body; their mass and strength are kept by use and enough protein, and fade with inactivity and age.","evidence":"","pos":[0.1,0.7,0.05]},{"id":"s_immune","col":"s","group":"Body","name":"Immune system","sub":"","how":"White blood cells, gut immune tissue and brain microglia; defends against microbes and drives inflammation.","evidence":"Established physiology. California workers' comp law (education, not advice): some infections are presumed work-related for listed safety workers. Blood-borne infectious disease and MRSA skin infection: police, sheriffs, peace officers and firefighters (Cal. Labor Code § 3212.8). Meningitis: full-time police, sheriffs, Highway Patrol, probation officers, DA investigators and firefighters (§ 3212.9) and correctional officers (§ 3212.10). Lyme disease: certain peace officers and California Conservation Corps field staff (§ 3212.12). Illness from biological, chemical or radiological weapon agents: peace officers and fire department members (§ 3212.85). All can be rebutted with other evidence. The COVID-19 presumptions (§§ 3212.86–3212.88) expired and were repealed on 1 Jan 2024. Each claim turns on its facts and current law.","pos":[0,1.37,0.05]},{"id":"s_bones","col":"s","group":"Body","name":"Bones & joints","sub":"skeleton, bone density","how":"The skeleton holds the body up and protects organs; bone is living tissue that is constantly rebuilt, needing calcium, vitamin D and use (load-bearing) to stay dense. Joints are where bones meet, lined with smooth cartilage.","evidence":"Textbook anatomy.","pos":[0.09,0.9,0]},{"id":"s_marrow","col":"s","group":"Body","name":"Bone marrow","sub":"makes blood cells","how":"Soft tissue inside bones. In adults the blood-making red marrow is mainly in the pelvis, spine, ribs, breastbone, skull and the upper ends of the thigh and arm bones; elsewhere it turns to fatty yellow marrow. Step by step: (1) blood stem cells divide to make red blood cells, platelets and every kind of white blood cell; (2) B cells mature here and are tested so most that react against the body are removed, which makes the marrow, with the thymus, a primary lymphoid organ; (3) T-cell precursors leave for the thymus to finish training; (4) long-lived plasma cells return to the marrow and keep making antibodies for years. It also stores iron.","evidence":"Textbook anatomy.","pos":[0.11,0.98,-0.03]},{"id":"s_kidneys","col":"s","group":"Body","name":"Kidneys","sub":"filter blood, make urine","how":"Two bean-shaped filters at the back of the abdomen that clean waste from the blood, balance water and salt, and help set blood pressure; urine passes from them to the bladder.","evidence":"Textbook anatomy.","pos":[0.056,1.11,-0.035]},{"id":"s_skin","col":"s","group":"Body","name":"Skin","sub":"barrier, touch, sweat","how":"The body's outer barrier: keeps water in and microbes out, senses touch, pain and temperature, sweats to cool the body, and makes vitamin D in sunlight.","evidence":"Textbook anatomy. California workers' comp law (education, not advice): skin cancer is presumed work-related for city, county and state lifeguards employed more than three consecutive months a year (Cal. Labor Code § 3212.11), and MRSA skin infection for police, sheriffs, peace officers and firefighters (§ 3212.8; lasts only 90 days after leaving service). Both can be rebutted with other evidence. Each claim turns on its facts and current law.","pos":[0,1.28,0.12]},{"id":"s_lymph","col":"s","group":"Lymphatic system","name":"Lymphatic system","sub":"lymph nodes, lymph vessels, spleen","how":"A one-way drainage network: thin lymph vessels collect fluid that leaks out of blood vessels, pass it through lymph nodes (small filters in the neck, armpits, groin and gut) where immune cells meet microbes, and return it to the blood through the thoracic duct. The spleen filters the blood itself.","evidence":"Textbook anatomy.","pos":[0.1,1.15,-0.04]},{"id":"s_reproductive","col":"s","group":"Body","name":"Reproductive organs","sub":"structure","how":"The organs for making children: in women the uterus, fallopian tubes and vagina; in men the prostate, seminal vesicles and penis. (The hormone-making ovaries and testes are listed with the glands.)","evidence":"Textbook anatomy.","pos":[0,0.88,0]},{"id":"s_ureters","col":"s","group":"Body","name":"Ureters","sub":"kidney-to-bladder tubes","how":"Two thin muscular tubes that squeeze urine down from each kidney into the bladder. Kidney stones most often get stuck here, which causes sharp pain in the side.","evidence":"Established anatomy.","pos":[0.042,1,-0.027]},{"id":"s_heart","col":"s","group":"Circulation","name":"Heart","sub":"the pump","how":"A four-chambered muscle that pumps blood through the lungs and then the whole body, about 60–100 beats a minute at rest; its rate is set by the autonomic nerves.","evidence":"Textbook anatomy.","pos":[0.03,1.3,0.04]},{"id":"s_blood","col":"s","group":"Circulation","name":"Blood vessels & blood","sub":"arteries, veins, blood pressure","how":"Arteries carry blood out from the heart, capillaries swap oxygen and nutrients with tissues, and veins bring it back. Arteries tighten or relax to hold blood pressure steady; blood carries oxygen, nutrients, hormones and immune cells.","evidence":"Textbook anatomy.","pos":[0.01,1.22,-0.03]},{"id":"s_aorta","col":"s","group":"Circulation","name":"Aorta","sub":"the main artery","how":"The body's largest artery (about 2.5 cm across): it rises from the left ventricle, arches over the heart behind the breastbone and runs down in front of the spine to split into the leg arteries in the lower belly. Its elastic wall smooths each heartbeat into steady flow; with age and high blood pressure it stiffens, and it can balloon (aneurysm).","evidence":"Textbook anatomy and physiology.","pos":[-0.006,1.38,0.032]},{"id":"s_veins","col":"s","group":"Circulation","name":"Veins","sub":"including the deep leg veins","how":"Thin-walled vessels carrying blood back to the heart at low pressure. In the legs, one-way valves and the squeeze of calf muscles push blood upward, so sitting still for long periods slows the flow. A clot in the deep veins of the leg or pelvis is a deep vein thrombosis.","evidence":"Textbook anatomy and physiology.","pos":[0.09,0.45,-0.01]},{"id":"vn_superior_vena_cava","col":"s","group":"Circulation","name":"Superior vena cava","sub":"the great vein from the upper body","how":"Formed behind the right first rib cartilage by the two brachiocephalic veins, it carries blood from the head, neck and arms down into the right atrium. A lung tumour or swollen lymph nodes pressing on it cause a swollen face and arms (superior vena cava obstruction). Central lines for medicines end near it.","evidence":"Textbook anatomy","pos":[-0.024,1.37,0.035]},{"id":"vn_inferior_vena_cava","col":"s","group":"Circulation","name":"Inferior vena cava","sub":"the great vein from the lower body","how":"Formed by the two common iliac veins at about L5, it runs up the right side of the aorta, behind the liver (receiving the hepatic and renal veins) and through the diaphragm into the right atrium. It carries all the blood from the legs, pelvis and belly. Clots from the leg veins pass through it to the lungs (pulmonary embolism).","evidence":"Textbook anatomy","pos":[-0.022,1.1,-0.022]},{"id":"vn_brachiocephalic","col":"s","group":"Circulation","name":"Brachiocephalic vein","sub":"joins the neck and arm veins on each side","how":"Formed behind each collarbone joint where the internal jugular and subclavian veins meet; the two (the left crossing in front of the aortic arch) join to form the superior vena cava. The main lymph ducts empty into the angle where it forms.","evidence":"Textbook anatomy","pos":[0.014,1.432,0.03]},{"id":"vn_internal_jugular","col":"s","group":"Circulation","name":"Internal jugular vein","sub":"the large vein down each side of the neck","how":"Drains the brain, face and neck from the skull base down beside the carotid artery to join the subclavian vein. Doctors judge the pressure in the right side of the heart by how high its pulsation shows in the neck, and it is a common route for central lines.","evidence":"Textbook anatomy","pos":[0.033,1.51,0.01]},{"id":"vn_subclavian","col":"s","group":"Circulation","name":"Subclavian vein","sub":"the vein from the arm under the collarbone","how":"Continues the axillary vein over the first rib, in front of the scalene muscle and under the collarbone, to join the internal jugular vein. Repeated overhead arm work can squeeze it and cause an arm clot (effort thrombosis); it is also used for central lines.","evidence":"Textbook anatomy","pos":[0.09,1.425,0.01]},{"id":"vn_brachial","col":"s","group":"Circulation","name":"Brachial and axillary veins","sub":"the deep veins of the upper arm and armpit","how":"Paired veins run beside the brachial artery up the inner arm and join to form the axillary vein in the armpit, which receives the basilic and cephalic veins and continues as the subclavian vein. Removing armpit lymph nodes can scar around them and contribute to arm swelling.","evidence":"Textbook anatomy","pos":[0.21,1.28,0.005]},{"id":"vn_cephalic","col":"s","group":"Circulation","name":"Cephalic vein","sub":"the surface vein on the thumb side of the arm","how":"Runs up under the skin from the back of the hand along the thumb side of the forearm and the outer upper arm, then in the groove between the deltoid and pectoralis major to join the axillary vein. It is often used for drips and blood draws.","evidence":"Textbook anatomy","pos":[0.2,1.3,0.03]},{"id":"vn_common_iliac","col":"s","group":"Circulation","name":"Common iliac vein","sub":"joins pelvic and leg veins on each side","how":"Formed in front of the sacroiliac joint by the internal and external iliac veins; the two join at L5 to form the inferior vena cava. The left one is crossed by the right common iliac artery, which can press on it and favour left-leg clots (May-Thurner syndrome).","evidence":"Textbook anatomy","pos":[0.022,0.955,-0.028]},{"id":"vn_external_iliac","col":"s","group":"Circulation","name":"External iliac vein","sub":"the vein from the leg along the pelvic brim","how":"Continues the femoral vein above the groin ligament, along the pelvic brim, to join the internal iliac vein. Deep clots can extend up into it from the thigh.","evidence":"Textbook anatomy","pos":[0.056,0.9,0.012]},{"id":"vn_femoral","col":"s","group":"Circulation","name":"Femoral vein","sub":"the main deep vein of the thigh","how":"Runs up the thigh beside the femoral artery (behind it in the adductor canal, inside it at the groin) and receives the great saphenous vein just below the groin. It is a common site of deep vein thrombosis (DVT), which can break off and travel to the lungs. Long sitting, surgery and immobility raise the risk.","evidence":"Textbook anatomy","pos":[0.068,0.8,0.05]},{"id":"vn_popliteal","col":"s","group":"Circulation","name":"Popliteal vein","sub":"the deep vein behind the knee","how":"Formed by the veins of the calf, it runs up through the back of the knee next to the popliteal artery and becomes the femoral vein. The calf muscle pump drives blood up through it; DVT often reaches here from the calf veins.","evidence":"Textbook anatomy","pos":[0.1,0.49,-0.04]},{"id":"vn_great_saphenous","col":"s","group":"Circulation","name":"Great saphenous vein","sub":"the long surface vein of the leg","how":"The longest vein in the body: it starts in front of the inner ankle and runs up under the skin of the inner leg and thigh to join the femoral vein below the groin. Weak valves in it cause varicose veins; surgeons take it to use for heart bypass grafts.","evidence":"Textbook anatomy","pos":[0.05,0.7,0.02]},{"id":"ar_ascending_aorta","col":"s","group":"Circulation","name":"Ascending aorta","sub":"the first few centimetres of the aorta","how":"Rises from the left ventricle just above the aortic valve, behind the breastbone; the two coronary arteries branch off its root. It takes the full force of each heartbeat, and with high blood pressure or some inherited conditions it can widen (aneurysm) or tear along its wall (dissection), which causes sudden tearing chest pain.","evidence":"Textbook anatomy","pos":[-0.006,1.345,0.04]},{"id":"ar_aortic_arch","col":"s","group":"Circulation","name":"Aortic arch","sub":"the curve of the aorta over the heart","how":"Arches backward and to the left over the root of the left lung, giving off the three great branches to the head and arms: the brachiocephalic trunk, the left common carotid and the left subclavian artery. Pressure sensors in its wall help keep blood pressure steady when you stand up, a reflex that weakens in Parkinson's-related autonomic failure (orthostatic hypotension).","evidence":"Textbook anatomy","pos":[0.008,1.405,0.012]},{"id":"ar_descending_thoracic_aorta","col":"s","group":"Circulation","name":"Descending thoracic aorta","sub":"the aorta running down the chest","how":"Runs down the left side of the spine behind the heart, giving branches to the ribs (intercostal arteries), the gullet and the airways, then passes through the diaphragm. Tears of the aortic wall (dissection) often start or spread here.","evidence":"Textbook anatomy","pos":[0.022,1.3,-0.045]},{"id":"ar_abdominal_aorta","col":"s","group":"Circulation","name":"Abdominal aorta","sub":"the aorta in the belly","how":"Runs down in front of the spine from the diaphragm to the level of the navel, where it splits into the two common iliac arteries. It gives the arteries to the gut (coeliac trunk, superior and inferior mesenteric), the kidneys and the adrenal glands. It is the usual site of an abdominal aortic aneurysm, a silent widening in older people, especially smokers, which can burst.","evidence":"Textbook anatomy","pos":[0.008,1.08,-0.02]},{"id":"ar_brachiocephalic_trunk","col":"s","group":"Circulation","name":"Brachiocephalic trunk","sub":"the first branch of the aortic arch, on the right","how":"A short, wide artery from the aortic arch that splits behind the right collarbone joint into the right common carotid (to the head) and the right subclavian (to the arm). There is only one, on the right.","evidence":"Textbook anatomy","pos":[-0.01,1.428,0.023]},{"id":"ar_common_carotid","col":"s","group":"Circulation","name":"Common carotid artery","sub":"the main artery up each side of the neck","how":"The left one comes straight from the aortic arch, the right from the brachiocephalic trunk; each runs up the neck beside the windpipe and splits at the level of the upper voice box into the internal and external carotids. Its pulse is felt beside the voice box. Pressure sensors at the split (carotid sinus) help control blood pressure.","evidence":"Textbook anatomy","pos":[0.022,1.48,0.016]},{"id":"ar_internal_carotid","col":"s","group":"Circulation","name":"Internal carotid artery","sub":"carries blood to the front of the brain and the eye","how":"Runs up from the carotid split, without branches in the neck, through a canal in the skull base to supply most of the front and middle of the brain and the eye. Fatty plaque where it starts is a major source of the clots that cause strokes and mini-strokes (TIAs); a brief loss of vision in one eye can be a warning sign.","evidence":"Textbook anatomy","pos":[0.028,1.588,-0.008]},{"id":"ar_external_carotid","col":"s","group":"Circulation","name":"External carotid artery","sub":"supplies the face, scalp and neck","how":"Runs up from the carotid split behind the jaw, giving branches to the thyroid, tongue, face, scalp, jaw and the lining of the brain (middle meningeal artery). The pulse in front of the ear (superficial temporal artery) is one of its end branches.","evidence":"Textbook anatomy","pos":[0.04,1.585,0.012]},{"id":"ar_subclavian","col":"s","group":"Circulation","name":"Subclavian artery","sub":"the artery to the arm under the collarbone","how":"The left comes from the aortic arch, the right from the brachiocephalic trunk; it arches over the first rib, between the scalene muscles, under the collarbone. It gives the vertebral artery to the back of the brain and the internal thoracic artery down the inside of the chest wall. It can be squeezed between the first rib and collarbone (thoracic outlet syndrome).","evidence":"Textbook anatomy","pos":[0.06,1.445,0.002]},{"id":"ar_axillary","col":"s","group":"Circulation","name":"Axillary artery","sub":"the artery through the armpit","how":"Continues the subclavian artery from the outer edge of the first rib through the armpit, surrounded by the cords of the brachial plexus, and gives branches to the chest wall and shoulder. It can be injured in shoulder dislocations and fractures of the upper humerus in older people.","evidence":"Textbook anatomy","pos":[0.12,1.42,-0.003]},{"id":"ar_brachial","col":"s","group":"Circulation","name":"Brachial artery","sub":"the artery of the upper arm","how":"Runs down the inner side of the upper arm beside the median nerve and splits in the bend of the elbow into the radial and ulnar arteries. Blood pressure is measured over it with a cuff on the upper arm, and its pulse is felt in the elbow crease. Elbow fractures in children can injure it.","evidence":"Textbook anatomy","pos":[0.2,1.28,0]},{"id":"ar_radial","col":"s","group":"Circulation","name":"Radial artery","sub":"the forearm artery on the thumb side, where the wrist pulse is felt","how":"Runs from the elbow down the thumb side of the forearm to the wrist, where its pulse is felt, and into the palm, forming the deep palmar arch. It is a common entry point for heart catheters and is used to take arterial blood samples.","evidence":"Textbook anatomy","pos":[0.311,0.991,0.04]},{"id":"ar_ulnar","col":"s","group":"Circulation","name":"Ulnar artery","sub":"the forearm artery on the little-finger side","how":"Runs from the elbow down the little-finger side of the forearm into the palm, where it forms the main (superficial) palmar arch. It joins the radial artery in the hand, so the hand has two supplies; repeated pounding with the heel of the hand can damage it (hypothenar hammer syndrome).","evidence":"Textbook anatomy","pos":[0.3,0.99,0]},{"id":"ar_common_iliac","col":"s","group":"Circulation","name":"Common iliac artery","sub":"one of the two branches the aorta ends in","how":"The aorta splits at about the level of the navel (L4) into the left and right common iliac arteries, each of which splits again in front of the sacroiliac joint into the internal (pelvis) and external (leg) iliac arteries. Narrowing here causes buttock and thigh pain when walking.","evidence":"Textbook anatomy","pos":[0.028,0.965,-0.02]},{"id":"ar_internal_iliac","col":"s","group":"Circulation","name":"Internal iliac artery","sub":"supplies the pelvis and buttocks","how":"Dives into the pelvis to supply the bladder, rectum, reproductive organs, pelvic-floor muscles and the gluteal muscles. Bleeding from its branches is what makes high-energy pelvic fractures dangerous.","evidence":"Textbook anatomy","pos":[0.05,0.915,-0.04]},{"id":"ar_external_iliac","col":"s","group":"Circulation","name":"External iliac artery","sub":"carries blood toward the leg along the pelvic brim","how":"Runs along the inner rim of the pelvis and passes under the groin ligament to become the femoral artery. Narrowing here is part of peripheral artery disease of the legs.","evidence":"Textbook anatomy","pos":[0.062,0.905,0.018]},{"id":"ar_femoral","col":"s","group":"Circulation","name":"Femoral artery","sub":"the main artery of the thigh","how":"Enters the thigh at the middle of the groin, where its pulse is felt, runs down the front and inner thigh through the adductor canal and passes behind the knee to become the popliteal artery. Its deep branch (profunda femoris) supplies most thigh muscles. It is the usual entry for many catheter procedures, and narrowing of it causes calf pain on walking (claudication).","evidence":"Textbook anatomy","pos":[0.078,0.8,0.06]},{"id":"ar_popliteal","col":"s","group":"Circulation","name":"Popliteal artery","sub":"the artery behind the knee","how":"Continues the femoral artery through the back of the knee and splits below it into the anterior and posterior tibial arteries; it supplies the knee joint. It is fixed in place and can be torn in knee dislocations; it is also a site of aneurysms in older men.","evidence":"Textbook anatomy","pos":[0.093,0.47,-0.03]},{"id":"ar_anterior_tibial","col":"s","group":"Circulation","name":"Anterior tibial artery","sub":"the artery of the front of the leg","how":"Passes forward through the membrane between the shin bones and runs down the front of the leg with the deep peroneal nerve, supplying the muscles that lift the foot, and continues on the top of the foot as the dorsalis pedis artery.","evidence":"Textbook anatomy","pos":[0.105,0.28,0.01]},{"id":"ar_posterior_tibial","col":"s","group":"Circulation","name":"Posterior tibial artery","sub":"the artery of the back of the leg and the sole","how":"Runs down the back of the leg with the tibial nerve, supplying the calf muscles, then behind the inner ankle bone (where its pulse is felt) into the sole. Weak or absent pulses here and on the top of the foot are a sign of poor leg circulation, important to check in diabetes.","evidence":"Textbook anatomy","pos":[0.09,0.28,-0.03]},{"id":"ar_dorsalis_pedis","col":"s","group":"Circulation","name":"Dorsalis pedis artery","sub":"the artery on the top of the foot","how":"Continues the anterior tibial artery over the top of the foot, where its pulse is felt between the first two long foot bones, and joins the arteries of the sole. Checking it is part of a routine foot check for poor circulation.","evidence":"Textbook anatomy","pos":[0.11,0.04,0.06]},{"id":"ar_coeliac_trunk","col":"s","group":"Circulation","name":"Coeliac trunk","sub":"the first gut branch of the abdominal aorta","how":"A short artery from the front of the aorta just below the diaphragm that splits into three: the left gastric (stomach), the common hepatic (liver, gallbladder, duodenum, pancreas) and the splenic artery. It supplies the foregut: the lower gullet, stomach, liver, gallbladder, pancreas and spleen.","evidence":"Textbook anatomy","pos":[0.004,1.14,-0.01]},{"id":"s_hepatic_artery","col":"s","group":"Circulation","name":"Hepatic artery","sub":"carries oxygen-rich blood to the liver","how":"The common hepatic artery leaves the coeliac trunk, gives off the gastroduodenal artery and continues as the proper hepatic artery into the liver at the porta hepatis, beside the portal vein and bile duct, splitting into right and left branches and then into tiny arterioles that feed each lobule. It brings about a quarter of the liver's blood but much of its oxygen, and it is the bile ducts' only supply, so its blockage after a transplant damages them.","evidence":"Textbook anatomy","pos":[-0.042,1.17,0.038]},{"id":"s_hepatic_veins","col":"s","group":"Circulation","name":"Hepatic veins","sub":"drain the liver into the inferior vena cava","how":"Usually three large veins (right, middle and left) that start as the central veins of the lobules and empty straight into the inferior vena cava just below the diaphragm. They run between the liver segments and mark the surgeon's planes. A clot in them (Budd-Chiari syndrome) swells the liver and fills the belly with fluid.","evidence":"Textbook anatomy","pos":[-0.042,1.19,0.022]},{"id":"s_cystic_artery","col":"s","group":"Circulation","name":"Cystic artery","sub":"the artery to the gallbladder","how":"A small branch, usually of the right hepatic artery, that supplies the gallbladder and the cystic duct. Surgeons find and close it during gallbladder removal; its course varies a lot from person to person.","evidence":"Textbook anatomy","pos":[-0.05,1.14,0.022]},{"id":"s_splenic_artery","col":"s","group":"Circulation","name":"Splenic artery","sub":"the winding artery to the spleen","how":"The largest branch of the coeliac trunk; it winds along the upper border of the pancreas to the spleen, giving branches to the pancreas and the top of the stomach. It is the commonest site of aneurysms of the gut arteries.","evidence":"Textbook anatomy","pos":[0.041,1.125,-0.014]},{"id":"s_splenic_vein","col":"s","group":"Circulation","name":"Splenic vein","sub":"drains the spleen toward the portal vein","how":"Runs behind the pancreas from the spleen and joins the superior mesenteric vein behind the neck of the pancreas to form the portal vein; it also drains the pancreas. Pancreatitis or pancreatic cancer can cause a clot in it, which backs blood up into the spleen and stomach veins.","evidence":"Textbook anatomy","pos":[0.043,1.096,-0.02]},{"id":"s_superior_mesenteric_artery","col":"s","group":"Circulation","name":"Superior mesenteric artery","sub":"supplies the small intestine and first half of the colon","how":"Leaves the front of the aorta just below the coeliac trunk, passes behind the neck of the pancreas and over the third part of the duodenum, and fans out in the mesentery to the small intestine, appendix and the colon up to its middle. A sudden block (from a clot, often in atrial fibrillation) starves the gut and causes severe belly pain out of proportion to the findings.","evidence":"Textbook anatomy","pos":[0.012,1.057,0.014]},{"id":"s_superior_mesenteric_vein","col":"s","group":"Circulation","name":"Superior mesenteric vein","sub":"drains the small intestine toward the liver","how":"Collects blood from the small intestine, appendix and first half of the colon, rich in absorbed nutrients, and joins the splenic vein behind the neck of the pancreas to form the portal vein, which takes it to the liver.","evidence":"Textbook anatomy","pos":[0.003,1.037,0.019]},{"id":"s_pancreaticoduodenal_arteries","col":"s","group":"Circulation","name":"Gastroduodenal and pancreaticoduodenal arteries","sub":"the arteries around the head of the pancreas","how":"The gastroduodenal artery (from the common hepatic) runs down behind the first part of the duodenum and gives the superior pancreaticoduodenal arteries, which form loops with the inferior ones from the superior mesenteric artery around the head of the pancreas and the duodenum. A duodenal ulcer at the back of the bulb can erode into the gastroduodenal artery and bleed heavily.","evidence":"Textbook anatomy","pos":[-0.025,1.075,0.028]},{"id":"s_arteries","col":"s","group":"Circulation","name":"Arteries","sub":"carry blood away from the heart","how":"Thick, muscular tubes that carry blood from the heart out to every organ and limb under pressure. Their elastic walls stretch with each heartbeat and spring back, keeping blood moving between beats.","evidence":"Textbook anatomy and physiology.","pos":[0.078,0.8,0.06]},{"id":"s_lungs","col":"s","group":"Breathing","name":"Lungs & airways","sub":"breathing, oxygen","how":"The windpipe branches into ever-smaller airways ending in millions of tiny air sacs, where oxygen enters the blood and carbon dioxide leaves; coughing clears anything that goes down the wrong way.","evidence":"Textbook anatomy.","pos":[-0.07,1.33,0]},{"id":"s_nose","col":"s","group":"Breathing","name":"Nose & sinuses","sub":"nasal cavity, turbinates, paranasal sinuses","how":"The nose warms, moistens and filters air before it reaches the lungs. Curled shelves (turbinates) slow the air, and sticky mucus swept by tiny hairs carries trapped dust and germs to the throat. Air-filled sinuses in the cheekbones, forehead and between the eyes drain into the nose through small openings. Smell receptors line the roof of the nose.","evidence":"Textbook anatomy.","pos":[0,1.6,0.065]},{"id":"s_larynx","col":"s","group":"Breathing","name":"Voice box (larynx) & vocal cords","sub":"vocal folds, epiglottis","how":"A cartilage box at the top of the windpipe (the Adam's apple is its front). Two vocal folds inside come together and vibrate as air passes to make voice; breath support and how firmly they close set loudness. During each swallow the larynx lifts, the vocal folds shut and the epiglottis tips over to keep food and drink out of the airway.","evidence":"Textbook anatomy and physiology.","pos":[0,1.47,0.04]},{"id":"s_airways","col":"s","group":"Breathing","name":"Windpipe & bronchi","sub":"trachea, bronchi, bronchioles","how":"The windpipe (trachea) runs from the voice box down behind the breastbone and splits into two main bronchi, which keep branching into smaller tubes (bronchioles). Rings of cartilage hold the larger tubes open; smooth muscle in the walls can tighten; a lining of mucus and tiny beating hairs (cilia) carries dust and germs up to be coughed or swallowed.","evidence":"Textbook anatomy. Asthma narrows these tubes by muscle tightening, swelling and mucus; smoking paralyses the cilia and thickens the mucus (chronic bronchitis).","pos":[0,1.38,0.01]},{"id":"s_alveoli","col":"s","group":"Breathing","name":"Air sacs (alveoli)","sub":"where oxygen enters the blood","how":"Hundreds of millions of tiny balloon-like sacs at the ends of the smallest airways, each wrapped in a net of capillaries. Their walls are thinner than a cell, so oxygen passes into the blood and carbon dioxide passes out. A soapy coating (surfactant) stops them collapsing, and resident immune cells swallow particles that reach them.","evidence":"Textbook anatomy and physiology. Emphysema destroys the walls between sacs; pneumonia fills them with fluid and pus; fine dust (silica, PM2.5) reaches them.","pos":[0.08,1.3,-0.01]},{"id":"s_pleura","col":"s","group":"Breathing","name":"Pleura","sub":"the lining around the lungs","how":"Two thin, smooth layers: one covers each lung, the other lines the inside of the chest wall. A film of fluid between them lets the lungs glide as you breathe and keeps them stuck to the chest wall, so the lungs expand when the chest does. Air (pneumothorax) or fluid (effusion) in the gap lets the lung collapse.","evidence":"Textbook anatomy. Asbestos causes pleural plaques, thickening and mesothelioma, a cancer of this lining.","pos":[-0.12,1.3,0]},{"id":"s_diaphragm","col":"s","group":"Breathing","name":"Diaphragm","sub":"the main breathing muscle","how":"A dome-shaped sheet of muscle separating the chest from the belly. When it contracts it flattens and pulls air into the lungs; when it relaxes, air flows out. It is driven by the phrenic nerves, which leave the spinal cord in the neck, so neck-level spinal injury can stop breathing.","evidence":"Textbook anatomy and physiology.","pos":[0,1.21,0]},{"id":"s_pulmonary_arteries","col":"s","group":"Breathing","name":"Lung arteries (pulmonary arteries)","sub":"blood from the heart to the lungs","how":"The right side of the heart pumps oxygen-poor blood into the pulmonary trunk, which splits into right and left pulmonary arteries and branches alongside the airways down to the capillaries around the air sacs. Pressure here is normally low; a blockage (pulmonary embolism) or long-term narrowing (pulmonary hypertension) strains the right side of the heart.","evidence":"Textbook anatomy and physiology.","pos":[0.01,1.35,0]},{"id":"s_eyes","col":"s","group":"Senses","name":"Eyes","sub":"vision","how":"The lens focuses light onto the retina at the back of the eye, whose cells (some using dopamine) turn it into nerve signals sent to the brain; small muscles aim the eyes.","evidence":"Textbook anatomy.","pos":[0.032,1.63,0.08]},{"id":"s_ears","col":"s","group":"Senses","name":"Ears & hearing","sub":"hearing, balance","how":"The outer and middle ear carry sound to the cochlea, which turns it into nerve signals; next to it, the inner ear's balance organs sense head movement and tilt.","evidence":"Textbook anatomy.","pos":[0.06,1.62,0]},{"id":"s_middle_ear","col":"s","group":"Senses","name":"Ear canal, eardrum & middle ear","sub":"ossicles (hammer, anvil, stirrup), Eustachian tube; both sides","how":"The ear canal funnels sound to the eardrum, which vibrates three tiny bones (hammer, anvil and stirrup) that pass the sound into the cochlea. The Eustachian tube links the middle ear to the back of the nose to keep its air pressure equal and let fluid drain.","evidence":"Textbook anatomy.","pos":[0.056,1.62,0.002]},{"id":"s_vestibular","col":"s","group":"Senses","name":"Balance organs (vestibular system)","sub":"semicircular canals, utricle and saccule; both sides","how":"Three fluid-filled loops (semicircular canals) sense head turning, and two small sacs (utricle and saccule) with tiny crystals sense tilt and straight-line movement. They signal the brainstem and cerebellum, which keep the eyes steady and the body upright.","evidence":"Textbook anatomy.","pos":[0.046,1.622,-0.004]},{"id":"s_cochlea","col":"s","group":"Senses","name":"Cochlea (inner ear, hearing)","sub":"snail-shaped hearing organ; both sides","how":"A fluid-filled, snail-shaped tube deep in the skull bone. Sound waves passed in from the middle ear ripple the fluid and bend rows of hair cells, which turn sound into nerve signals; high pitches are sensed near the entrance, low pitches near the tip. Hair cells lost to age, noise or some drugs do not grow back.","evidence":"Textbook anatomy.","pos":[0.042,1.62,0.005]},{"id":"s_adrenal","col":"s","group":"Glands","name":"Adrenal glands","sub":"on top of each kidney","how":"Two small glands sitting on the kidneys. The outer layer (cortex) makes cortisol and aldosterone; the inner core (medulla) releases adrenaline and some noradrenaline into the blood when the nervous system signals stress.","evidence":"","pos":[0.06,1.17,-0.06]},{"id":"s_thyroid","col":"s","group":"Glands","name":"Thyroid gland","sub":"front of the neck","how":"A butterfly-shaped gland wrapped around the front of the windpipe below the Adam's apple. It takes up iodine from the blood to build thyroid hormone.","evidence":"","pos":[0,1.44,0.05]},{"id":"s_ovaries","col":"s","group":"Glands","name":"Ovaries","sub":"either side of the womb","how":"Two almond-sized glands in the pelvis that release eggs and make oestrogen and progesterone in a monthly cycle, plus small amounts of testosterone. Production falls sharply at menopause.","evidence":"","pos":[0.056,0.912,-0.012]},{"id":"s_testes","col":"s","group":"Glands","name":"Testes","sub":"in the scrotum","how":"Two glands in the scrotum, outside the body because sperm need a slightly cooler temperature. Under orders from the pituitary (LH and FSH), they make sperm and most of a man's testosterone. Sperm mature in the epididymis on the back of each testis.","evidence":"","pos":[0,0.79,0.085]},{"id":"s_pancreas","col":"s","group":"Glands","name":"Pancreas (islets)","sub":"behind the stomach","how":"A long gland lying behind the stomach. Most of it makes digestive juice; scattered clusters of cells (islets) release insulin and glucagon straight into the blood.","evidence":"","pos":[0.03,1.12,0]},{"id":"s_fat","col":"s","group":"Glands","name":"Fat tissue","sub":"under the skin and around the organs","how":"Body fat is not just storage: it is a gland that releases leptin, some oestrogen and inflammatory signals. Fat around the organs (belly) is the most active.","evidence":"","pos":[0,1.05,0.08]},{"id":"s_pineal","col":"s","group":"Glands","name":"Pineal gland","sub":"deep in the centre of the brain","how":"A pea-sized gland near the centre of the brain. It releases melatonin into the blood at night, under the control of the body clock (SCN) in the hypothalamus.","evidence":"","pos":[0,1.665,-0.025]},{"id":"s_pituitary","col":"s","group":"Glands","name":"Pituitary gland","sub":"base of the brain, behind the eyes","how":"A pea-sized gland hanging below the hypothalamus. Called the master gland, it sends hormones that switch on the thyroid, adrenal glands, ovaries and testes, and releases growth hormone, prolactin, oxytocin and vasopressin.","evidence":"","pos":[0,1.62,0.02]},{"id":"s_glymphatic","col":"s","group":"Lymphatic system","name":"Glymphatic system","sub":"brain fluid clearance","how":"A proposed flushing route for the brain, which has no ordinary lymph vessels. Step by step: (1) cerebrospinal fluid flows into the brain along the fluid-filled spaces around arteries, pushed by the arteries' pulsing; (2) brain support cells (astrocytes), whose end-feet wrap the vessels and carry water channels (aquaporin-4), let it pass into the fluid between brain cells; (3) it mixes there and picks up dissolved waste, such as amyloid-beta, tau and alpha-synuclein; (4) it leaves along the spaces around veins and drains out of the skull, partly through the meningeal lymph vessels to the deep neck lymph nodes. It is thought to be more active in deep sleep, but this is disputed.","evidence":"Described in mice (Iliff 2012). Mouse studies disagree on whether it speeds up during sleep (Xie 2013 found faster clearance; Miao 2024 found slower). In people, small MRI tracer studies found one night without sleep slowed clearance (Eide 2021), and an indirect MRI marker is lower in Parkinson's (McKnight 2021). No study shows that improving it changes Parkinson's or Alzheimer's.","pos":[0,1.67,0]},{"id":"s_meningeal_lymph","col":"s","group":"Lymphatic system","name":"Meningeal lymph vessels","sub":"brain's lymph drains","how":"True lymph vessels lining the large veins inside the tough brain covering (dura). They carry spinal fluid, waste molecules and immune cells out of the skull to the deep neck lymph nodes. They become less effective with age in mice.","evidence":"Found in mice in 2015 (Louveau, PMID 26030524) and since seen in people on MRI. Their role in disease is shown mainly in animals.","pos":[0,1.73,-0.02]},{"id":"s_lymph_neck","col":"s","group":"Lymphatic system","name":"Neck lymph nodes","sub":"cervical nodes","how":"Chains of lymph nodes, about 300 in all, around the head and along both sides of the neck: under the chin and jaw (submental, submandibular), in front of and behind the ear, at the back of the skull, and a deep chain along the internal jugular vein. Step by step, lymph from the scalp, face, mouth, teeth, tonsils, throat and the brain's coverings passes first through the outer groups and then the deep chain, which empties through the jugular trunk into the venous angle. These are the \"glands\" that swell with a sore throat. Doctors divide them into levels to describe where a cancer of the head and neck has spread.","evidence":"Textbook anatomy.","pos":[0.05,1.5,0.02]},{"id":"s_lymph_armpit","col":"s","group":"Lymphatic system","name":"Armpit lymph nodes","sub":"axillary nodes","how":"About 20 to 40 nodes in each armpit arranged in groups (front, back, side, central and apex) that filter lymph from the arm, the chest wall, the upper back and most of the breast. Lymph flows from the outer groups to the central and then the apical group under the collarbone, and on through the subclavian trunk to the venous angle. The first node a breast cancer drains to (the sentinel node) is usually here, so these nodes are checked or removed in breast cancer surgery, which can leave the arm prone to swelling (lymphoedema).","evidence":"Textbook anatomy.","pos":[0.15,1.3,0]},{"id":"s_lymph_groin","col":"s","group":"Lymphatic system","name":"Groin lymph nodes","sub":"inguinal nodes","how":"Two layers of nodes in the crease of each groin. The superficial nodes (about 10, along the top of the great saphenous vein) filter lymph from the skin of the leg, the buttock, the lower belly wall, the genital skin and the anus. The deep nodes, next to the femoral vein, also take lymph from the deep leg via the popliteal nodes. All drain up to the iliac nodes in the pelvis. Removing them in cancer surgery can leave the leg prone to swelling.","evidence":"Textbook anatomy.","pos":[0.09,0.88,0.06]},{"id":"s_lymph_gut","col":"s","group":"Lymphatic system","name":"Gut lymph tissue (GALT)","sub":"gut-associated lymphoid tissue","how":"The gut wall holds the body's largest store of immune cells, called gut-associated lymphoid tissue (GALT): Peyer's patches mostly in the last part of the small intestine, the appendix, thousands of single lymph follicles along the small and large intestine, and countless immune cells scattered in the lining. Lymph from the gut, with absorbed fat, then passes through the mesenteric lymph nodes. Together they learn to tolerate food and normal gut bacteria while blocking harmful microbes, mainly by secreting IgA antibody into the gut.","evidence":"Textbook anatomy.","pos":[-0.03,1,0.05]},{"id":"s_thoracic_duct","col":"s","group":"Lymphatic system","name":"Thoracic duct","sub":"main lymph channel","how":"The body's largest lymph vessel, about 40 cm long and a few millimetres wide, carrying lymph from both legs, the belly, the gut, the left chest, the left arm and the left side of the head: about three quarters of the body. Its route, step by step: (1) it starts at the cisterna chyli in front of the first lumbar vertebrae; (2) passes up through the diaphragm beside the aorta; (3) climbs the back of the chest in front of the spine, between the aorta and the azygos vein; (4) around the fifth chest vertebra it crosses behind the oesophagus to the left side; (5) at the base of the neck it arches forward and outward behind the carotid artery; (6) it empties into the left venous angle, where the left internal jugular vein joins the left subclavian vein, usually after receiving the left jugular, subclavian and bronchomediastinal trunks. A valve at its end stops blood running back in. It has valves along its length, and breathing in lowers chest pressure, which helps draw lymph upward. After a fatty meal it carries milky chyle.","evidence":"Textbook anatomy and physiology.","pos":[0.004,1.3,-0.042]},{"id":"s_lymph_vessels","col":"s","group":"Lymphatic system","name":"Lymph vessels (collecting vessels)","sub":"the lymph drainage network","how":"Collecting lymph vessels gather lymph from the capillaries and carry it through one or more groups of lymph nodes, then into the lymph trunks and ducts that empty into the great veins of the neck. In the limbs a superficial set runs under the skin beside the superficial veins (for example along the great saphenous vein of the leg and the cephalic and basilic veins of the arm) and a deep set runs with the deep arteries and veins. Their walls have valves every few millimetres and a muscle layer, so each segment (lymphangion) pumps lymph on to the next. Lymph is pushed along by this own pumping, by nearby muscles moving and by breathing. When drainage fails, fluid collects and the limb swells (lymphoedema).","evidence":"Textbook physiology.","pos":[0.09,0.72,0.03]},{"id":"s_tonsils","col":"s","group":"Lymphatic system","name":"Tonsils & adenoids (Waldeyer's ring)","sub":"the ring of lymph tissue around the throat","how":"A ring of lymph tissue around the entrance to the throat, where the mouth and nose meet the pharynx: the adenoids on the back wall of the nose, the two small tubal tonsils at the ear-tube openings, the two palatine tonsils at the sides of the back of the mouth, and the lingual tonsil on the back of the tongue. Every breath and swallow passes them, so they sample germs early and start immune responses, mostly IgA antibody. They are largest in childhood and shrink with age.","evidence":"Textbook anatomy.","pos":[0,1.575,0.035]},{"id":"s_thymus","col":"s","group":"Lymphatic system","name":"Thymus","sub":"where T cells are trained; shrinks with age","how":"A soft, two-lobed organ behind the upper breastbone, in front of the heart and great vessels. Each lobe is divided into lobules with a dark outer cortex and a pale inner medulla. Step by step: (1) young T-cell precursors arrive from the bone marrow into the cortex; (2) they build a unique receptor and are tested: those whose receptor can't recognise the body's own presenting molecules die (positive selection); (3) in the medulla, special cells display samples of proteins from all over the body, and T cells that react strongly to self are killed or turned into regulatory T cells (negative selection), the main defence against autoimmunity; (4) only about 2 to 5 in every 100 survive and leave as mature naive T cells. Age involution: the thymus is largest relative to body size in infancy and reaches its peak weight around puberty; from then on its working tissue is steadily replaced by fat, so an older adult makes far fewer new T cells and relies on long-lived ones, which is one reason immune responses to new germs and vaccines weaken with age.","evidence":"Textbook anatomy and immunology. Babies born without a thymus (DiGeorge syndrome) have almost no T cells.","pos":[0,1.383,0.057]},{"id":"s_spleen","col":"s","group":"Lymphatic system","name":"Spleen","sub":"blood filter","how":"A fist-sized, soft organ in the upper left belly under the 9th to 11th ribs, behind the stomach and against the diaphragm, shaped like a coffee bean with a notched upper edge; its blood vessels enter at a dent (hilum) facing the stomach. It filters blood, not lymph. Inside: red pulp (about three quarters of it), where blood trickles through spongy cords and narrow slits; old, stiff or damaged red cells can't squeeze through and are eaten by macrophages, which recycle their iron; and white pulp, sleeves of T cells around small arteries with B-cell follicles, where immune cells check the blood for germs and make antibodies, especially against bacteria with sugary capsules (pneumococcus, meningococcus, Hib). The spleen also holds a reserve of platelets and monocytes. An enlarged spleen can tear after a knock. People without a spleen can live normally but are at higher risk of severe infection with those capsulated bacteria, so they are offered extra vaccines.","evidence":"Textbook anatomy.","pos":[0.097,1.157,-0.045]},{"id":"s_spleen_white_pulp","col":"s","group":"Lymphatic system","name":"Spleen white pulp","sub":"the spleen's immune tissue","how":"Small greyish-white islands scattered through the spleen, each built around a small artery. Step by step: (1) a sleeve of T cells wraps the artery (the periarteriolar lymphoid sheath); (2) B-cell follicles sit beside it and form germinal centres when activated; (3) around them lies the marginal zone, where blood from the artery spills out slowly past macrophages and specialised B cells that react fast to bacteria with sugary capsules. This is the body's main defence against germs that get into the blood itself.","evidence":"Textbook histology and immunology.","pos":[0.095,1.162,-0.043]},{"id":"s_spleen_red_pulp","col":"s","group":"Lymphatic system","name":"Spleen red pulp","sub":"the spleen's blood filter","how":"Most of the spleen's bulk: spongy cords of tissue (splenic cords) between wide, leaky veins (sinusoids). Step by step: (1) blood flows from small arteries into the cords; (2) to get back into the veins, red cells must squeeze through slits narrower than themselves; (3) healthy, flexible cells pass, while old, stiff, damaged or parasite-infected cells get stuck and are eaten by macrophages; (4) the iron from their haemoglobin is recycled to the bone marrow. It also pits out particles inside red cells, and stores platelets and monocytes that can be released in an emergency.","evidence":"Textbook histology and physiology.","pos":[0.1,1.15,-0.048]},{"id":"s_lymph_supraclavicular","col":"s","group":"Lymphatic system","name":"Supraclavicular lymph nodes","sub":"nodes above the collarbone","how":"A small group of nodes in the hollow just above each collarbone, the last stop before lymph enters the veins. They receive lymph from the neck, the armpit, the chest and, on the left, from the thoracic duct region, which drains the belly. That is why a hard, enlarged left supraclavicular node (Virchow's node) can be a sign of cancer in the stomach or another belly organ, and a right one can point to the chest. Normally they cannot be felt.","evidence":"Textbook anatomy and clinical medicine.","pos":[0.05,1.452,0.008]},{"id":"s_lymph_mediastinal","col":"s","group":"Lymphatic system","name":"Mediastinal and hilar lymph nodes","sub":"nodes around the windpipe and lung roots","how":"Chains of nodes in the middle of the chest: beside the windpipe, under its split into the two main bronchi, and at the root (hilum) of each lung. They filter lymph from the lungs, the heart and the oesophagus, and drain on into the bronchomediastinal trunks. Inhaled dust, soot and germs end up here, so they are often blackened in city dwellers and smokers. They enlarge in tuberculosis, sarcoidosis, lymphoma and lung cancer, and are sampled through a bronchoscope or by surgery to stage lung cancer.","evidence":"Textbook anatomy and clinical medicine.","pos":[0,1.33,0.01]},{"id":"s_lymph_mesenteric","col":"s","group":"Lymphatic system","name":"Mesenteric lymph nodes","sub":"nodes in the gut's fold","how":"Over a hundred nodes, the largest group in the body, scattered through the mesentery, the fan-shaped fold that holds the small intestine and colon. They filter lymph and chyle from the gut wall, where immune cells carrying samples of gut contents arrive to train T and B cells, which helps the body tolerate food and normal gut bacteria while fighting harmful ones. Their lymph drains to the intestinal trunk and the cisterna chyli. In children they often swell with a viral illness and can mimic appendicitis.","evidence":"Textbook anatomy and immunology.","pos":[0,1.02,0.03]},{"id":"s_lymph_para_aortic","col":"s","group":"Lymphatic system","name":"Para-aortic lymph nodes","sub":"nodes along the aorta","how":"Chains of nodes along both sides of the abdominal aorta and inferior vena cava, at the back of the belly. They receive lymph from the iliac nodes (and so the legs and pelvis), the kidneys and adrenals, and directly from the testes or ovaries, because those organs began life near the kidneys. Their lymph flows into the lumbar trunks and the cisterna chyli. They are checked when staging testicular, ovarian, womb and cervical cancers and lymphoma.","evidence":"Textbook anatomy.","pos":[0.022,1.04,-0.025]},{"id":"s_lymph_iliac","col":"s","group":"Lymphatic system","name":"Iliac lymph nodes","sub":"nodes along the pelvic arteries","how":"Nodes strung along the external, internal and common iliac arteries and veins inside the pelvis. The external group receives lymph from the groin nodes (and so the leg); the internal group from the pelvic organs (bladder, prostate, womb, cervix, rectum); all pass lymph up to the common iliac and then the para-aortic nodes. Removing or irradiating them for pelvic cancers can cause leg or genital lymphoedema.","evidence":"Textbook anatomy.","pos":[0.05,0.93,-0.015]},{"id":"s_lymph_popliteal","col":"s","group":"Lymphatic system","name":"Popliteal lymph nodes","sub":"nodes behind the knee","how":"A few small nodes in the fat behind the knee, around the popliteal vein. They receive lymph from the deep tissues of the lower leg and from the outer side of the foot and calf (along the small saphenous vein) and pass it up along the femoral vessels to the deep groin nodes. They are rarely felt; they can enlarge with an infected wound of the heel or foot.","evidence":"Textbook anatomy.","pos":[0.095,0.5,-0.03]},{"id":"s_malt","col":"s","group":"Lymphatic system","name":"Mucosa-associated lymphoid tissue (MALT)","sub":"immune tissue in the body's linings","how":"Clusters of lymph tissue, without capsules, in the linings of the gut (GALT), airways (BALT), nose and throat (NALT, including the tonsils), eyes, salivary glands, breast, bladder and genital tract. Most germs enter through these linings, so the body places immune sentries there. Step by step: (1) special lining cells (M cells) grab samples from the surface and pass them to immune cells just beneath; (2) B and T cells are activated in the local follicles; (3) activated cells travel through the lymph and blood and home back to linings all over the body; (4) the B cells become plasma cells that secrete IgA antibody across the lining, which neutralises germs and toxins before they get in. MALT lymphoma is a slow-growing cancer of these cells, often triggered by long-standing infection such as H. pylori in the stomach.","evidence":"Textbook immunology.","pos":[0,0.94,0.06]},{"id":"s_palatine_tonsils","col":"s","group":"Lymphatic system","name":"Palatine tonsils","sub":"the tonsils at the back of the mouth","how":"The two almond-shaped lumps on each side of the back of the mouth, between the two arches of the soft palate; what people usually mean by \"tonsils\". Their surface dips into 10 to 30 deep pits (crypts), which greatly increases the area where swallowed and breathed-in germs touch immune cells; under the lining lie B-cell follicles and T-cell zones like a lymph node's. They drain to the upper deep neck nodes just below the angle of the jaw (the jugulodigastric node). They are biggest at age 4 to 10 and shrink after puberty. They can become infected (tonsillitis), and debris trapped in the crypts can harden into tonsil stones.","evidence":"Textbook anatomy.","pos":[0.014,1.552,0.02]},{"id":"s_adenoids","col":"s","group":"Lymphatic system","name":"Adenoids (pharyngeal tonsil)","sub":"lymph tissue at the back of the nose","how":"A pad of lymph tissue high on the back wall of the nasopharynx, the space behind the nose above the soft palate, near the openings of the Eustachian (ear) tubes. It samples germs breathed in through the nose. Largest at age 3 to 7 and mostly gone by the teens. Large adenoids in children can block nose breathing, causing mouth breathing and snoring, and can block the ear tubes, contributing to glue ear and ear infections.","evidence":"Textbook anatomy.","pos":[0,1.598,0.012]},{"id":"s_lingual_tonsil","col":"s","group":"Lymphatic system","name":"Lingual tonsil","sub":"lymph tissue on the back of the tongue","how":"Bumpy lymph tissue covering the back third of the tongue, behind the V-shaped row of large taste buds. Like the other tonsils it has crypts lined with immune tissue. With the palatine tonsils, the adenoids and the small tubal tonsils at the ear-tube openings, it forms Waldeyer's ring, the ring of lymph tissue that guards the entrance to the throat.","evidence":"Textbook anatomy.","pos":[0,1.545,0.024]},{"id":"s_peyers_patches","col":"s","group":"Lymphatic system","name":"Peyer's patches","sub":"lymph follicles in the small intestine wall","how":"Oval patches, a few centimetres long, of tightly grouped lymph follicles in the lining of the small intestine, about 100 to 200 in a young adult and most numerous in the last part (the ileum), always on the side opposite the mesentery. Step by step: (1) a dome of special lining cells (M cells) carries bacteria, viruses and food particles from the gut into the patch; (2) dendritic cells there show them to T and B cells; (3) B cells switch to making IgA, the antibody that is secreted into the gut; (4) the activated cells travel via the mesenteric nodes and blood and settle in the gut lining. This keeps the balance between tolerating food and normal bacteria and fighting harmful ones. Some germs, such as Salmonella and polio virus, use the M cells as a doorway in.","evidence":"Textbook anatomy and immunology.","pos":[-0.06,0.94,0.035]},{"id":"s_lymph_node","col":"s","group":"Lymphatic system","name":"A lymph node (inside view)","sub":"how one lymph node works","how":"A bean-shaped filter, usually a few millimetres to about two centimetres long; the body has about 450 to 800. Step by step: (1) lymph arrives through several afferent vessels that pierce the curved outer side; (2) it trickles into the sinus just under the capsule and then through channels toward the centre, past lining macrophages that eat germs and debris; (3) dendritic cells carrying pieces of microbes from the tissues settle in the T-cell zone; (4) T and B cells, which arrive from the blood through special venules, check whether anything matches their receptor; (5) a match makes those cells multiply (which is why nodes swell during infection), B cells make antibodies, and activated cells leave; (6) filtered lymph, now carrying antibodies and immune cells, leaves through one or two efferent vessels at the dented side (hilum), where the artery enters and the vein leaves.","evidence":"Textbook anatomy and immunology.","pos":[0.16,1.35,-0.012]},{"id":"s_lymph_node_capsule","col":"s","group":"Lymphatic system","name":"Lymph node capsule and sinuses","sub":"the node's outer wall and lymph channels","how":"A tough coat of connective tissue around each node, with partitions (trabeculae) running inward to hold it in shape. Just under it lies the subcapsular sinus, where lymph from the afferent vessels first arrives; the lymph then runs through trabecular and medullary sinuses to the hilum. The sinuses are lined with macrophages that catch microbes, dead cells and particles such as soot or tattoo ink, which is why tattooed people's nodes can be coloured. Cancer cells that spread by lymph often lodge first in the subcapsular sinus.","evidence":"Textbook histology.","pos":[0.164,1.352,-0.01]},{"id":"s_lymph_follicles","col":"s","group":"Lymphatic system","name":"Lymph node follicles (B-cell zone)","sub":"outer cortex, where antibodies are made","how":"Round clusters of B cells in the outer cortex just under the capsule, held together by follicular dendritic cells that display intact microbe pieces. Step by step: (1) resting follicles are full of naive B cells; (2) when a B cell's receptor binds a match and it gets help from a T cell at the follicle edge, it starts dividing; (3) the follicle develops a pale germinal centre where B cells rapidly divide and mutate their antibody genes, and only those that bind the target best survive; (4) the winners become plasma cells that make large amounts of antibody, or long-lived memory B cells. This is why a second exposure, or a vaccine booster, gives a faster and stronger response.","evidence":"Textbook immunology.","pos":[0.163,1.353,-0.014]},{"id":"s_lymph_paracortex","col":"s","group":"Lymphatic system","name":"Lymph node paracortex (T-cell zone)","sub":"deep cortex, where T cells are activated","how":"The deep part of the cortex between the follicles and the medulla, packed with T cells. Dendritic cells that picked up microbe pieces in the tissues travel here in the lymph and show those pieces to passing T cells. A T cell whose receptor matches is activated: it multiplies into an army of killer T cells (which destroy infected cells) or helper T cells (which help B cells and macrophages). The high endothelial venules, where T and B cells enter the node from the blood, sit in this zone. HIV damages it, which is part of how the virus wears down the immune system.","evidence":"Textbook immunology.","pos":[0.16,1.349,-0.011]},{"id":"s_lymph_medulla","col":"s","group":"Lymphatic system","name":"Lymph node medulla","sub":"the node's inner core","how":"The inner part of the node around the hilum, made of medullary cords (strands of plasma cells, macrophages and lymphocytes) separated by medullary sinuses through which lymph flows on its way out. Plasma cells here release antibodies straight into the outgoing lymph, and macrophages catch what the cortex missed. Lymph then leaves through the efferent vessel at the hilum toward the next node or the lymph trunks.","evidence":"Textbook histology.","pos":[0.158,1.348,-0.012]},{"id":"s_high_endothelial_venules","col":"s","group":"Lymphatic system","name":"High endothelial venules","sub":"where immune cells enter a lymph node from the blood","how":"Small veins in the T-cell zone of lymph nodes (and in tonsils and Peyer's patches) lined with unusually tall, plump cells. Step by step: (1) naive T and B cells circulating in the blood roll along their wall; (2) adhesion molecules and chemical signals made by these cells catch and stop them; (3) the lymphocytes squeeze through the wall into the node. Each lymphocyte tours many nodes a day this way, checking each one for its target; about a quarter of lymphocytes in the blood leave through these venules on every pass.","evidence":"Textbook immunology.","pos":[0.161,1.349,-0.009]},{"id":"s_lymph_capillaries","col":"s","group":"Lymphatic system","name":"Lymph capillaries","sub":"where fluid enters the lymph","how":"The smallest, blind-ended lymph vessels, woven through the skin and almost every tissue except the brain and the bone marrow. Step by step: (1) blood plasma seeps out of the blood capillaries into the spaces between cells; most is soaked back, but some fluid, protein and cells are left behind; (2) lymph capillary walls are a single layer of overlapping cells whose edges act as flap valves; (3) when fluid builds up, tiny anchoring threads tied to the tissue pull the flaps open and fluid, protein, fat droplets, microbes and immune cells flow in; (4) as pressure inside rises the flaps close, so the lymph cannot leak back; (5) the capillaries join into pre-collectors and then collecting vessels. This is how protein that escapes the blood gets back, and how germs and dendritic immune cells reach the lymph nodes.","evidence":"Textbook anatomy and physiology.","pos":[0.095,0.3,0.06]},{"id":"s_lymphangion","col":"s","group":"Lymphatic system","name":"Lymphangion (valves and pump)","sub":"the lymph vessel's own pump","how":"A collecting lymph vessel is built as a chain of short segments called lymphangions, each a few millimetres to a couple of centimetres long, with a one-way valve at each end and a ring of smooth muscle in its wall. Step by step: (1) lymph fills a segment and stretches it; (2) the stretch triggers the muscle to squeeze, several times a minute; (3) the valve ahead opens and the valve behind shuts, pushing lymph into the next segment, which then fills and squeezes in turn, like a chain of tiny hearts; (4) outside forces add to this pump: contracting skeletal muscles and pulsing arteries next door squeeze the vessels, and breathing in lowers chest pressure. Because the valves only open one way, every squeeze moves lymph toward the nodes and the heart. When valves fail or the muscle tires, lymph pools and the limb swells.","evidence":"Textbook physiology.","pos":[0.07,0.33,-0.005]},{"id":"s_lacteals","col":"s","group":"Lymphatic system","name":"Lacteals","sub":"fat-absorbing lymph vessels of the gut","how":"A single lymph capillary in the centre of each finger-like villus of the small intestine. Step by step: (1) gut cells absorb digested fat and repackage it, with fat-soluble vitamins, into droplets called chylomicrons; (2) these droplets are too big to enter blood capillaries, so they pass into the lacteal; (3) the milky lymph that results is called chyle; small muscle fibres in the villus squeeze the lacteal to move it along; (4) chyle flows through the mesentery and its lymph nodes to the cisterna chyli and up the thoracic duct into the blood. So most dietary fat reaches the bloodstream through the lymph, bypassing the liver at first.","evidence":"Textbook anatomy and physiology.","pos":[0.01,0.99,0.045]},{"id":"s_cisterna_chyli","col":"s","group":"Lymphatic system","name":"Cisterna chyli","sub":"lymph collecting sac at the start of the thoracic duct","how":"A thin-walled sac about the size of a little finger lying in front of the first and second lumbar vertebrae, just to the right of and behind the aorta. Step by step: (1) the two lumbar lymph trunks bring lymph from both legs, the pelvis, the kidneys and the back wall of the belly (after it has passed the iliac and para-aortic nodes); (2) the intestinal trunk brings milky chyle from the gut, via the mesenteric nodes; (3) the sac collects them and narrows upward into the thoracic duct, which passes through the diaphragm beside the aorta. Each breath helps: the diaphragm and the change in belly and chest pressure squeeze lymph up from here.","evidence":"Textbook anatomy. Its shape varies between people; in some it is only a widening of the duct.","pos":[-0.008,1.075,-0.026]},{"id":"s_right_lymph_duct","col":"s","group":"Lymphatic system","name":"Right lymphatic duct","sub":"drains the upper right body","how":"A short lymph vessel, about a centimetre long, at the root of the right side of the neck. It collects the right jugular trunk (from the right side of the head and neck), the right subclavian trunk (from the right arm and the right armpit nodes) and the right bronchomediastinal trunk (from the right lung and chest) and empties into the right venous angle, where the right internal jugular vein meets the right subclavian vein. So lymph from the upper right quarter of the body returns to the blood here; everything else goes through the thoracic duct on the left. Often the three trunks simply open into the veins separately.","evidence":"Textbook anatomy; its form varies a lot between people.","pos":[-0.032,1.442,0.02]},{"id":"s_spleen_hilum","col":"s","group":"Lymphatic system","name":"Splenic hilum","sub":"where the spleen's vessels enter","how":"A long slit on the spleen's inner (visceral) surface, on the ridge between the hollows made by the stomach and the left kidney. Step by step: (1) the splenic artery, which runs from the coeliac trunk in a winding course along the upper border of the pancreas, divides into about five segmental branches just before or inside the hilum; (2) each branch supplies its own segment of the spleen, so a surgeon can sometimes remove part of the spleen and keep the rest; (3) blood that has passed through the red pulp collects in segmental veins that join at the hilum into the splenic vein; (4) the splenic vein runs behind the pancreas and joins the vein from the gut to form the portal vein to the liver; (5) lymph vessels from the capsule leave here to the small splenic hilar lymph nodes. The tail of the pancreas often reaches the hilum, which matters in surgery on either organ.","evidence":"Textbook anatomy.","pos":[0.094,1.156,-0.042]},{"id":"s_retina","col":"s","group":"Eye","name":"Retina","sub":"the eye's light-sensing film","how":"A thin sheet of brain tissue lining the back of the eye, in layers: light-catching rods and cones at the back, middle cells that process the signal (including a small group of dopamine-making amacrine cells that switch the retina between night and day mode and sharpen contrast), and ganglion cells at the front whose fibres form the optic nerve. Because it is an outgrowth of the brain, eye scans (OCT) of its layers are studied as a window on brain diseases.","evidence":"Textbook anatomy. Retinal dopamine cells are lost in Parkinson's, and retinal electrical responses are slower and weaker (review of human and animal studies).","pos":[0.032,1.629,0.0585]},{"id":"s_photoreceptors","col":"s","group":"Eye","name":"Rods & cones","sub":"light-catching cells","how":"The light-catching cells of the retina. About 120 million rods work in dim light and see only shades of grey; about 6 million cones work in daylight and see colour and fine detail, packed most tightly in the fovea. Each uses a vitamin A-based pigment that light changes shape, starting the nerve signal.","evidence":"Textbook anatomy.","pos":[0.032,1.629,0.0583]},{"id":"s_retinal_ganglion","col":"s","group":"Eye","name":"Retinal ganglion cells","sub":"the retina's output neurons","how":"The retina's output nerve cells, in its innermost layer. Their long fibres run across the retina's surface (the nerve fibre layer) and leave the eye as the optic nerve. A small set contain their own light pigment (melanopsin) and report overall brightness to the body clock and the pupil. These are the cells that die in glaucoma, and their layer is the one found thinner on OCT in Parkinson's.","evidence":"Textbook anatomy.","pos":[0.032,1.63,0.0588]},{"id":"s_rpe","col":"s","group":"Eye","name":"Retinal pigment epithelium","sub":"the rods' and cones' support layer","how":"A single layer of dark cells behind the rods and cones. It absorbs stray light, recycles the used vitamin A pigment, eats the worn-out tips of the photoreceptors every day, and passes nutrients from the choroid. Its failure is central to age-related macular degeneration.","evidence":"Textbook anatomy.","pos":[0.032,1.628,0.058]},{"id":"s_macula","col":"s","group":"Eye","name":"Macula & fovea","sub":"sharp central vision","how":"The yellowish centre of the retina, about 5 mm across, directly behind the lens. Its central pit (the fovea) holds only tightly packed cones and gives the sharp detail used for reading and faces. Lutein and zeaxanthin collect here as a yellow filter that absorbs blue light.","evidence":"Textbook anatomy.","pos":[0.0335,1.629,0.0584]},{"id":"s_choroid","col":"s","group":"Eye","name":"Choroid","sub":"blood layer behind the retina","how":"A layer of blood vessels between the retina and the white sclera, with one of the highest blood flows in the body. It feeds the outer retina (the rods, cones and pigment layer) and carries away heat from light.","evidence":"Textbook anatomy.","pos":[0.032,1.629,0.0577]},{"id":"s_cornea","col":"s","group":"Eye","name":"Cornea","sub":"clear front window","how":"The clear dome at the front of the eye. It does about two-thirds of the eye's focusing and is one of the most nerve-rich tissues in the body, which is why a speck of dust hurts. It has no blood vessels and is kept wet and fed by the tear film; blinking spreads the tears across it.","evidence":"Textbook anatomy.","pos":[0.032,1.629,0.082]},{"id":"s_iris","col":"s","group":"Eye","name":"Iris & pupil","sub":"coloured ring, adjustable opening","how":"The iris is the coloured ring of muscle behind the cornea; the pupil is the hole in its centre. Two small muscles widen the pupil in dim light (sympathetic nerves) and narrow it in bright light or for near work (parasympathetic nerves), like a camera aperture.","evidence":"Textbook anatomy.","pos":[0.032,1.629,0.0795]},{"id":"s_lens","col":"s","group":"Eye","name":"Lens","sub":"fine focus","how":"A clear, flexible disc of tightly packed protein behind the iris. It changes shape to focus near or far. Its cells are never replaced, so the proteins it is born with must last a lifetime; with age it stiffens (needing reading glasses) and can cloud (cataract).","evidence":"Textbook anatomy.","pos":[0.032,1.629,0.0775]},{"id":"s_ciliary_body","col":"s","group":"Eye","name":"Ciliary body","sub":"focus muscle and fluid pump","how":"A ring of muscle and tissue around the lens. Its muscle tightens to let the lens round up for near focus, and its lining makes the clear watery fluid (aqueous humour) that fills the front of the eye and sets eye pressure; the fluid drains out at the angle between iris and cornea.","evidence":"Textbook anatomy.","pos":[0.032,1.635,0.0775]},{"id":"s_sclera","col":"s","group":"Eye","name":"Sclera","sub":"white outer wall","how":"The tough white coat that forms most of the eyeball's outer wall and keeps its shape; the eye muscles attach to it and the optic nerve leaves through it at the back.","evidence":"Textbook anatomy.","pos":[0.032,1.629,0.057]},{"id":"s_vitreous","col":"s","group":"Eye","name":"Vitreous","sub":"clear gel filling the eye","how":"The clear jelly that fills the large space between the lens and the retina. With age it liquefies and can pull away from the retina, which causes floaters and, rarely, a retinal tear.","evidence":"Textbook anatomy.","pos":[0.032,1.629,0.069]},{"id":"s_lacrimal","col":"s","group":"Eye","name":"Tear glands & tear film","sub":"keeps the eye surface wet","how":"The main tear gland sits under the upper outer edge of the eye socket, with many tiny helper glands in the lids; oil glands along the lid margins (meibomian glands) add a fatty layer that stops tears evaporating. Tears drain through small holes at the inner corner into the nose. The tear film feeds and protects the cornea and gives a smooth surface for clear sight.","evidence":"Textbook anatomy.","pos":[0.046,1.642,0.068]},{"id":"s_eyelids","col":"s","group":"Eye","name":"Eyelids & blinking","sub":"shield and wiper","how":"Thin folds of skin, muscle and a firm plate that close over the eye. Each blink (normally about 15-20 a minute, partly automatic, run from the brainstem) spreads fresh tears, squeezes oil from the lid glands and clears debris. Fewer blinks means faster drying of the eye surface.","evidence":"Textbook anatomy.","pos":[0.032,1.629,0.0845]},{"id":"s_eye_muscles","col":"s","group":"Eye","name":"Eye muscles","sub":"aim the eyes together","how":"Six small muscles on each eyeball, run by three cranial nerves from the brainstem, turn the eyes so both point at the same target; a seventh lifts the upper lid. Turning both eyes inward for near work is called convergence. If the eyes are not aligned, the brain receives two different images: double vision.","evidence":"Textbook anatomy.","pos":[0.03,1.63,0.052]},{"id":"s_enamel","col":"s","group":"Mouth & teeth","name":"Tooth enamel","sub":"the hard outer layer of each tooth crown","how":"The hardest material in the body: tightly packed crystals of calcium phosphate (hydroxyapatite). It has no living cells, so once lost it cannot regrow. Acid from plaque bacteria dissolves the crystals; saliva and fluoride help put minerals back in early on.","evidence":"Textbook anatomy.","pos":[0,1.557,0.08]},{"id":"s_dentine","col":"s","group":"Mouth & teeth","name":"Dentine","sub":"the yellowish layer under enamel","how":"Makes up most of the tooth under the enamel and the root covering. It is softer than enamel and full of tiny fluid-filled tubes that run to the pulp, which is why exposed dentine feels cold and sweet things sharply.","evidence":"Textbook anatomy.","pos":[0,1.556,0.077]},{"id":"s_dental_pulp","col":"s","group":"Mouth & teeth","name":"Dental pulp","sub":"the nerve and blood vessels inside each tooth","how":"Soft living tissue in the centre of the tooth with nerves and blood vessels. It keeps the tooth alive and senses temperature and pain. When decay or a crack reaches it, it becomes inflamed or infected, which causes toothache and can lead to an abscess at the root tip.","evidence":"Textbook anatomy.","pos":[0,1.556,0.074]},{"id":"s_tooth_roots","col":"s","group":"Mouth & teeth","name":"Tooth roots","sub":"roots, cementum, periodontal ligament","how":"The part of the tooth hidden in the jaw bone, covered by a thin bone-like layer (cementum) and held in its socket by a sling of fibres (the periodontal ligament) that cushions chewing forces. When gums shrink back, root surfaces are exposed and decay easily because they have no enamel.","evidence":"Textbook anatomy.","pos":[0,1.548,0.07]},{"id":"s_gums","col":"s","group":"Mouth & teeth","name":"Gums & periodontium","sub":"gingiva, periodontal ligament, tooth-socket bone","how":"The gums (gingiva) are firm pink tissue that seal around each tooth's neck. Beneath them, the periodontal ligament and the socket bone (alveolar bone) hold the tooth in place. Together they are the periodontium: the tooth's support system.","evidence":"Textbook anatomy.","pos":[0,1.557,0.079]},{"id":"s_salivary_glands","col":"s","group":"Mouth & teeth","name":"Salivary glands","sub":"parotid, submandibular, sublingual; both sides","how":"Three pairs of large glands, in front of the ears (parotid), under the jaw (submandibular) and under the tongue (sublingual), plus many tiny ones in the lips and cheeks, make saliva. Saliva wets food for chewing and swallowing, starts starch digestion, washes away food and bacteria, neutralises plaque acid and carries calcium and phosphate that help repair early enamel damage. The autonomic nerves switch it on, mainly through acetylcholine, so medicines that block acetylcholine dry the mouth. The glands also concentrate dietary nitrate into saliva for the mouth's nitrate-reducing bacteria.","evidence":"Textbook anatomy and physiology.","pos":[0.055,1.585,0.01]},{"id":"s_tongue","col":"s","group":"Mouth & teeth","name":"Tongue","sub":"muscle, taste buds","how":"A muscular organ that moves food between the teeth, shapes it into a soft lump and pushes it back to start swallowing, and shapes speech sounds. Its surface carries taste buds, and the back of it hosts the mouth's nitrate-reducing bacteria.","evidence":"Textbook anatomy.","pos":[0,1.55,0.05]},{"id":"s_jaw_tmj","col":"s","group":"Mouth & teeth","name":"Jaw bone & jaw joint (TMJ)","sub":"mandible, temporomandibular joints, chewing muscles; both sides","how":"The lower jaw (mandible) hinges and slides at two temporomandibular joints, one just in front of each ear, each with a small cushioning disc. Powerful chewing muscles (masseter, temporalis) close the jaw.","evidence":"Textbook anatomy.","pos":[0.052,1.6,0.012]},{"id":"s_optic_nerve","col":"s","group":"Visual pathway","name":"Optic disc & optic nerve","sub":"cable from eye to brain","how":"About a million ganglion-cell fibres gather at the optic disc (the eye's natural blind spot, where vessels also enter) and leave the eye as the optic nerve, a cable about 4-5 cm long that runs back through the eye socket into the skull. It is part of the brain, wrapped in the same coverings, so it cannot regrow once damaged. The disc is what doctors see when they look into the eye; its cupping is a sign of glaucoma.","evidence":"Textbook anatomy.","pos":[0.024,1.635,0.04]},{"id":"s_optic_chiasm","col":"s","group":"Visual pathway","name":"Optic chiasm","sub":"where the nerves cross","how":"An X-shaped junction on the underside of the brain, just above the pituitary gland, where fibres from the inner half of each retina cross to the other side. After it, each side of the brain receives the opposite half of what both eyes see. A pituitary tumour pressing here typically blinds the outer side of vision in both eyes.","evidence":"Textbook anatomy.","pos":[0,1.645,0.017]},{"id":"s_lgn","col":"s","group":"Visual pathway","name":"Lateral geniculate nucleus","sub":"the thalamus relay for sight","how":"A small knee-shaped relay at the back of the thalamus on each side. Most optic-tract fibres end here, and its cells pass the signal along the optic radiation to the visual cortex, with strong feedback from the cortex itself.","evidence":"Textbook anatomy.","pos":[0.0215,1.661,-0.0135]},{"id":"s_uterus","col":"s","group":"Female reproductive","name":"Uterus (womb)","sub":"behind the bladder","how":"A pear-shaped muscular organ, about the size of a small fist, tipped forward over the bladder. Each month its lining (endometrium) thickens under oestrogen, is readied by progesterone after an egg is released, and is shed as a period if no pregnancy starts. In pregnancy it stretches to hold the baby, and its muscle contracts in labour.","evidence":"Textbook anatomy and physiology.","pos":[0,0.9,0.005]},{"id":"s_cervix","col":"s","group":"Female reproductive","name":"Cervix","sub":"the neck of the womb","how":"The narrow lower end of the womb, opening into the top of the vagina. Its mucus changes through the cycle, it stays closed in pregnancy and opens in labour. Where its two kinds of surface cells meet (the transformation zone) is where long-lasting high-risk HPV infection can turn cells precancerous.","evidence":"Textbook anatomy. High-risk HPV is found in almost all cervical cancers (Walboomers 1999). Cervical screening (HPV testing and smear tests) finds precancerous changes so they can be treated before cancer forms.","pos":[0,0.879,-0.016]},{"id":"s_fallopian_tubes","col":"s","group":"Female reproductive","name":"Fallopian tubes","sub":"oviducts; one on each side","how":"Two thin tubes, about 10 cm long, running from the top corners of the womb out to each ovary, where finger-like ends catch the released egg. Fertilisation usually happens inside a tube; scarring from infection or endometriosis can block them or let a pregnancy lodge in the tube (ectopic pregnancy).","evidence":"Textbook anatomy.","pos":[0.045,0.925,0.008]},{"id":"s_breasts","col":"s","group":"Female reproductive","name":"Breasts","sub":"mammary glands","how":"Milk-making lobules and the ducts that carry milk to the nipple, set in fat over the chest muscle, with a 'tail' reaching toward the armpit. They grow at puberty under oestrogen, swell and can be tender before a period under progesterone, make milk after birth under prolactin, and let it down when the baby feeds under oxytocin. Lymph drains mainly to the armpit nodes. Men have a small amount of breast tissue and can also get breast cancer, though rarely.","evidence":"Textbook anatomy and physiology.","pos":[0.087,1.3,0.1]},{"id":"s_vagina","col":"s","group":"Female reproductive","name":"Vagina","sub":"birth canal","how":"A muscular, stretchy tube about 7 to 10 cm long running up and back from the vulva to the cervix, behind the bladder and urethra and in front of the rectum. Its lining is kept thick, moist and slightly acidic by oestrogen and by lactobacilli, which protect against infection. It stretches greatly in childbirth.","evidence":"Textbook anatomy.","pos":[0,0.858,0.004]},{"id":"s_urethra","col":"s","group":"Urinary tract","name":"Urethra","sub":"tube from the bladder to the outside","how":"The tube that carries urine out of the bladder, opened and closed by sphincter muscles in the pelvic floor. In women it is short (a few centimetres), which is why bladder infections are much more common in women. In men it is long: it runs through the prostate (where semen joins it), through the pelvic floor and along the penis, carrying both urine and semen.","evidence":"Textbook anatomy.","pos":[0,0.835,0.05]},{"id":"s_prostate","col":"s","group":"Male reproductive","name":"Prostate","sub":"walnut-sized gland under the bladder","how":"A walnut-sized gland sitting just below the bladder and in front of the rectum, wrapped around the first part of the urethra. It makes part of the fluid in semen, including the enzyme PSA, which thins semen; a little PSA leaks into the blood. Its growth depends on testosterone, which the gland turns into the stronger DHT. It slowly grows from middle age, and because it surrounds the urethra, growth can squeeze the urine flow.","evidence":"Textbook anatomy and physiology.","pos":[0,0.845,0.02]},{"id":"s_seminal_vesicles","col":"s","group":"Male reproductive","name":"Seminal vesicles","sub":"two pouches behind the bladder","how":"Two coiled pouches behind the bladder and above the prostate. They make most of the fluid in semen (rich in fructose sugar, which feeds sperm) and join the sperm ducts to empty through the prostate into the urethra.","evidence":"Textbook anatomy.","pos":[0,0.866,-0.005]},{"id":"s_penis","col":"s","group":"Male reproductive","name":"Penis","sub":"erectile tissue and urethra","how":"Contains three columns of spongy erectile tissue; the urethra runs through the lower one to carry both urine and semen. An erection happens when nerve signals release nitric oxide, which relaxes the small arteries and spongy tissue so blood rushes in and the outflow veins are squeezed shut.","evidence":"Textbook anatomy and physiology.","pos":[0,0.815,0.1]},{"id":"s_sperm_ducts","col":"s","group":"Male reproductive","name":"Epididymis & vas deferens","sub":"sperm storage and transport","how":"The epididymis is a tightly coiled tube on the back of each testis where sperm mature and are stored. The vas deferens carries them up through the groin, behind the bladder, to join the seminal vesicle duct inside the prostate. Cutting the vas is a vasectomy.","evidence":"Textbook anatomy.","pos":[0,0.8,0.075]},{"id":"s_renal_cortex","col":"s","group":"Kidney & nephron","name":"Renal cortex","sub":"outer layer of the kidney","how":"The outer, paler layer of the kidney, under a tough capsule. It holds the filters (glomeruli) and the twisted first and last parts of the tubules, and it dips down between the pyramids as the renal columns. Most blood flow into the kidney goes here.","evidence":"Textbook anatomy.","pos":[0.08,1.115,-0.026]},{"id":"s_renal_pyramids","col":"s","group":"Kidney & nephron","name":"Renal pyramids (medulla)","sub":"inner striped cones","how":"About 8 to 18 cone-shaped wedges that make up the inner kidney (the medulla). Their stripes are the loops of Henle and collecting ducts running side by side. The salt gradient built up here lets the kidney make concentrated urine and save water.","evidence":"Textbook anatomy and physiology.","pos":[0.07,1.113,-0.027]},{"id":"s_renal_papillae","col":"s","group":"Kidney & nephron","name":"Renal papillae","sub":"tips of the pyramids","how":"The rounded tip of each pyramid, pointing in toward the middle of the kidney. The collecting ducts open on its surface, so finished urine drips from here into a cup-shaped minor calyx. The tip has a thin blood supply and can die off (papillary necrosis), for example with long heavy painkiller use, diabetes or sickle cell disease.","evidence":"Textbook anatomy; papillary necrosis causes are textbook pathology.","pos":[0.065,1.112,-0.03]},{"id":"s_renal_calyces","col":"s","group":"Kidney & nephron","name":"Renal calyces","sub":"cups that collect urine","how":"Small cups (minor calyces) fit over each papilla and catch the urine; they join into two or three larger major calyces that empty into the renal pelvis. Their walls have smooth muscle that pushes urine on.","evidence":"Textbook anatomy.","pos":[0.047,1.108,-0.039]},{"id":"s_renal_pelvis","col":"s","group":"Kidney & nephron","name":"Renal pelvis","sub":"funnel into the ureter","how":"The funnel in the middle of the kidney where the calyces meet. It narrows at the hilum (the kidney's inner notch) into the ureter. A kidney infection (pyelonephritis) involves the pelvis and the kidney tissue; a blockage further down makes it swell (hydronephrosis).","evidence":"Textbook anatomy.","pos":[0.039,1.102,-0.042]},{"id":"s_renal_arteries","col":"s","group":"Kidney & nephron","name":"Renal arteries","sub":"blood supply from the aorta","how":"One artery from the aorta to each kidney, entering at the hilum and splitting into segmental branches. The kidneys get about a fifth of all the blood the heart pumps. Cells next to the filters sense the pressure in these arteries and release renin when it falls, which raises blood pressure; a narrowed renal artery can therefore cause high blood pressure.","evidence":"Textbook anatomy and physiology.","pos":[0.033,1.108,-0.04]},{"id":"s_renal_veins","col":"s","group":"Kidney & nephron","name":"Renal veins","sub":"drain to the inferior vena cava","how":"Carry cleaned blood from each kidney to the inferior vena cava. The left one is longer and passes in front of the aorta; the left testicular or ovarian vein drains into it.","evidence":"Textbook anatomy.","pos":[0.035,1.105,-0.046]},{"id":"s_renal_interlobar_vessels","col":"s","group":"Kidney & nephron","name":"Interlobar arteries and veins","sub":"run between the pyramids","how":"Branches of the renal artery (with matching veins) that run out through the renal columns between neighbouring pyramids toward the cortex.","evidence":"Textbook anatomy.","pos":[0.069,1.122,-0.028]},{"id":"s_renal_arcuate_vessels","col":"s","group":"Kidney & nephron","name":"Arcuate arteries and veins","sub":"arch over the pyramid bases","how":"Arching vessels along the border between the cortex and the medulla, over the base of each pyramid. Small interlobular branches rise from them into the cortex and feed the filters.","evidence":"Textbook anatomy.","pos":[0.074,1.127,-0.025]},{"id":"s_nephron","col":"s","group":"Kidney & nephron","name":"Nephrons","sub":"the kidney's filtering units","how":"About a million per kidney. Each is a filter (glomerulus) followed by a long tube that takes back almost everything useful and adds some wastes: proximal tubule, loop of Henle, distal tubule, then a shared collecting duct. Together they filter about 180 litres of blood plasma a day and return all but one to two litres. Lost nephrons are not replaced; the rest work harder.","evidence":"Textbook anatomy and physiology.","pos":[0.067,1.135,-0.027]},{"id":"s_glomeruli","col":"s","group":"Kidney & nephron","name":"Glomeruli","sub":"the filters","how":"A tiny knot of capillaries inside a cup (Bowman's capsule), each about a fifth of a millimetre across, all in the cortex. Blood pressure pushes water, salts, sugar and wastes through a three-layer sieve while keeping blood cells and most proteins in. The filtering rate (GFR) is the main measure of kidney function. Damage lets protein leak into the urine, which is an early sign of diabetic and high-blood-pressure kidney disease.","evidence":"Textbook anatomy and physiology.","pos":[0.066,1.145,-0.025]},{"id":"s_renal_tubules","col":"s","group":"Kidney & nephron","name":"Renal tubules (proximal and distal)","sub":"take back salt, sugar and water","how":"The coiled tubes in the cortex before and after the loop of Henle. The proximal tubule takes back about two thirds of the filtered salt and water and all the sugar and amino acids, and makes active vitamin D; it uses a lot of energy, so it is the part most hurt by low blood flow and by toxins such as cadmium, mercury and some medicines. The distal tubule fine-tunes sodium, potassium, calcium and acid under hormones such as aldosterone and parathyroid hormone.","evidence":"Textbook anatomy and physiology.","pos":[0.082,1.082,-0.031]},{"id":"s_loop_of_henle","col":"s","group":"Kidney & nephron","name":"Loop of Henle","sub":"builds the salt gradient","how":"A hairpin of the tubule that dips down into a pyramid and back up. Its descending side lets water out and its ascending side pumps salt out, building a salty gradient in the medulla that lets the kidney make concentrated urine. Loop water pills (furosemide-type diuretics) work here.","evidence":"Textbook anatomy and physiology.","pos":[0.065,1.13,-0.03]},{"id":"s_collecting_ducts","col":"s","group":"Kidney & nephron","name":"Collecting ducts","sub":"final water and potassium control","how":"Many nephrons drain into each collecting duct, which runs down through a pyramid and opens at the papilla. Vasopressin inserts water channels here so water is pulled back into the salty medulla; aldosterone makes it keep sodium and let potassium go. Lithium can blunt the vasopressin response here, causing large amounts of dilute urine.","evidence":"Textbook anatomy and physiology.","pos":[0.069,1.1,-0.034]},{"id":"s_heart_ra","col":"s","group":"Heart","name":"Right atrium","sub":"receives blood from the body","how":"The upper right chamber. Used blood from the body returns into it through the two large veins (venae cavae) and the heart's own veins (coronary sinus). Its wall holds the heart's natural pacemaker (the sinus node). It squeezes blood down through the tricuspid valve into the right ventricle.","evidence":"Textbook anatomy and physiology.","pos":[-0.032,1.298,0.03]},{"id":"s_heart_rv","col":"s","group":"Heart","name":"Right ventricle","sub":"pumps blood to the lungs","how":"The lower right chamber, a thin-walled crescent wrapped round the front of the left ventricle. It pumps blood through the pulmonary valve into the lung arteries at low pressure, so it can fail when lung pressure rises (for example after clots in the lungs).","evidence":"Textbook anatomy and physiology.","pos":[0.023,1.279,0.048]},{"id":"s_heart_la","col":"s","group":"Heart","name":"Left atrium","sub":"receives blood from the lungs","how":"The upper left chamber at the back of the heart. Four lung veins bring oxygen-rich blood into it, and it passes through the mitral valve to the left ventricle. It stretches when blood pressure is high or the mitral valve leaks, and a stretched left atrium is where atrial fibrillation most often starts; clots form in its small pouch (the left atrial appendage).","evidence":"Textbook anatomy and physiology.","pos":[0.008,1.306,-0.003]},{"id":"s_heart_lv","col":"s","group":"Heart","name":"Left ventricle","sub":"the main pump to the body","how":"The lower left chamber with the thickest wall (about a centimetre). It pumps oxygen-rich blood through the aortic valve into the aorta at full blood pressure. Long-term high blood pressure thickens it; a heart attack scars it; and when it pumps or fills poorly the result is heart failure.","evidence":"Textbook anatomy and physiology.","pos":[0.047,1.27,0.029]},{"id":"s_valve_mitral","col":"s","group":"Heart","name":"Mitral valve","sub":"left atrium to left ventricle","how":"A two-leaflet valve tethered by cords to muscles in the left ventricle, so it shuts tight when the ventricle squeezes. It can leak (regurgitation) or narrow (stenosis, most often after rheumatic fever).","evidence":"Textbook anatomy and physiology.","pos":[0.028,1.29,0.006]},{"id":"s_valve_tricuspid","col":"s","group":"Heart","name":"Tricuspid valve","sub":"right atrium to right ventricle","how":"A three-leaflet valve between the right-side chambers. It usually leaks because the right ventricle has stretched, for example from high lung pressure.","evidence":"Textbook anatomy and physiology.","pos":[-0.02,1.277,0.044]},{"id":"s_valve_aortic","col":"s","group":"Heart","name":"Aortic valve","sub":"left ventricle to aorta","how":"Three half-moon cusps at the exit of the left ventricle; the two main heart arteries start just above it. With age it can stiffen with calcium and narrow (aortic stenosis), making the ventricle work harder.","evidence":"Textbook anatomy and physiology.","pos":[0.008,1.288,0.032]},{"id":"s_valve_pulmonary","col":"s","group":"Heart","name":"Pulmonary valve","sub":"right ventricle to lung arteries","how":"Three half-moon cusps at the exit of the right ventricle into the lung (pulmonary) trunk. Problems are usually present from birth.","evidence":"Textbook anatomy and physiology.","pos":[0.02,1.33,0.054]},{"id":"s_coronary_arteries","col":"s","group":"Heart","name":"Coronary arteries","sub":"the heart's own blood supply","how":"Two arteries leave the aorta just above the aortic valve and run in grooves on the heart's surface: the left main splits into the front artery down the septum (LAD) and the circumflex round the left side; the right coronary runs round the right side to the back. Fatty plaque narrowing them causes angina, and a clot on a plaque causes a heart attack.","evidence":"Textbook anatomy and physiology.","pos":[0.047,1.29,0.054]},{"id":"s_conduction_system","col":"s","group":"Heart","name":"Heart's electrical system","sub":"sinus node, AV node, bundle branches","how":"The sinus node in the right atrium fires each beat; the signal spreads over both atria, is delayed at the AV node so the ventricles can fill, then runs down the bundle of His and its left and right branches to fine Purkinje fibres so the ventricles squeeze from the tip upward. Autonomic nerves speed or slow the sinus node. Faults cause slow rhythms (heart block), fast rhythms, or atrial fibrillation.","evidence":"Textbook anatomy and physiology.","pos":[-0.037,1.322,0.042]},{"id":"mu_temporalis","col":"s","group":"Muscles","name":"Temporalis","sub":"fan-shaped chewing muscle at the temple","how":"Origin: the wide shallow hollow on the side of the skull (temporal fossa). Insertion: the coronoid process of the lower jaw, passing under the cheekbone arch. Action: Closes the jaw and pulls it backward; you can feel it tighten at the temple when you clench. Nerve: Deep temporal branches of the mandibular nerve (from the trigeminal nerve, cranial nerve V). Blood supply: Deep temporal branches of the maxillary artery and the superficial temporal artery. There is one on each side. Tension and clenching here are a common source of temple headaches and jaw (TMJ) pain. Chewing gets slower and weaker in Parkinson's, which adds to long mealtimes.","evidence":"Textbook anatomy","pos":[0.065,1.658,0.009]},{"id":"mu_masseter","col":"s","group":"Muscles","name":"Masseter","sub":"the main chewing muscle at the angle of the jaw","how":"Origin: the cheekbone and its arch (zygomatic arch). Insertion: the outer surface of the angle and lower branch of the jaw. Action: Closes the jaw with force; it is one of the strongest muscles for its size. Nerve: Masseteric nerve (mandibular branch of the trigeminal nerve). Blood supply: Masseteric branch of the maxillary artery and the facial artery. There is one on each side. Night-time teeth grinding overworks it and can cause jaw pain and worn teeth. Slow, weak chewing in Parkinson's leaves food in the mouth longer, which matters for swallowing safety.","evidence":"Textbook anatomy","pos":[0.051,1.593,0.016]},{"id":"mu_medial_pterygoid","col":"s","group":"Muscles","name":"Medial pterygoid","sub":"deep chewing muscle inside the jaw","how":"Origin: the inner side of the lateral pterygoid plate at the base of the skull. Insertion: the inner surface of the angle of the jaw. Action: Closes the jaw and helps grind food from side to side, working as a sling with the masseter. Nerve: Nerve to medial pterygoid (mandibular branch of the trigeminal nerve). Blood supply: Pterygoid branches of the maxillary artery. There is one on each side. Spasm here limits how wide the mouth opens, for example after a dental injection.","evidence":"Textbook anatomy","pos":[0.03,1.584,0.012]},{"id":"mu_lateral_pterygoid","col":"s","group":"Muscles","name":"Lateral pterygoid","sub":"the jaw-opening muscle in front of the jaw joint","how":"Origin: the outer side of the lateral pterygoid plate and the underside of the skull. Insertion: the neck of the jaw bone and the disc of the jaw joint. Action: Pulls the jaw forward and opens the mouth; acting on one side swings the jaw to the other side for grinding. Nerve: Nerve to lateral pterygoid (mandibular branch of the trigeminal nerve). Blood supply: Pterygoid branches of the maxillary artery. There is one on each side. It steers the disc of the jaw joint, so it is involved in clicking jaws and TMJ disorders.","evidence":"Textbook anatomy","pos":[0.038,1.608,0.016]},{"id":"mu_buccinator","col":"s","group":"Muscles","name":"Buccinator","sub":"the cheek muscle","how":"Origin: the outer jaw bones beside the back teeth and the band behind the last molar (pterygomandibular raphe). Insertion: the corner of the mouth, blending with the lip muscle. Action: Presses the cheek against the teeth to keep food between them while chewing, and blows air out (as in a trumpet). Nerve: Buccal branches of the facial nerve (cranial nerve VII). Blood supply: Buccal branch of the maxillary artery and the facial artery. There is one on each side. When it is weak, as after a facial-nerve palsy, food collects in the cheek. Reduced cheek and lip movement in Parkinson's adds to food pocketing.","evidence":"Textbook anatomy","pos":[0.031,1.569,0.049]},{"id":"mu_zygomaticus_major","col":"s","group":"Muscles","name":"Zygomaticus major","sub":"the smiling muscle","how":"Origin: the outer surface of the cheekbone. Insertion: the corner of the mouth. Action: Pulls the corner of the mouth up and out, as in a smile. Nerve: Zygomatic and buccal branches of the facial nerve. Blood supply: Superior labial branch of the facial artery. There is one on each side. A reduced, slower smile is part of the masked face (hypomimia) of Parkinson's; it is one of the easiest signs for others to notice.","evidence":"Textbook anatomy","pos":[0.035,1.588,0.073]},{"id":"mu_levator_labii_superioris","col":"s","group":"Muscles","name":"Levator labii superioris","sub":"lifts the upper lip","how":"Origin: the lower rim of the eye socket, above the opening for the infraorbital nerve. Insertion: the skin and muscle of the upper lip. Action: Raises the upper lip and deepens the fold from nose to mouth. Nerve: Buccal branches of the facial nerve. Blood supply: Facial artery and the infraorbital artery. There is one on each side. Like the other expression muscles it moves less in the masked face of Parkinson's.","evidence":"Textbook anatomy","pos":[0.015,1.595,0.085]},{"id":"mu_depressor_anguli_oris","col":"s","group":"Muscles","name":"Depressor anguli oris","sub":"turns the corners of the mouth down","how":"Origin: the outer surface of the lower jaw below the canine and premolar teeth. Insertion: the corner of the mouth. Action: Pulls the corner of the mouth down and out, as in a frown. Nerve: Marginal mandibular and buccal branches of the facial nerve. Blood supply: Inferior labial branch of the facial artery. There is one on each side. Its branch of the facial nerve runs close to the jaw line and can be injured in neck surgery, giving a lopsided lower lip.","evidence":"Textbook anatomy","pos":[0.027,1.547,0.081]},{"id":"mu_orbicularis_oris","col":"s","group":"Muscles","name":"Orbicularis oris","sub":"the ring muscle of the lips","how":"Origin: muscle fibres from the surrounding face muscles and the jaw bones near the midline. Insertion: the skin and lining of the lips, forming a ring. Action: Closes and purses the lips, and seals the mouth when chewing, swallowing and speaking. Nerve: Buccal and marginal mandibular branches of the facial nerve. Blood supply: Superior and inferior labial branches of the facial artery. A weak lip seal, together with less frequent swallowing, contributes to drooling in Parkinson's.","evidence":"Textbook anatomy","pos":[-0.001,1.573,0.087]},{"id":"mu_orbicularis_oculi","col":"s","group":"Muscles","name":"Orbicularis oculi","sub":"the ring muscle round the eye","how":"Origin: the inner rim of the eye socket and the inner eyelid ligament. Insertion: the skin around the eye and the outer eyelid band, forming a ring. Action: Closes the eyelids: gently for blinking and sleep, tightly for squinting; it also helps tears drain. Nerve: Temporal and zygomatic branches of the facial nerve. Blood supply: Branches of the facial, superficial temporal and ophthalmic arteries. There is one on each side. Blinking is less frequent in Parkinson's, which dries the eye surface; involuntary forced closure of this muscle is blepharospasm.","evidence":"Textbook anatomy","pos":[0.029,1.62,0.08]},{"id":"mu_frontalis","col":"s","group":"Muscles","name":"Frontalis","sub":"the forehead muscle","how":"Origin: the scalp's tendon sheet (galea aponeurotica). Insertion: the skin of the eyebrows and forehead. Action: Raises the eyebrows and wrinkles the forehead. Nerve: Temporal branches of the facial nerve. Blood supply: Supraorbital and supratrochlear arteries and the superficial temporal artery. There is one on each side. A still forehead is part of the masked face of Parkinson's; the forehead is also spared in a stroke-related facial droop but not in Bell's palsy, which helps doctors tell them apart.","evidence":"Textbook anatomy","pos":[0.028,1.685,0.081]},{"id":"mu_occipitalis","col":"s","group":"Muscles","name":"Occipitalis","sub":"the back-of-head scalp muscle","how":"Origin: the upper ridge at the back of the skull (superior nuchal line). Insertion: the scalp's tendon sheet (galea aponeurotica). Action: Pulls the scalp backward, working with the frontalis. Nerve: Posterior auricular branch of the facial nerve. Blood supply: Occipital artery. There is one on each side. Tightness in the muscles at the back of the head and neck is a common source of tension-type headache.","evidence":"Textbook anatomy","pos":[0.031,1.658,-0.1]},{"id":"mu_platysma","col":"s","group":"Muscles","name":"Platysma","sub":"thin sheet of muscle in the skin of the neck","how":"Origin: the skin and fascia over the upper chest and shoulder. Insertion: the lower border of the jaw and the skin of the lower face. Action: Tenses the skin of the neck and helps pull the corners of the mouth down. Nerve: Cervical branch of the facial nerve. Blood supply: Branches of the facial artery and the submental artery. There is one on each side. It thins with age, giving vertical neck bands; surgeons repair it in neck operations.","evidence":"Textbook anatomy","pos":[0.042,1.466,0.036]},{"id":"mu_sternocleidomastoid","col":"s","group":"Muscles","name":"Sternocleidomastoid","sub":"the long strap muscle on each side of the neck","how":"Origin: the top of the breastbone and the inner third of the collarbone. Insertion: the bony bump behind the ear (mastoid process). Action: On one side, tilts the head to the same side and turns the face to the other; both together bend the neck forward and help lift the ribs in hard breathing. Nerve: Accessory nerve (cranial nerve XI), with feeling from the upper cervical nerves. Blood supply: Occipital and superior thyroid arteries. There is one on each side. Spasm here causes a twisted neck (torticollis, a form of dystonia). The forward-bent head posture of Parkinson's (antecollis) involves the neck flexors, while weak neck extensors cannot hold the head up.","evidence":"Textbook anatomy","pos":[0.04,1.523,0.007]},{"id":"mu_scalenes","col":"s","group":"Muscles","name":"Scalene muscles","sub":"three muscles on the side of the neck","how":"Origin: the side processes of the neck vertebrae C2 to C7. Insertion: the first and second ribs. Action: Lift the top ribs when breathing hard and bend the neck to the side. Nerve: Branches of the cervical spinal nerves (C3 to C8). Blood supply: Ascending and transverse cervical arteries. There is one on each side. The nerves to the arm (brachial plexus) and the subclavian artery pass between two of them, so tight or extra-thick scalenes can squeeze these (thoracic outlet syndrome).","evidence":"Textbook anatomy","pos":[0.043,1.497,-0.002]},{"id":"mu_sternohyoid","col":"s","group":"Muscles","name":"Sternohyoid","sub":"strap muscle in the front of the neck","how":"Origin: the back of the top of the breastbone and inner end of the collarbone. Insertion: the hyoid bone (the U-shaped bone above the voice box). Action: Pulls the hyoid bone down after it has been raised in swallowing and speaking. Nerve: Ansa cervicalis (from cervical nerves C1 to C3). Blood supply: Superior thyroid artery. There is one on each side. It is one of the strap muscles that move the voice box and hyoid during swallowing; slowed, smaller swallowing movements are common in Parkinson's.","evidence":"Textbook anatomy","pos":[0.004,1.487,0.03]},{"id":"mu_splenius_capitis","col":"s","group":"Muscles","name":"Splenius capitis","sub":"bandage-like muscle at the back of the neck","how":"Origin: the lower half of the neck ligament (ligamentum nuchae) and the spines of C7 to T3. Insertion: the mastoid process and the side of the back of the skull. Action: Both sides together tilt the head back; one side turns the head to the same side. Nerve: Back branches of the middle cervical spinal nerves. Blood supply: Occipital artery and muscular branches of the aorta's neck branches. There is one on each side. It holds the head up against gravity. Neck extensors that cannot hold the head up give a dropped head; whiplash often strains it.","evidence":"Textbook anatomy","pos":[0.022,1.541,-0.061]},{"id":"mu_levator_scapulae","col":"s","group":"Muscles","name":"Levator scapulae","sub":"lifts the shoulder blade","how":"Origin: the side processes of the top four neck vertebrae (C1 to C4). Insertion: the upper inner corner of the shoulder blade. Action: Lifts the shoulder blade and tips it so the shoulder drops, and helps bend the neck to the side. Nerve: Dorsal scapular nerve (C5) and branches of C3 and C4. Blood supply: Dorsal scapular and transverse cervical arteries. There is one on each side. A very common site of knotted, painful neck tension after desk work or sleeping in an awkward position.","evidence":"Textbook anatomy","pos":[0.051,1.49,-0.06]},{"id":"mu_trapezius_upper","col":"s","group":"Muscles","name":"Trapezius (upper fibres)","sub":"the top part of the large diamond muscle of the upper back","how":"Origin: the base of the skull and the neck ligament. Insertion: the outer third of the collarbone. Action: Shrugs the shoulders and helps rotate the shoulder blade upward when lifting the arm overhead. Nerve: Accessory nerve (cranial nerve XI), with feeling from C3 and C4. Blood supply: Transverse cervical artery and the occipital artery. There is one on each side. The upper trapezius is the classic site of neck-and-shoulder tension; rigidity here adds to neck and shoulder pain in Parkinson's.","evidence":"Textbook anatomy","pos":[0.08,1.489,-0.045]},{"id":"mu_trapezius_middle","col":"s","group":"Muscles","name":"Trapezius (middle fibres)","sub":"the middle part of the trapezius","how":"Origin: the spines of the lowest neck and upper chest vertebrae (C7 to T3). Insertion: the bony ridge across the shoulder blade (spine of scapula) and the acromion. Action: Pulls the shoulder blades together toward the spine. Nerve: Accessory nerve (cranial nerve XI). Blood supply: Transverse cervical artery. There is one on each side. Weakness lets the shoulders round forward, part of a stooped, slumped posture.","evidence":"Textbook anatomy","pos":[0.069,1.431,-0.077]},{"id":"mu_trapezius_lower","col":"s","group":"Muscles","name":"Trapezius (lower fibres)","sub":"the lower part of the trapezius","how":"Origin: the spines of the middle and lower chest vertebrae (T4 to T12). Insertion: the inner end of the spine of the shoulder blade. Action: Pulls the shoulder blade down and helps rotate it upward when lifting the arm. Nerve: Accessory nerve (cranial nerve XI). Blood supply: Dorsal scapular artery and branches of the back (intercostal) arteries. There is one on each side. Working against rounded shoulders, it is a common target of posture exercises. Damage to the accessory nerve in neck surgery weakens the whole trapezius and drops the shoulder.","evidence":"Textbook anatomy","pos":[0.043,1.347,-0.106]},{"id":"mu_rhomboid_minor","col":"s","group":"Muscles","name":"Rhomboid minor","sub":"small muscle between the spine and shoulder blade","how":"Origin: the spines of C7 and T1. Insertion: the inner edge of the shoulder blade at the level of its spine. Action: Pulls the shoulder blade toward the spine and holds it against the chest wall. Nerve: Dorsal scapular nerve (C5). Blood supply: Dorsal scapular artery. There is one on each side. Pain between the shoulder blades from long hours hunched over a desk often comes from here.","evidence":"Textbook anatomy","pos":[0.039,1.425,-0.085]},{"id":"mu_rhomboid_major","col":"s","group":"Muscles","name":"Rhomboid major","sub":"the larger rhomboid, below rhomboid minor","how":"Origin: the spines of T2 to T5. Insertion: the inner edge of the shoulder blade below its spine. Action: Pulls the shoulder blade toward the spine and helps rotate it downward. Nerve: Dorsal scapular nerve (C5). Blood supply: Dorsal scapular artery. There is one on each side. Like the middle trapezius it braces the shoulders back; weakness lets them round forward.","evidence":"Textbook anatomy","pos":[0.044,1.356,-0.096]},{"id":"mu_pectoralis_major","col":"s","group":"Muscles","name":"Pectoralis major","sub":"the large fan-shaped chest muscle","how":"Origin: the inner half of the collarbone, the breastbone, the upper rib cartilages and the abdominal sheath. Insertion: the outer lip of the groove at the top of the upper-arm bone. Action: Pulls the arm across the body and turns it inward; its lower part pulls a raised arm down. Nerve: Medial and lateral pectoral nerves (C5 to T1). Blood supply: Pectoral branch of the thoraco-acromial artery and branches of the internal thoracic artery. There is one on each side. A shortened, stiff chest muscle pulls the shoulders forward and adds to a stooped posture, which is common in Parkinson's. It can tear in heavy bench pressing.","evidence":"Textbook anatomy","pos":[0.125,1.359,0.032]},{"id":"mu_pectoralis_minor","col":"s","group":"Muscles","name":"Pectoralis minor","sub":"thin muscle under the pectoralis major","how":"Origin: the third to fifth ribs near their cartilages. Insertion: the coracoid process (a hook at the front of the shoulder blade). Action: Pulls the shoulder blade forward and down, and lifts the ribs in hard breathing. Nerve: Medial pectoral nerve (C8, T1). Blood supply: Pectoral branch of the thoraco-acromial artery. There is one on each side. When tight it tips the shoulder blade forward (rounded shoulders); the nerves and vessels to the arm pass beneath it.","evidence":"Textbook anatomy","pos":[0.106,1.384,0.048]},{"id":"mu_serratus_anterior","col":"s","group":"Muscles","name":"Serratus anterior","sub":"saw-toothed muscle on the side of the ribs","how":"Origin: the outer surfaces of the upper eight or nine ribs. Insertion: the inner edge of the shoulder blade, on its front surface. Action: Pulls the shoulder blade forward around the chest (as in punching) and rotates it up so the arm can go overhead. Nerve: Long thoracic nerve (C5 to C7). Blood supply: Lateral thoracic and thoracodorsal arteries. There is one on each side. If its nerve is injured (for example in armpit surgery) the shoulder blade sticks out like a wing and lifting the arm overhead becomes hard.","evidence":"Textbook anatomy","pos":[0.126,1.309,-0.042]},{"id":"mu_subclavius","col":"s","group":"Muscles","name":"Subclavius","sub":"small muscle under the collarbone","how":"Origin: the first rib and its cartilage. Insertion: the underside of the middle of the collarbone. Action: Steadies the collarbone and pulls it down toward the first rib. Nerve: Nerve to subclavius (C5, C6). Blood supply: Clavicular branch of the thoraco-acromial artery. There is one on each side. It cushions the vessels and nerves to the arm when the collarbone breaks.","evidence":"Textbook anatomy","pos":[0.067,1.426,0.044]},{"id":"mu_rectus_abdominis","col":"s","group":"Muscles","name":"Rectus abdominis","sub":"the 'six-pack' muscle down the front of the belly","how":"Origin: the pubic bone and the joint between the pubic bones. Insertion: the cartilages of the fifth to seventh ribs and the lower tip of the breastbone. Action: Bends the trunk forward, pulls the pelvis up and raises pressure in the belly for coughing and straining. Nerve: Lower intercostal nerves (T7 to T11) and the subcostal nerve (T12). Blood supply: Superior and inferior epigastric arteries. There is one on each side. The severely bent-forward trunk (camptocormia) seen in some people with Parkinson's reflects an imbalance between the trunk flexors, including this muscle, and the back extensors. Its two halves can separate after pregnancy.","evidence":"Textbook anatomy","pos":[0.041,1.1,0.093]},{"id":"mu_external_oblique","col":"s","group":"Muscles","name":"External oblique","sub":"the outer flat muscle on the side of the belly","how":"Origin: the outer surfaces of the lower eight ribs. Insertion: the iliac crest, the pubic bone and the central abdominal seam (linea alba) through a broad tendon sheet. Action: Bends and twists the trunk, and squeezes the belly. Nerve: Lower intercostal nerves (T7 to T11), subcostal nerve and the iliohypogastric nerve. Blood supply: Lower intercostal, subcostal and deep circumflex iliac arteries. There is one on each side. Its tendon sheet forms the front wall of the groin canal, so it is part of the anatomy of an inguinal hernia. Trunk twisting is reduced in Parkinson's, which makes turning in bed harder.","evidence":"Textbook anatomy","pos":[0.116,1.114,0.055]},{"id":"mu_internal_oblique","col":"s","group":"Muscles","name":"Internal oblique","sub":"the middle flat muscle of the belly wall","how":"Origin: the iliac crest, the band in the groin (inguinal ligament) and the low-back fascia. Insertion: the lower ribs and, through a tendon sheet, the central abdominal seam. Action: Bends and twists the trunk (to the same side) and squeezes the belly. Nerve: Lower intercostal nerves, iliohypogastric and ilio-inguinal nerves. Blood supply: Lower intercostal, superior and inferior epigastric and deep circumflex iliac arteries. There is one on each side. Its lower fibres form the roof of the groin canal; weakness there is part of how inguinal hernias form.","evidence":"Textbook anatomy","pos":[0.09,1.048,0.068]},{"id":"mu_transversus_abdominis","col":"s","group":"Muscles","name":"Transversus abdominis","sub":"the deepest belly muscle, running round like a corset","how":"Origin: the inner surfaces of the lower six rib cartilages, the low-back fascia, the iliac crest and inguinal ligament. Insertion: the central abdominal seam and the pubic bone through a tendon sheet. Action: Tightens the belly wall like a corset, raising pressure inside it and helping to steady the lower spine. Nerve: Lower intercostal nerves, iliohypogastric and ilio-inguinal nerves. Blood supply: Lower intercostal, deep circumflex iliac and epigastric arteries. There is one on each side. Core-stability exercises for back pain and balance target this deep muscle.","evidence":"Textbook anatomy","pos":[0.112,1.08,0.031]},{"id":"mu_iliocostalis","col":"s","group":"Muscles","name":"Iliocostalis","sub":"the outer column of the back-straightening muscles (erector spinae)","how":"Origin: the back of the iliac crest, the sacrum and the angles of the ribs. Insertion: the angles of the ribs higher up and the side processes of the neck vertebrae. Action: Straightens and bends the spine sideways, and holds the trunk upright. Nerve: Back branches of the spinal nerves along its length. Blood supply: Back branches of the intercostal and lumbar arteries. There is one on each side. The erector spinae hold you upright; when they are weak or cannot overcome stiff trunk flexors the trunk bends forward, as in the stooped posture and camptocormia of Parkinson's. Back strains often involve this group.","evidence":"Textbook anatomy","pos":[0.062,1.205,-0.078]},{"id":"mu_longissimus","col":"s","group":"Muscles","name":"Longissimus","sub":"the middle and longest column of the erector spinae","how":"Origin: the sacrum, the iliac crest and the side processes of lower vertebrae. Insertion: the side processes of higher vertebrae, the ribs and the mastoid process of the skull. Action: Straightens and bends the spine sideways, and helps hold the head up. Nerve: Back branches of the spinal nerves. Blood supply: Back branches of the intercostal and lumbar arteries. There is one on each side. The main postural extensor of the back; stooped posture in Parkinson's involves this group. Low back strain often affects it.","evidence":"Textbook anatomy","pos":[0.026,1.199,-0.074]},{"id":"mu_spinalis","col":"s","group":"Muscles","name":"Spinalis","sub":"the innermost column of the erector spinae, next to the spine","how":"Origin: the spines of the upper lumbar and lower chest vertebrae. Insertion: the spines of higher chest vertebrae. Action: Straightens the spine. Nerve: Back branches of the spinal nerves. Blood supply: Back branches of the intercostal arteries. There is one on each side. It works with the other erector spinae to hold the trunk upright.","evidence":"Textbook anatomy","pos":[0.015,1.221,-0.077]},{"id":"mu_multifidus","col":"s","group":"Muscles","name":"Multifidus","sub":"deep short muscles packed beside the spine","how":"Origin: the sacrum, the iliac crest and the side processes of the vertebrae. Insertion: the spines of vertebrae two to four levels higher. Action: Steadies each spinal joint and straightens and twists the spine. Nerve: Back branches of the spinal nerves. Blood supply: Back branches of the lumbar and intercostal arteries. There is one on each side. It is thickest in the low back, where it wastes and fills with fat in long-lasting low back pain; retraining it is a focus of back rehabilitation.","evidence":"Textbook anatomy","pos":[0.018,1.076,-0.061]},{"id":"mu_quadratus_lumborum","col":"s","group":"Muscles","name":"Quadratus lumborum","sub":"the square muscle of the low back","how":"Origin: the back of the iliac crest. Insertion: the twelfth rib and the side processes of L1 to L4. Action: Bends the trunk to the side, hitches the hip up, and holds the twelfth rib steady when breathing in. Nerve: Branches of the subcostal nerve and L1 to L4. Blood supply: Lumbar and subcostal arteries. There is one on each side. A common source of one-sided low back pain; it is also involved in leaning to one side.","evidence":"Textbook anatomy","pos":[0.064,1.065,-0.043]},{"id":"mu_deltoid","col":"s","group":"Muscles","name":"Deltoid","sub":"the rounded shoulder-cap muscle","how":"Origin: the outer third of the collarbone, the acromion and the spine of the shoulder blade. Insertion: the deltoid tuberosity on the outer side of the upper-arm bone. Action: Lifts the arm out to the side (after the first few degrees); its front part lifts it forward and its back part pulls it back. Nerve: Axillary nerve (C5, C6). Blood supply: Posterior circumflex humeral artery and the deltoid branch of the thoraco-acromial artery. There is one on each side. The axillary nerve can be damaged in a dislocated shoulder or a broken upper-arm neck, weakening the arm. Shoulder stiffness and pain is a common early complaint in Parkinson's.","evidence":"Textbook anatomy","pos":[0.215,1.373,-0.017]},{"id":"mu_supraspinatus","col":"s","group":"Muscles","name":"Supraspinatus","sub":"rotator cuff muscle on top of the shoulder blade","how":"Origin: the hollow above the spine of the shoulder blade (supraspinous fossa). Insertion: the top facet of the greater tubercle of the upper-arm bone. Action: Starts lifting the arm out to the side and holds the ball of the shoulder in its socket. Nerve: Suprascapular nerve (C5, C6). Blood supply: Suprascapular artery. There is one on each side. Its tendon passes under the acromion and is the most often torn or inflamed rotator cuff tendon, especially in older people and after falls on the arm.","evidence":"Textbook anatomy","pos":[0.137,1.426,-0.055]},{"id":"mu_infraspinatus","col":"s","group":"Muscles","name":"Infraspinatus","sub":"rotator cuff muscle on the back of the shoulder blade","how":"Origin: the hollow below the spine of the shoulder blade (infraspinous fossa). Insertion: the middle facet of the greater tubercle of the upper-arm bone. Action: Turns the arm outward and holds the ball of the shoulder in its socket. Nerve: Suprascapular nerve (C5, C6). Blood supply: Suprascapular and circumflex scapular arteries. There is one on each side. Part of the rotator cuff; it is often involved in cuff tears along with supraspinatus.","evidence":"Textbook anatomy","pos":[0.131,1.374,-0.077]},{"id":"mu_teres_minor","col":"s","group":"Muscles","name":"Teres minor","sub":"small rotator cuff muscle below infraspinatus","how":"Origin: the upper outer edge of the shoulder blade. Insertion: the lowest facet of the greater tubercle of the upper-arm bone. Action: Turns the arm outward and holds the ball of the shoulder in its socket. Nerve: Axillary nerve (C5, C6). Blood supply: Circumflex scapular and posterior circumflex humeral arteries. There is one on each side. Part of the rotator cuff; it shares its nerve with the deltoid.","evidence":"Textbook anatomy","pos":[0.141,1.354,-0.075]},{"id":"mu_subscapularis","col":"s","group":"Muscles","name":"Subscapularis","sub":"rotator cuff muscle on the front of the shoulder blade","how":"Origin: the front (rib-side) surface of the shoulder blade. Insertion: the lesser tubercle at the front of the upper-arm bone. Action: Turns the arm inward and holds the front of the shoulder joint steady. Nerve: Upper and lower subscapular nerves (C5 to C7). Blood supply: Subscapular artery. There is one on each side. The largest rotator cuff muscle; it guards against the shoulder dislocating forward.","evidence":"Textbook anatomy","pos":[0.131,1.367,-0.041]},{"id":"mu_teres_major","col":"s","group":"Muscles","name":"Teres major","sub":"thick round muscle below the shoulder blade","how":"Origin: the lower outer corner of the back of the shoulder blade. Insertion: the inner lip of the groove at the top of the upper-arm bone. Action: Pulls the arm down and back and turns it inward, working with latissimus dorsi. Nerve: Lower subscapular nerve (C5 to C7). Blood supply: Circumflex scapular and thoracodorsal arteries. There is one on each side. It forms the lower edge of the gaps through which nerves and vessels reach the back of the arm.","evidence":"Textbook anatomy","pos":[0.137,1.324,-0.063]},{"id":"mu_latissimus_dorsi","col":"s","group":"Muscles","name":"Latissimus dorsi","sub":"the broad back muscle","how":"Origin: the spines of the lower six chest vertebrae, the low-back fascia, the iliac crest and the lower ribs. Insertion: the floor of the groove at the top of the upper-arm bone. Action: Pulls the arm down and back and turns it inward, as in climbing, rowing or pushing up from a chair. Nerve: Thoracodorsal nerve (C6 to C8). Blood supply: Thoracodorsal artery. There is one on each side. It is used to push up from chair arms and in transfers; surgeons often use it as a flap to rebuild a breast after mastectomy.","evidence":"Textbook anatomy","pos":[0.139,1.242,-0.043]},{"id":"mu_coracobrachialis","col":"s","group":"Muscles","name":"Coracobrachialis","sub":"small muscle on the inner upper arm","how":"Origin: the coracoid process of the shoulder blade. Insertion: the middle of the inner surface of the upper-arm bone. Action: Helps bend the shoulder (lift the arm forward) and bring the arm in. Nerve: Musculocutaneous nerve (C5 to C7), which pierces it. Blood supply: Muscular branches of the brachial artery. There is one on each side. A landmark for the nerves and artery of the upper arm, which run just beside it.","evidence":"Textbook anatomy","pos":[0.181,1.338,0.003]},{"id":"mu_biceps_brachii","col":"s","group":"Muscles","name":"Biceps brachii","sub":"the two-headed muscle at the front of the upper arm","how":"Origin: long head: just above the shoulder socket; short head: the coracoid process of the shoulder blade. Insertion: the radial tuberosity on the forearm bone below the elbow, and the forearm fascia. Action: Bends the elbow and turns the palm up (supination); also helps lift the arm forward. Nerve: Musculocutaneous nerve (C5, C6). Blood supply: Branches of the brachial artery. There is one on each side. The long-head tendon can rupture in older people, leaving a 'Popeye' bulge; rigidity in Parkinson's is often felt as resistance when the elbow is moved passively.","evidence":"Textbook anatomy","pos":[0.222,1.268,0.011]},{"id":"mu_brachialis","col":"s","group":"Muscles","name":"Brachialis","sub":"the deep elbow-bending muscle","how":"Origin: the lower half of the front of the upper-arm bone. Insertion: the coronoid process and tuberosity of the ulna. Action: Bends the elbow in every position; it is the main elbow flexor. Nerve: Musculocutaneous nerve (C5, C6), with a small part from the radial nerve. Blood supply: Branches of the brachial and radial recurrent arteries. There is one on each side. It can be injured in elbow dislocations and fractures.","evidence":"Textbook anatomy","pos":[0.234,1.208,0.003]},{"id":"mu_triceps_brachii","col":"s","group":"Muscles","name":"Triceps brachii","sub":"the three-headed muscle at the back of the upper arm","how":"Origin: long head: below the shoulder socket; lateral and medial heads: the back of the upper-arm bone. Insertion: the olecranon (the bony point of the elbow). Action: Straightens the elbow; the long head also helps pull the arm back. Nerve: Radial nerve (C6 to C8). Blood supply: Deep brachial (profunda brachii) artery. There is one on each side. Strong triceps are needed to push up from a chair or catch yourself with the arms in a fall.","evidence":"Textbook anatomy","pos":[0.226,1.26,-0.038]},{"id":"mu_pronator_teres","col":"s","group":"Muscles","name":"Pronator teres","sub":"turns the palm down","how":"Origin: the inner bony point of the elbow (medial epicondyle) and the coronoid process of the ulna. Insertion: the middle of the outer side of the radius. Action: Turns the palm down (pronation) and helps bend the elbow. Nerve: Median nerve (C6, C7). Blood supply: Ulnar and anterior ulnar recurrent arteries. There is one on each side. The median nerve passes between its two heads and can be squeezed there (pronator syndrome). Its origin is involved in golfer's elbow.","evidence":"Textbook anatomy","pos":[0.27,1.075,0.018]},{"id":"mu_flexor_carpi_radialis","col":"s","group":"Muscles","name":"Flexor carpi radialis","sub":"wrist flexor on the thumb side","how":"Origin: the medial epicondyle of the upper-arm bone (common flexor origin). Insertion: the base of the second and third hand bones (metacarpals). Action: Bends the wrist and tips it toward the thumb. Nerve: Median nerve (C6, C7). Blood supply: Radial artery. There is one on each side. Its shared origin at the inner elbow is the site of golfer's elbow (medial epicondylitis).","evidence":"Textbook anatomy","pos":[0.29,1.003,0.025]},{"id":"mu_palmaris_longus","col":"s","group":"Muscles","name":"Palmaris longus","sub":"slender wrist flexor, missing in some people","how":"Origin: the medial epicondyle of the upper-arm bone. Insertion: the palm's tough sheet (palmar aponeurosis) and the band over the wrist. Action: Tightens the palm sheet and helps bend the wrist. Nerve: Median nerve (C7, C8). Blood supply: Ulnar artery. There is one on each side. About one person in seven lacks it; its tendon is a favourite spare for tendon grafts.","evidence":"Textbook anatomy","pos":[0.276,1.019,0.009]},{"id":"mu_flexor_digitorum_superficialis","col":"s","group":"Muscles","name":"Flexor digitorum superficialis","sub":"bends the middle joints of the fingers","how":"Origin: the medial epicondyle, the coronoid process of the ulna and the front of the radius. Insertion: the sides of the middle bones of the four fingers. Action: Bends the middle joints of the fingers and helps bend the wrist. Nerve: Median nerve (C7 to T1). Blood supply: Ulnar and radial arteries. There is one on each side. Its tendons run through the carpal tunnel; cuts on the palm side of the fingers often damage them.","evidence":"Textbook anatomy","pos":[0.295,1,0.003]},{"id":"mu_flexor_carpi_ulnaris","col":"s","group":"Muscles","name":"Flexor carpi ulnaris","sub":"wrist flexor on the little-finger side","how":"Origin: the medial epicondyle and the back edge of the ulna. Insertion: the pisiform bone at the base of the palm and the fifth hand bone. Action: Bends the wrist and tips it toward the little finger. Nerve: Ulnar nerve (C7 to T1). Blood supply: Ulnar artery. There is one on each side. The ulnar nerve enters the forearm between its two heads, a common spot for ulnar nerve squeezing at the elbow (cubital tunnel syndrome).","evidence":"Textbook anatomy","pos":[0.294,1,0]},{"id":"mu_flexor_digitorum_profundus","col":"s","group":"Muscles","name":"Flexor digitorum profundus","sub":"bends the fingertips","how":"Origin: the front and inner side of the ulna and the membrane between the forearm bones. Insertion: the base of the end bones of the four fingers. Action: Bends the fingertip joints, then the rest of the fingers, for a strong grip. Nerve: Median nerve (anterior interosseous branch, index and middle fingers) and ulnar nerve (ring and little fingers). Blood supply: Ulnar and anterior interosseous arteries. There is one on each side. Grip strength depends on it; grip strength is a widely used marker of overall muscle strength in older people.","evidence":"Textbook anatomy","pos":[0.305,1,0.003]},{"id":"mu_flexor_pollicis_longus","col":"s","group":"Muscles","name":"Flexor pollicis longus","sub":"bends the tip of the thumb","how":"Origin: the front of the radius and the membrane between the forearm bones. Insertion: the base of the end bone of the thumb. Action: Bends the thumb tip, needed for pinching and writing. Nerve: Anterior interosseous branch of the median nerve (C7, C8). Blood supply: Anterior interosseous artery. There is one on each side. Fine pinch and handwriting depend on it; handwriting that gets smaller (micrographia) is an early sign of Parkinson's, a problem of movement control rather than of this muscle.","evidence":"Textbook anatomy","pos":[0.308,0.964,0.032]},{"id":"mu_brachioradialis","col":"s","group":"Muscles","name":"Brachioradialis","sub":"the muscle along the thumb side of the forearm","how":"Origin: the ridge above the outer elbow on the upper-arm bone. Insertion: the lower end of the radius just above the wrist. Action: Bends the elbow, especially with the thumb pointing up (as when holding a cup). Nerve: Radial nerve (C5, C6). Blood supply: Radial recurrent artery. There is one on each side. Its reflex is used in neurological examination of the C5 and C6 nerve roots.","evidence":"Textbook anatomy","pos":[0.297,1.061,0.029]},{"id":"mu_extensor_carpi_radialis_longus","col":"s","group":"Muscles","name":"Extensor carpi radialis longus","sub":"long wrist extensor on the thumb side","how":"Origin: the ridge above the outer elbow on the upper-arm bone. Insertion: the back of the base of the second hand bone. Action: Lifts the wrist back and tips it toward the thumb; steadies the wrist in a grip. Nerve: Radial nerve (C6, C7). Blood supply: Radial artery and radial recurrent artery. There is one on each side. Wrist extensors hold the wrist steady while the fingers grip, so they are loaded in every grasp.","evidence":"Textbook anatomy","pos":[0.318,1.037,0.023]},{"id":"mu_extensor_carpi_radialis_brevis","col":"s","group":"Muscles","name":"Extensor carpi radialis brevis","sub":"short wrist extensor; the classic tennis-elbow muscle","how":"Origin: the outer bony point of the elbow (lateral epicondyle, common extensor origin). Insertion: the back of the base of the third hand bone. Action: Lifts the wrist back and steadies it during gripping. Nerve: Deep branch of the radial nerve (C7, C8). Blood supply: Radial artery. There is one on each side. Overload of its tendon where it attaches at the outer elbow is the main cause of tennis elbow (lateral epicondylitis).","evidence":"Textbook anatomy","pos":[0.325,1.016,0.015]},{"id":"mu_extensor_digitorum","col":"s","group":"Muscles","name":"Extensor digitorum","sub":"straightens the fingers","how":"Origin: the lateral epicondyle of the upper-arm bone. Insertion: the back of the four fingers, through the extensor hoods. Action: Straightens the fingers and helps lift the wrist back. Nerve: Posterior interosseous nerve (deep branch of the radial nerve, C7, C8). Blood supply: Posterior interosseous artery. There is one on each side. It shares the tennis-elbow origin; a cut tendon or 'mallet finger' leaves a finger that cannot straighten.","evidence":"Textbook anatomy","pos":[0.322,1.014,0.011]},{"id":"mu_extensor_carpi_ulnaris","col":"s","group":"Muscles","name":"Extensor carpi ulnaris","sub":"wrist extensor on the little-finger side","how":"Origin: the lateral epicondyle and the back edge of the ulna. Insertion: the base of the fifth hand bone. Action: Lifts the wrist back and tips it toward the little finger. Nerve: Posterior interosseous nerve (C7, C8). Blood supply: Posterior interosseous artery. There is one on each side. Its tendon can slip or become inflamed at the wrist in racquet sports.","evidence":"Textbook anatomy","pos":[0.318,1.012,-0.004]},{"id":"mu_anconeus","col":"s","group":"Muscles","name":"Anconeus","sub":"small triangular muscle at the back of the elbow","how":"Origin: the lateral epicondyle of the upper-arm bone. Insertion: the outer side of the olecranon and the upper ulna. Action: Helps straighten the elbow and steadies the joint. Nerve: Radial nerve (C7, C8). Blood supply: Recurrent interosseous artery. There is one on each side. It is a landmark for surgical approaches to the elbow.","evidence":"Textbook anatomy","pos":[0.293,1.121,-0.023]},{"id":"mu_supinator","col":"s","group":"Muscles","name":"Supinator","sub":"turns the palm up","how":"Origin: the lateral epicondyle, the ligaments of the outer elbow and the ulna. Insertion: the upper third of the radius. Action: Turns the palm up (supination), as in turning a key or doorknob. Nerve: Deep branch of the radial nerve (C6, C7), which passes through it. Blood supply: Recurrent interosseous artery. There is one on each side. The radial nerve can be squeezed where it passes through it (radial tunnel syndrome), causing forearm pain or weak finger straightening.","evidence":"Textbook anatomy","pos":[0.285,1.104,0.004]},{"id":"mu_abductor_pollicis_longus","col":"s","group":"Muscles","name":"Abductor pollicis longus","sub":"moves the thumb out","how":"Origin: the back of the ulna, the radius and the membrane between them. Insertion: the base of the first hand bone (thumb metacarpal). Action: Moves the thumb away from the palm and helps steady the wrist. Nerve: Posterior interosseous nerve (C7, C8). Blood supply: Posterior interosseous artery. There is one on each side. Its tendon, with extensor pollicis brevis, becomes inflamed in De Quervain's tenosynovitis, a painful wrist condition common in new parents.","evidence":"Textbook anatomy","pos":[0.331,0.991,0.022]},{"id":"mu_extensor_pollicis_brevis","col":"s","group":"Muscles","name":"Extensor pollicis brevis","sub":"straightens the thumb's base joint","how":"Origin: the back of the radius and the membrane between the forearm bones. Insertion: the base of the first bone of the thumb. Action: Straightens the thumb at its knuckle and moves it out. Nerve: Posterior interosseous nerve (C7, C8). Blood supply: Posterior interosseous artery. There is one on each side. Involved in De Quervain's tenosynovitis with abductor pollicis longus; its tendon borders the 'anatomical snuffbox', where scaphoid fractures cause tenderness.","evidence":"Textbook anatomy","pos":[0.337,0.961,0.032]},{"id":"mu_extensor_pollicis_longus","col":"s","group":"Muscles","name":"Extensor pollicis longus","sub":"straightens the tip of the thumb","how":"Origin: the back of the ulna and the membrane between the forearm bones. Insertion: the base of the end bone of the thumb. Action: Straightens the thumb tip and pulls the thumb back. Nerve: Posterior interosseous nerve (C7, C8). Blood supply: Posterior interosseous artery. There is one on each side. Its tendon can rupture weeks after a broken wrist (a Colles fracture from a fall on an outstretched hand), because it runs over the broken bone.","evidence":"Textbook anatomy","pos":[0.327,0.981,0.012]},{"id":"mu_thenar","col":"s","group":"Muscles","name":"Thenar muscles","sub":"the ball of the thumb (abductor and flexor pollicis brevis, opponens pollicis)","how":"Origin: the bones of the wrist on the thumb side and the band across the carpal tunnel (flexor retinaculum). Insertion: the first bone of the thumb and its metacarpal. Action: Move the thumb across the palm to touch the fingertips (opposition), the basis of a fine pinch. Nerve: Recurrent branch of the median nerve (C8, T1), with part from the ulnar nerve. Blood supply: Superficial palmar branch of the radial artery. There is one on each side. Wasting of the ball of the thumb is a late sign of carpal tunnel syndrome, where the median nerve is squeezed at the wrist.","evidence":"Textbook anatomy","pos":[0.345,0.868,0.062]},{"id":"mu_hypothenar","col":"s","group":"Muscles","name":"Hypothenar muscles","sub":"the fleshy edge of the palm below the little finger","how":"Origin: the pisiform and hamate bones of the wrist and the flexor retinaculum. Insertion: the first bone of the little finger and its metacarpal. Action: Move and bend the little finger and cup the palm. Nerve: Deep branch of the ulnar nerve (C8, T1). Blood supply: Ulnar artery. There is one on each side. Wasting here points to ulnar nerve damage, at the elbow or the wrist.","evidence":"Textbook anatomy","pos":[0.352,0.848,0.012]},{"id":"mu_interossei","col":"s","group":"Muscles","name":"Interossei","sub":"small muscles between the bones of the hand","how":"Origin: the sides of the hand bones (metacarpals). Insertion: the bases of the finger bones and the extensor hoods. Action: Spread the fingers apart and bring them together, and help bend the knuckles while straightening the finger joints. Nerve: Deep branch of the ulnar nerve (C8, T1). Blood supply: Deep palmar arch and metacarpal arteries. There is one on each side. Thin gaps between the hand bones on the back of the hand show their wasting in ulnar nerve damage or in motor neuron disease.","evidence":"Textbook anatomy","pos":[0.359,0.84,0.041]},{"id":"mu_levator_ani","col":"s","group":"Muscles","name":"Levator ani","sub":"the main muscle of the pelvic floor","how":"Origin: the back of the pubic bone, a band of fascia on the side wall of the pelvis and the ischial spine. Insertion: the coccyx, the band behind the anus, and the walls of the rectum, vagina or prostate. Action: Holds up the pelvic organs, keeps urine and stool in, and relaxes to let them out. Nerve: Nerve to levator ani (S4) and branches of the pudendal nerve. Blood supply: Inferior gluteal, internal pudendal and inferior vesical arteries. There is one on each side. Childbirth, ageing and straining weaken it, leading to leaks and prolapse; pelvic-floor training strengthens it. In Parkinson's the pelvic floor may fail to relax when pushing, which adds to constipation.","evidence":"Textbook anatomy","pos":[0.028,0.856,-0.006]},{"id":"mu_piriformis","col":"s","group":"Muscles","name":"Piriformis","sub":"pear-shaped muscle deep in the buttock","how":"Origin: the front of the sacrum. Insertion: the top of the greater trochanter (the bony point at the outside of the hip). Action: Turns the thigh outward and helps steady the hip. Nerve: Nerve to piriformis (S1, S2). Blood supply: Superior and inferior gluteal arteries. There is one on each side. The sciatic nerve runs just below (sometimes through) it, so a tight piriformis can cause buttock pain running down the leg (piriformis syndrome).","evidence":"Textbook anatomy","pos":[0.084,0.92,-0.052]},{"id":"mu_gluteus_maximus","col":"s","group":"Muscles","name":"Gluteus maximus","sub":"the large buttock muscle","how":"Origin: the back of the ilium, the sacrum, the coccyx and the low-back fascia. Insertion: the iliotibial band and the gluteal ridge at the back of the upper thigh bone. Action: Straightens the hip powerfully for climbing stairs, rising from a chair and running, and turns the thigh outward. Nerve: Inferior gluteal nerve (L5 to S2). Blood supply: Inferior and superior gluteal arteries. There is one on each side. Strong hip extensors are key to standing up from a chair and recovering from a stumble; their weakening with age and inactivity raises fall risk.","evidence":"Textbook anatomy","pos":[0.105,0.885,-0.072]},{"id":"mu_gluteus_medius","col":"s","group":"Muscles","name":"Gluteus medius","sub":"the hip-steadying muscle on the side of the pelvis","how":"Origin: the outer surface of the ilium between its ridges. Insertion: the outer side of the greater trochanter. Action: Moves the leg out to the side and, most importantly, keeps the pelvis level when standing on one leg in each step. Nerve: Superior gluteal nerve (L4 to S1). Blood supply: Superior gluteal artery. There is one on each side. When it is weak the pelvis drops on the other side with each step (Trendelenburg gait), making walking and sideways balance less steady.","evidence":"Textbook anatomy","pos":[0.136,0.965,-0.015]},{"id":"mu_gluteus_minimus","col":"s","group":"Muscles","name":"Gluteus minimus","sub":"the smallest, deepest gluteal muscle","how":"Origin: the outer surface of the ilium below gluteus medius. Insertion: the front of the greater trochanter. Action: Moves the leg out, turns it inward and helps keep the pelvis level when walking. Nerve: Superior gluteal nerve (L4 to S1). Blood supply: Superior gluteal artery. There is one on each side. Its tendon can tear or become painful in older people, causing pain on the outside of the hip.","evidence":"Textbook anatomy","pos":[0.132,0.954,0.005]},{"id":"mu_psoas_major","col":"s","group":"Muscles","name":"Psoas major","sub":"the deep hip flexor running from the spine","how":"Origin: the sides of the vertebrae T12 to L5 and their discs. Insertion: the lesser trochanter (a bony knob on the inner upper thigh bone), joined with iliacus. Action: Bends the hip (lifts the thigh) and helps bend the trunk forward. Nerve: Branches of the lumbar nerves L1 to L3. Blood supply: Lumbar arteries and branches of the iliolumbar artery. There is one on each side. Long sitting shortens the hip flexors; tight hip flexors pull the pelvis forward and add to a flexed, stooped standing posture as in Parkinson's.","evidence":"Textbook anatomy","pos":[0.071,0.973,-0.001]},{"id":"mu_iliacus","col":"s","group":"Muscles","name":"Iliacus","sub":"the hip flexor lining the inside of the pelvis","how":"Origin: the inner hollow of the ilium (iliac fossa). Insertion: the lesser trochanter of the thigh bone, joined with psoas major. Action: Bends the hip, together with psoas major (the pair is called iliopsoas). Nerve: Femoral nerve (L2, L3). Blood supply: Iliolumbar artery and deep circumflex iliac artery. There is one on each side. A bleed into this muscle (for example in people taking blood thinners) can press on the femoral nerve.","evidence":"Textbook anatomy","pos":[0.099,0.917,0.023]},{"id":"mu_tensor_fasciae_latae","col":"s","group":"Muscles","name":"Tensor fasciae latae","sub":"small muscle at the front-outer hip","how":"From: the front of the iliac crest near the anterior superior iliac spine. To: the iliotibial band, which runs down the outside of the thigh to the shinbone. Action: Tightens the iliotibial band, helps bend the hip and move the leg out, and steadies the knee. Nerve: Superior gluteal nerve (L4 to S1). Blood supply: Lateral circumflex femoral and superior gluteal arteries. There is one on each side. Tightness of the band it pulls on is linked with pain on the outside of the knee in runners (iliotibial band syndrome).","evidence":"Textbook anatomy","pos":[0.163,0.727,0.006]},{"id":"mu_pectineus","col":"s","group":"Muscles","name":"Pectineus","sub":"flat muscle at the top of the inner thigh","how":"Origin: the upper ridge of the pubic bone. Insertion: a line on the back of the thigh bone below the lesser trochanter. Action: Brings the thigh in toward the body and bends the hip. Nerve: Femoral nerve (L2, L3), sometimes also the obturator nerve. Blood supply: Medial circumflex femoral and obturator arteries. There is one on each side. It forms part of the floor of the femoral triangle at the groin, where the femoral artery and vein run.","evidence":"Textbook anatomy","pos":[0.07,0.864,0.02]},{"id":"mu_adductor_longus","col":"s","group":"Muscles","name":"Adductor longus","sub":"the most forward of the inner-thigh adductors","how":"Origin: the front of the pubic bone. Insertion: the middle third of the back of the thigh bone. Action: Brings the thigh in toward the body. Nerve: Obturator nerve (L2 to L4). Blood supply: Deep femoral (profunda femoris) and obturator arteries. There is one on each side. The classic 'groin strain' in football and skating is a tear here.","evidence":"Textbook anatomy","pos":[0.05,0.802,0.017]},{"id":"mu_adductor_brevis","col":"s","group":"Muscles","name":"Adductor brevis","sub":"short adductor under adductor longus","how":"Origin: the front of the pubic bone. Insertion: the upper part of the back of the thigh bone. Action: Brings the thigh in toward the body. Nerve: Obturator nerve (L2 to L4). Blood supply: Deep femoral and obturator arteries. There is one on each side. With the other adductors it steadies the legs when standing and walking.","evidence":"Textbook anatomy","pos":[0.061,0.819,-0.004]},{"id":"mu_adductor_magnus","col":"s","group":"Muscles","name":"Adductor magnus","sub":"the largest of the inner-thigh adductors","how":"Origin: the lower branch of the pubic bone and the sitting bone (ischial tuberosity). Insertion: the whole length of the back of the thigh bone and the adductor tubercle above the inner knee. Action: Brings the thigh in and helps straighten the hip. Nerve: Obturator nerve (adductor part) and the tibial part of the sciatic nerve (hamstring part). Blood supply: Deep femoral, obturator and femoral arteries. There is one on each side. The femoral artery passes through a gap in its tendon to reach the back of the knee, where it becomes the popliteal artery.","evidence":"Textbook anatomy","pos":[0.068,0.727,-0.026]},{"id":"mu_gracilis","col":"s","group":"Muscles","name":"Gracilis","sub":"long thin strap muscle on the inner thigh","how":"Origin: the lower body of the pubic bone. Insertion: the inner surface of the top of the shinbone (as part of the pes anserinus). Action: Brings the thigh in and bends the knee. Nerve: Obturator nerve (L2, L3). Blood supply: Deep femoral and medial circumflex femoral arteries. There is one on each side. Surgeons often use its tendon to rebuild a torn knee ligament.","evidence":"Textbook anatomy","pos":[0.043,0.647,0.003]},{"id":"mu_rectus_femoris","col":"s","group":"Muscles","name":"Rectus femoris","sub":"the quadriceps head that crosses both hip and knee","how":"Origin: the anterior inferior iliac spine and the rim just above the hip socket. Insertion: the kneecap and, through the patellar tendon, the tibial tuberosity. Action: Straightens the knee and bends the hip, as in kicking. Nerve: Femoral nerve (L2 to L4). Blood supply: Lateral circumflex femoral artery. There is one on each side. The quadriceps (this and the three vasti) is the main muscle for standing up, climbing stairs and catching a stumble; it weakens with age and inactivity, which makes all three harder. Kicking sports often strain this head.","evidence":"Textbook anatomy","pos":[0.093,0.747,0.051]},{"id":"mu_vastus_lateralis","col":"s","group":"Muscles","name":"Vastus lateralis","sub":"the largest quadriceps head, on the outer thigh","how":"Origin: the greater trochanter and the outer lip of the ridge on the back of the thigh bone. Insertion: the outer side of the kneecap and, through the patellar tendon, the tibia. Action: Straightens the knee. Nerve: Femoral nerve (L2 to L4). Blood supply: Lateral circumflex femoral artery. There is one on each side. It is the usual site for muscle biopsies and studies of muscle loss with age, because it is large and easy to reach.","evidence":"Textbook anatomy","pos":[0.126,0.708,0.013]},{"id":"mu_vastus_medialis","col":"s","group":"Muscles","name":"Vastus medialis","sub":"the teardrop-shaped quadriceps head above the inner knee","how":"Origin: the inner lip of the ridge on the back of the thigh bone. Insertion: the inner side of the kneecap and, through the patellar tendon, the tibia. Action: Straightens the knee and keeps the kneecap tracking straight. Nerve: Femoral nerve (L2 to L4). Blood supply: Femoral artery and deep femoral artery. There is one on each side. It wastes quickly after knee injury or surgery; weakness is linked to kneecap pain.","evidence":"Textbook anatomy","pos":[0.067,0.695,0.027]},{"id":"mu_vastus_intermedius","col":"s","group":"Muscles","name":"Vastus intermedius","sub":"the deep quadriceps head on the front of the thigh bone","how":"Origin: the front and outer surface of the thigh bone. Insertion: the kneecap and, through the patellar tendon, the tibia. Action: Straightens the knee. Nerve: Femoral nerve (L2 to L4). Blood supply: Lateral circumflex femoral and deep femoral arteries. There is one on each side. A hard blow to the thigh can bruise it against the bone (a 'dead leg').","evidence":"Textbook anatomy","pos":[0.126,0.713,0.015]},{"id":"mu_sartorius","col":"s","group":"Muscles","name":"Sartorius","sub":"the long strap muscle crossing the front of the thigh","how":"Origin: the anterior superior iliac spine (the bony point at the front of the hip). Insertion: the inner surface of the top of the shinbone (pes anserinus). Action: Bends, moves out and turns out the hip and bends the knee, as when sitting cross-legged. Nerve: Femoral nerve (L2, L3). Blood supply: Femoral artery branches. There is one on each side. The longest muscle in the body; it forms the outer edge of the femoral triangle in the groin.","evidence":"Textbook anatomy","pos":[0.062,0.702,0.053]},{"id":"mu_biceps_femoris_long_head","col":"s","group":"Muscles","name":"Biceps femoris (long head)","sub":"the outer hamstring, long head","how":"Origin: the sitting bone (ischial tuberosity). Insertion: the head of the fibula at the outer knee. Action: Bends the knee, straightens the hip and turns the bent knee outward. Nerve: Tibial part of the sciatic nerve (L5 to S2). Blood supply: Perforating branches of the deep femoral artery. There is one on each side. The most often torn hamstring in sprinting. Hamstring and calf tightness adds to the bent-knee posture seen in Parkinson's.","evidence":"Textbook anatomy","pos":[0.119,0.659,-0.032]},{"id":"mu_biceps_femoris_short_head","col":"s","group":"Muscles","name":"Biceps femoris (short head)","sub":"the outer hamstring, short head","how":"Origin: the outer lip of the ridge on the back of the thigh bone. Insertion: the head of the fibula. Action: Bends the knee and turns it outward. Nerve: Common peroneal (fibular) part of the sciatic nerve (L5 to S2). Blood supply: Perforating branches of the deep femoral artery. There is one on each side. It is the only part of the hamstrings supplied by the common peroneal nerve, which helps doctors locate nerve injuries.","evidence":"Textbook anatomy","pos":[0.129,0.572,-0.009]},{"id":"mu_semitendinosus","col":"s","group":"Muscles","name":"Semitendinosus","sub":"inner hamstring with a long tendon","how":"Origin: the sitting bone (ischial tuberosity). Insertion: the inner surface of the top of the shinbone (pes anserinus). Action: Bends the knee, straightens the hip and turns the bent knee inward. Nerve: Tibial part of the sciatic nerve (L5 to S2). Blood supply: Perforating branches of the deep femoral artery. There is one on each side. Its tendon is commonly used to rebuild a torn anterior cruciate ligament.","evidence":"Textbook anatomy","pos":[0.064,0.627,-0.029]},{"id":"mu_semimembranosus","col":"s","group":"Muscles","name":"Semimembranosus","sub":"the deep inner hamstring","how":"Origin: the sitting bone (ischial tuberosity). Insertion: the back of the inner side of the top of the shinbone. Action: Bends the knee, straightens the hip and turns the bent knee inward. Nerve: Tibial part of the sciatic nerve (L5 to S2). Blood supply: Perforating branches of the deep femoral artery. There is one on each side. A fluid swelling behind the knee (Baker's cyst) often forms between it and the gastrocnemius.","evidence":"Textbook anatomy","pos":[0.076,0.653,-0.028]},{"id":"mu_popliteus","col":"s","group":"Muscles","name":"Popliteus","sub":"small muscle behind the knee","how":"Origin: the outer side of the lower thigh bone (lateral condyle). Insertion: the back of the top of the shinbone. Action: Unlocks the straight knee by turning the shin slightly, so the knee can start to bend. Nerve: Tibial nerve (L4 to S1). Blood supply: Branches of the popliteal artery. There is one on each side. It can be strained in running downhill, causing pain behind the knee.","evidence":"Textbook anatomy","pos":[0.102,0.461,-0.018]},{"id":"mu_patellar_tendon","col":"s","group":"Muscles","name":"Patellar tendon","sub":"the tendon from the kneecap to the shinbone","how":"From: the lower tip of the kneecap. To: the tibial tuberosity, the bump at the top of the front of the shinbone. Action: Carries the pull of the quadriceps to the shinbone to straighten the knee (strictly a ligament between two bones, but it works as the quadriceps tendon). Nerve: It is not a muscle; feeling comes from branches of the femoral and saphenous nerves. Blood supply: The arteries around the knee (genicular arteries). There is one on each side. Tapping it gives the knee-jerk reflex (L3, L4). Overuse from jumping causes patellar tendinopathy ('jumper's knee').","evidence":"Textbook anatomy","pos":[0.096,0.474,0.038]},{"id":"mu_gastrocnemius","col":"s","group":"Muscles","name":"Gastrocnemius","sub":"the two-headed calf muscle","how":"Origin: the back of the inner and outer lower thigh bone, just above the knee. Insertion: the heel bone, through the Achilles tendon. Action: Points the foot down (push-off when walking and running) and helps bend the knee. Nerve: Tibial nerve (S1, S2). Blood supply: Sural branches of the popliteal artery. There is one on each side. Calf strength drives the push-off of each step; calf cramps are common, and leg-muscle pumping helps return blood to the heart. Shortened, weak push-off contributes to the shuffling steps of Parkinson's.","evidence":"Textbook anatomy","pos":[0.094,0.399,-0.041]},{"id":"mu_soleus","col":"s","group":"Muscles","name":"Soleus","sub":"the deep, flat calf muscle","how":"Origin: the back of the top of the fibula and the soleal line of the tibia. Insertion: the heel bone, through the Achilles tendon. Action: Points the foot down and, crucially, keeps the body from tipping forward over the ankles when standing. Nerve: Tibial nerve (S1, S2). Blood supply: Posterior tibial, peroneal and popliteal arteries. There is one on each side. It is the main anti-gravity muscle of standing balance, and its large veins are the 'calf pump' that returns blood from the leg; still legs (long flights, bed rest) let blood pool there, where deep vein clots often start.","evidence":"Textbook anatomy","pos":[0.114,0.311,-0.037]},{"id":"mu_achilles_tendon","col":"s","group":"Muscles","name":"Achilles tendon","sub":"the thick heel tendon","how":"From: the joined tendons of the gastrocnemius and soleus. To: the back of the heel bone (calcaneus). Action: Carries the pull of the calf muscles to the heel, pushing the foot down for walking, running and jumping. Nerve: It is not a muscle; feeling comes from the sural and tibial nerves. Blood supply: Posterior tibial and peroneal arteries (its middle part has a poor blood supply). There is one on each side. The strongest tendon in the body; it can tear in a sudden push-off, most often in middle age, and its poorly supplied middle part is where overuse pain usually sits.","evidence":"Textbook anatomy","pos":[0.099,0.157,-0.057]},{"id":"mu_tibialis_anterior","col":"s","group":"Muscles","name":"Tibialis anterior","sub":"the shin muscle","how":"Origin: the outer surface of the upper shinbone and the membrane between the leg bones. Insertion: the inner side of the foot (medial cuneiform and the base of the first metatarsal). Action: Pulls the foot up (dorsiflexion) so the toes clear the ground when the leg swings, and turns the sole inward. Nerve: Deep peroneal (fibular) nerve (L4, L5). Blood supply: Anterior tibial artery. There is one on each side. When it is weak the foot slaps or drops (foot drop), the toes catch, and trips and falls follow; common causes are a squeezed peroneal nerve at the knee or an L5 nerve root problem.","evidence":"Textbook anatomy","pos":[0.107,0.234,0.022]},{"id":"mu_peroneus_longus","col":"s","group":"Muscles","name":"Peroneus (fibularis) longus","sub":"long muscle on the outside of the leg","how":"Origin: the head and upper outer surface of the fibula. Insertion: under the foot to the base of the first metatarsal and the medial cuneiform. Action: Turns the sole outward and helps point the foot down; supports the arch. Nerve: Superficial peroneal (fibular) nerve (L5, S1). Blood supply: Peroneal (fibular) artery. There is one on each side. It guards against ankle sprains by catching an inward roll of the foot; slow reactions here are part of why ankles sprain.","evidence":"Textbook anatomy","pos":[0.127,0.194,-0.025]},{"id":"mu_peroneus_brevis","col":"s","group":"Muscles","name":"Peroneus (fibularis) brevis","sub":"short muscle on the outside of the leg","how":"Origin: the lower outer surface of the fibula. Insertion: the base of the fifth metatarsal on the outer foot. Action: Turns the sole outward and helps point the foot down. Nerve: Superficial peroneal (fibular) nerve (L5, S1). Blood supply: Peroneal (fibular) artery. There is one on each side. In an inward ankle sprain it can pull off a flake of the fifth metatarsal where it attaches.","evidence":"Textbook anatomy","pos":[0.126,0.145,-0.027]},{"id":"mu_extensor_digitorum_longus","col":"s","group":"Muscles","name":"Extensor digitorum longus","sub":"lifts the four small toes","how":"Origin: the outer side of the top of the tibia, the fibula and the membrane between them. Insertion: the top of the four small toes. Action: Lifts the toes and helps pull the foot up. Nerve: Deep peroneal (fibular) nerve (L5, S1). Blood supply: Anterior tibial artery. There is one on each side. It helps the toes clear the floor when walking.","evidence":"Textbook anatomy","pos":[0.121,0.202,0.01]},{"id":"mu_extensor_hallucis_longus","col":"s","group":"Muscles","name":"Extensor hallucis longus","sub":"lifts the big toe","how":"Origin: the middle front of the fibula and the membrane between the leg bones. Insertion: the top of the end bone of the big toe. Action: Lifts the big toe and helps pull the foot up. Nerve: Deep peroneal (fibular) nerve (L5). Blood supply: Anterior tibial artery. There is one on each side. Its strength is tested to check the L5 nerve root. An upgoing, cramped big toe is a common form of foot dystonia in Parkinson's, often in the early morning.","evidence":"Textbook anatomy","pos":[0.114,0.173,0.016]},{"id":"mu_tibialis_posterior","col":"s","group":"Muscles","name":"Tibialis posterior","sub":"deep calf muscle that holds up the arch","how":"Origin: the back of the tibia, the fibula and the membrane between them. Insertion: the navicular bone and other bones under the inner foot. Action: Turns the sole inward, points the foot down and holds up the inner arch. Nerve: Tibial nerve (L4, L5). Blood supply: Posterior tibial artery. There is one on each side. When its tendon fails, the arch collapses (adult flatfoot). An inward-turned foot from dystonia, seen in Parkinson's, often involves this muscle.","evidence":"Textbook anatomy","pos":[0.094,0.214,-0.017]},{"id":"mu_flexor_digitorum_longus","col":"s","group":"Muscles","name":"Flexor digitorum longus","sub":"curls the four small toes","how":"Origin: the back of the tibia. Insertion: the base of the end bones of the four small toes. Action: Curls the toes and helps point the foot down; the toes grip the floor for balance. Nerve: Tibial nerve (S2, S3). Blood supply: Posterior tibial artery. There is one on each side. Painful toe curling is a common form of 'off'-period foot dystonia in Parkinson's.","evidence":"Textbook anatomy","pos":[0.089,0.179,-0.026]},{"id":"mu_flexor_hallucis_longus","col":"s","group":"Muscles","name":"Flexor hallucis longus","sub":"curls the big toe","how":"Origin: the lower back of the fibula. Insertion: the base of the end bone of the big toe. Action: Curls the big toe and gives the final push-off of each step. Nerve: Tibial nerve (S2, S3). Blood supply: Peroneal (fibular) artery. There is one on each side. Its tendon can become inflamed in dancers who work on the balls of their feet.","evidence":"Textbook anatomy","pos":[0.096,0.143,-0.034]},{"id":"mu_extensor_digitorum_brevis","col":"s","group":"Muscles","name":"Extensor digitorum brevis","sub":"small muscle on the top of the foot","how":"Origin: the top and outer side of the heel bone. Insertion: the tendons to the second to fourth toes (and the big toe, as extensor hallucis brevis). Action: Helps lift the toes. Nerve: Deep peroneal (fibular) nerve (S1, S2). Blood supply: Dorsalis pedis artery (lateral tarsal branch). There is one on each side. Doctors feel it on the top of the foot when testing the deep peroneal nerve.","evidence":"Textbook anatomy","pos":[0.119,0.036,0.033]},{"id":"mu_abductor_hallucis","col":"s","group":"Muscles","name":"Abductor hallucis","sub":"muscle along the inner edge of the sole","how":"Origin: the inner side of the heel bone and the plantar fascia. Insertion: the inner side of the base of the big toe. Action: Moves the big toe away from the others and supports the inner arch. Nerve: Medial plantar nerve (S1, S2). Blood supply: Medial plantar artery. There is one on each side. The tibial nerve passes under it to reach the sole and can be squeezed there (tarsal tunnel area).","evidence":"Textbook anatomy","pos":[0.098,0.018,0.026]},{"id":"mu_flexor_digitorum_brevis","col":"s","group":"Muscles","name":"Flexor digitorum brevis","sub":"the central short toe flexor in the sole","how":"Origin: the heel bone and the plantar fascia. Insertion: the middle bones of the four small toes. Action: Bends the small toes and supports the arch. Nerve: Medial plantar nerve (S1, S2). Blood supply: Medial and lateral plantar arteries. There is one on each side. Small foot muscles help keep balance by gripping the floor; they weaken with age.","evidence":"Textbook anatomy","pos":[0.118,0.029,0.016]},{"id":"mu_abductor_digiti_minimi","col":"s","group":"Muscles","name":"Abductor digiti minimi (foot)","sub":"muscle along the outer edge of the sole","how":"Origin: the heel bone and the plantar fascia. Insertion: the outer side of the base of the little toe. Action: Moves and bends the little toe and supports the outer arch. Nerve: Lateral plantar nerve (S2, S3). Blood supply: Lateral plantar artery. There is one on each side. A branch of the lateral plantar nerve running near it can be squeezed and cause heel pain.","evidence":"Textbook anatomy","pos":[0.144,0.016,0.012]},{"id":"mu_plantar_fascia","col":"s","group":"Muscles","name":"Plantar fascia","sub":"the tough band under the sole","how":"From: the underside of the heel bone. To: the bases of the toes. Action: Ties the heel to the toes like a bowstring, holding up the arch; it tightens as the toes bend up at push-off. Nerve: It is not a muscle; feeling comes from the medial and lateral plantar nerves. Blood supply: Medial and lateral plantar arteries. There is one on each side. Irritation where it attaches to the heel (plantar fasciitis) is the most common cause of heel pain, worst with the first steps in the morning.","evidence":"Textbook anatomy","pos":[0.121,0.016,0.029]},{"id":"n_trigeminal","col":"s","group":"Cranial nerves","name":"Trigeminal nerve (cranial nerve V)","sub":"feeling in the face, eye and mouth; chewing muscles","how":"The largest cranial nerve. It leaves the side of the pons, swells into the trigeminal ganglion, and splits into three branches: the ophthalmic branch (forehead, eye surface), the maxillary branch (cheek, upper teeth) and the mandibular branch (jaw, lower teeth, front of the tongue), which also works the chewing muscles. It carries touch, pain and temperature from the face, and the pain fibres from the coverings of the brain, which is why it is central to migraine. Damage: numbness of part of the face, a weak bite, loss of the blink reflex when the eye is touched; irritation of the nerve root causes trigeminal neuralgia, and shingles can reactivate in its ganglion.","evidence":"Textbook neuroanatomy.","pos":[0.025,1.615,0]},{"id":"n_facial","col":"s","group":"Cranial nerves","name":"Facial nerve (cranial nerve VII)","sub":"face muscles, eye closing, tears, saliva, taste","how":"Leaves the brainstem beside the hearing nerve, runs through a narrow bony canal in the skull, exits just below the ear and fans out through the parotid gland to all the muscles of facial expression, including the one that closes the eye. It also carries fibres to the tear glands and two of the saliva glands, taste from the front two-thirds of the tongue, and a nerve to a tiny muscle that damps loud sounds in the middle ear. Damage: one side of the face droops and the eye will not close (Bell's palsy, shingles, ear or parotid surgery); a stroke instead spares the forehead, because the forehead gets signals from both sides of the brain.","evidence":"Textbook neuroanatomy.","pos":[0.045,1.6,0]},{"id":"n_olfactory","col":"s","group":"Cranial nerves","name":"Olfactory nerve (cranial nerve I)","sub":"smell; roof of the nose to the olfactory bulb","how":"Bundles of tiny smell-sensing nerve fibres that start in the lining at the roof of the nose and pass up through the sieve-like bone under the brain (the cribriform plate) into the olfactory bulb. It is the only sensory nerve whose cells are replaced throughout life. Damage: reduced or lost smell (and so much of taste), from viral infections, chronic sinus disease, or a blow to the head that shears the fibres where they cross the bone. In Parkinson's, smell loss is common and often early, but the change is mostly in the olfactory bulb and smell areas of the brain rather than in this nerve.","evidence":"Textbook neuroanatomy.","pos":[0.006,1.625,0.055]},{"id":"n_oculomotor","col":"s","group":"Cranial nerves","name":"Oculomotor nerve (cranial nerve III)","sub":"most eye movements, eyelid lift, pupil and focusing","how":"Leaves the front of the midbrain and runs forward to the eye socket. It works four of the six muscles that move each eye (looking up, down and inward), lifts the upper eyelid, and carries the fibres that narrow the pupil and let the lens focus up close. Damage: the eye turns down and out, the eyelid droops, double vision, and sometimes a large pupil; pressure on this nerve from a brain aneurysm or swelling is a medical emergency, while diabetes can cause a painful palsy that usually spares the pupil and recovers.","evidence":"Textbook neuroanatomy.","pos":[0.012,1.635,0]},{"id":"n_trochlear","col":"s","group":"Cranial nerves","name":"Trochlear nerve (cranial nerve IV)","sub":"superior oblique eye muscle","how":"The thinnest cranial nerve and the only one that leaves the back of the brainstem; it wraps around the midbrain to reach one eye muscle (the superior oblique), which turns the eye down and inward and twists it. Damage, often from head injury: vertical or tilted double vision that is worst looking down, such as on stairs or when reading; people tilt the head to compensate.","evidence":"Textbook neuroanatomy.","pos":[0.015,1.635,-0.01]},{"id":"n_abducens","col":"s","group":"Cranial nerves","name":"Abducens nerve (cranial nerve VI)","sub":"turns the eye outward","how":"Leaves the brainstem between the pons and medulla and has a long path along the base of the skull to one eye muscle (the lateral rectus), which turns the eye outward. Because its route is long it is easily stretched: raised pressure inside the skull, head injury and diabetes can all weaken it. Damage: horizontal double vision that is worse looking toward the affected side, with the eye turned in.","evidence":"Textbook neuroanatomy.","pos":[0.008,1.605,-0.005]},{"id":"n_vestibulocochlear","col":"s","group":"Cranial nerves","name":"Vestibulocochlear nerve (cranial nerve VIII)","sub":"hearing and balance","how":"Carries hearing signals from the cochlea and balance signals from the inner-ear balance organs to the brainstem, travelling with the facial nerve through the internal ear canal of the skull. Damage: hearing loss, ringing in the ear and vertigo; a slow-growing benign tumour of its sheath (vestibular schwannoma) typically causes hearing loss in one ear, and inflammation of its balance part (vestibular neuritis) causes days of severe spinning.","evidence":"Textbook neuroanatomy.","pos":[0.035,1.618,-0.005]},{"id":"n_glossopharyngeal","col":"s","group":"Cranial nerves","name":"Glossopharyngeal nerve (cranial nerve IX)","sub":"throat feeling, gag, back of tongue, parotid saliva, blood-pressure sensor","how":"Leaves the medulla just above the vagus and works closely with it. It carries feeling and taste from the back third of the tongue and the throat (the sensing half of the gag reflex), sends saliva signals to the parotid gland, and carries signals from the carotid sinus and carotid body in the neck, which sense blood pressure and oxygen. Damage on its own is rare; together with the vagus it causes a weak gag and swallowing problems.","evidence":"Textbook neuroanatomy.","pos":[0.03,1.57,0]},{"id":"n_accessory","col":"s","group":"Cranial nerves","name":"Accessory nerve (cranial nerve XI)","sub":"turning the head and shrugging","how":"Starts in the upper neck part of the spinal cord, rises into the skull and leaves again with the vagus, then crosses the side of the neck just under the skin to the sternocleidomastoid (turns the head) and trapezius (shrugs and steadies the shoulder blade). Because it is so shallow in the neck, it can be cut during lymph-node biopsy or neck surgery. Damage: a drooping shoulder, weak shrug, shoulder blade that sticks out, and aching shoulder.","evidence":"Textbook neuroanatomy.","pos":[0.05,1.5,-0.03]},{"id":"n_hypoglossal","col":"s","group":"Cranial nerves","name":"Hypoglossal nerve (cranial nerve XII)","sub":"moves the tongue","how":"Leaves the medulla and runs under the jaw to all the muscles of the tongue, which shape speech sounds and push food back for swallowing. Damage: the tongue wastes on one side and points toward the weak side when stuck out, with slurred speech and difficulty moving food in the mouth. In motor neurone disease the tongue twitches and wastes. A stimulator on this nerve is one treatment option for obstructive sleep apnoea.","evidence":"Textbook neuroanatomy.","pos":[0.025,1.55,0.03]},{"id":"h_oral_corticosteroids","col":"h","group":"Medical treatments","name":"Corticosteroid tablets (short course)","sub":"prednisolone and similar","how":"Steroid medicines that damp down inflammation and swelling. A short course is used for conditions such as Bell's palsy, where swelling squeezes a nerve; longer use has side effects including raised blood sugar, bone thinning and infections, so they are prescribed for specific conditions only.","evidence":"Proven for Bell's palsy when started early (randomised trials)."},{"id":"h_ivig_plasma_exchange","col":"h","group":"Medical treatments","name":"Immunoglobulin infusion or plasma exchange","sub":"immune treatments for nerve attacks","how":"Two hospital treatments for immune attacks on the nerves. Intravenous immunoglobulin is pooled antibody from donated blood given by drip, which damps the harmful immune response; plasma exchange filters the patient's blood plasma to remove the harmful antibodies and replaces it.","evidence":"Proven to speed recovery from Guillain–Barré syndrome in randomised trials (Cochrane reviews)."},{"id":"n_cervical_plexus","col":"s","group":"Nerve plexuses","name":"Cervical plexus","sub":"C1 to C4: neck skin and muscles, phrenic nerve","how":"A network formed by the top four neck nerves, lying under the big muscle at the side of the neck. Its skin branches supply the neck, the back of the scalp and around the ear; its muscle branches work the strap muscles of the neck; and it gives rise to most of the phrenic nerve to the diaphragm. Damage is uncommon but can occur in neck surgery, causing numb patches of the neck and ear.","evidence":"Textbook neuroanatomy.","pos":[0.045,1.52,-0.02]},{"id":"n_brachial_plexus","col":"s","group":"Nerve plexuses","name":"Brachial plexus","sub":"C5 to T1: all the nerves of the arm","how":"A network formed by the lower four neck nerves and the first chest nerve. It passes between the neck muscles, under the collarbone and over the first rib into the armpit, where it splits into the five main arm nerves (musculocutaneous, axillary, radial, median and ulnar). Damage: a traction injury from a motorcycle fall or a hard pull on the arm can tear its roots (sometimes the whole arm is paralysed); a stretched upper part at birth gives Erb's palsy; squeezing between the collarbone and first rib (thoracic outlet) causes arm tingling; and an inflammatory attack (neuralgic amyotrophy) causes sudden severe shoulder pain then weakness.","evidence":"Textbook neuroanatomy.","pos":[0.1,1.42,-0.005]},{"id":"n_lumbar_plexus","col":"s","group":"Nerve plexuses","name":"Lumbar plexus","sub":"L1 to L4: front and inner thigh, groin","how":"A network formed by the upper lower-back nerves, lying inside the psoas muscle along the lower spine. It gives the femoral nerve (front of the thigh), the obturator nerve (inner thigh) and smaller nerves to the groin and outer thigh, including the one trapped under the groin ligament in meralgia paraesthetica (burning outer thigh). It can be damaged by a bleed into the psoas, abdominal surgery or diabetes.","evidence":"Textbook neuroanatomy.","pos":[0.04,1.02,-0.05]},{"id":"n_sacral_plexus","col":"s","group":"Nerve plexuses","name":"Sacral plexus","sub":"L4 to S4: back of thigh, leg, foot, buttock, pelvic floor","how":"A network formed by the lowest lumbar and the sacral nerves on the back wall of the pelvis. Its largest product is the sciatic nerve; it also supplies the buttock muscles, the pelvic floor, and gives the pudendal nerve to the genitals and the bladder and bowel sphincters. It can be damaged by pelvic fractures, childbirth or pelvic tumours.","evidence":"Textbook neuroanatomy.","pos":[0.04,0.9,-0.08]},{"id":"n_phrenic","col":"s","group":"Limb & trunk nerves","name":"Phrenic nerve","sub":"C3 to C5: the nerve to the diaphragm","how":"Formed mainly from the third to fifth neck nerves, it runs down the front of the neck over the scalene muscle, through the chest beside the heart, to the diaphragm, the main breathing muscle (hence \"C3, 4, 5 keeps the diaphragm alive\"). It also carries feeling from the diaphragm, so irritation under the diaphragm is felt as shoulder-tip pain. Damage: a paralysed half of the diaphragm causes breathlessness lying flat; injury to the upper neck cord above this level stops breathing. It can be harmed in heart and neck surgery, by tumours, or by nerve inflammation.","evidence":"Textbook neuroanatomy.","pos":[0.05,1.32,0.03]},{"id":"n_intercostal","col":"s","group":"Limb & trunk nerves","name":"Intercostal nerves","sub":"T1 to T11: chest wall and upper belly","how":"The front branches of the twelve chest spinal nerves run in a groove under each rib with an artery and vein, supplying the muscles between the ribs (which help breathing) and the skin of the chest and belly wall in bands. Damage: band-like pain around the chest after rib fractures, chest surgery, or shingles, which most often appears in one of these bands.","evidence":"Textbook neuroanatomy.","pos":[0.12,1.28,-0.02]},{"id":"n_median","col":"s","group":"Limb & trunk nerves","name":"Median nerve","sub":"thumb side of the hand; carpal tunnel","how":"From the brachial plexus it runs down the inside of the upper arm, through the front of the elbow and the middle of the forearm, then through the carpal tunnel at the wrist. It works most of the forearm muscles that bend the wrist and fingers, the thumb muscles for pinching, and carries feeling from the thumb, index, middle and half the ring finger. Damage: squeezed in the carpal tunnel it causes night-time tingling and later a weak pinch with a wasted thumb pad; a cut at the wrist numbs these fingers.","evidence":"Textbook neuroanatomy.","pos":[0.335,0.88,0.045]},{"id":"n_ulnar","col":"s","group":"Limb & trunk nerves","name":"Ulnar nerve","sub":"little-finger side; the \"funny bone\"","how":"Runs down the inside of the upper arm and passes behind the inner bony bump of the elbow (the cubital tunnel), where it lies just under the skin, then along the little-finger side of the forearm into the hand through Guyon's canal. It works most of the small muscles of the hand that fine-tune grip and finger spreading, and carries feeling from the little finger and half the ring finger. Damage: tingling in these fingers, clumsy hand, wasting between thumb and index finger and, when severe, a clawed hand.","evidence":"Textbook neuroanatomy.","pos":[0.245,1.13,-0.03]},{"id":"n_radial","col":"s","group":"Limb & trunk nerves","name":"Radial nerve","sub":"straightens elbow, wrist and fingers","how":"The largest arm nerve. It spirals around the back of the humerus in a groove, crosses to the outside of the elbow and supplies all the muscles that straighten the elbow, wrist and fingers, plus feeling on the back of the hand. Damage: wrist drop, from a fracture of the middle of the humerus or from sleeping with the arm hung over a chair (\"Saturday night palsy\").","evidence":"Textbook neuroanatomy.","pos":[0.23,1.28,-0.03]},{"id":"n_musculocutaneous","col":"s","group":"Limb & trunk nerves","name":"Musculocutaneous nerve","sub":"biceps; skin of outer forearm","how":"Leaves the brachial plexus in the armpit, pierces the coracobrachialis muscle and runs between the biceps and brachialis, which it works (bending the elbow and turning the palm up), then becomes the skin nerve of the outer forearm. Isolated damage is uncommon (heavy weight training, shoulder surgery) and causes a weak biceps and a numb strip of forearm.","evidence":"Textbook neuroanatomy.","pos":[0.215,1.3,0.02]},{"id":"n_axillary","col":"s","group":"Limb & trunk nerves","name":"Axillary nerve","sub":"deltoid; skin over the shoulder","how":"Runs from the brachial plexus through a gap behind the armpit and wraps around the neck of the humerus to work the deltoid (lifts the arm out to the side) and a small rotator-cuff muscle, and carries feeling from a patch over the outer shoulder. Damage: in shoulder dislocations and fractures of the top of the humerus, causing weakness lifting the arm and a numb \"regimental badge\" patch.","evidence":"Textbook neuroanatomy.","pos":[0.18,1.4,-0.03]},{"id":"n_femoral","col":"s","group":"Limb & trunk nerves","name":"Femoral nerve","sub":"L2 to L4: front of the thigh, straightens the knee","how":"The largest branch of the lumbar plexus. It runs down inside the pelvis beside the psoas muscle, passes under the groin ligament just outside the femoral artery, and supplies the quadriceps (straightens the knee, needed for stairs and standing up) and feeling on the front of the thigh and, through its saphenous branch, the inner shin. Damage: the knee buckles; causes include a bleed into the psoas, hip or pelvic surgery, and diabetes.","evidence":"Textbook neuroanatomy.","pos":[0.08,0.86,0.06]},{"id":"n_obturator","col":"s","group":"Limb & trunk nerves","name":"Obturator nerve","sub":"L2 to L4: inner thigh muscles","how":"Runs down the side wall of the pelvis and out through a hole in the pelvic bone (the obturator foramen) to the adductor muscles that pull the legs together, and to a patch of skin on the inner thigh. It can be pressed in pelvic surgery, childbirth or by an obturator hernia, causing inner-thigh pain and a weak, outward-swinging leg.","evidence":"Textbook neuroanatomy.","pos":[0.05,0.82,0.02]},{"id":"n_sciatic","col":"s","group":"Limb & trunk nerves","name":"Sciatic nerve","sub":"L4 to S3: the largest nerve in the body","how":"About as thick as a thumb, it leaves the pelvis below the piriformis muscle, runs behind the hip joint and down the back of the thigh, supplying the hamstrings, and splits above the back of the knee into the tibial and common peroneal nerves, which run everything below the knee. \"Sciatica\" usually means a nerve root in the lower back is pinched, with pain along the nerve's course; the nerve itself can be hurt by a dislocated hip, hip replacement surgery, or a badly placed buttock injection.","evidence":"Textbook neuroanatomy.","pos":[0.09,0.75,-0.06]},{"id":"n_tibial","col":"s","group":"Limb & trunk nerves","name":"Tibial nerve","sub":"calf, sole of the foot; tarsal tunnel","how":"The larger branch of the sciatic nerve, running straight down the middle of the back of the knee and calf, behind the inner ankle bone through the tarsal tunnel, into the sole. It works the calf muscles (pushing off, standing on tiptoe) and the small foot muscles, and carries feeling from the sole. Damage: weak push-off and a numb sole; squeezing at the inner ankle causes burning sole pain (tarsal tunnel syndrome).","evidence":"Textbook neuroanatomy.","pos":[0.095,0.4,-0.04]},{"id":"n_common_peroneal","col":"s","group":"Limb & trunk nerves","name":"Common peroneal (fibular) nerve","sub":"lifts the foot; outer shin and top of foot","how":"The smaller branch of the sciatic nerve. It wraps around the neck of the fibula just below the outer knee, where it lies on bone under the skin, then divides to lift the foot and toes and turn the foot out, and to carry feeling from the outer shin and top of the foot. Damage: foot drop and tripping, from leg crossing, weight loss, a tight cast or kneeling for long periods, or a knee injury.","evidence":"Textbook neuroanatomy.","pos":[0.135,0.45,-0.01]},{"id":"n_sural","col":"s","group":"Limb & trunk nerves","name":"Sural nerve","sub":"skin of the outer ankle and foot","how":"A purely sensory nerve formed from branches of the tibial and common peroneal nerves, running down the back of the calf and behind the outer ankle bone to the outer edge of the foot. Because it is long and carries only feeling, it is where nerve conduction tests and nerve biopsies usually look for neuropathy, and it is a common donor for nerve grafts.","evidence":"Textbook neuroanatomy.","pos":[0.12,0.15,-0.05]},{"id":"n_pudendal","col":"s","group":"Limb & trunk nerves","name":"Pudendal nerve","sub":"S2 to S4: pelvic floor, sphincters, genital feeling","how":"Leaves the pelvis, hooks around a ligament behind the hip bone, and re-enters to run along the side of the pelvic floor in a fascial tunnel (Alcock's canal). It works the outer sphincters that hold urine and stool and the pelvic floor muscles, and carries feeling from the genitals and the skin around the back passage, including the signals needed for orgasm. Damage: stretching during childbirth, long-distance cycling or pelvic surgery can cause leakage, numbness or burning pelvic pain that is worse sitting (pudendal neuralgia).","evidence":"Textbook neuroanatomy.","pos":[0.02,0.83,-0.03]},{"id":"n_sympathetic_chain","col":"s","group":"Autonomic nerves","name":"Sympathetic chain & ganglia","sub":"fight-or-flight nerves; cervical and stellate ganglia","how":"A pair of beaded nerve cords running beside the spine from the base of the skull to the tailbone. Signals from the chest and upper lower-back segments of the spinal cord relay in its ganglia (including the superior cervical ganglion in the neck and the stellate ganglion at the base of the neck) and go out to the heart, blood vessels, sweat glands, pupils and hair-raising muscles: they speed the heart, tighten blood vessels to hold up blood pressure when standing, dilate the pupils and make you sweat. Damage: a small pupil, droopy eyelid and dry face on one side if the neck chain is cut (Horner syndrome); widespread failure causes dizziness on standing. In Parkinson's the sympathetic nerves to the heart are lost, which heart scans can show, and this contributes to blood pressure falls on standing.","evidence":"Textbook neuroanatomy.","pos":[0.025,1.25,-0.055]},{"id":"n_prevertebral_ganglia","col":"s","group":"Autonomic nerves","name":"Coeliac & mesenteric ganglia","sub":"sympathetic relays in front of the aorta","how":"Clumps of sympathetic nerve cells lying on the front of the aorta in the upper belly (the coeliac ganglia around the coeliac artery, the \"solar plexus\", and the superior and inferior mesenteric ganglia). Nerves from the spinal cord relay here and go on to the stomach, liver, pancreas, spleen, intestines, kidneys and pelvic organs, where they slow digestion and narrow gut blood vessels during stress or exercise. Pain from pancreatic cancer travels through the coeliac plexus, which can be numbed by an injection (coeliac plexus block).","evidence":"Textbook neuroanatomy.","pos":[0,1.13,-0.02]},{"id":"n_parasympathetic","col":"s","group":"Autonomic nerves","name":"Parasympathetic outflow (cranial & sacral)","sub":"rest-and-digest nerves","how":"The \"rest and digest\" half of the automatic nervous system. Its fibres leave from the brainstem in four cranial nerves (oculomotor to the pupil, facial to tears and saliva, glossopharyngeal to the parotid, and the vagus to the heart, lungs and gut as far as the middle of the colon) and from the sacral spinal cord (the pelvic splanchnic nerves, S2 to S4) to the lower colon, rectum, bladder and genitals. It slows the heart, drives digestion, empties the bladder and bowel, and produces erection. Damage to the sacral part (cauda equina injury, pelvic surgery) causes a bladder that does not empty, constipation and erectile problems.","evidence":"Textbook neuroanatomy.","pos":[0.03,0.9,-0.05]},{"id":"n_myenteric_plexus","col":"s","group":"Autonomic nerves","name":"Myenteric (Auerbach's) plexus","sub":"gut-wall nerve net that drives movement","how":"A mesh of nerve cells between the two muscle layers of the gut wall from the gullet to the anus; with the submucosal plexus it forms the enteric nervous system (about as many neurons as the spinal cord), which can run the gut on its own. The myenteric plexus coordinates the squeezing waves (peristalsis) that move food along and relaxes the sphincters at the right moment; the vagus and sympathetic nerves tune it. Damage: loss of these nerves causes failure of the gut to move, as in achalasia of the gullet, Hirschsprung disease (missing in part of the colon from birth) and Chagas disease, and slow transit constipation.","evidence":"Textbook neuroanatomy.","pos":[0,1.07,0.07]},{"id":"n_submucosal_plexus","col":"s","group":"Autonomic nerves","name":"Submucosal (Meissner's) plexus","sub":"gut-wall nerve net for secretion and blood flow","how":"The inner nerve mesh of the gut wall, in the layer just beneath the lining. It senses the gut contents and controls the release of fluid and digestive juices, the local blood flow and the absorption by the lining. It is mainly found in the small and large intestine. It is also where gut biopsies taken to look for Parkinson's-type protein deposits often sample.","evidence":"Textbook neuroanatomy.","pos":[0.01,1.07,0.075]},{"id":"n_meissner","col":"s","group":"Sensory endings","name":"Meissner corpuscles","sub":"light touch in hairless skin","how":"Tiny capsules of stacked flattened cells wrapped around a nerve ending, sitting just under the outer skin in the ridges of the fingertips, palms, soles and lips. They fire when something brushes the skin or slips across it, which lets you feel texture and adjust grip. Their number falls with age, and they are lost early in small- and large-fibre neuropathy, which skin biopsies can count.","evidence":"Textbook neuroanatomy.","pos":[0.385,0.76,0.055]},{"id":"n_pacinian","col":"s","group":"Sensory endings","name":"Pacinian corpuscles","sub":"vibration and deep pressure","how":"Onion-like capsules about the size of a grain of rice, deep in the skin of the hands and feet and around joints and some organs. Their layers let only rapid change through, so they detect vibration and fast pressure, such as feeling through a tool. A tuning fork on the big toe tests the large nerve fibres that come from them; loss of vibration sense is an early sign of neuropathy.","evidence":"Textbook neuroanatomy.","pos":[0.36,0.82,0.04]},{"id":"n_nociceptors","col":"s","group":"Sensory endings","name":"Nociceptors (pain nerve endings)","sub":"free nerve endings that sense harm","how":"Bare nerve endings throughout the skin, muscles, joints and organs that respond to damaging heat, cold, pressure or chemicals released by injured or inflamed tissue. They connect through thin, slow fibres to the spinal cord, where pain signals can be turned up or down before reaching the brain. Inflammation makes them more sensitive (why a sunburn hurts to touch); damage to them causes the burning pain or numbness of small-fibre neuropathy.","evidence":"Textbook neuroanatomy.","pos":[0.12,1.28,0.11]},{"id":"bn_clavicle","col":"s","group":"Bones","name":"Clavicle (collarbone)","sub":"the strut between breastbone and shoulder","how":"Holds the shoulder out from the chest so the arm can swing freely, and passes the force of a fall on the hand to the trunk. It is one of the most commonly broken bones, usually from a fall onto the shoulder or an outstretched hand, most often in its middle third. The vessels and nerves to the arm run just behind it.","evidence":"Textbook anatomy","pos":[0.09,1.437,0.04]},{"id":"bn_scapula","col":"s","group":"Bones","name":"Scapula (shoulder blade)","sub":"the flat triangular bone on the upper back","how":"Carries the socket of the shoulder joint and anchors seventeen muscles, including the rotator cuff; it glides over the back of the ribs so the arm can reach overhead. It is well protected by muscle, so fractures need high-energy injuries; a winged scapula points instead to weakness of the serratus anterior.","evidence":"Textbook anatomy","pos":[0.11,1.35,-0.085]},{"id":"bn_humerus","col":"s","group":"Bones","name":"Humerus","sub":"the upper-arm bone","how":"Runs from the shoulder joint, where its rounded head sits in the shallow socket of the shoulder blade, to the elbow. A break at its neck just below the head is one of the typical fragility fractures of older people with thin bones, usually from a fall onto the outstretched hand or the side; a break of the shaft can injure the radial nerve that winds round it, causing wrist drop.","evidence":"Textbook anatomy","pos":[0.218,1.278,-0.012]},{"id":"bn_radius","col":"s","group":"Bones","name":"Radius","sub":"the forearm bone on the thumb side","how":"Turns around the ulna to rotate the palm up and down, and carries most of the wrist joint. Its lower end is the most commonly broken bone in adults: a fall onto an outstretched hand gives the classic wrist fracture (Colles fracture). In older women a wrist fracture from a simple fall is often the first sign of osteoporosis and predicts later hip fracture.","evidence":"Textbook anatomy","pos":[0.3,1.02,0.02]},{"id":"bn_ulna","col":"s","group":"Bones","name":"Ulna","sub":"the forearm bone on the little-finger side","how":"Forms the hinge of the elbow with the humerus (its tip is the point of the elbow, the olecranon) and is the stable bone around which the radius turns. It can break when the forearm is raised to block a blow (nightstick fracture), and its tip breaks in falls onto the elbow. Its small end at the wrist often breaks together with the radius.","evidence":"Textbook anatomy","pos":[0.3,1.02,-0.005]},{"id":"bn_carpals","col":"s","group":"Bones","name":"Carpal bones","sub":"the eight small wrist bones","how":"Eight bones in two rows (scaphoid, lunate, triquetrum, pisiform; trapezium, trapezoid, capitate, hamate) that let the wrist bend and tilt; with a band across their front they form the carpal tunnel, through which the median nerve and finger tendons pass. Falls onto the hand can break them or tear their ligaments.","evidence":"Textbook anatomy","pos":[0.35,0.87,0.03]},{"id":"bn_scaphoid","col":"s","group":"Bones","name":"Scaphoid","sub":"the boat-shaped wrist bone on the thumb side","how":"The most often broken wrist bone, from a fall onto an outstretched hand; tenderness in the hollow at the base of the thumb (anatomical snuffbox) is the clue. Its blood supply enters at the far end, so a break across the middle can starve the near part and leave it dead or unhealed if missed.","evidence":"Textbook anatomy","pos":[0.348,0.875,0.04]},{"id":"bn_metacarpals","col":"s","group":"Bones","name":"Metacarpals","sub":"the five bones of the palm","how":"Join the wrist to the fingers and form the knuckles. A punch with a closed fist commonly breaks the neck of the fifth (little-finger) metacarpal (boxer's fracture); the thumb metacarpal can break at its base in falls or ball sports.","evidence":"Textbook anatomy","pos":[0.36,0.84,0.035]},{"id":"bn_phalanges_hand","col":"s","group":"Bones","name":"Phalanges of the hand","sub":"the finger bones","how":"Fourteen in each hand: three in each finger, two in the thumb, for gripping and fine movement. Crush injuries, catching a ball and falls often break them; the joints between them are where hand osteoarthritis forms bony lumps.","evidence":"Textbook anatomy","pos":[0.37,0.79,0.04]},{"id":"bn_pelvis","col":"s","group":"Bones","name":"Pelvis (hip bones)","sub":"the bony ring of the hips","how":"The two hip bones (each fused from ilium, ischium and pubis) and the sacrum form a ring that carries the body's weight to the legs, holds the hip sockets and shelters the bladder, bowel and reproductive organs. In older people with thin bones, a simple fall can crack the pubic rami at the front of the ring; high-energy pelvic fractures can bleed heavily.","evidence":"Textbook anatomy","pos":[0.08,0.93,0]},{"id":"bn_ilium","col":"s","group":"Bones","name":"Ilium","sub":"the wide wing at the top of each hip bone","how":"The large flared upper part of the hip bone: its crest is the top of the hip you can feel at the waist, the glutes and iliacus attach to its surfaces, and it joins the sacrum at the sacroiliac joint. Bone marrow for transplants and bone grafts is often taken from its crest. A fall onto the side can bruise the crest (hip pointer).","evidence":"Textbook anatomy","pos":[0.1,0.98,0]},{"id":"bn_ischium","col":"s","group":"Bones","name":"Ischium","sub":"the lower back part of the hip bone, the sitting bone","how":"Its tuberosity is the bone you sit on, and the hamstrings start there. It forms the back of the hip socket. Sprinters can pull a flake of it off with the hamstring tendon; pressure sores form over it in people who sit for long periods without moving.","evidence":"Textbook anatomy","pos":[0.07,0.85,-0.03]},{"id":"bn_pubis","col":"s","group":"Bones","name":"Pubis","sub":"the front part of the hip bone","how":"The two pubic bones meet at the front in a cartilage joint (pubic symphysis) and give origin to the groin (adductor) muscles. Their thin branches (pubic rami) are a common site of low-energy fractures from simple falls in older people with osteoporosis, causing groin pain and difficulty walking.","evidence":"Textbook anatomy","pos":[0.03,0.9,0.055]},{"id":"bn_femur","col":"s","group":"Bones","name":"Femur","sub":"the thigh bone, the longest bone in the body","how":"Runs from the hip socket (its round head on an angled neck) to the knee, carrying the body's weight when standing and walking. A break of the neck or just below it is the 'hip fracture' of older people with thin bones, nearly always from a fall; it often needs surgery and has serious consequences for independence. Hip fractures are much more common in Parkinson's, where falls, low bone density and low vitamin D come together.","evidence":"Textbook anatomy","pos":[0.095,0.71,0]},{"id":"bn_patella","col":"s","group":"Bones","name":"Patella (kneecap)","sub":"the bone in the front of the knee","how":"A bone that sits inside the quadriceps tendon and acts as a pulley, increasing the quadriceps' leverage to straighten the knee. It can break in a fall straight onto the knee or from a sudden strong quadriceps pull, and it can slip out to the side (dislocation), mostly in young people. Pain behind it is common in runners.","evidence":"Textbook anatomy","pos":[0.097,0.49,0.045]},{"id":"bn_tibia","col":"s","group":"Bones","name":"Tibia (shinbone)","sub":"the main weight-bearing bone of the lower leg","how":"Carries the body's weight from the knee to the ankle; its inner ankle bump is the medial malleolus. Its front edge lies just under the skin, so fractures are often open (through the skin). A twisting fall can break its upper surface into the knee joint (tibial plateau fracture), and the lower end breaks with the fibula in ankle fractures. Repeated running can cause stress fractures.","evidence":"Textbook anatomy","pos":[0.1,0.29,0]},{"id":"bn_fibula","col":"s","group":"Bones","name":"Fibula","sub":"the thin outer bone of the lower leg","how":"Carries little weight but anchors muscles and forms the outer ankle bump (lateral malleolus), which holds the ankle joint together. A twisted ankle commonly breaks its lower end (ankle fracture). The common peroneal nerve winds round its neck just below the knee and can be damaged there, causing foot drop.","evidence":"Textbook anatomy","pos":[0.122,0.29,-0.01]},{"id":"bn_tarsals","col":"s","group":"Bones","name":"Tarsal bones","sub":"the seven bones of the back of the foot and ankle","how":"Talus, calcaneus, navicular, cuboid and three cuneiforms form the back half of the foot and the arches, passing the body's weight from the leg to the heel and the front of the foot. Twisting injuries and falls from a height can break them.","evidence":"Textbook anatomy","pos":[0.11,0.045,0.01]},{"id":"bn_talus","col":"s","group":"Bones","name":"Talus","sub":"the ankle bone that the leg rests on","how":"Sits between the tibia and fibula above and the heel bone below; it forms the ankle joint and lets the foot point up and down and tilt. Much of it is covered in cartilage and its blood supply is fragile, so a break of its neck (in falls from a height or car crashes) can leave part of it dead.","evidence":"Textbook anatomy","pos":[0.104,0.06,-0.005]},{"id":"bn_calcaneus","col":"s","group":"Bones","name":"Calcaneus (heel bone)","sub":"the heel bone","how":"The largest foot bone; it takes the impact of each heel strike and is the lever for the calf muscles through the Achilles tendon. A fall or jump from a height onto the feet can crush it, often together with a fracture of the spine; the plantar fascia pulls on its underside.","evidence":"Textbook anatomy","pos":[0.104,0.035,-0.04]},{"id":"bn_metatarsals","col":"s","group":"Bones","name":"Metatarsals","sub":"the five long bones of the forefoot","how":"Join the tarsal bones to the toes and carry the weight at push-off. Repeated marching or running can cause stress fractures (march fracture), especially in thin bones; an inward ankle twist can break the base of the fifth.","evidence":"Textbook anatomy","pos":[0.115,0.025,0.06]},{"id":"bn_phalanges_foot","col":"s","group":"Bones","name":"Phalanges of the foot","sub":"the toe bones","how":"Fourteen in each foot: two in the big toe, three in each of the others. The big toe gives the final push-off of each step and helps balance. Stubbing or dropping something on a toe often breaks one; bunions and arthritis of the big toe joint make walking painful.","evidence":"Textbook anatomy","pos":[0.12,0.015,0.11]},{"id":"bn_skull","col":"s","group":"Bones","name":"Skull","sub":"the bony case of the brain and face","how":"Twenty-two bones locked together by wavy seams (sutures): eight form the brain case (cranium) and fourteen the face. It protects the brain, eyes and inner ears and anchors the chewing muscles. Skull fractures come from direct blows and falls; a fracture at the base of the skull can tear the lining of the brain and leak fluid from the nose or ear. In older people, and in Parkinson's where falls are common, a fall onto the head can also tear veins under the skull and cause a slow bleed (subdural haematoma), even without a fracture.","evidence":"Textbook anatomy","pos":[0,1.7,0]},{"id":"bn_frontal","col":"s","group":"Bones","name":"Frontal bone","sub":"the forehead bone","how":"Forms the forehead, the roofs of the eye sockets and the front of the brain case; it holds the frontal sinuses above the eyes. It is thick and strong but can be fractured by a hard blow such as a fall face-first or a car accident, and a break through the sinus can leak fluid or air.","evidence":"Textbook anatomy","pos":[0,1.71,0.08]},{"id":"bn_parietal","col":"s","group":"Bones","name":"Parietal bone","sub":"the bone of the top and side of the head","how":"Two parietal bones, one each side, form the roof and upper sides of the brain case, meeting at the top seam (sagittal suture). Falls onto the side of the head can crack them.","evidence":"Textbook anatomy","pos":[0.06,1.73,-0.01]},{"id":"bn_temporal","col":"s","group":"Bones","name":"Temporal bone","sub":"the bone at the side of the skull holding the ear","how":"Forms the side and base of the skull at the temple; it houses the middle and inner ear (hearing and balance organs), forms the socket of the jaw joint and the mastoid bump behind the ear. Its thin part at the temple lies over the middle meningeal artery, so a fracture there can cause a dangerous bleed above the brain lining (extradural haematoma). Fractures through it can damage hearing or the facial nerve.","evidence":"Textbook anatomy","pos":[0.07,1.64,-0.01]},{"id":"bn_occipital","col":"s","group":"Bones","name":"Occipital bone","sub":"the back of the skull","how":"Forms the back and base of the brain case, with the large hole (foramen magnum) where the brainstem joins the spinal cord, and the joints with the first neck vertebra on which the head nods. The neck muscles that hold the head up attach to it. Backward falls can fracture it.","evidence":"Textbook anatomy","pos":[0,1.66,-0.09]},{"id":"bn_sphenoid","col":"s","group":"Bones","name":"Sphenoid bone","sub":"the butterfly-shaped bone at the centre of the skull base","how":"Sits in the middle of the skull base, linking the brain case and the face; it forms part of the eye sockets, holds the pituitary gland in a saddle-shaped hollow (sella turcica) and gives openings for the nerves to the eyes and face. The pterygoid plates hanging from it anchor two chewing muscles. Base-of-skull fractures may run through it.","evidence":"Textbook anatomy","pos":[0,1.63,0.01]},{"id":"bn_maxilla","col":"s","group":"Bones","name":"Maxilla","sub":"the upper jaw bone","how":"The two maxillae form the upper jaw, holding the upper teeth, the floor of the eye sockets, the sides of the nose and most of the hard palate, with a large air sinus inside each. Facial fractures through it (Le Fort fractures) follow heavy blows; the upper teeth sit in it, so bone loss here matters for dentures and implants.","evidence":"Textbook anatomy","pos":[0.02,1.59,0.08]},{"id":"bn_zygomatic","col":"s","group":"Bones","name":"Zygomatic bone","sub":"the cheekbone","how":"Forms the prominence of the cheek and the outer wall and floor of the eye socket, and with the temporal bone makes the arch the masseter hangs from. It is often broken by a punch or a fall onto the face, which can flatten the cheek and cause double vision.","evidence":"Textbook anatomy","pos":[0.055,1.61,0.06]},{"id":"bn_mandible","col":"s","group":"Bones","name":"Mandible","sub":"the lower jaw bone","how":"The only movable bone of the skull: it holds the lower teeth and hinges and slides at the jaw joints in front of the ears for chewing and speaking. It often breaks in two places at once (for example at the chin and the opposite angle), after falls onto the chin or blows. A fall forward onto the chin, common when protective reactions are slow, can also dislocate the jaw joints.","evidence":"Textbook anatomy","pos":[0.04,1.54,0.04]},{"id":"bn_vertebral_column","col":"s","group":"Bones","name":"Vertebral column (spine)","sub":"the backbone of 33 vertebrae","how":"A stack of 33 vertebrae (7 neck, 12 chest, 5 lumbar, then the fused sacrum and coccyx) joined by discs and small joints. It holds the body upright, carries the weight of head and trunk, lets the trunk bend and twist, and encloses the spinal cord. Its gentle S-curves absorb shock. Thinning bone (osteoporosis) lets vertebrae collapse, which causes height loss and a forward-rounded upper back; stooped posture in Parkinson's adds forward load on the front of the vertebrae.","evidence":"Textbook anatomy","pos":[0,1.3,-0.06]},{"id":"bn_cervical_vertebrae","col":"s","group":"Bones","name":"Cervical vertebrae (C1 to C7)","sub":"the seven neck bones","how":"The smallest and most mobile vertebrae; they carry the head and allow most nodding and turning. Holes in their side processes carry the vertebral arteries up to the brain. Neck fractures come from diving, car accidents and, in older people, falls onto the head; wear of the discs and joints (cervical spondylosis) can pinch nerve roots or the cord.","evidence":"Textbook anatomy","pos":[0,1.53,-0.03]},{"id":"bn_atlas_c1","col":"s","group":"Bones","name":"Atlas (C1)","sub":"the first neck vertebra, which holds up the skull","how":"A ring of bone with no body, on which the skull rocks for nodding 'yes'. It can burst outward from a heavy load straight down through the head (Jefferson fracture), as in diving into shallow water.","evidence":"Textbook anatomy","pos":[0,1.585,-0.022]},{"id":"bn_axis_c2","col":"s","group":"Bones","name":"Axis (C2)","sub":"the second neck vertebra, the pivot for turning the head","how":"Has an upward peg (the dens or odontoid process) around which the atlas turns for shaking the head 'no'; about half of all head turning happens here. Fracture of the peg is the most common neck fracture in older people, typically from a simple fall onto the head or face.","evidence":"Textbook anatomy","pos":[0,1.565,-0.025]},{"id":"bn_thoracic_vertebrae","col":"s","group":"Bones","name":"Thoracic vertebrae (T1 to T12)","sub":"the twelve chest vertebrae that carry the ribs","how":"Each joins a pair of ribs, so this part of the spine is stiffer and protects the heart and lungs with the rib cage. It is the most common site of osteoporotic compression fractures, often after minor strain such as lifting or a cough; several of these give the rounded upper back (kyphosis) and height loss of older age, which also shifts balance forward.","evidence":"Textbook anatomy","pos":[0,1.31,-0.06]},{"id":"bn_lumbar_vertebrae","col":"s","group":"Bones","name":"Lumbar vertebrae (L1 to L5)","sub":"the five big low-back vertebrae","how":"The largest vertebrae; they carry the most body weight and allow bending forward and back. The discs between the lower ones (L4/L5, L5/S1) are where disc herniations most often press on nerve roots (sciatica). The upper lumbar vertebrae, with the lower thoracic ones, are a common site of osteoporotic compression fractures.","evidence":"Textbook anatomy","pos":[0,1.08,-0.03]},{"id":"bn_sacrum","col":"s","group":"Bones","name":"Sacrum","sub":"the triangle of five fused vertebrae at the back of the pelvis","how":"Joins the spine to the pelvis at the sacroiliac joints, carrying the body's weight into the hips. Openings in it let out the sacral nerves for the bladder, bowel and legs. In older people with thin bones it can crack from a simple fall onto the bottom (sacral insufficiency fracture), causing low back and buttock pain.","evidence":"Textbook anatomy","pos":[0,0.92,-0.075]},{"id":"bn_coccyx","col":"s","group":"Bones","name":"Coccyx","sub":"the tailbone","how":"Three to five tiny fused vertebrae at the bottom of the spine; pelvic-floor muscles and the gluteus maximus attach to it. Falling backward onto the bottom can bruise or break it, causing long-lasting pain when sitting (coccydynia).","evidence":"Textbook anatomy","pos":[0,0.85,-0.072]},{"id":"bn_ribs","col":"s","group":"Bones","name":"Ribs","sub":"twelve pairs of curved bones around the chest","how":"Twelve pairs joined to the thoracic vertebrae at the back; the upper seven join the breastbone through cartilage, the next three join the cartilage above, and the last two float free. They protect the heart, lungs, liver and spleen and move up and out with each breath. Rib fractures are common after falls onto furniture or the floor; they make breathing painful and shallow, which can lead to pneumonia in older people. Thin bones break more easily, even from coughing.","evidence":"Textbook anatomy","pos":[0.12,1.3,0]},{"id":"bn_sternum","col":"s","group":"Bones","name":"Sternum (breastbone)","sub":"the flat bone in the middle of the chest","how":"Three parts (manubrium, body and the xiphoid tip) joined to the collarbones and the upper rib cartilages; it protects the heart and is where chest compressions are given. It can break in car crashes against a seat belt or steering wheel, and in osteoporosis, especially when the upper back is very rounded. Surgeons split it for open-heart surgery.","evidence":"Textbook anatomy","pos":[0,1.335,0.091]},{"id":"iron","col":"min","group":"Trace minerals","name":"Iron","sub":"","how":"Carried in blood by transferrin and stored as ferritin. Inside the brain it is the cofactor of tyrosine hydroxylase, the first enzyme in making dopamine, and it is needed for myelin. In the gut, iron binds levodopa and blocks its absorption if taken together.","evidence":"Proven for restless legs when iron stores are low (trials, mostly intravenous iron). Too much iron is harmful; take only when tests show it is low."},{"id":"zinc","col":"min","group":"Trace minerals","name":"Zinc","sub":"","how":"Zinc is built into hundreds of enzymes and the proteins that read genes. It is needed for immune cells, wound healing, growth, and the senses of taste and smell. Lack causes poor wound healing, frequent infections, hair loss, a rash, and dulled taste and smell.","evidence":"Needed; extra isn't shown to help people who aren't low (zinc lozenges for colds give mixed results). Long-term high zinc intake, including from some denture creams, blocks copper absorption and can cause anaemia and spinal-cord damage. Zinc gels sprayed into the nose have caused permanent loss of smell."},{"id":"copper","col":"min","group":"Trace minerals","name":"Copper","sub":"","how":"Copper is the working part of enzymes that make energy in mitochondria, neutralise free radicals, build connective tissue and myelin, and turn dopamine into noradrenaline. Lack (after stomach surgery, from poor absorption or too much zinc) causes anaemia, low white cells and a spinal-cord disease with an unsteady, stiff walk.","evidence":"Needed; deficiency is uncommon but under-recognised, and it looks like B12 deficiency. Excess from supplements is rare; inherited copper build-up (Wilson's disease) is a separate condition that causes tremor and liver disease."},{"id":"manganese","col":"min","group":"Trace minerals","name":"Manganese","sub":"","how":"Manganese is the working part of an antioxidant enzyme in mitochondria and of enzymes that make glucose and cartilage. Food supplies plenty, and the liver clears the excess into bile. Dietary deficiency is almost unknown.","evidence":"Needed in tiny amounts, harmful in excess: heavy exposure (welding and mining fumes, contaminated water, some injected street drugs) or poor liver clearance lets it build up in the basal ganglia and cause manganism, a parkinsonism with stiffness, slowness and falls that responds poorly to levodopa."},{"id":"thiamine","col":"vit","group":"Water-soluble","name":"Thiamine (vitamin B1)","sub":"","how":"Thiamine is the helper the cells need to burn sugar for energy; the brain and nerves, which run almost entirely on sugar, suffer first. Severe lack causes beriberi (nerve damage in the legs, heart failure) and Wernicke–Korsakoff syndrome (confusion, unsteady walking, and lasting memory loss). Heavy drinking, vomiting and weight-loss surgery are the usual causes.","evidence":"Needed; treating a deficiency urgently prevents permanent memory loss. Extra beyond a normal diet isn't shown to help healthy people; claims of benefit from high-dose thiamine in Parkinson's come only from small uncontrolled reports."},{"id":"riboflavin","col":"vit","group":"Water-soluble","name":"Riboflavin (vitamin B2)","sub":"","how":"Riboflavin is built into FAD and FMN, helpers that let mitochondria turn food into energy. It is also needed to activate vitamin B6 and to run the enzyme that recycles folate. Lack causes cracked lips and mouth corners, a sore red tongue and eye irritation.","evidence":"Needed; deficiency is uncommon. Extra is harmless (it simply turns urine bright yellow) but isn't shown to help beyond a normal diet."},{"id":"niacin","col":"vit","group":"Water-soluble","name":"Niacin (vitamin B3)","sub":"nicotinic acid, nicotinamide","how":"Niacin is made into NAD, a molecule used in hundreds of energy and repair reactions in every cell. The body can also make some from the amino acid tryptophan. Severe lack causes pellagra: rash on sun-exposed skin, diarrhoea and confusion or dementia.","evidence":"Needed; deficiency is rare where diets are varied. High-dose nicotinic acid causes flushing and can damage the liver, and in large heart trials it did not prevent heart attacks. Forms that raise NAD are being studied in Parkinson's, without proven benefit so far."},{"id":"pantothenic","col":"vit","group":"Water-soluble","name":"Pantothenic acid (vitamin B5)","sub":"","how":"Pantothenic acid is built into coenzyme A, which every cell uses to burn fat and sugar and to make fats, cholesterol and the nerve messenger acetylcholine. It is in almost every food, so deficiency is very rare (burning feet and tiredness were seen in starvation).","evidence":"Needed; extra isn't shown to help."},{"id":"biotin","col":"vit","group":"Water-soluble","name":"Biotin (vitamin B7)","sub":"","how":"Biotin is the helper for enzymes that make glucose and fat and break down some amino acids. Lack is rare (thinning hair, scaly rash, numbness); eating many raw egg whites can cause it, because they contain avidin, which locks biotin up.","evidence":"Needed; extra isn't shown to help hair or nails in people who aren't deficient. High-dose biotin can make some blood tests (thyroid, heart-attack troponin) read falsely, so tell the lab. In progressive multiple sclerosis a large trial of high-dose biotin failed."},{"id":"folate","col":"vit","group":"Water-soluble","name":"Folate (vitamin B9)","sub":"folic acid in supplements and fortified flour","how":"Folate supplies the one-carbon pieces the body needs to copy DNA and make new cells, especially red blood cells in the bone marrow, and, together with B12, to recycle homocysteine. Low folate causes anaemia with oversized red cells, and in early pregnancy raises the risk of spina bifida in the baby.","evidence":"Proven: folic acid before and in early pregnancy prevents most neural-tube defects. Otherwise, extra beyond a normal diet isn't shown to help, and high folic acid can hide the anaemia of B12 deficiency while B12 nerve damage carries on, so B12 should be checked too."},{"id":"choline","col":"c","group":"Vitamins & minerals","name":"Choline","sub":"","how":"The body uses choline to build cell membranes, to make acetylcholine (a nerve messenger for attention, memory and muscle control), to carry fat out of the liver, and, as betaine, to donate methyl groups that recycle homocysteine. The liver makes some but not enough; too little causes fatty liver and muscle damage.","evidence":"Needed, and many people eat less than advised. Choline supplements have not been shown to improve memory in adults. Very high intakes cause a fishy body odour, sweating and low blood pressure."},{"id":"limonene","col":"c","group":"Aromatic compounds","name":"Limonene","sub":"citrus terpene; orange, lemon, bergamot, spearmint","how":"The main compound in citrus peel oils, giving the orange-peel smell. Fresh it is mild, but in air it oxidises to hydroperoxides that are skin allergens.","evidence":"Lab only for most health claims. Association: oxidised limonene is a common fragrance allergen on patch testing."},{"id":"bergapten","col":"c","group":"Aromatic compounds","name":"Bergapten (5-MOP)","sub":"furocoumarin in bergamot and some other citrus oils","how":"A psoralen: it slips between the strands of DNA in skin cells and, when struck by ultraviolet light, binds them, causing a delayed sunburn-like reaction with blisters and lasting dark marks. Doctors once used the same chemistry deliberately for psoriasis.","evidence":"Established: phototoxic on human skin. Furocoumarin-free (labelled 'FCF' or 'bergapten-free') bergamot oil avoids this."},{"id":"menthol","col":"c","group":"Aromatic compounds","name":"Menthol","sub":"the cooling compound in mint oils","how":"The main compound in peppermint oil. It switches on TRPM8, the skin's and mouth's cold sensor, so it feels cool without changing temperature; in the gut it relaxes smooth muscle by blocking calcium entry.","evidence":"Established: the cooling sensation via TRPM8. Pain relief from that cooling is shown only modestly (peppermint oil for tension headache in one small trial)."},{"id":"linalool","col":"c","group":"Aromatic compounds","name":"Linalool","sub":"floral terpene alcohol; lavender, clary sage, ylang-ylang, bergamot","how":"A light floral-smelling compound, the main ingredient (with linalyl acetate) of lavender and clary sage oils. Fresh linalool is mild, but on contact with air it slowly forms hydroperoxides that are strong skin allergens.","evidence":"Lab: calming effects in animals. Association: oxidised linalool is one of the commonest fragrance allergens on patch testing."},{"id":"methyl_salicylate","col":"c","group":"Aromatic compounds","name":"Methyl salicylate","sub":"oil of wintergreen, sweet birch; muscle rubs","how":"An aspirin relative that passes readily through skin and gut and is turned into salicylate in the body. On skin it warms and reddens (a 'rubefacient'). Because the oil is almost pure methyl salicylate, a small amount carries a very large salicylate load.","evidence":"Established harm: poisoning (ringing ears, vomiting, fast breathing, confusion, seizures, death), especially in small children who swallow it. Mixed: weak evidence that rubs ease pain."},{"id":"cineole","col":"c","group":"Aromatic compounds","name":"1,8-Cineole (eucalyptol)","sub":"eucalyptus, rosemary, tea tree, cajeput","how":"The camphor-like, 'clearing' smell of eucalyptus. Inhaled or swallowed it is absorbed into the blood and reaches the brain. Swallowed as a purified capsule it thins airway mucus and calms airway inflammation in lab studies; at high exposure it excites the brain and can trigger seizures.","evidence":"Mixed: maker-funded trials found fewer COPD flare-ups and faster bronchitis relief with capsules. Association: seizures after heavy exposure. One of the four classic smell-training odours."},{"id":"camphor","col":"c","group":"Aromatic compounds","name":"Camphor","sub":"camphor laurel, rosemary, chest rubs","how":"A waxy aromatic compound that feels cool, then warm, on the skin. It passes easily through skin and gut into the brain, where at higher amounts it overexcites nerve cells.","evidence":"Established: a known cause of seizures in poisoning, especially in young children, by swallowing or repeated rubbing on the skin. The US restricts camphor content in medicines for this reason."},{"id":"carvacrol","col":"c","group":"Aromatic compounds","name":"Carvacrol","sub":"oregano, thyme","how":"A spicy phenol, the main compound in oregano oil. It disrupts bacterial membranes in lab dishes and irritates skin and mouth lining when concentrated.","evidence":"Lab only: antimicrobial and anti-inflammatory in cells and animals; no reliable human trials of oregano oil for infections."},{"id":"thymol","col":"c","group":"Aromatic compounds","name":"Thymol","sub":"thyme, oregano; antiseptic mouthwashes","how":"A phenol from thyme that kills mouth bacteria and breaks up dental plaque film; it is one of the active ingredients of essential-oil mouthwashes.","evidence":"Proven as part of a fixed essential-oil mouthrinse for plaque and gum inflammation; other health claims are lab only."},{"id":"eugenol","col":"c","group":"Aromatic compounds","name":"Eugenol","sub":"clove, cinnamon leaf, bay","how":"The main compound of clove oil. It blocks nerve signals in a way similar to local anaesthetics, which is why dentists use it in zinc oxide–eugenol dressings; it is also a known skin allergen. One of the four classic smell-training odours.","evidence":"Established: used in dental dressings. Mixed: clove gel numbed the gum in one small trial."},{"id":"terpinen4ol","col":"c","group":"Aromatic compounds","name":"Terpinen-4-ol","sub":"main compound of tea tree oil","how":"The main antimicrobial compound in tea tree oil; it damages the outer membranes of bacteria and fungi in lab tests.","evidence":"Lab: kills skin bacteria and fungi in dishes. Human benefit is judged from trials of the whole oil."},{"id":"alpha_pinene","col":"c","group":"Aromatic compounds","name":"Alpha-pinene","sub":"pine-scented terpene; frankincense, rosemary, pine","how":"The pine-forest smell; a common terpene in conifer, frankincense and rosemary oils. Inhaled it is absorbed in small amounts.","evidence":"Lab only: anti-inflammatory and airway effects in cells and animals."},{"id":"calcium","col":"min","group":"Major minerals","name":"Calcium","sub":"","how":"Almost all the body's calcium is stored in bone and teeth; the small amount in blood is held very steady because every muscle contraction, heartbeat, nerve signal and blood clot depends on it. Vitamin D controls how much the gut absorbs. When intake is low for years, the body takes calcium from bone, which thins it (osteoporosis).","evidence":"Needed for bone; getting enough from food matters most. Calcium supplements alone prevent fractures only weakly at best, and can cause constipation and kidney stones. Calcium blocks absorption of iron, thyroid hormone and some antibiotics if taken at the same time."},{"id":"phosphorus","col":"min","group":"Major minerals","name":"Phosphorus","sub":"phosphate","how":"Phosphate joins calcium to form the mineral of bone and teeth, and it is part of ATP (the cell's energy currency), DNA and cell membranes. It is in nearly all protein foods, so lack is rare except in severe malnutrition or during refeeding.","evidence":"Needed; most people get plenty, partly from phosphate additives in processed foods and colas. In kidney disease, phosphate builds up and harms bones and blood vessels, so intake is limited then."},{"id":"potassium","col":"min","group":"Major minerals","name":"Potassium","sub":"","how":"Potassium is the main salt inside cells. Nerves fire and muscles (including the heart) contract by letting potassium and sodium swap across their membranes. Low potassium, usually from vomiting, diarrhoea or water tablets, causes weakness, cramps and an irregular heartbeat.","evidence":"Needed, and diets rich in fruit and vegetables supply more of it along with lower blood pressure. Supplements and salt substitutes can push potassium dangerously high in kidney disease or with some blood-pressure medicines; check first."},{"id":"sodium","col":"min","group":"Major minerals","name":"Sodium","sub":"salt (sodium chloride)","how":"Sodium is the main salt outside cells. It controls how much water the body holds, and with it blood volume and blood pressure, and it carries the electrical signal along nerves. The kidneys keep its level steady.","evidence":"Needed; most people eat far more than they need, and lowering salt lowers blood pressure in trials. The exception is low blood pressure on standing, where doctors sometimes advise more salt and water. Too little blood sodium (often from medicines or drinking very large amounts of water) causes confusion and falls."},{"id":"vite","col":"vit","group":"Fat-soluble","name":"Vitamin E","sub":"tocopherols","how":"Vitamin E is the main fat-soluble antioxidant: it sits in cell membranes, including the fatty insulation of nerves, and stops chain reactions of oxidation. Deficiency is rare and mostly seen when fat cannot be absorbed (some liver, pancreas or gut diseases, rare genetic conditions); it damages nerves and the cerebellum, causing numbness and unsteady walking.","evidence":"Needed, but extra doesn't help: in the large DATATOP trial, high-dose vitamin E did not slow early Parkinson's. Large trials also found no protection against heart disease or cancer (one raised prostate-cancer risk). High doses can increase bleeding, especially with blood thinners."},{"id":"vitk","col":"vit","group":"Fat-soluble","name":"Vitamin K","sub":"K1 from leaves; K2 from fermented foods and gut bacteria","how":"Vitamin K lets the liver make the clotting proteins that stop bleeding, and it switches on bone proteins that hold calcium in bone. K1 comes from green leaves; K2 is made by bacteria (in fermented foods and the gut). Deficiency causes easy bleeding; newborns are given it at birth because they start with very little.","evidence":"Needed; extra isn't shown to help healthy bones. Important interaction: warfarin works by blocking vitamin K, so a sudden big change in how much leafy green food someone eats can push warfarin's effect up or down. Keep intake steady rather than avoiding greens. Newer blood thinners don't interact this way."},{"id":"vita","col":"vit","group":"Fat-soluble","name":"Vitamin A","sub":"retinol; beta-carotene from plants","how":"Vitamin A forms the light-catching pigment in the eye that lets us see in dim light, and it acts as a gene switch that keeps the linings of the eyes, gut and lungs healthy and the immune system working. Animal foods supply ready-made retinol; orange and dark-green plants supply beta-carotene, which the body converts as needed. Lack causes night blindness, dry damaged eyes and more severe infections; it is a leading cause of preventable childhood blindness worldwide.","evidence":"Needed, but harmful in excess: too much ready-made retinol (supplements, frequent liver) damages the liver, thins bones and causes birth defects in pregnancy. High-dose beta-carotene supplements raised lung-cancer risk in smokers in large trials. Beta-carotene from food is safe."},{"id":"vitc","col":"vit","group":"Water-soluble","name":"Vitamin C","sub":"ascorbic acid","how":"Vitamin C is needed to make collagen, the protein that holds skin, gums, blood-vessel walls, bones and wounds together, and it is the main water-soluble antioxidant. It also helps the gut absorb iron from plant foods and helps make noradrenaline. Lack causes scurvy: bleeding gums, easy bruising, slow wound healing and tiredness.","evidence":"Needed; extra beyond a normal diet isn't shown to prevent colds in most people or to slow disease. Very high supplement doses can cause diarrhoea and, in some people, kidney stones."},{"id":"selenium","col":"min","group":"Trace minerals","name":"Selenium","sub":"","how":"Selenium is built into about 25 selenoproteins, including antioxidant enzymes (glutathione peroxidases) and the enzymes that activate thyroid hormone. How much food contains depends on the soil it grew in. Lack, seen in low-selenium regions, can weaken heart muscle and joints and worsen thyroid problems.","evidence":"Needed, harmful in excess: in a large cancer-prevention trial (SELECT) selenium supplements did not prevent cancer, and too much causes selenosis (brittle hair and nails, garlic breath, rash, nerve damage). A few Brazil nuts a day can already exceed the safe amount."},{"id":"iodine","col":"min","group":"Trace minerals","name":"Iodine","sub":"","how":"The thyroid gland uses iodine to make thyroid hormone, which sets the body's energy rate and is essential for brain development before birth and in early childhood. Lack causes a swollen thyroid (goitre) and an underactive thyroid (tiredness, feeling cold, slow thinking, weight gain); in pregnancy it can permanently harm the baby's brain. Iodised salt prevents most deficiency.","evidence":"Needed; extra doesn't help. Too much, often from kelp tablets or large amounts of seaweed, can make the thyroid under- or over-active. Plant-based diets without iodised salt or dairy can run low."},{"id":"keto","col":"h","group":"Habits & therapies","name":"Ketogenic diet","sub":"very low carbohydrate, medically supervised","how":"Starving the body of carbohydrate makes the liver produce ketones, which the brain uses for fuel; this shifts brain energy metabolism and raises inhibition (GABA) relative to excitation, making seizures less likely.","evidence":"Proven: randomised trials in children with drug-resistant epilepsy. Needs medical supervision."},{"id":"fewfoods","col":"h","group":"Habits & therapies","name":"Few-foods elimination diet","sub":"with a dietitian","how":"Removes most foods for a few weeks, then re-introduces them one at a time to see whether any affect behaviour.","evidence":"Mixed: one trial in children with ADHD found a large improvement (INCA 2011), but it is hard to sustain, needs supervision and hasn't been widely replicated."},{"id":"cbt","col":"h","group":"Habits & therapies","name":"Talking therapy (CBT)","sub":"cognitive behavioural therapy","how":"Practises noticing and testing anxious thoughts and gradually facing feared situations, so the fear system learns they are safe.","evidence":"Proven for anxiety disorders and depression in many randomised trials."},{"id":"pelvic","col":"h","group":"Habits & therapies","name":"Bladder & pelvic-floor training","sub":"","how":"Gradually lengthening the time between toilet visits and strengthening pelvic-floor muscles retrains the bladder reflex.","evidence":"Proven for overactive bladder in the general population; smaller studies in Parkinson's."},{"id":"vaccine","col":"h","group":"Habits & therapies","name":"Shingles vaccination","sub":"","how":"Trains the immune system to keep the varicella-zoster virus (chickenpox) asleep in nerve roots, so it doesn't reactivate as shingles.","evidence":"Natural experiment in Wales (Eyting 2025): people just eligible by birth date were about 20% less likely to be diagnosed with dementia over 7 years than those just too old. Strong for an observational design, but not a randomised trial."},{"id":"h_ergonomics","col":"h","group":"Habits & therapies","name":"Ergonomic redesign","sub":"lifting devices, adjustable workstations, job rotation","how":"Changes the job instead of the worker: hoists and lifting aids, lower load weights, work heights that keep arms low and the back straight, and breaks or rotation away from repetitive tasks.","evidence":"Patient-lifting devices are linked with fewer injuries and less back pain in health-care staff. Teaching 'safe lifting' technique alone does not prevent back pain (Cochrane, moderate quality). Office ergonomic changes show little clear effect on arm and neck problems."},{"id":"h_early_activity","col":"h","group":"Habits & therapies","name":"Early physical therapy & graded activity","sub":"for back pain after injury","how":"Staying active, early guided exercise and gradually returning to normal tasks, rather than bed rest, keep muscles conditioned and reduce fear of movement.","evidence":"Exercise therapy reduces chronic low back pain (moderate certainty, Cochrane). For brand-new back pain, early physical therapy helped only slightly, below a clinically important amount."},{"id":"h_hearing_protection","col":"h","group":"Habits & therapies","name":"Hearing protection","sub":"earplugs, earmuffs, quieter machines","how":"Reduces the sound energy reaching the inner ear. Quieter machines and enclosures come first; earplugs only work if inserted properly and worn throughout exposure.","evidence":"Training in earplug fitting reduces noise exposure (moderate quality); evidence that hearing-protection programmes prevent hearing loss is very low quality, mainly for lack of good studies."},{"id":"h_respiratory_protection","col":"h","group":"Habits & therapies","name":"Dust control & respiratory protection","sub":"wet cutting, extraction, respirators","how":"Wet cutting and local extraction stop dust at the source; a correctly fitted respirator filters what remains. Respirators are the last line, after controlling the dust itself.","evidence":"Established that filtering and controlling dust lowers what is breathed in; silicosis and asbestos disease fell where exposure was controlled."},{"id":"deworming","col":"h","group":"Habits & therapies","name":"Deworming medicines","sub":"albendazole, mebendazole, ivermectin; school deworming programmes","how":"Medicines that kill or expel gut worms. Where worms are common, many countries give them to all schoolchildren at regular intervals whether or not each child is infected.","evidence":"Proven: they cure most Ascaris roundworm infections (Conterno 2020). Failed: regularly treating all children in programmes did not improve average growth, haemoglobin, thinking-test scores or school performance in pooled trials (Taylor-Robinson 2019; Welch 2019). Treating a diagnosed infection is a separate question."},{"id":"h_saline_irrigation","col":"h","group":"Habits & therapies","name":"Saline nasal rinsing","sub":"salty-water nasal irrigation","how":"Rinsing the nose with salty water washes out mucus, allergens and crusts and may help the tiny hairs that clear the lining. Water used for rinsing should be sterile or boiled, never straight from the tap.","evidence":"Small randomised trials found better sinus symptom scores than usual care; certainty is low (Chong 2016 Cochrane)."},{"id":"h_epley","col":"h","group":"Habits & therapies","name":"Repositioning manoeuvres (Epley)","sub":"for BPPV","how":"A sequence of head and body positions, done by a clinician or taught for home use, that rolls loose crystals out of the semicircular canal back to where they do no harm.","evidence":"Randomised trials show the Epley manoeuvre cures posterior-canal BPPV far more often than sham (Hilton 2014 Cochrane). Nausea during the manoeuvre is common; neck problems can limit it."},{"id":"h_vestibular_rehab","col":"h","group":"Habits & therapies","name":"Vestibular rehabilitation","sub":"balance and gaze exercises","how":"Graded head, eye and balance exercises that train the brain to compensate for a damaged balance organ, reducing dizziness and steadying walking.","evidence":"Randomised trials show it reduces dizziness after one-sided inner-ear balance loss (Hillier and McDonnell 2016, Cochrane). For BPPV, repositioning manoeuvres work faster."},{"id":"h_hearing_aids","col":"h","group":"Habits & therapies","name":"Hearing aids","sub":"and cochlear implants for severe loss","how":"Hearing aids make sound louder and clearer in the pitch ranges a person has lost; cochlear implants bypass dead hair cells and stimulate the hearing nerve directly. Fitting by an audiologist and wearing them regularly matter for benefit.","evidence":"Randomised trials show hearing aids improve everyday hearing and hearing-related quality of life (Ferguson 2026 Cochrane). Effects on memory and thinking are uncertain (ACHIEVE trial)."},{"id":"h_cpap","col":"h","group":"Habits & therapies","name":"CPAP for sleep apnoea","sub":"continuous positive airway pressure","how":"A mask worn in sleep blows gentle air pressure that holds the throat open, stopping the breathing pauses. Benefit depends on wearing it most of the night.","evidence":"Randomised trials show less daytime sleepiness and better quality of life in moderate to severe sleep apnoea (Giles 2006 Cochrane)."},{"id":"h_hpv_vaccine","col":"h","group":"Habits & therapies","name":"HPV vaccination","sub":"","how":"A vaccine that trains the immune system to block infection by the main cancer-causing HPV types; it works best given before any exposure, usually in early adolescence, to all sexes.","evidence":"Randomised trials show it prevents infection and precancer of the cervix; one trial found far fewer oral HPV infections (Herrero 2013). Prevention of throat cancer itself is expected but not yet directly measured."},{"id":"h_fluoride_toothpaste","col":"h","group":"Habits & therapies","name":"Brushing with fluoride toothpaste","sub":"toothbrushing","how":"Brushing removes plaque, the sticky bacterial film that causes decay and gum inflammation. Fluoride in the paste is taken up into the enamel surface, making it more resistant to acid and helping early decay re-harden.","evidence":"Proven: Cochrane reviews of dozens of trials found fluoride toothpaste prevents decay compared with non-fluoride toothpaste in children and adolescents, with a stronger effect at higher fluoride levels (Marinho 2003; Walsh 2019). Swallowing too much fluoride in early childhood can cause white marks on teeth (fluorosis), which is why a small amount is used for young children."},{"id":"h_fluoride_varnish","col":"h","group":"Habits & therapies","name":"Fluoride varnish","sub":"painted on by a dental professional","how":"A sticky fluoride coating painted onto teeth that slowly releases fluoride into the enamel surface over hours.","evidence":"Proven, moderate certainty: Cochrane review of 22 trials found a substantial reduction in decay in both baby and adult teeth of children, though many trials had a high risk of bias (Marinho 2013)."},{"id":"h_water_fluoridation","col":"h","group":"Habits & therapies","name":"Community water fluoridation","sub":"public health measure","how":"Adjusting the fluoride level in public drinking water so that teeth are bathed in low levels of fluoride throughout the day.","evidence":"Association: the 2024 Cochrane review found no randomised trials; in non-randomised controlled studies, starting fluoridation brought large reductions in decay before 1975 but only slightly greater reductions in contemporary studies, now that fluoride toothpaste is widespread. No eligible studies measured decay in adults. Higher fluoride levels in water are linked with more dental fluorosis (white marks on teeth). Other claimed health effects are debated and outside this link."},{"id":"h_interdental","col":"h","group":"Habits & therapies","name":"Flossing & interdental brushes","sub":"cleaning between teeth","how":"Floss or small brushes reach the plaque between teeth that a toothbrush misses.","evidence":"Mixed, low certainty: in a Cochrane review, adding floss or interdental brushes to toothbrushing may reduce gingivitis or plaque a little more than brushing alone over weeks to months; interdental brushes may beat floss. Trials were short and the size of the benefit may not be clinically important; effects on decay between teeth and on periodontitis were not measured (Worthington 2019)."},{"id":"h_mouthwash","col":"h","group":"Habits & therapies","name":"Antiseptic mouthwash","sub":"chlorhexidine; essential-oil rinses","how":"Rinses that kill or slow plaque bacteria. Chlorhexidine sticks to teeth and gums and keeps working for hours; essential-oil rinses use thymol, eucalyptol and menthol. They kill helpful mouth bacteria as well, including those that turn dietary nitrate into nitrite.","evidence":"Proven: used with brushing, chlorhexidine rinse greatly reduces plaque in trials, but the reduction in mild gingivitis is small (Cochrane, James 2017); essential-oil rinse also reduces plaque and gingivitis (see thymol). Established: chlorhexidine can stain teeth and change taste, and rarely causes allergy. Association: it lowers the mouth's nitrite production in small studies; a 2026 meta-analysis found no meaningful effect on blood pressure (Toonen 2026)."},{"id":"h_botox_saliva","col":"h","group":"Habits & therapies","name":"Botulinum toxin for drooling","sub":"injections into the salivary glands","how":"A specialist injects botulinum toxin into the parotid and/or submandibular glands. It blocks the nerve signal (acetylcholine) that tells the glands to make saliva, so less saliva pools in the mouth for some months, then wears off.","evidence":"Proven: in placebo-controlled trials in Parkinson's, it reduced drooling severity and frequency (meta-analysis of 8 trials, high certainty); side effects such as dry mouth and chewing or swallowing trouble were more common than with placebo (Yang 2023). It treats the pooling of saliva, not the underlying slow swallowing."},{"id":"h_psa_screening","col":"h","group":"Habits & therapies","name":"PSA screening test","sub":"blood test for prostate cancer","how":"A blood test for PSA, a protein made by the prostate. Levels rise with cancer but also with an enlarged prostate, infection, recent ejaculation or cycling, so a raised level leads to MRI and often a biopsy rather than a diagnosis.","evidence":"Trials show a small benefit with real trade-offs: screening likely prevents about 2 prostate cancer deaths per 1000 men screened over many years, but finds many slow cancers that would never have caused harm (overdiagnosis), leading to biopsies and treatments with side effects. Overall death rates change little. Guidelines therefore advise an informed, shared decision, mostly for men in their 50s and 60s."},{"id":"h_mld","col":"h","group":"Habits & therapies","name":"Manual lymphatic drainage","sub":"a gentle skin-stretching massage","how":"A light, rhythmic massage given by a trained therapist that stretches the skin rather than pressing the muscles. Step by step: (1) the therapist first works on healthy areas near the trunk and neck to \"empty\" the nodes and vessels there; (2) then strokes the swollen area slowly toward those working routes; (3) the gentle stretch opens lymph capillaries and stimulates the lymphangions to pump faster. It is usually one part of complete decongestive therapy, together with compression bandaging, skin care and exercise.","evidence":"Mixed. A Cochrane review (Ezzo 2015) found adding it to compression gave inconsistent extra reduction in swelling, though most people felt less pain and heaviness whatever they received. Later meta-analyses disagree: one found less new lymphoedema and less pain but no change in arm volume (Lin 2022), another no significant reduction (Liang 2020)."},{"id":"h_compression","col":"h","group":"Habits & therapies","name":"Compression garments & bandaging","sub":"sleeves, stockings and wraps","how":"Firm elastic sleeves, stockings or layered bandages that press on a limb from outside, tightest at the hand or foot and looser toward the trunk. They stop fluid leaking out of the blood vessels as easily, give the muscles something to push against so each movement pumps lymph harder, and help keep a limb from swelling back after it has been reduced. Garments for lymphoedema are fitted by a therapist.","evidence":"In a randomised trial, compression sleeves worn after breast cancer surgery lowered and delayed arm swelling in women at high risk (Paramanandam 2022); a 2025 meta-analysis agreed. Bandaging is a standard part of treating established lymphoedema."},{"id":"h_asplenia_vaccines","col":"h","group":"Habits & therapies","name":"Vaccines when the spleen is missing","sub":"pneumococcal, meningococcal, Hib, yearly flu","how":"Vaccines train antibodies against the sugar-coated bacteria that a missing spleen can no longer filter well, so the body can clear them before they flood the blood.","evidence":"Recommended by guidelines for everyone without a working spleen, ideally before planned surgery, with boosters; paired with a plan to get antibiotics fast if fever starts (BCSH guideline, Davies 2002)."},{"id":"h_emst","col":"h","group":"Habits & therapies","name":"Breathing-out muscle training (EMST)","sub":"expiratory muscle strength training","how":"Blowing hard through a small hand-held device with a spring valve that only opens at a set pressure, practised regularly over several weeks, usually guided by a speech and language therapist. It strengthens the muscles used to breathe out and cough, and the muscles under the chin that lift the voice box during a swallow.","evidence":"Proven in one sham-controlled randomised trial in Parkinson's: safer swallowing on X-ray swallow studies (Troche 2010). Whether it lowers pneumonia rates has not been tested; a 2023 trial found a sensorimotor cough-training programme improved cough more than EMST."},{"id":"h_cardiac_rehab","col":"h","group":"Habits & therapies","name":"Cardiac rehabilitation","sub":"supervised exercise and education for heart patients","how":"A programme after a heart attack, stent, bypass or with heart failure: graded, supervised exercise plus education on medicines, diet, smoking and mood. Training improves how muscles use oxygen, so the heart works less hard for the same effort.","evidence":"Proven: Cochrane reviews of randomised trials found fewer heart attacks and hospital admissions in coronary disease (Dibben 2021) and fewer hospital admissions and better quality of life in heart failure (Long 2019)."},{"id":"h_compression_stockings","col":"h","group":"Habits & therapies","name":"Compression stockings","sub":"graduated stockings for the legs","how":"Tight at the ankle and looser up the leg, they squeeze the leg veins narrower so blood flows back faster and pools less.","evidence":"Proven for long flights: in randomised trials, airline passengers wearing them had far fewer symptomless deep vein clots (Clarke 2021 Cochrane)."},{"id":"h_low_fodmap","col":"h","group":"Habits & therapies","name":"Low-FODMAP diet","sub":"short elimination then reintroduction, with a dietitian","how":"FODMAPs are short-chain carbohydrates (in wheat, onions, garlic, beans, some fruits, milk sugar, sugar alcohols) that are poorly absorbed, draw water into the bowel and are fermented into gas. Cutting them for a few weeks, then adding foods back one at a time, finds which ones trigger symptoms in sensitive guts.","evidence":"Best-supported diet for IBS in pooled trials. It is meant to be temporary: long-term strict restriction reduces fibre and helpful bacteria such as Bifidobacterium, so it is done with a dietitian."},{"id":"h_pulmonary_rehab","col":"h","group":"Habits & therapies","name":"Pulmonary rehabilitation","sub":"supervised exercise and education for lung disease","how":"A programme of several weeks of supervised exercise training (walking or cycling plus strength work), breathing techniques and education about the condition, its medicines and flare-ups. Training the leg and arm muscles lets them do more with less oxygen, so the same task causes less breathlessness.","evidence":"Proven in COPD: a Cochrane review of 65 randomised trials found less breathlessness and fatigue, better quality of life and more exercise capacity (McCarthy 2015). Benefits fade if activity is not kept up afterwards."},{"id":"h_smoking_cessation","col":"h","group":"Habits & therapies","name":"Stopping smoking","sub":"with counselling and stop-smoking medicines","how":"After the last cigarette, carbon monoxide clears within a day, airway irritation and cough settle over weeks to months, and the rate at which lung function is lost falls back toward that of a non-smoker. Counselling combined with nicotine replacement or other stop-smoking medicines roughly doubles the chance of quitting.","evidence":"Proven: in the Lung Health Study, people randomised to a quit-smoking programme lost lung function more slowly (Anthonisen 1994) and had lower death rates 14.5 years later (Anthonisen 2005). Damage already done does not reverse."},{"id":"h_sglt2_inhibitors","col":"h","group":"Habits & therapies","name":"SGLT2 inhibitor medicines","sub":"'flozins' (dapagliflozin, empagliflozin)","how":"Tablets first made for diabetes that block sugar and salt reabsorption in the proximal tubule. This lowers pressure inside the glomeruli, which seems to protect the remaining nephrons; they also help the heart. Prescribed by a doctor; not for everyone (for example some with type 1 diabetes or very low kidney function at the start).","evidence":"Proven: large RCTs (DAPA-CKD 2020, EMPA-KIDNEY 2023) in people with CKD, with or without diabetes, lowered kidney-disease progression or cardiovascular death."},{"id":"h_ras_blockers","col":"h","group":"Habits & therapies","name":"ACE inhibitors and angiotensin blockers","sub":"'prils' and 'sartans'","how":"Blood-pressure medicines that block the renin-angiotensin hormone system. Besides lowering pressure, they relax the outflow vessel of the glomerulus, so less protein leaks and the filters are spared. They can raise potassium and briefly lower filtering, so blood tests are checked after starting.","evidence":"Proven for diabetic kidney disease with protein in the urine (RENAAL and IDNT trials 2001); standard care for proteinuric CKD."},{"id":"h_dialysis","col":"h","group":"Habits & therapies","name":"Dialysis","sub":"haemodialysis or peritoneal dialysis","how":"Replaces the kidneys' cleaning when they fail. Haemodialysis pumps blood through a filter machine, usually several sessions a week at a unit or at home, through an arm fistula or a line. Peritoneal dialysis fills the belly with fluid through a soft tube and uses the belly lining as the filter, done daily at home. It removes waste, extra potassium and fluid, but does not replace the kidneys' hormones.","evidence":"Established life-sustaining treatment for kidney failure; a kidney transplant usually gives longer and better life where possible."},{"id":"h_slow_breathing","col":"h","group":"Habits & therapies","name":"Slow breathing","sub":"paced or 'resonance' breathing, about six breaths a minute","how":"Breathing in and out slowly and evenly, with long out-breaths. The vagus slows the heart on each out-breath and lets it speed up on each in-breath, so slow, deep breathing exaggerates this swing, which shows up as higher heart-rate variability, a common sign of vagus activity.","evidence":"Raises heart-rate measures of vagus activity during practice and after a course of practice (meta-analysis of 223 studies, Laborde 2022). Whether this improves any illness is much less certain."},{"id":"h_early_allergen_intro","col":"h","group":"Habits & therapies","name":"Early introduction of allergen foods in infancy","sub":"peanut, egg and other common allergens in the first year","how":"Giving babies common allergen foods (smooth peanut products, well-cooked egg and others) in age-appropriate forms during the first year, alongside other solids, and keeping them in the diet regularly. Eating the food trains oral tolerance before the immune system meets it first through inflamed skin. Babies with severe eczema or known egg allergy are at highest risk, and families are advised to ask a doctor before starting peanut in these babies.","evidence":"Proven for peanut in high-risk babies: in the LEAP trial regular peanut from 4 to 11 months cut peanut allergy at age five from about 14% to 2% (Du Toit 2015). A meta-analysis of trials found that introducing several allergenic foods early roughly halved food allergy (moderate certainty; Scarpone 2023). Egg evidence is weaker (mixed). Early solids did not prevent eczema (PreventADALL)."},{"id":"pp_p6","col":"h","group":"Pressure points","name":"P6 Neiguan (inner wrist)","sub":"both sides; also called PC6","how":"A point on the palm side of the forearm, about three finger-widths above the wrist crease, between the two central tendons, over the median nerve. Pressing it is the basis of anti-sickness wristbands. How it works is not known.","evidence":"The best-tested acupressure point. Cochrane reviews of 59 and 77 trials found wrist stimulation, including wristbands, reduced nausea and vomiting after surgery versus sham, about as much as anti-sickness drugs, with low-certainty evidence (Lee 2015, 2025). Sham wristbands make these trials easier to blind than most acupressure research. Evidence in early pregnancy is limited (Cochrane 2015), and in chemotherapy acupressure gave only a small drop in nausea on top of standard drugs (Cochrane 2006). Side effects: skin irritation or redness.","pos":[0.318,0.94,0.022]},{"id":"h_acupressure","col":"h","group":"Pressure points","name":"Acupressure & massage of points","sub":"pressing named points by hand or band; see the individual points","how":"Firm pressure on specific skin points named in traditional Chinese medicine. Physiologically, pressure stimulates nerves in skin, muscle and the tissue around bone; animal studies show such signals can drive reflexes through the spinal cord and brainstem (Liu 2021), and the calm, attention and touch involved also relax people. Whether the exact point matters, rather than pressing anywhere, is the unresolved question.","evidence":"Many small trials, mostly positive, but with high bias and very different results between studies. Pressure trials are hard to blind: the person pressing knows which point is real, and patients may guess. Where a sham point is used, the gap is usually smaller, and sham pressure itself often helps (Tan 2015; Hu 2024). Best evidence: P6 for nausea after surgery. Safe when gentle; bruising is the usual side effect."},{"id":"pp_gb20","col":"h","group":"Pressure points","name":"GB20 Fengchi (base of skull)","sub":"both sides; hollows below the back of the skull","how":"At the back of the neck just below the skull, in the hollow between the two big neck muscles (sternocleidomastoid and trapezius), near where the lesser occipital nerve and occipital artery run. Traditionally used for headache, neck stiffness and dizziness; pressing here also massages tight neck muscles, a known contributor to tension headache.","evidence":"Weak. One small trial found a month of acupressure (points including GB20) beat a muscle relaxant for chronic headache, with no sham (Hsieh 2010). For needle acupuncture in tension-type headache, real needling beat sham needling only slightly (Linde 2016).","pos":[0.035,1.575,-0.07]},{"id":"pp_yintang","col":"h","group":"Pressure points","name":"Yintang (between the eyebrows)","sub":"single point on the midline; also called EX-HN3","how":"On the midline of the forehead, midway between the inner ends of the eyebrows, over branches of the supratrochlear nerve. Traditionally used to calm the mind and help sleep.","evidence":"Five small randomised trials, mostly before surgery, found pressing or needling Yintang alone lowered anxiety (Kwon 2018 review); in one, a sham point did not (Acar 2013). Trials are small and single-centre.","pos":[0,1.655,0.095]},{"id":"pp_ht7","col":"h","group":"Pressure points","name":"HT7 Shenmen (wrist crease, little-finger side)","sub":"both sides; palm side of the wrist","how":"On the wrist crease, on the palm side, at the little-finger edge on the thumb side of the tendon of flexor carpi ulnaris, close to the ulnar nerve and artery. Traditionally used for sleep, anxiety and palpitations.","evidence":"Weak. A sham-controlled trial of self-pressure on HT7 with SP6 in nurses showed better sleep scores but the authors judged the improvement not significant (Cam Yanik 2025). Usually tested together with other points, so its own effect is unknown.","pos":[0.33,0.895,0.018]},{"id":"pp_ear_shenmen","col":"h","group":"Pressure points","name":"Ear points (auricular, e.g. ear Shenmen)","sub":"both sides; seeds or pellets taped on the ear","how":"Points on the outer ear, such as Shenmen in the upper hollow (triangular fossa), usually pressed with seeds or small pellets taped on. Based on a map of the whole body drawn onto the ear, which has not been confirmed anatomically; the ear does carry a branch of the vagus nerve (in the concha, the bowl of the ear), which is one proposed route for effects.","evidence":"Pooled trials (mostly Chinese, many points) report better sleep (Jun 2024) and less anxiety (Hu 2024), but heterogeneity and bias are high, and effects were larger in trials that avoided a sham control, hinting that pressing anywhere helps. Cochrane found limited evidence for ear pressure in pregnancy nausea (Matthews 2015).","pos":[0.085,1.64,-0.01]},{"id":"pp_li4","col":"h","group":"Pressure points","name":"LI4 Hegu (hand web)","sub":"both sides; back of hand between thumb and index finger","how":"On the back of the hand, in the fleshy web between the thumb and index finger bones, over the first dorsal interosseous muscle and branches of the radial nerve. Traditionally used for pain anywhere, especially head, face and teeth.","evidence":"Labour-pain trials of LI4 pressure report lower pain scores, but include non-randomised studies and are hard to blind (Deniz 2026; Chen 2021). No good trial of LI4 alone for headache. Traditionally avoided in pregnancy because it is believed to bring on labour; Cochrane found only limited evidence that acupressure or acupuncture starts labour (Smith 2017) and acupuncture in pregnancy had few, mostly mild side effects (Park 2014), but the tradition is still widely followed.","pos":[0.36,0.853,0.05]},{"id":"pp_sp6","col":"h","group":"Pressure points","name":"SP6 Sanyinjiao (inner shin)","sub":"both sides; about four finger-widths above the inner ankle bone","how":"On the inner lower leg, just behind the back edge of the shin bone (tibia), about four finger-widths above the tip of the inner ankle bone, near the great saphenous vein and branches of the saphenous and tibial nerves. Traditionally used for period pain and gynaecological complaints. Traditionally avoided in pregnancy, like LI4.","evidence":"Small trials report less period pain, including against sham pressure, but are low quality with high risk of bias (Abaraogu 2016; Yu 2025). A sleep trial pairing it with HT7 was not clearly positive (Cam Yanik 2025).","pos":[0.072,0.16,0.01]},{"id":"pp_st36","col":"h","group":"Pressure points","name":"ST36 Zusanli (below the knee)","sub":"both sides; about four finger-widths below the kneecap, outside the shin bone","how":"On the front-outer lower leg, about four finger-widths below the lower edge of the kneecap and one finger-width to the outside of the shin bone's crest, in the tibialis anterior muscle over the deep fibular nerve. Traditionally used for digestion, fatigue and general strengthening.","evidence":"Lab: in mice, electrical stimulation here (not on the belly) drove a vagus-to-adrenal reflex that damped body-wide inflammation, through specific deep sensory nerves (Liu 2021). In people, five minutes of pressure on ST36 changed heart rhythm and skin blood flow no more than sham (Watanabe 2025). No good point-specific trials for fatigue or digestion.","pos":[0.125,0.41,0.05]},{"id":"h_areds","col":"h","group":"Eye care","name":"AREDS eye-vitamin formula","sub":"for intermediate AMD only","how":"A specific supplement mix tested in the Age-Related Eye Disease Studies: vitamins C and E, zinc with copper, and lutein/zeaxanthin (beta-carotene in the original version, dropped because it raised lung cancer in smokers and former smokers). It is a treatment for people with a particular stage of AMD, not a general eye vitamin.","evidence":"Proven to modestly slow progression to late AMD in people with intermediate AMD (or late AMD in one eye); little benefit in early AMD and no evidence it prevents AMD in people without it."},{"id":"h_eye_pressure","col":"h","group":"Eye care","name":"Eye-pressure lowering","sub":"glaucoma drops, laser, surgery","how":"Treatments that lower the pressure inside the eye, either by making less fluid or helping it drain: eye drops, laser to the drainage angle, or surgery to make a new drain. Lowering pressure takes strain off the optic nerve.","evidence":"Proven in randomised trials to slow glaucoma and to delay it in people with raised eye pressure; it cannot restore vision already lost."},{"id":"h_mammography","col":"h","group":"Screening & check-ups","name":"Breast screening (mammography)","sub":"","how":"Low-dose X-ray pictures of the breasts that can find cancers too small to feel. Many countries invite women in midlife and older at regular intervals; the ages and intervals differ between countries. An abnormal picture leads to more imaging and sometimes a needle biopsy, and most of these turn out not to be cancer.","evidence":"Randomised trials show screening lowers breast-cancer deaths modestly. The UK independent review estimated about one death prevented for every three women overdiagnosed, that is, treated for a cancer that would never have harmed them (Marmot 2012). The Cochrane review judged the benefit smaller and the overdiagnosis larger, and noted that better modern treatment likely shrinks the gain (Gotzsche 2013). False alarms are common. It is a real trade-off best weighed with clear information."},{"id":"h_lung_ct_screening","col":"h","group":"Screening & check-ups","name":"Lung cancer screening (low-dose CT)","sub":"for people with a heavy smoking history","how":"A quick, low-radiation CT scan of the chest, repeated at intervals, looks for small lung nodules before they cause symptoms. Programmes invite older current and former heavy smokers; who qualifies differs between countries. Most nodules found are not cancer and are watched with repeat scans.","evidence":"Proven in large randomised trials: fewer lung-cancer deaths with CT screening than with chest X-ray (NLST 2011) or no screening (NELSON 2020). Trade-offs: many false-positive results, radiation, some overdiagnosis and occasional harm from follow-up tests."},{"id":"h_bowel_screening","col":"h","group":"Screening & check-ups","name":"Bowel cancer screening","sub":"stool blood test (FIT), sigmoidoscopy or colonoscopy","how":"A home stool test looks for tiny amounts of blood from polyps or cancers; a positive test leads to colonoscopy, a camera look at the whole colon, where polyps can be removed on the spot. Sigmoidoscopy checks the lower part only.","evidence":"Proven in randomised trials to reduce bowel cancer deaths, and for camera tests also new cancers by removing polyps. Programmes offer it from middle age."},{"id":"h_hrt","col":"h","group":"Medical treatments","name":"Menopausal hormone therapy (HRT)","sub":"oestrogen, with a progestogen if the womb is present","how":"Replaces oestrogen after the ovaries stop making it, as tablets, skin patches, gels or vaginal forms. Women who still have a womb also take a progestogen, because oestrogen alone thickens the womb lining and raises womb-cancer risk. Vaginal oestrogen acts mainly on local dryness.","evidence":"Proven: relieves hot flushes and night sweats (MacLennan 2004) and reduces fractures (Cauley 2003). The Women's Health Initiative trials in women aged 50 to 79 (average 63) found oestrogen plus progestin raised breast cancer, strokes and blood clots and slightly raised heart attacks, while oestrogen alone (in women without a womb) did not raise breast cancer; neither changed overall death rates, and women in their 50s fared better (Manson 2013). Combined therapy for longer raises breast-cancer risk more (Collaborative Group 2019). It is used for symptoms, not to prevent chronic disease, and the balance depends on age, type and how long it is used."},{"id":"h_bp_medicines","col":"h","group":"Medical treatments","name":"Blood-pressure medicines","sub":"water tablets, ACE inhibitors, ARBs, calcium blockers, beta blockers","how":"Different classes lower pressure in different ways: water tablets (diuretics) shrink blood volume, ACE inhibitors and ARBs block the hormone signal that tightens arteries, calcium-channel blockers relax artery muscle, and beta blockers slow and soften the heartbeat. Many people need two or more.","evidence":"Proven: a meta-analysis of 123 randomised trials found that lowering systolic blood pressure cut strokes, heart attacks and heart failure in proportion to how far it fell (Ettehad 2016). They can cause dizziness on standing, which matters in Parkinson's."},{"id":"h_statins","col":"h","group":"Medical treatments","name":"Statins","sub":"cholesterol-lowering medicines","how":"Statins block the liver's main cholesterol-making enzyme, so the liver pulls more LDL ('bad') cholesterol out of the blood. Less LDL means less fat delivered into artery-wall plaques, and plaques become more stable.","evidence":"Proven: in randomised trials of about 170,000 people, lowering LDL with statins reduced heart attacks and ischaemic strokes in proportion to how far it fell (CTT 2010). Muscle aches are the usual side effect."},{"id":"h_anticoagulants","col":"h","group":"Medical treatments","name":"Blood thinners (anticoagulants)","sub":"warfarin and the newer direct anticoagulants","how":"They slow the chemical chain that turns liquid blood into a clot: warfarin blocks the vitamin K-dependent clotting factors (so vitamin K intake has to stay steady), and the newer direct anticoagulants block thrombin or factor Xa. Used to prevent stroke in atrial fibrillation and to treat or prevent deep vein clots. The trade-off is a higher risk of bleeding.","evidence":"Proven: in randomised trials in atrial fibrillation, warfarin cut strokes by about two-thirds (Hart 2007 meta-analysis)."},{"id":"h_inhaled_steroids","col":"h","group":"Medical treatments","name":"Inhaled steroid preventer","sub":"inhaled corticosteroids for asthma","how":"A corticosteroid breathed in from an inhaler goes straight to the airway lining, where it calms the allergic inflammation and swelling that make asthmatic airways twitchy. Used regularly, it prevents attacks rather than relieving them. Rinsing the mouth afterwards reduces the local side effects (hoarse voice, mouth thrush).","evidence":"Proven: a Cochrane review of 86 placebo-controlled trials found better lung function and symptoms and less reliever use (Adams 2008). Regular low-dose use was linked to fewer asthma deaths in a large population study (Suissa 2000). In COPD it helps mainly people with frequent flare-ups and raises pneumonia risk."},{"id":"h_flu_vaccine","col":"h","group":"Medical treatments","name":"Flu vaccination","sub":"seasonal influenza vaccine","how":"A yearly injection of inactivated influenza virus parts trains the immune system to recognise that season's expected strains, so infection is less likely or milder. Flu is a common trigger of dangerous flare-ups in COPD.","evidence":"In COPD, inactivated flu vaccine reduced flare-ups in a Cochrane review, but the evidence came from only two small trials (low quality) (Kopsaftis 2018). Mild sore arm is common."},{"id":"h_ppi","col":"h","group":"Medical treatments","name":"Acid-suppressing medicines","sub":"proton pump inhibitors (omeprazole, lansoprazole etc.), H2 blockers","how":"Proton pump inhibitors switch off the acid pumps in the stomach lining's cells; H2 blockers block one of the signals that turn them on. Less acid reaches the oesophagus, so heartburn eases and inflamed lining heals. They are also part of H. pylori treatment and protect against ulcers.","evidence":"Proven in trials for heartburn, oesophagitis and ulcer healing. Long-term use is linked with lower B12 and magnesium and some gut infections, so ongoing need is reviewed."},{"id":"h_vns","col":"h","group":"Medical treatments","name":"Vagus nerve stimulation (implanted)","sub":"pacemaker-like device; wire to the left vagus in the neck","how":"A small battery unit placed under the skin below the left collarbone sends regular, mild electrical pulses up a wire wrapped around the left vagus nerve in the neck. Most of the effect is thought to come from signals travelling up the nerve into the brainstem, which then changes activity in brain networks for seizures and mood, and in the reflex that damps inflammation. The left side is used because the right vagus has more control over the heartbeat.","evidence":"Proven for drug-resistant focal epilepsy (Cochrane, Panebianco 2022). Mixed for treatment-resistant depression (RECOVER trial). One large sham-controlled trial reduced rheumatoid arthritis activity (RESET-RA, Tesser 2026). Paired with arm exercises it improved arm function after stroke in a sham-controlled trial (VNS-REHAB, Dawson 2021, PMID 33894832). Common side effects while it fires: hoarse voice, cough, shortness of breath.","pos":[0.025,1.46,0.01]},{"id":"h_tvns","col":"h","group":"Medical treatments","name":"Vagus stimulation through the skin (ear or neck)","sub":"transcutaneous VNS: ear clip or handheld neck device","how":"A small electrode on the bowl of the ear (where a branch of the vagus nerve reaches the skin) or a handheld device pressed on the side of the neck sends mild electrical pulses through the skin, aiming to reach the vagus without surgery. How much of the signal reaches the vagus nerve's brain connections is still debated.","evidence":"Mixed. Small Parkinson's trials disagree: pooled trials found less freezing of gait but no change in standard movement scores (Abouelmagd 2025). It failed in a sham-controlled rheumatoid arthritis trial (Baker 2023). Across 16 sham-controlled studies it did not change heart-rate variability, a common sign of vagus activity (Wolf 2021, PMID 34473846). Side effects are usually mild skin irritation or tingling.","pos":[0.07,1.615,-0.005]},{"id":"h_hpylori_eradication","col":"h","group":"Medical treatments","name":"H. pylori eradication treatment","sub":"a short course of two antibiotics plus an acid-suppressing medicine","how":"A combination of antibiotics with a proton pump inhibitor (sometimes with bismuth) given together for one to two weeks to clear H. pylori from the stomach. A breath or stool test afterwards checks it has gone, because resistance to some antibiotics is common.","evidence":"Proven in trials to heal duodenal ulcers and prevent ulcers coming back; lowered stomach cancer in trials in healthy infected people, mostly in Asia. A trial in Parkinson's found no improvement in levodopa response."},{"id":"h_allergen_immunotherapy","col":"h","group":"Medical treatments","name":"Allergen immunotherapy","sub":"injections (SCIT) or under-the-tongue tablets/drops (SLIT)","how":"Regular, gradually built-up exposure to the allergen itself (grass or tree pollen, house-dust mite, cat, or insect venom), given as injections under the skin or as a tablet or drops under the tongue, usually for about three years and only under a specialist. It retrains the immune system: regulatory T cells increase, B cells make 'blocking' IgG4 antibodies that catch the allergen before it reaches IgE on mast cells, and the type-2 response quietens. Unlike antihistamines or steroids, the benefit can last for years after stopping.","evidence":"Proven in placebo-controlled trials for hay fever (Cochrane reviews of injections, Calderon 2007, and under-the-tongue treatment, Radulovic 2010), for house-dust-mite allergic asthma (fewer attacks, Virchow 2016) and for venom allergy (Boyle 2012). Injections carry a small risk of whole-body reactions, so they are given where these can be treated; under-the-tongue treatment mostly causes mouth itch. Not used for food allergy in this form (see oral immunotherapy)."},{"id":"h_oral_immunotherapy","col":"h","group":"Medical treatments","name":"Oral immunotherapy for food allergy (OIT)","sub":"eating tiny, slowly rising amounts of the food under a specialist","how":"The person eats a very small, carefully measured amount of the food they are allergic to (most studied for peanut, also milk and egg), increased step by step in clinic and then taken every day. This 'desensitises' the mast cells so that more of the food is needed to cause a reaction, giving protection against accidental bites. It mostly does not cure the allergy: protection often fades if daily eating stops.","evidence":"Proven: in the PALISADE trial two-thirds of treated children could eat a meaningful amount of peanut protein at the end, against 4% on placebo (2018). Proven harm: a meta-analysis of 12 trials found oral immunotherapy roughly tripled the risk of anaphylaxis and raised adrenaline use and vomiting compared with avoidance (PACE, Chu 2019). The trade-off is chosen with a specialist; it is never done at home without one."},{"id":"h_antihistamines","col":"h","group":"Medical treatments","name":"Antihistamines","sub":"non-drowsy (cetirizine, loratadine, fexofenadine and similar) and older drowsy ones","how":"They block the H1 receptor that histamine from mast cells acts on, so vessels leak less and itch nerves fire less: hives fade, sneezing, runny nose and itchy eyes ease. They do not block the other mast-cell chemicals (leukotrienes, prostaglandins), so they do little for a blocked nose, asthma or the late phase, and they cannot reverse the airway and blood-pressure collapse of anaphylaxis. Older 'drowsy' antihistamines cross into the brain, cause sleepiness and slowed thinking, and have anticholinergic effects that older people and people with Parkinson's are more sensitive to.","evidence":"Proven: better than placebo for chronic hives (Cochrane review, Sharma 2014, low-quality evidence) and for hay-fever symptoms (network meta-analysis of 74 trials, Vieira 2026). Not a treatment for anaphylaxis: adrenaline is. Prescribed or recommended by a doctor or pharmacist."},{"id":"h_nasal_steroids","col":"h","group":"Medical treatments","name":"Steroid nasal sprays","sub":"intranasal corticosteroids (mometasone, fluticasone, budesonide and similar)","how":"A steroid sprayed onto the nose lining calms the type-2 inflammation there: fewer mast cells and eosinophils, less swelling and mucus. They work over days rather than minutes and act on the late phase as well as the early phase, so they are the most effective single treatment for a blocked nose from hay fever. Very little reaches the rest of the body when used as directed.","evidence":"Proven: better than placebo for seasonal and year-round hay fever in many trials (network meta-analysis, Soe 2023), and improve allergy-related sleep quality (meta-analysis of 18 trials, Tabata 2025). Prescribed or recommended by a doctor or pharmacist; nosebleeds and dryness are the commonest side effects."},{"id":"h_adrenaline_autoinjector","col":"h","group":"Medical treatments","name":"Adrenaline (epinephrine) auto-injector","sub":"the emergency pen for anaphylaxis","how":"A spring-loaded pen injects adrenaline into the thigh muscle. Adrenaline tightens leaking blood vessels (raising blood pressure), relaxes the airway muscles, reduces throat swelling and stops mast cells releasing more chemicals, which is why it is the only first treatment for anaphylaxis. It is used at the first signs of a severe reaction, followed by an emergency call, because symptoms can return as it wears off. People at risk are prescribed it and taught when and how to use it by their doctor.","evidence":"Established emergency treatment in every anaphylaxis guideline; delays in giving it are linked with deaths. There are no placebo trials (they would be unethical). Antihistamines and steroids do not replace it."},{"id":"h_anti_ige","col":"h","group":"Medical treatments","name":"Anti-IgE biologic (omalizumab)","sub":"antibody injection that mops up IgE","how":"A laboratory-made antibody that binds free IgE so it cannot attach to mast cells and basophils; over weeks the cells also lose many of their IgE receptors, so allergens and other triggers set them off less easily. Prescribed by specialists by injection for severe allergic asthma, chronic hives that antihistamines don't control, nasal polyps and, more recently, multiple food allergies.","evidence":"Proven in placebo-controlled trials: fewer asthma attacks in moderate-to-severe allergic asthma (Cochrane, Normansell 2014); less itch and fewer hives in chronic hives (Maurer 2013); raised the amount of peanut and other foods children with multiple food allergies could eat without reacting (OUtMATCH, Wood 2024). It reduces, but does not remove, the need for allergen avoidance."},{"id":"h_anti_il4r","col":"h","group":"Medical treatments","name":"Anti-IL-4 receptor biologic (dupilumab)","sub":"antibody injection that blocks IL-4 and IL-13","how":"A laboratory-made antibody that blocks the shared receptor for IL-4 and IL-13, the two main type-2 signals. This lowers IgE making, mucus and airway twitchiness, eosinophil entry into tissues and the type-2 suppression of skin barrier proteins. Prescribed by specialists by injection for moderate-to-severe eczema, type-2 asthma, nasal polyps and eosinophilic oesophagitis.","evidence":"Proven in placebo-controlled trials: clearer skin in moderate-to-severe eczema (SOLO 1 and 2, Simpson 2016); about half the rate of severe asthma attacks (Castro 2018); healing of the oesophagus lining in EoE (Dellon 2022). Eye surface inflammation (conjunctivitis) is a common side effect in eczema."},{"id":"h_antibiotics","col":"h","group":"Medical treatments","name":"Antibiotics","sub":"as a course for an infection","how":"Antibiotics kill or stop bacteria. They cannot tell the target apart from the residents, so a course also clears out much of the gut, mouth and skin community. Most of it grows back over weeks to months, but some members return slowly or not at all, and the gap lets tough survivors such as Clostridioides difficile, Enterococcus and yeasts take over.","evidence":"Proven for treating bacterial infections. The collateral effect on the gut community is measured: in healthy adults most species returned within about six months, but several common ones were still missing.","pos":[0,1.05,0.08]},{"id":"h_fmt","col":"h","group":"Medical treatments","name":"Faecal microbiota transplant","sub":"FMT, stool from a screened donor","how":"Screened donor stool, given into the bowel, restores a whole working gut community at once, including the bile-acid converting bacteria that make the colon inhospitable to Clostridioides difficile.","evidence":"Proven in randomised trials for Clostridioides difficile infection that keeps coming back. For everything else (IBD, IBS, obesity) it is still experimental.","pos":[0,1.07,0.085]},{"id":"h_emollients","col":"h","group":"Allergy prevention & skin care","name":"Moisturisers (emollients) to treat eczema","sub":"creams, ointments and soap substitutes","how":"Greasy creams and ointments put a layer of fats back on the skin, slowing water loss and filling the gaps between dried skin cells, so the barrier works better and less irritant and allergen gets in. Used generously and often, and as a soap substitute, they are the base of eczema care alongside anti-inflammatory creams a doctor prescribes.","evidence":"Proven for treatment: moisturisers lowered eczema severity, reduced flares and the amount of steroid cream needed in a Cochrane review of 77 trials (van Zuuren 2017). No moisturiser was reliably better than another. Not proven for prevention (see 'Emollients from birth')."},{"id":"h_emollients_from_birth","col":"h","group":"Allergy prevention & skin care","name":"Emollients from birth to prevent eczema","sub":"daily moisturiser on healthy newborn skin","how":"The idea was that strengthening a baby's skin barrier from the first weeks would stop allergens getting in and so prevent eczema and food allergy (the barrier and 'dual-allergen exposure' ideas). Parents applied moisturiser to the whole body every day through the first year.","evidence":"Failed: in two large trials daily emollient from birth did not prevent eczema (BEEP, 1,394 babies, Chalmers 2020; PreventADALL, about 2,400 babies, Skjerven 2020). A 2022 Cochrane review concluded it probably does not prevent eczema, may increase food allergy and probably increases skin infections (Kelleher 2022)."},{"id":"h_breastfeeding","col":"h","group":"Allergy prevention & skin care","name":"Breastfeeding (longer duration)","sub":"","how":"Breast milk carries antibodies (IgA), immune signals and sugars (human milk oligosaccharides) that feed Bifidobacterium in the baby's gut, which may help train immune tolerance. Its effect on allergy is hard to study because families who breastfeed longer differ in many other ways.","evidence":"Association only. A meta-analysis found more breastfeeding was linked with less asthma at ages 5 to 18 (stronger in lower-income countries) and possibly less hay fever under 5 and eczema under 2, with low-quality evidence; no link with food allergy (Lodge 2015). It has many other benefits for mother and baby beyond allergy."},{"id":"h_farm_pets_early","col":"h","group":"Allergy prevention & skin care","name":"Farm life and pets in early life","sub":"livestock, barns, raw farm milk, dogs and cats","how":"Babies and young children who live on traditional farms or with several dogs and cats breathe and swallow a much wider range of microbes and microbial products (such as endotoxin). These seem to train the innate immune system and regulatory T cells away from allergic responses: the 'hygiene' or 'old friends' idea. Raw farm milk carries serious infection risks and is not a safe way to copy this.","evidence":"Association. Farm children had less asthma and allergy, and more diverse microbial exposure tracked with lower asthma risk (Ege 2011); Amish children (traditional farming, high house-dust endotoxin) had 4 to 6 times less asthma and sensitisation than Hutterite children (Stein 2016). Two or more dogs or cats in the first year was linked with less sensitisation (Ownby 2002), with a dose-response for allergy (Hesselmar 2018). No trial has tested deliberately getting pets to prevent allergy, and in a child who is already allergic, pet exposure worsens symptoms."},{"id":"h_allergen_avoidance","col":"h","group":"Allergy prevention & skin care","name":"Allergen avoidance","sub":"reading labels, avoiding known triggers, mite-proof covers","how":"For a confirmed food allergy, avoiding the food (reading labels, asking about ingredients in restaurants) is what prevents reactions. For breathed-in allergens, avoidance is harder: pollen counts can guide timing outdoors, a pet can be kept out of the bedroom, and mattress covers and hot washing reduce dust-mite levels. Avoiding foods that are not proven allergens can cause harm by losing tolerance.","evidence":"Established for preventing reactions to a confirmed food allergen. Failed for dust mites: in 54 trials, physical and chemical mite-control measures did not improve asthma (Gotzsche 2008, Cochrane), probably because they don't lower exposure enough. Strict avoidance of allergen foods in infancy can raise food allergy risk (LEAP)."},{"id":"h_hepb_vaccine","col":"h","group":"Vaccines","name":"Hepatitis B vaccination","sub":"given at birth in most countries","how":"A protein from the hepatitis B coat trains antibodies that block the virus before it reaches the liver. Given to newborns (to stop mother-to-baby spread), health workers and others at risk. Because hepatitis D needs hepatitis B, it protects against both.","evidence":"Proven: prevents hepatitis B infection in randomised trials. Association: whole birth cohorts vaccinated as infants in Taiwan have far less liver cancer."},{"id":"h_hepa_vaccine","col":"h","group":"Vaccines","name":"Hepatitis A vaccination","sub":"","how":"An inactivated hepatitis A virus vaccine that trains antibodies against the virus; used for children in many countries, travellers, and people with chronic liver disease.","evidence":"Proven: one dose prevented clinical hepatitis A in a placebo-controlled trial in children (Werzberger 1992)."},{"id":"h_covid_vaccine","col":"h","group":"Vaccines","name":"COVID-19 vaccination","sub":"","how":"Vaccines (mRNA, protein or viral-vector) teach the immune system to recognise the spike protein of SARS-CoV-2. Protection against infection fades over months as the virus changes, but protection against severe illness lasts longer; updated boosters target newer variants.","evidence":"Proven: 95% protection against symptomatic COVID-19 in the main placebo-controlled trial (Polack 2020)."},{"id":"h_rsv_vaccine","col":"h","group":"Vaccines","name":"RSV vaccination","sub":"for older adults and in pregnancy","how":"A vaccine against the RSV fusion protein. Given to older adults to protect themselves, or late in pregnancy so the mother's antibodies cross the placenta and protect the newborn in its first months.","evidence":"Proven: prevented RSV lung infection in adults 60+ (Papi 2023) and severe RSV illness in infants of vaccinated mothers (Kampmann 2023)."},{"id":"h_rota_vaccine","col":"h","group":"Vaccines","name":"Rotavirus vaccination","sub":"oral drops for babies","how":"A weakened live rotavirus given by mouth in early infancy, which trains gut immunity against the real virus.","evidence":"Proven: prevents rotavirus diarrhoea in randomised trials, with no increase in serious harms (Bergman 2021 Cochrane)."},{"id":"h_mmr_vaccine","col":"h","group":"Vaccines","name":"MMR vaccination","sub":"measles, mumps and rubella","how":"A combined live, weakened vaccine against measles, mumps and rubella given in two doses in childhood. High coverage is needed to stop outbreaks because measles is so infectious.","evidence":"Proven for measles in a controlled trial; very high effectiveness against measles (about 95% after one dose) and good protection against mumps and rubella in cohort studies; no link to autism (Di Pietrantonj 2021 Cochrane)."},{"id":"h_polio_vaccine","col":"h","group":"Vaccines","name":"Polio vaccination","sub":"injected (IPV) or oral (OPV)","how":"Injected inactivated vaccine protects the person from paralysis; oral live vaccine also blocks gut infection and so spread. Mass vaccination has wiped out wild polio from nearly every country.","evidence":"Proven: the 1954 placebo-controlled field trial showed the inactivated vaccine prevents paralytic polio."},{"id":"h_malaria_vaccine","col":"h","group":"Vaccines","name":"Malaria vaccination","sub":"RTS,S and R21 for children","how":"Vaccines against the stage of Plasmodium falciparum that enters the liver after a mosquito bite, given to young children in areas with high malaria.","evidence":"Proven: RTS,S prevented many cases of clinical malaria over 3-4 years in African children in a phase 3 trial (2015); protection is partial, so nets are still needed."},{"id":"h_pcv_vaccine","col":"h","group":"Vaccines","name":"Pneumococcal vaccination","sub":"conjugate (PCV) and polysaccharide (PPV) vaccines","how":"Vaccines against the sugar coats of the commonest pneumococcus types. Given to babies, older adults and people at high risk (no spleen, chronic illness, weak immunity). Vaccinating children also protects adults by cutting carriage and spread.","evidence":"Proven: prevented vaccine-type pneumococcal pneumonia and invasive disease in adults 65+ in a large trial (Bonten 2015), but not pneumonia from all causes."},{"id":"h_men_vaccine","col":"h","group":"Vaccines","name":"Meningococcal vaccination","sub":"MenACWY, MenB, MenA","how":"Vaccines against the capsule (groups A, C, W, Y) or surface proteins (group B) of meningococcus, given to infants, teenagers, pilgrims and travellers, and people without a spleen. Conjugate vaccines also reduce throat carriage, which protects others.","evidence":"Proven: the group A vaccine protected against group A meningitis in trials (Patel 2005 Cochrane); later vaccines are judged mainly by large population studies."},{"id":"h_hib_vaccine","col":"h","group":"Vaccines","name":"Hib vaccination","sub":"","how":"A conjugate vaccine joining Hib's sugar coat to a protein so infants' immune systems respond to it; part of routine infant combination vaccines.","evidence":"Proven: prevented nearly all Hib meningitis and pneumonia in a randomised trial in Gambian infants (Mulholland 1997)."},{"id":"h_dtp_vaccine","col":"h","group":"Vaccines","name":"Diphtheria, tetanus and whooping cough vaccination","sub":"DTaP / Tdap","how":"Combination vaccines with inactivated diphtheria and tetanus toxins (toxoids) and parts of the whooping cough bacterium. Given in infancy with boosters, and in pregnancy to protect newborns from whooping cough and tetanus.","evidence":"Proven: acellular pertussis vaccines prevent whooping cough in trials (Zhang 2014 Cochrane); tetanus toxoid given to women prevented newborn tetanus deaths in trials (Demicheli 2015 Cochrane)."},{"id":"h_bcg","col":"h","group":"Vaccines","name":"BCG vaccination","sub":"tuberculosis vaccine","how":"A live weakened cousin of the tuberculosis bacterium given at birth in countries where TB is common. It protects young children best, especially against TB meningitis and widespread TB; protection in adults varies a lot between regions.","evidence":"Proven for infants: reduced tuberculosis by over half on average (Colditz 1995 meta-analysis of trials and case-control studies)."},{"id":"h_condoms","col":"h","group":"Infection prevention","name":"Condoms","sub":"male and female condoms","how":"A barrier that stops semen, vaginal fluid and much skin contact passing between partners during sex, blocking infections that travel in body fluids (HIV, gonorrhoea, chlamydia, hepatitis B). It protects less against infections spread by skin contact outside the covered area (herpes, HPV, syphilis sores).","evidence":"Association: consistent use was linked with about 80% less HIV infection in couples studies, and with less gonorrhoea, chlamydia, herpes, syphilis and trichomoniasis. Randomised trials of condoms themselves are not ethical, so the evidence is observational."},{"id":"h_prep","col":"h","group":"Infection prevention","name":"HIV pre-exposure prevention (PrEP)","sub":"anti-HIV medicine taken before exposure","how":"HIV-negative people at high risk take anti-HIV medicine (as pills or long-acting injections) so that if the virus enters the body it cannot establish infection. It does not protect against other sexual infections.","evidence":"Proven: cut new HIV infections by about two-thirds or more versus placebo in randomised trials when taken (Baeten 2012)."},{"id":"h_hand_washing","col":"h","group":"Infection prevention","name":"Hand washing","sub":"soap and water, hand hygiene","how":"Soap lifts germs and grease off the skin so water can rinse them away, breaking the faecal-oral and hand-to-face routes. Alcohol gel kills many germs but not norovirus or C. difficile spores well.","evidence":"Proven: hand-washing promotion probably cuts diarrhoea episodes by about 30% (Ejemot-Nwadiaro 2021 Cochrane); hand hygiene modestly reduces respiratory illness (Jefferson 2023 Cochrane)."},{"id":"h_safe_water","col":"h","group":"Infection prevention","name":"Safe drinking water","sub":"filtering, chlorinating, safe storage","how":"Removing or killing germs in drinking water (filters, chlorine, boiling, sunlight disinfection) and storing it safely stops waterborne infections such as cholera, typhoid, hepatitis A and E and Cryptosporidium.","evidence":"Proven: household water filters and disinfection reduced diarrhoea in mostly cluster-randomised trials, though most were not blinded (Clasen 2015 Cochrane)."},{"id":"h_bed_nets","col":"h","group":"Infection prevention","name":"Insecticide-treated bed nets","sub":"","how":"Nets treated with insecticide hung over beds stop night-biting Anopheles mosquitoes reaching sleepers and kill those that land on them, protecting the whole household and, with wide use, the community.","evidence":"Proven: reduce child deaths and malaria episodes in randomised trials (Pryce 2018 Cochrane)."},{"id":"m_iron","col":"m","group":"Control circuits","name":"Brain iron & dopamine making","sub":"","how":"Iron lets tyrosine hydroxylase turn tyrosine into L-DOPA. Low iron in the substantia nigra and striatum (seen on scans and in spinal fluid in restless legs) weakens dopamine signalling, especially at night.","evidence":""},{"id":"m_allergy","col":"m","group":"Immune responses","name":"Allergy brake (immune tolerance)","sub":"oral tolerance, regulatory T cells","how":"Step by step: (1) every day the gut, skin and airways meet harmless proteins from food, pollen, dust and pets; (2) immune 'scout' cells in the gut lining carry these proteins to nearby lymph nodes; (3) there, with signals helped by vitamin A and gut-bacteria products such as butyrate, they train regulatory T cells (Tregs) that recognise the protein; (4) the Tregs release calming signals (IL-10, TGF-beta) that stop type-2 cells and B cells from making allergy IgE, and push B cells towards harmless IgG4 and IgA instead. This is 'oral tolerance'. Eating a food regularly keeps it up; meeting it first through broken skin tends to cause sensitisation instead. When this brake fails, the allergy steps that follow (IgE sensitisation, mast cells, type-2 inflammation) take over.","evidence":"Established immunology. Why tolerance fails is only partly known. Proven: eating peanut regularly from infancy builds tolerance in high-risk babies (LEAP, Du Toit 2015), and allergen immunotherapy partly retrains it. Association: children raised on traditional farms, with more varied microbes at home, have less asthma and allergy (Ege 2011; Amish vs Hutterite children, Stein 2016). Lab: gut bacteria that make butyrate train tolerance in mice. Some allergy look-alikes do not use this route: coeliac disease is autoimmune, lactose intolerance is a missing enzyme, nickel rashes are a delayed T-cell reaction, and EoE and FPIES are non-IgE gut reactions."},{"id":"m_ige_sensitisation","col":"m","group":"Immune responses","name":"IgE sensitisation (kept low)","sub":"B cells switching to allergy antibodies","how":"Step by step: (1) a harmless protein (pollen, peanut, cat, mite) gets past a lining, often one that is damaged or inflamed; (2) scout cells show it to a T helper cell, which, in a type-2 setting, becomes a Th2 or T-follicular helper cell; (3) that cell's IL-4 and IL-13 tell B cells to switch from making IgM/IgG to making IgE against that protein; (4) the IgE spreads through the body and sticks to high-affinity receptors on mast cells and basophils, which can stay armed for months. The person is now 'sensitised'. No symptoms happen yet: symptoms come on the next exposure. Here 'better' means less of this.","evidence":"Established immunology. Sensitisation (a positive skin-prick or IgE blood test) is common and does not by itself mean allergy: many sensitised people eat the food or meet the pollen without symptoms, so a test alone does not diagnose allergy."},{"id":"m_mast_cells","col":"m","group":"Immune responses","name":"Mast cells & basophils (kept calm)","sub":"histamine, tryptase, leukotrienes, prostaglandins","how":"Step by step: (1) mast cells sit just under the skin and the linings of the nose, airways and gut, near blood vessels and nerves; basophils are their cousins in the blood; (2) both carry IgE on their surface; (3) when the allergen bridges two IgE molecules, the cell empties its granules within minutes; (4) histamine makes blood vessels leak (swelling, hives), nerves itch and the nose run; tryptase and other enzymes add to it; (5) within minutes to hours the cell also makes leukotrienes and prostaglandins, which squeeze the airway muscles and keep the reaction going, and cytokines that call in other cells (the late phase). When this happens all over the body at once, blood pressure falls: anaphylaxis. Some medicines, venom peptides, cold, pressure or exercise can also trigger mast cells without IgE. Here 'better' means calmer, fewer cells emptying.","evidence":"Established immunology. Antihistamines block only the histamine part, which is why they help hives and sneezing but cannot treat anaphylaxis; adrenaline counters all of its effects on vessels and airways."},{"id":"m_type2","col":"m","group":"Immune responses","name":"Type-2 (allergic) inflammation (kept in balance)","sub":"Th2 cells, ILC2s, IL-4, IL-5, IL-13","how":"Step by step: (1) damaged or irritated linings release 'alarm' signals (TSLP, IL-33, IL-25); (2) these switch on type-2 innate lymphoid cells (ILC2s) and Th2 helper cells; (3) IL-4 and IL-13 make B cells produce IgE, make airways produce sticky mucus and become twitchy, and lower filaggrin and other barrier proteins in the skin; (4) IL-5 makes the bone marrow produce eosinophils and keeps them alive in tissues; (5) the inflamed lining then releases more alarm signals, so the loop can keep itself going. Type-2 immunity evolved to expel worms and repair tissue; in allergy it is aimed at harmless proteins. Here 'better' means in balance, not overactive.","evidence":"Established immunology. Proven in trials: medicines that block this pathway (anti-IL-4 receptor, which blocks IL-4 and IL-13; anti-IL-5) reduce eczema, asthma attacks and EoE in people whose disease is type-2 driven."},{"id":"m_eosinophils","col":"m","group":"Immune responses","name":"Eosinophils (kept in check)","sub":"IL-5-driven tissue white cells","how":"Step by step: (1) IL-5 from type-2 cells tells the bone marrow to make eosinophils; (2) eotaxin signals from inflamed linings call them into the airways, gut or oesophagus; (3) once there they release toxic granule proteins and leukotrienes that damage the lining, make airways twitchy and lay down scar-like stiffening over time; (4) high counts in blood or sputum mark 'eosinophilic' asthma, and a build-up in the oesophagus lining is eosinophilic oesophagitis (EoE). Here 'better' means fewer of them in the tissues.","evidence":"Established immunology. Raised eosinophils are also seen in worm infections and some drug reactions, so a high count is not specific to allergy."},{"id":"m_skin_barrier","col":"m","group":"Immune responses","name":"Skin barrier","sub":"filaggrin, skin fats, tight junctions","how":"Step by step: (1) the outer skin layer is like a brick wall: flattened dead cells (bricks) held in fats (mortar); (2) the protein filaggrin packs the bricks and breaks down into natural moisturising factor; (3) skin fats (ceramides) and tight junctions below seal the gaps, keeping water in and microbes, irritants and allergens out; (4) when filaggrin is low (by inherited variants or from inflammation) or the fats are stripped by soap, detergents and wet work, water escapes, the skin dries and cracks, and allergens slip in; (5) damaged skin cells release alarm signals that push the immune system towards type-2 (allergic) responses, so proteins first met through broken skin tend to sensitise rather than build tolerance.","evidence":"Established physiology. Association: inherited filaggrin loss-of-function variants are a major risk factor for eczema (Palmer 2006) and for peanut allergy even after allowing for eczema (Brown 2011). Failed: daily emollients from birth did not prevent eczema in large trials (BEEP, PreventADALL), so the barrier idea has not yet become a way to prevent allergy."},{"id":"m_airway_barrier","col":"m","group":"Immune responses","name":"Airway lining barrier","sub":"epithelium, mucus, cilia, alarmins","how":"Step by step: (1) the nose, sinuses and bronchi are lined with a single sheet of cells sealed by tight junctions, covered by mucus that tiny hairs (cilia) sweep out; (2) this traps pollen, mould and mite particles and clears them before they reach immune cells; (3) some allergens (house-dust mite and cockroach enzymes) cut the tight junctions, and smoke, diesel particles, ozone and cold viruses damage the sheet; (4) the damaged cells release alarm signals (TSLP, IL-33, IL-25) that switch on type-2 inflammation, which then makes more mucus and keeps the lining leaky. Nose and lungs share this lining, which is why hay fever and asthma so often go together ('one airway').","evidence":"Established physiology. Linking damage by pollutants to the onset of allergy in people rests on population studies and lab work, graded on each link."},{"id":"m_late_phase","col":"m","group":"Immune responses","name":"Late-phase reaction (kept short)","sub":"the second wave, hours after exposure","how":"Step by step: (1) in the minutes after an allergen, mast cells cause the early reaction (sneezing, itch, wheeze, hives); (2) they also release cytokines and leukotrienes that call eosinophils, basophils and Th2 cells out of the blood; (3) these arrive over about four to twelve hours and cause a second, slower wave: a blocked nose, renewed wheeze and twitchy airways, or a swollen, sore patch of skin; (4) repeated late-phase reactions keep the lining inflamed and more sensitive to the next exposure, which is how seasonal hay fever or asthma becomes persistent. Here 'better' means a shorter, smaller second wave.","evidence":"Established immunology, shown in allergen challenge studies in people. Steroids damp the late phase much more than antihistamines do."},{"id":"faecali","col":"gb","group":"Butyrate makers","name":"Faecalibacterium","sub":"F. prausnitzii","how":"One of the most abundant gut bacteria and a major butyrate maker. It ferments fibre and products of other bacteria. Reduced in Parkinson's, inflammatory bowel disease and depression in many studies.","evidence":"","pos":[-0.03,1.08,0.08]},{"id":"roseburia","col":"gb","group":"Butyrate makers","name":"Roseburia","sub":"","how":"A butyrate-making bacterium that ferments fibre and resistant starch; reduced in Parkinson's in several studies.","evidence":"","pos":[0.04,1.08,0.08]},{"id":"prevotella","col":"gb","group":"Butyrate makers","name":"Prevotella","sub":"","how":"Fibre-loving bacteria common in plant-rich diets; make propionate and other short-chain fatty acids. Prevotellaceae were lower in Parkinson's in an early study (Scheperjans 2015) and several since.","evidence":"","pos":[-0.09,1.03,0.05]},{"id":"erectale","col":"gb","group":"Butyrate makers","name":"Eubacterium rectale","sub":"Agathobacter rectalis","how":"One of the most common bacteria in the colon. It ferments fibre and starch fragments and turns them into butyrate, the main fuel of the cells lining the colon.","evidence":"Textbook gut microbiology: a major butyrate producer. It cannot break down resistant starch well on its own and relies on Ruminococcus bromii to start the job (lab).","pos":[-0.08,1.06,0.06]},{"id":"bifido","col":"gb","group":"Fermenters","name":"Bifidobacterium","sub":"","how":"Ferment fibre and sugars into acetate and lactate, which butyrate makers then use (cross-feeding). Common in probiotics and fermented dairy.","evidence":"","pos":[0.1,1.02,0.04]},{"id":"lacto","col":"gb","group":"Fermenters","name":"Lactobacillus","sub":"","how":"Lactic-acid bacteria in fermented foods and probiotics. Curiously, found at higher levels in Parkinson's in several studies, possibly as a side effect of medicines or slow transit.","evidence":"","pos":[-0.04,0.98,0.06]},{"id":"akk","col":"gb","group":"Fermenters","name":"Akkermansia","sub":"A. muciniphila","how":"Lives in the gut's mucus layer and feeds on it. Linked with healthy metabolism, but raised in Parkinson's in many studies; one idea is that on a low-fibre diet it thins the protective mucus.","evidence":"","pos":[0.09,1.06,0.05]},{"id":"sthermo","col":"gb","group":"Fermenters","name":"Streptococcus thermophilus","sub":"yogurt culture","how":"A lactic-acid bacterium used with Lactobacillus bulgaricus to make yogurt and some cheeses. It passes through the gut rather than settling there, and its enzymes help break down milk sugar (lactose).","evidence":"Established: a standard yogurt starter culture. Not a long-term gut resident.","pos":[0.02,1.04,0.075]},{"id":"oral_nitrate","col":"gb","group":"Mouth","name":"Mouth nitrate reducers","sub":"Rothia, Neisseria, Veillonella","how":"Harmless bacteria on the back of the tongue that turn nitrate (from leafy greens and beetroot, concentrated in saliva) into nitrite, which the body can turn into nitric oxide, a blood-vessel relaxer.","evidence":"Mixed: wiping them out with antiseptic mouthwash raised blood pressure in one study (Kapil 2013), but later studies are split (Singh 2026 review).","pos":[0,1.555,0.065]},{"id":"gordonibacter","col":"gb","group":"Polyphenol converters","name":"Gordonibacter","sub":"urolithin makers","how":"Colon bacteria that turn ellagitannins and ellagic acid (from walnuts, pomegranate, raspberries) into urolithins. Only some people carry the bacteria needed to make urolithins.","evidence":"Lab: urolithins calm inflammation in animal studies (Selma 2014). Human studies show who makes urolithins depends on these bacteria, not yet that it changes health outcomes.","pos":[-0.07,1.01,0.06]},{"id":"equol_makers","col":"gb","group":"Polyphenol converters","name":"Equol makers","sub":"Adlercreutzia, Slackia","how":"Colon bacteria that turn daidzein, a plant oestrogen in soybeans, into equol. Only about a third to a half of people carry them.","evidence":"Established that only some adults make equol (Setchell 2010); whether equol producers get more health benefit from soy is still unproven.","pos":[0.085,1.02,0.05]},{"id":"ruminococcus","col":"gb","group":"Fibre & starch breakers","name":"Ruminococcus bromii","sub":"resistant-starch specialist","how":"Lives in the colon and is the specialist that starts breaking down resistant starch (in cooled potatoes, rice, beans, green bananas). It releases sugars that other bacteria, including butyrate makers, then use.","evidence":"Lab: in co-culture it was the only one of four starch-using species that unlocked resistant starch for the others, and people lacking it fermented this starch poorly (Ze 2012).","pos":[0,1.08,0.085]},{"id":"btheta","col":"gb","group":"Fibre & starch breakers","name":"Bacteroides thetaiotaomicron","sub":"B. theta","how":"A colon bacterium with hundreds of enzymes for plant fibres; when fibre is short it can graze on the gut's mucus layer. Makes acetate and propionate.","evidence":"Lab: in germ-free rats it boosted the mucus-making goblet cells; with F. prausnitzii (which eats its acetate) the response changed (Wrzosek 2013).","pos":[0.07,1.07,0.07]},{"id":"christensenella","col":"gb","group":"Lean-linked","name":"Christensenella","sub":"C. minuta","how":"A small family of colon bacteria whose amount is strongly shaped by a person's genes.","evidence":"Association: the most heritable gut family in a large twin study and more common in lean people; adding it to an obese-type microbiome reduced weight gain in mice (Goodrich 2014). No human trials.","pos":[0.1,0.99,0.045]},{"id":"oscillospira","col":"gb","group":"Lean-linked","name":"Oscillospira","sub":"","how":"Colon bacteria that have never been grown alone in the lab; known mostly from DNA sequencing of stool.","evidence":"Association: consistently more common in lean people and probably a butyrate maker; also linked with slower transit (Yang 2021 review).","pos":[0.03,0.92,0.06]},{"id":"gb_bacteroides","col":"gb","group":"Gut: colon","name":"Bacteroides","sub":"the colon's most abundant genus","how":"A large group of bacteria that live in the colon and carry hundreds of enzymes for breaking down plant fibre and the body's own mucus sugars. They ferment what we cannot digest into acetate and propionate, which the gut wall and liver use for energy.","evidence":"Textbook gut physiology. Individual species differ a lot, so genus-level links to disease are weak.","pos":[-0.06,1.1,0.07]},{"id":"gb_bfragilis","col":"gb","group":"Gut: colon","name":"Bacteroides fragilis","sub":"commensal strains","how":"A normal colon resident whose capsule sugar (polysaccharide A) is recognised by the gut immune system and helps it build calming regulatory T cells. Strains that make a toxin behave differently and are not the same thing as the ordinary resident.","evidence":"Immune training shown in germ-free mice (lab). Toxin-making strains are studied separately.","pos":[-0.04,1.11,0.06]},{"id":"gb_bvulgatus","col":"gb","group":"Gut: colon","name":"Phocaeicola vulgatus","sub":"formerly Bacteroides vulgatus","how":"One of the commonest bacteria in the adult colon. It ferments plant fibre into acetate and propionate and competes for the same food as less welcome gut bacteria.","evidence":"Textbook gut physiology; disease links are inconsistent between studies.","pos":[0.05,1.1,0.06]},{"id":"gb_pcopri","col":"gb","group":"Gut: colon","name":"Prevotella copri","sub":"the main human Prevotella","how":"The species behind most of the Prevotella seen in people who eat a lot of plants and fibre. It ferments fibre and starch into short-chain fatty acids.","evidence":"In a human study, people whose gut carried more P. copri had the biggest improvement in blood sugar after a barley-fibre meal; others find no benefit, so this is an association.","pos":[-0.08,1.05,0.055]},{"id":"gb_blautia","col":"gb","group":"Gut: colon","name":"Blautia","sub":"acetate maker","how":"A common colon bacterium that can make acetate directly from hydrogen and carbon dioxide left over from other bacteria's fermentation. That acetate is then food for the butyrate makers.","evidence":"Textbook gut physiology. Links with body weight are mixed.","pos":[0.02,1.1,0.07]},{"id":"gb_anaerostipes","col":"gb","group":"Gut: colon","name":"Anaerostipes","sub":"turns lactate into butyrate","how":"Takes the lactate that lactobacilli and bifidobacteria leave behind and converts it into butyrate, the main fuel of the colon lining. This keeps lactate from building up.","evidence":"Textbook cross-feeding in the gut.","pos":[-0.02,1.05,0.075]},{"id":"gb_ehallii","col":"gb","group":"Gut: colon","name":"Anaerobutyricum hallii","sub":"formerly Eubacterium hallii","how":"A colon bacterium that makes butyrate and propionate from lactate and from the sugar alcohols left by other bacteria.","evidence":"Textbook cross-feeding in the gut.","pos":[0.01,1.07,0.065]},{"id":"gb_coprococcus","col":"gb","group":"Gut: colon","name":"Coprococcus","sub":"butyrate maker","how":"A butyrate-making colon bacterium. It is one of the groups found at lower levels in people with depression in large population studies, though that does not show which way the arrow points.","evidence":"Lower in depression in two Belgian and Dutch population cohorts (association only).","pos":[-0.05,1.04,0.07]},{"id":"gb_dialister","col":"gb","group":"Gut: colon","name":"Dialister","sub":"D. invisus","how":"A small colon bacterium that ferments fibre into propionate. Like Coprococcus, it is found at lower levels in people with depression in population studies.","evidence":"Lower in depression in large population cohorts (association only).","pos":[0.04,1.05,0.07]},{"id":"gb_subdoligranulum","col":"gb","group":"Gut: colon","name":"Subdoligranulum","sub":"close relative of Faecalibacterium","how":"A butyrate-making colon bacterium closely related to Faecalibacterium. It is one of the groups that fall away when the diet is low in fibre.","evidence":"Textbook fermentation; metabolic links are association only.","pos":[-0.07,1.07,0.075]},{"id":"gb_butyricicoccus","col":"gb","group":"Gut: colon","name":"Butyricicoccus pullicaecorum","sub":"butyrate maker","how":"A colon bacterium named for the butyrate it makes. Butyrate feeds the cells lining the colon and helps keep the junctions between them tight.","evidence":"Textbook fermentation; studied as a possible probiotic, not proven in people.","pos":[0.07,1.09,0.06]},{"id":"gb_odoribacter","col":"gb","group":"Gut: colon","name":"Odoribacter splanchnicus","sub":"propionate maker","how":"A colon bacterium that ferments fibre into propionate, a short-chain fatty acid the liver uses and that signals fullness to the brain.","evidence":"Textbook fermentation.","pos":[0.09,1.04,0.055]},{"id":"gb_cscindens","col":"gb","group":"Gut: colon","name":"Clostridium scindens","sub":"bile acid converter","how":"One of the few gut bacteria that can take the bile acids the liver sends into the gut and convert them into secondary bile acids. Those converted bile acids make the colon a harder place for Clostridioides difficile to grow.","evidence":"Shown in mice and in human stool transplant data (lab-level for the C. difficile effect).","pos":[-0.03,1.02,0.065]},{"id":"gb_lachnospira","col":"gb","group":"Gut: colon","name":"Lachnospira","sub":"pectin specialist","how":"A colon bacterium that breaks down pectin, the fibre in apples, citrus peel and carrots, and feeds the products to other short-chain fatty acid makers.","evidence":"Textbook fermentation.","pos":[-0.1,1.06,0.06]},{"id":"gb_clostridia_clusters","col":"gb","group":"Gut: colon","name":"Clostridia clusters IV and XIVa","sub":"spore-forming fibre fermenters","how":"A broad family of harmless spore-forming colon bacteria (the group Faecalibacterium and Roseburia belong to) whose short-chain fatty acids prompt the gut to make regulatory T cells, the brake on the immune system.","evidence":"A defined mixture of 17 human Clostridia strains induced regulatory T cells and calmed colitis in mice (lab).","pos":[0,1.03,0.07]},{"id":"gb_msmithii","col":"gb","group":"Gut: colon","name":"Methanobrevibacter smithii","sub":"an archaeon, not a bacterium","how":"The main methane maker in the human colon. It belongs to the archaea, a separate branch of life from bacteria. By consuming the hydrogen other microbes release, it lets fibre fermentation keep running; the methane it makes is breathed out and can slow the bowel.","evidence":"Textbook hydrogen disposal. Higher levels in constipation-predominant IBS with methane on the breath (association).","pos":[-0.09,1.02,0.06]},{"id":"gb_ecoli_commensal","col":"gb","group":"Gut: colon","name":"Escherichia coli (commensal strains)","sub":"the harmless resident type","how":"Almost everyone carries E. coli in the colon as a small, harmless part of the community. It uses up oxygen that leaks into the gut, which suits the oxygen-hating helpful bacteria, and it makes vitamin K2. Different strains of the same species cause food poisoning or urine infections; carrying the resident type is not the same thing.","evidence":"Textbook gut physiology. Which strain a person carries matters more than the species.","pos":[-0.05,1,0.05]},{"id":"gb_bifido_longum","col":"gb","group":"Gut: colon","name":"Bifidobacterium longum","sub":"the commonest adult Bifidobacterium","how":"The Bifidobacterium species most often found in adults. It ferments fibre and inulin into lactate and acetate, which other bacteria turn into butyrate.","evidence":"Textbook fermentation; inulin-type fibre reliably raises bifidobacteria.","pos":[0.1,1.07,0.05]},{"id":"gb_bifido_adolescentis","col":"gb","group":"Gut: colon","name":"Bifidobacterium adolescentis","sub":"starch user","how":"A Bifidobacterium of the older child and adult gut that is good at using resistant starch and inulin-type fibre.","evidence":"Textbook fermentation.","pos":[0.08,1.05,0.045]},{"id":"gb_bacteroides_plebeius","col":"gb","group":"Gut: colon","name":"Bacteroides plebeius","sub":"seaweed fibre specialist","how":"A colon bacterium carried mainly by people who eat seaweed; it borrowed the enzymes for seaweed fibre from marine bacteria. A good example of the gut community adapting to what a population eats.","evidence":"Textbook example of gut gene transfer.","pos":[0.06,1.03,0.06]},{"id":"gb_phascolarctobacterium","col":"gb","group":"Gut: colon","name":"Phascolarctobacterium","sub":"propionate from succinate","how":"Lives off the succinate that Bacteroides leave behind and turns it into propionate. Without it, succinate can build up and draw water into the bowel.","evidence":"Textbook cross-feeding in the gut.","pos":[0.03,1.01,0.08]},{"id":"gb_eubacterium_eligens","col":"gb","group":"Gut: colon","name":"Eubacterium eligens","sub":"pectin fermenter","how":"A colon bacterium that lives mainly on pectin, the fibre in fruit and vegetables, and turns it into short-chain fatty acids.","evidence":"Textbook fermentation.","pos":[-0.085,1.08,0.065]},{"id":"gb_bacteroides_uniformis","col":"gb","group":"Gut: colon","name":"Bacteroides uniformis","sub":"","how":"A common colon Bacteroides with a wide set of fibre-digesting enzymes; it ferments plant fibre into acetate and propionate.","evidence":"Textbook fermentation.","pos":[0,1.12,0.055]},{"id":"gb_gastric_residents","col":"gb","group":"Gut: stomach","name":"Acid-tolerant stomach residents","sub":"Streptococcus, Lactobacillus, Prevotella","how":"The stomach is not sterile: a thin community of acid-tolerant bacteria swallowed from the mouth lives in its mucus. Strong acid keeps their numbers low, which is one of the body's main defences against swallowed bugs.","evidence":"Textbook; shown by sequencing of stomach biopsies. Community shifts when acid is suppressed.","pos":[0.065,1.16,0.05]},{"id":"gb_lacto_gasseri","col":"gb","group":"Gut: stomach","name":"Lactobacillus gasseri","sub":"","how":"One of the lactobacilli found in the human stomach and upper small intestine, as well as in the vagina. It makes lactic acid, which lowers the local pH.","evidence":"Textbook. Weight-loss claims for this species are not proven.","pos":[0.085,1.14,0.045]},{"id":"gb_lacto_reuteri","col":"gb","group":"Gut: small intestine","name":"Limosilactobacillus reuteri","sub":"formerly Lactobacillus reuteri","how":"A lactobacillus of the human small intestine. It ferments sugars to lactate and makes reuterin, a substance that holds back competing bacteria.","evidence":"Textbook. Used as a probiotic; trial results vary by condition, so the genus-level probiotic links in this graph stay mixed.","pos":[-0.03,1,0.055]},{"id":"gb_lacto_rhamnosus","col":"gb","group":"Gut: small intestine","name":"Lacticaseibacillus rhamnosus","sub":"formerly Lactobacillus rhamnosus, strain GG","how":"A lactobacillus that sticks well to the gut lining and is the most studied probiotic strain. It makes lactic acid and competes with other bacteria for attachment sites.","evidence":"Textbook for what it does. Whether taking it changes an illness depends on the condition and is covered by the probiotics node.","pos":[0,0.99,0.06]},{"id":"gb_lacto_plantarum","col":"gb","group":"Gut: small intestine","name":"Lactiplantibacillus plantarum","sub":"formerly Lactobacillus plantarum","how":"A very adaptable lactic-acid bacterium found in fermented vegetables and in the human gut. It ferments a wide range of sugars into lactate.","evidence":"Textbook; it is one of the main bacteria in sauerkraut and kimchi.","pos":[0.03,1,0.055]},{"id":"gb_lacto_acidophilus","col":"gb","group":"Gut: small intestine","name":"Lactobacillus acidophilus","sub":"","how":"A lactic-acid bacterium of the small intestine, also added to many yoghurts. It makes its own lactase, so it helps digest milk sugar in the product it is in.","evidence":"Textbook. The proven lactose effect in this graph belongs to yoghurt cultures.","pos":[-0.01,1.02,0.06]},{"id":"gb_lacto_casei","col":"gb","group":"Gut: small intestine","name":"Lacticaseibacillus casei","sub":"formerly Lactobacillus casei","how":"A lactic-acid bacterium found in cheese, fermented milk drinks and the human gut, where it ferments sugars into lactate.","evidence":"Textbook.","pos":[0.02,0.97,0.06]},{"id":"gb_bifido_infantis","col":"gb","group":"Gut: small intestine","name":"Bifidobacterium infantis","sub":"B. longum subsp. infantis","how":"The bacterium that dominates the gut of a breastfed baby. It carries the full set of enzymes for the special sugars in human milk, which no other common gut bacterium can use whole, so breast milk feeds it almost exclusively.","evidence":"Textbook infant gut physiology. It is scarce in babies who are not breastfed.","pos":[-0.04,0.98,0.05]},{"id":"gb_bifido_breve","col":"gb","group":"Gut: small intestine","name":"Bifidobacterium breve","sub":"","how":"A Bifidobacterium of the infant and young-child gut that uses milk sugars and fibre and makes lactate and acetate.","evidence":"Textbook.","pos":[0.04,0.98,0.05]},{"id":"gb_bifido_bifidum","col":"gb","group":"Gut: small intestine","name":"Bifidobacterium bifidum","sub":"","how":"A Bifidobacterium that trims sugars off the gut's mucus layer and off milk sugars, sharing the pieces with other bifidobacteria.","evidence":"Textbook.","pos":[-0.02,0.96,0.055]},{"id":"gb_small_intestine_community","col":"gb","group":"Gut: small intestine","name":"Small-intestine community","sub":"Streptococcus, Veillonella, Lactobacillus","how":"The small intestine holds far fewer bacteria than the colon, and different ones: fast-growing sugar users that can cope with bile and with food rushing past. Bile, acid from the stomach and brisk movement all keep their numbers down.","evidence":"Textbook; sampled directly in studies of the upper gut. Too many of them in the wrong place is the overgrowth already in this graph.","pos":[-0.05,1.01,0.065]},{"id":"gb_rothia","col":"gb","group":"Mouth: tongue","name":"Rothia","sub":"R. mucilaginosa, R. aeria","how":"One of the main bacteria on the back of the tongue, and one of the best at the first step of the nitrate pathway: it turns the nitrate from leafy greens and beetroot into nitrite, which the body goes on to turn into nitric oxide.","evidence":"Textbook for nitrate reduction. Adding a nitrate-reducing Rothia strain to gum-disease plaque shifted it towards a healthier mix in the laboratory.","pos":[-0.02,1.549,0.048]},{"id":"gb_neisseria_commensal","col":"gb","group":"Mouth: tongue","name":"Commensal Neisseria","sub":"N. flavescens, N. subflava; not the gonorrhoea or meningitis species","how":"Harmless oxygen-using relatives of the disease-causing Neisseria, common on the tongue and cheek. They are strong nitrate reducers and are among the first bacteria lost when someone smokes.","evidence":"Textbook for nitrate reduction. Depleted in smokers in a large population study.","pos":[0.02,1.549,0.048]},{"id":"gb_veillonella_oral","col":"gb","group":"Mouth: tongue","name":"Veillonella (mouth)","sub":"V. atypica, V. parvula","how":"Cannot use sugar at all. It lives on the lactate that the streptococci make, turning it into propionate, which keeps acid from building up on the tooth surface and makes it a central partner in dental plaque.","evidence":"Textbook mouth ecology. A small trial of a Veillonella probiotic in athletes found no change in lactate or performance.","pos":[0,1.551,0.044]},{"id":"gb_strep_salivarius","col":"gb","group":"Mouth: tongue","name":"Streptococcus salivarius","sub":"","how":"One of the first bacteria to colonise a newborn's mouth and a dominant resident of the tongue and saliva for life. It takes up space and nutrients that less welcome streptococci would otherwise use.","evidence":"Textbook. Some strains are sold as throat probiotics; the evidence for that is weak.","pos":[-0.025,1.552,0.052]},{"id":"gb_strep_oralis","col":"gb","group":"Mouth: teeth plaque","name":"Streptococcus oralis and S. sanguinis","sub":"peroxide-making commensal streptococci","how":"The main early settlers on a clean tooth surface. They make hydrogen peroxide, which holds back Streptococcus mutans and the yeast Candida, so a plaque dominated by them is a healthier plaque.","evidence":"Their antagonism of S. mutans and Candida is shown in laboratory tooth-surface models.","pos":[-0.015,1.552,0.082]},{"id":"gb_actinomyces","col":"gb","group":"Mouth: teeth plaque","name":"Actinomyces","sub":"","how":"A filament-shaped bacterium that forms the early framework of dental plaque together with the commensal streptococci. In a healthy mouth it is part of normal plaque; on exposed root surfaces in older people it takes part in root decay.","evidence":"Textbook plaque ecology; both roles are well described.","pos":[0.015,1.552,0.082]},{"id":"gb_coryne_matruchotii","col":"gb","group":"Mouth: teeth plaque","name":"Corynebacterium matruchotii","sub":"the hedgehog bacterium","how":"A long filament that acts as the scaffold of dental plaque: other bacteria attach along it in a bottle-brush pattern, with oxygen users on the outside and oxygen haters sheltered inside. It is a marker of ordinary, stable plaque rather than disease.","evidence":"Textbook, shown directly by imaging of plaque structure.","pos":[0,1.553,0.084]},{"id":"gb_dolosigranulum","col":"gb","group":"Nose & throat","name":"Dolosigranulum pigrum","sub":"","how":"A harmless lactic-acid bacterium of the nose, common in healthy children and often found alongside nose Corynebacterium. The two together hold back the growth of pneumococcus, the commonest cause of middle-ear and chest infections.","evidence":"Joint inhibition of pneumococcus shown in the laboratory; in children, its presence goes with better respiratory health, which is an association.","pos":[-0.015,1.598,0.065]},{"id":"gb_coryne_nose","col":"gb","group":"Nose & throat","name":"Nose Corynebacterium","sub":"C. pseudodiphtheriticum, C. propinquum","how":"Harmless relatives of the diphtheria bacterium that live in the nostrils. They make fatty substances that interfere with Staphylococcus aureus and, with Dolosigranulum, hold back pneumococcus.","evidence":"Inhibition shown in the laboratory. Noses dominated by these bacteria go with fewer respiratory infections in infancy (association).","pos":[0.015,1.598,0.065]},{"id":"gb_throat_commensals","col":"gb","group":"Nose & throat","name":"Throat commensal streptococci","sub":"viridans group: S. mitis, S. oralis, S. salivarius","how":"The harmless streptococci that coat the back of the throat and tonsils. They occupy the surface and the nutrients that group A streptococcus, the strep-throat bacterium, would otherwise use.","evidence":"Textbook; competition for the throat surface is well described.","pos":[0,1.49,0.03]},{"id":"gb_lung_commensals","col":"gb","group":"Lungs","name":"Lung resident community","sub":"Prevotella, Veillonella, Streptococcus","how":"Healthy lungs are not sterile. A thin community, mostly bacteria breathed down from the mouth, lives on the airway surface and is constantly cleared again. When too many mouth bacteria build up there, the airway's inflammatory cells rise with them.","evidence":"Shown by washing out the lungs of healthy volunteers; the inflammation link is an association.","pos":[0.07,1.33,0]},{"id":"gb_conjunctival_residents","col":"gb","group":"Conjunctiva","name":"Eye surface residents","sub":"Corynebacterium mastitidis, coagulase-negative staphylococci","how":"The surface of the eye carries only a sparse community, kept down by tears, blinking and the antibacterial proteins in tear fluid. At least one resident coryneform bacterium prompts the eye to keep protective immune cells on standby.","evidence":"The immune effect was shown in mice (lab); in people the eye-surface community is known to be sparse and variable.","pos":[-0.03,1.628,0.084]},{"id":"gb_cutibacterium","col":"gb","group":"Skin: oily areas","name":"Cutibacterium acnes","sub":"formerly Propionibacterium acnes","how":"The dominant bacterium of healthy oily skin, living deep in hair follicles on sebum. It makes propionic acid, which keeps the skin surface slightly acidic and unwelcoming to Staphylococcus aureus. Everyone carries it; in acne the mix of its strains and the skin's reaction change, rather than the bacterium appearing from nowhere.","evidence":"Textbook resident. Acne-associated differences in the facial community are shown in a large adolescent study (association).","pos":[0,1.7,0.072]},{"id":"gb_staph_epidermidis","col":"gb","group":"Skin: moist areas","name":"Staphylococcus epidermidis","sub":"","how":"The commonest bacterium on human skin and a genuine good neighbour: it makes substances that interfere with Staphylococcus aureus and helps the skin's own immune cells learn restraint. On a plastic line or an artificial joint, the same bacterium can form a film and cause infection.","evidence":"Textbook resident; its antibacterial substances are shown in the laboratory. Device infections are well documented.","pos":[0.17,1.4,0]},{"id":"gb_staph_hominis","col":"gb","group":"Skin: moist areas","name":"Staphylococcus hominis","sub":"","how":"Another harmless skin staphylococcus. Some strains make small antibacterial molecules that specifically block Staphylococcus aureus, and people with eczema tend to carry fewer of those strains.","evidence":"The antibacterials and the shortfall in eczema were shown in human skin samples and mouse skin (lab).","pos":[0.175,1.395,-0.01]},{"id":"gb_coryne_skin","col":"gb","group":"Skin: moist areas","name":"Skin Corynebacterium","sub":"","how":"Lives in the armpit and other moist folds, where it breaks down the odourless compounds in sweat into the molecules responsible for body odour. Harmless, and part of the normal fold community.","evidence":"Textbook; body odour chemistry is well described.","pos":[0.165,1.405,0.01]},{"id":"gb_skin_dry","col":"gb","group":"Skin: dry areas","name":"Dry-skin community","sub":"forearm, palm; mixed and changeable","how":"The forearm and palm are dry, cool and poor in oil, so they hold the thinnest and most variable community on the body, picked up and lost from whatever the hands touch. Washing removes the passengers rather than the residents.","evidence":"Textbook skin ecology, mapped by sequencing different body sites.","pos":[0.25,1.1,0.05]},{"id":"gb_lacto_crispatus","col":"gb","group":"Vagina","name":"Lactobacillus crispatus","sub":"the most protective type","how":"The lactobacillus that makes a vagina dominated by it the most stable and the most resistant to trouble. It produces plenty of lactic acid, holding the pH around four, which most other bacteria cannot tolerate.","evidence":"In community-type studies, crispatus-dominated communities are the most stable and least often disturbed.","pos":[-0.015,0.862,0.004]},{"id":"gb_lacto_iners","col":"gb","group":"Vagina","name":"Lactobacillus iners","sub":"the unstable type","how":"The commonest vaginal lactobacillus worldwide, but a weaker guardian than L. crispatus: it makes less lactic acid, and communities it dominates flip more easily into bacterial vaginosis. It is also the lactobacillus that reappears first after treatment.","evidence":"Pooled studies found more bacterial vaginosis and more sexually transmitted infection with iners-dominated than crispatus-dominated communities.","pos":[0.015,0.862,0.004]},{"id":"gb_lacto_jensenii","col":"gb","group":"Vagina","name":"Lactobacillus jensenii","sub":"","how":"One of the less common vaginal lactobacilli. Like the others, it makes lactic acid and hydrogen peroxide and keeps the vaginal pH low.","evidence":"Textbook; one of the recognised vaginal community types.","pos":[0,0.868,0.008]},{"id":"gb_urinary_lacto","col":"gb","group":"Urinary tract","name":"Bladder lactobacilli","sub":"","how":"Urine is not sterile. The female bladder carries its own sparse community, in many women dominated by lactobacilli, probably seeded from the vagina next door.","evidence":"Found by culturing urine taken directly from the bladder; women with urgency incontinence carried a different mix, which is an association.","pos":[0,0.885,0.05]},{"id":"hpylori","col":"bb","group":"Stomach & small intestine","name":"Helicobacter pylori","sub":"","how":"A stomach bacterium that causes gastritis and ulcers. More common in people with Parkinson's, and linked to erratic levodopa response.","evidence":"Mixed: early small studies found better levodopa response after eradication; a randomised placebo-controlled trial (Tan 2020) found no motor benefit.","pos":[0.07,1.15,0.05]},{"id":"sibo","col":"bb","group":"Stomach & small intestine","name":"Small-intestine overgrowth","sub":"SIBO","how":"Not one species: too many colon-type bacteria in the small intestine, where levodopa is absorbed. Common when gut transit is slow, as in Parkinson's, and linked to more motor fluctuations (association).","evidence":"","pos":[0.01,1.01,0.07]},{"id":"salmonella","col":"bb","group":"Stomach & small intestine","name":"Salmonella","sub":"food poisoning, typhoid","how":"Picked up from contaminated food. It invades the lining of the lower small intestine, causing diarrhoea and fever; typhoid types spread into the blood.","evidence":"Established cause of food poisoning and typhoid fever.","pos":[-0.05,0.955,0.07]},{"id":"campylobacter","col":"bb","group":"Stomach & small intestine","name":"Campylobacter","sub":"C. jejuni","how":"The commonest bacterial cause of food poisoning (undercooked poultry). In about 1 in 1,000 cases, antibodies made against it cross-react with nerve coatings and cause Guillain-Barré syndrome, a sudden weakness that can paralyse.","evidence":"Established: the leading known trigger of Guillain-Barré syndrome; about 31% of cases follow Campylobacter (Poropatich 2010).","pos":[0.035,1.03,0.07]},{"id":"desulfo","col":"bb","group":"Colon","name":"Desulfovibrio","sub":"sulfate-reducing","how":"Bacteria that make hydrogen sulfide. Found at higher levels in Parkinson's in several studies (association). In the lab, sulfide damages the gut lining.","evidence":"","pos":[0.06,0.93,0.06]},{"id":"entero","col":"bb","group":"Colon","name":"Enterobacteriaceae","sub":"E. coli and relatives","how":"A family that thrives when oxygen leaks into the gut (as happens when butyrate is low). Its outer wall (LPS) strongly triggers inflammation. Higher levels went with more balance problems in Parkinson's (Scheperjans 2015).","evidence":"","pos":[-0.09,0.98,0.05]},{"id":"cdiff","col":"bb","group":"Colon","name":"Clostridioides difficile","sub":"C. diff","how":"A spore-forming colon bacterium that takes over when antibiotics wipe out normal gut bacteria. Its toxins damage the colon lining, causing diarrhoea and colitis.","evidence":"Established cause of antibiotic-associated colitis. Probiotics to prevent it: pooled trials positive, the largest single trial negative.","pos":[-0.06,1.09,0.07]},{"id":"klebsiella","col":"bb","group":"Colon","name":"Klebsiella","sub":"K. pneumoniae","how":"Lives harmlessly in the gut and mouth of many people, but can cause pneumonia and hospital infections and is often antibiotic-resistant.","evidence":"Lab: strains from saliva settled in the gut of mice and drove strong gut inflammation (Atarashi 2017).","pos":[0.08,0.96,0.05]},{"id":"bb_rumino_gnavus","col":"bb","group":"Colon","name":"Ruminococcus gnavus","sub":"","how":"A normal but usually minor colon bacterium. A particular branch of it blooms during flares of inflammatory bowel disease, and it makes a sugar polymer that provokes inflammatory signals from immune cells.","evidence":"Enriched in people with Crohn's disease in a sequencing study; the inflammatory effect of its polymer is shown in cells (lab).","pos":[-0.04,1.06,0.065]},{"id":"bb_bilophila","col":"bb","group":"Colon","name":"Bilophila wadsworthia","sub":"bile-loving, sulfide maker","how":"A bile-tolerant colon bacterium that lives off taurine, part of the bile the liver releases after fatty meals, and releases hydrogen sulfide. It becomes more common on a diet high in animal fat.","evidence":"In mice, it worsened the metabolic effects of a high-fat diet and irritated the gut lining (lab). Human data are observational.","pos":[0.05,1.02,0.065]},{"id":"bb_enterococcus","col":"bb","group":"Colon","name":"Enterococcus","sub":"E. faecalis, E. faecium","how":"A normal, small part of the gut community that is both: harmless in place, but tough, salt- and antibiotic-tolerant, so it takes over after a course of antibiotics and is a common cause of urine, wound and bloodstream infections in hospital.","evidence":"Textbook. Overgrowth after antibiotics and resistant strains are well documented.","pos":[0.03,1.07,0.055]},{"id":"bb_sgallolyticus","col":"bb","group":"Colon","name":"Streptococcus gallolyticus","sub":"formerly S. bovis","how":"A gut bacterium found more often in people who have bowel tumours, and a known cause of heart-valve infection. It seems to settle on tumour tissue, so finding it may be a sign rather than a cause.","evidence":"Repeated association with bowel tumours in observational work; whether it contributes or just colonises is unsettled.","pos":[-0.09,1.09,0.06]},{"id":"bb_ecoli_aiec","col":"bb","group":"Colon","name":"Adherent-invasive E. coli","sub":"AIEC strains","how":"A group of E. coli strains that stick to and get inside the cells lining the last part of the small bowel. They are found more often in the lining of people with Crohn's disease than in other people.","evidence":"Association from biopsy studies; it is not clear whether these strains start the disease or thrive in an already inflamed bowel.","pos":[-0.06,1.04,0.055]},{"id":"strep","col":"bb","group":"Throat","name":"Group A streptococcus","sub":"strep throat","how":"Causes strep throat and scarlet fever. The PANDAS hypothesis says it can trigger sudden-onset tics or OCD in some children through cross-reacting antibodies; this is debated.","evidence":"","pos":[0,1.51,0.02]},{"id":"hib","col":"bb","group":"Throat","name":"Haemophilus influenzae type b (Hib)","sub":"","how":"A capsule-coated bacterium spread by droplets that once was the main cause of meningitis in young children, and of epiglottitis (a swollen flap above the voice box that can block breathing). Routine infant vaccination has made it rare. Unrelated to the flu virus despite the name.","evidence":"Established (textbook). The conjugate vaccine prevents it in trials.","pos":[0,1.49,0.04]},{"id":"diphtheria","col":"bb","group":"Throat","name":"Corynebacterium diphtheriae","sub":"diphtheria","how":"Spread by droplets and skin sores. In the throat it forms a grey membrane that can block the airway, and its toxin travels in the blood to damage the heart muscle and nerves. Rare where children are vaccinated; outbreaks return when vaccination falls.","evidence":"Established (textbook): the toxin vaccine (toxoid) made it rare.","pos":[0,1.52,0.03]},{"id":"fuso","col":"bb","group":"Mouth","name":"Fusobacterium nucleatum","sub":"","how":"A gum-plaque bacterium that bridges other plaque bacteria; can travel to the colon and other sites.","evidence":"Association: found much more often in colorectal tumours than normal tissue (Castellarin 2012); in mice it created an inflamed tumour environment (Kostic 2013). Whether it causes cancer in people is not settled.","pos":[-0.02,1.555,0.075]},{"id":"pging","col":"bb","group":"Mouth","name":"Porphyromonas gingivalis","sub":"gum disease bacterium","how":"Lives in the pockets around teeth and is the key driver of chronic gum disease (periodontitis), which keeps the gums and body in a low-grade inflamed state.","evidence":"Association: gum disease is linked with cognitive impairment and dementia (Guo 2021 meta-analysis). The bacterium was found in Alzheimer brains and inflamed the brain in mice (Dominy 2019, lab). Not shown to cause Alzheimer's in people.","pos":[0.02,1.555,0.075]},{"id":"mtb","col":"bb","group":"Lungs","name":"Mycobacterium tuberculosis","sub":"TB","how":"A slow-growing bacterium caught by breathing in droplets. It usually settles in the upper lungs and can stay dormant for years; it can spread to the brain lining and spine.","evidence":"Established: TB meningitis and brain tuberculomas cause seizures and disability; HIV greatly raises the risk of active TB.","pos":[-0.07,1.38,0]},{"id":"chlamydia_pn","col":"bb","group":"Lungs","name":"Chlamydia pneumoniae","sub":"","how":"A common cause of mild pneumonia and bronchitis that lives inside cells and can persist.","evidence":"Association, inconsistent: linked with Alzheimer's in a Taiwanese cohort (Ou 2021) but not in Framingham (Zilli 2021).","pos":[0.07,1.33,0]},{"id":"bb_pseudomonas","col":"bb","group":"Lungs","name":"Pseudomonas aeruginosa","sub":"","how":"An environmental bacterium that does not colonise healthy lungs but settles permanently in airways already damaged by cystic fibrosis or bronchiectasis, where it forms a slime layer that resists both antibiotics and the immune system.","evidence":"Textbook. Chronic carriage goes with more flare-ups and worse lung function.","pos":[-0.07,1.3,0]},{"id":"pneumococcus","col":"bb","group":"Lungs","name":"Pneumococcus","sub":"Streptococcus pneumoniae","how":"Carried in the back of the nose, mostly by young children, and spread by droplets. It is the commonest bacterial cause of pneumonia, and also causes ear infections, sinusitis, meningitis and blood infection. Its sugar coat (capsule) hides it from immune cells, so people without a working spleen, older adults, and those with HIV, diabetes, or heart, lung or kidney disease are at higher risk.","evidence":"Established (textbook). Vaccines protect against the covered types in trials.","pos":[-0.09,1.32,0.01]},{"id":"pseudomonas","col":"bb","group":"Lungs","name":"Pseudomonas aeruginosa","sub":"","how":"A water-loving bacterium found in sinks, hot tubs and hospital equipment. It rarely harms healthy people (swimmer's ear, hot-tub rash) but causes pneumonia in people on ventilators, chronic lung infection in cystic fibrosis and bronchiectasis, and infections of burns and catheters. Many strains resist several antibiotics.","evidence":"Established (textbook): a major hospital-acquired and drug-resistant pathogen.","pos":[0.08,1.35,0]},{"id":"legionella","col":"bb","group":"Lungs","name":"Legionella","sub":"Legionnaires' disease","how":"Grows in warm water systems (cooling towers, hot-water pipes, spas, showers) and is caught by breathing in fine water droplets, not from other people. It causes a severe pneumonia, often with diarrhoea and confusion, mostly in older people, smokers and those with weak immunity.","evidence":"Established (textbook).","pos":[0.09,1.3,0.02]},{"id":"mycoplasma","col":"bb","group":"Lungs","name":"Mycoplasma pneumoniae","sub":"\"walking pneumonia\"","how":"A tiny bacterium without a cell wall, spread by droplets among school children and young adults. It causes a slow-onset chest infection with a lingering dry cough, often mild enough to keep walking about.","evidence":"Established (textbook).","pos":[-0.08,1.35,0]},{"id":"bordetella","col":"bb","group":"Lungs","name":"Bordetella pertussis","sub":"whooping cough","how":"Spread by droplets, it attaches to the windpipe lining and releases toxins that paralyse the hair-like cilia. Weeks of violent coughing fits follow, with a \"whoop\" breathing in and vomiting; it can last three months. Most dangerous for babies too young to be vaccinated, which is why it is given in pregnancy.","evidence":"Established (textbook). Acellular vaccines prevent it in trials.","pos":[0,1.42,0.02]},{"id":"borrelia","col":"bb","group":"Spread through the body","name":"Borrelia burgdorferi","sub":"Lyme disease","how":"A spiral bacterium passed on by tick bites. It starts in the skin around the bite (spreading rash) and can spread to joints, heart and nerves.","evidence":"Established: can cause facial palsy and painful nerve-root inflammation (neuroborreliosis). Long-lasting symptoms after treatment are debated.","pos":[0.1,0.75,0.07]},{"id":"treponema","col":"bb","group":"Spread through the body","name":"Treponema pallidum","sub":"syphilis","how":"The spiral bacterium that causes syphilis. Untreated, it can reach the brain and spinal cord years later (neurosyphilis); placed here at the brain for that reason.","evidence":"Established: untreated neurosyphilis causes dementia and personality change (general paresis) and spinal cord damage with unsteady walking (tabes dorsalis).","pos":[0,1.72,0.02]},{"id":"bb_strep_mutans","col":"bb","group":"Mouth: teeth plaque","name":"Streptococcus mutans","sub":"the decay bacterium","how":"Turns dietary sugar into acid on the tooth surface and into a sticky glue that holds plaque together. The acid dissolves enamel, which is how a cavity starts. It passes between children and from carers to children.","evidence":"Long established as the main bacterium of tooth decay; its transmission between children tracks with having cavities in a pooled analysis.","pos":[0,1.551,0.083]},{"id":"bb_tannerella","col":"bb","group":"Mouth: gum line","name":"Tannerella forsythia","sub":"","how":"One of the three bacteria of the so-called red complex found deep in the pockets between gum and tooth in destructive gum disease. It needs the other members to grow well, and together they keep the gum inflamed and the bone receding.","evidence":"Consistently found with the other red-complex bacteria in deep, bleeding pockets.","pos":[-0.02,1.557,0.079]},{"id":"bb_tdenticola","col":"bb","group":"Mouth: gum line","name":"Treponema denticola","sub":"a mouth spirochaete; not the syphilis species","how":"A corkscrew-shaped bacterium of the gum pocket, the third member of the red complex with Porphyromonas gingivalis and Tannerella forsythia. It breaks down proteins in the gum tissue and moves well through the sticky layer in the pocket.","evidence":"Consistently found in deep gum pockets in destructive gum disease.","pos":[0.02,1.557,0.079]},{"id":"bb_aggregatibacter","col":"bb","group":"Mouth: gum line","name":"Aggregatibacter actinomycetemcomitans","sub":"","how":"A gum-line bacterium that makes a toxin which kills the white cells sent to defend the gum. One highly toxic variant, the JP2 strain, is linked with the fast bone loss seen in aggressive gum disease in teenagers and young adults.","evidence":"In a study of young African Americans, over eight in ten with localised aggressive gum disease carried the highly toxic JP2 strain.","pos":[-0.03,1.556,0.077]},{"id":"bb_prevotella_intermedia","col":"bb","group":"Mouth: gum line","name":"Prevotella intermedia","sub":"","how":"A gum-pocket bacterium that becomes prominent in gum inflammation, including the gum swelling common in pregnancy. It lives on the proteins and blood products in an inflamed pocket.","evidence":"Repeatedly found in gingivitis and periodontitis samples.","pos":[0.03,1.556,0.077]},{"id":"bb_spneumo","col":"bb","group":"Nose & throat","name":"Streptococcus pneumoniae (carriage)","sub":"pneumococcus","how":"Lives quietly in the nose and throat of a large share of young children, causing nothing. From there it can spread to the middle ear, the sinuses or the lungs, and rarely into the blood. Carriage is the normal state; disease is the exception.","evidence":"Textbook. Carriage is how it spreads, and vaccination works partly by reducing carriage.","pos":[0,1.6,0.055]},{"id":"bb_moraxella","col":"bb","group":"Nose & throat","name":"Moraxella catarrhalis","sub":"","how":"One of the three bacteria carried in children's noses that cause most middle-ear infections. Carriage is common and usually silent; it also flares up in long-standing lung disease.","evidence":"Textbook as a cause of middle-ear infection and of flare-ups in chronic lung disease. Carriage in the community is well mapped.","pos":[0.025,1.597,0.06]},{"id":"bb_hinfluenzae","col":"bb","group":"Nose & throat","name":"Nontypeable Haemophilus influenzae","sub":"the non-vaccine type","how":"A nose and throat resident, not covered by the Hib vaccine, which protects only against one capsule type. It causes middle-ear and sinus infections and settles in the damaged airways of long-standing lung disease, where it drives flare-ups.","evidence":"Textbook. Nothing to do with influenza, which is a virus.","pos":[-0.025,1.597,0.06]},{"id":"bb_staph_aureus","col":"bb","group":"Skin: moist areas","name":"Staphylococcus aureus","sub":"","how":"Carried in the nostrils of roughly a third of people and on the skin of many more, usually without trouble. It is the main cause of boils, infected wounds and infected eczema, and its toxins irritate skin that is already inflamed.","evidence":"Textbook as a skin pathogen. Carriage and eczema severity track together in pooled trial data (association).","pos":[0.16,1.39,0.02]},{"id":"bb_malassezia","col":"bb","group":"Fungi & yeasts","name":"Malassezia","sub":"a yeast, not a bacterium","how":"A fungus, not a bacterium: a yeast that cannot make its own fats and so lives only where skin is oily, on the scalp, face and upper back. It is on everyone. Its breakdown products irritate susceptible skin, which is the basis of dandruff, seborrhoeic dermatitis and the patchy discolouration of pityriasis versicolor.","evidence":"Found at higher levels on seborrhoeic dermatitis lesions than on healthy scalp; because everyone carries it, this is an association plus the fact that antifungal treatment helps.","pos":[0,1.72,0]},{"id":"bb_candida","col":"bb","group":"Fungi & yeasts","name":"Candida albicans","sub":"a yeast, not a bacterium","how":"A yeast carried harmlessly in the mouth, gut and vagina of many people, held in check by the resident bacteria and by the immune system. When antibiotics clear the bacteria, or immunity drops, it overgrows and causes thrush on the tongue or in the vagina.","evidence":"Textbook. Overgrowth after antibiotics is well documented; claims that it causes widespread symptoms in otherwise healthy people are not supported.","pos":[0.02,1.03,0.05]},{"id":"bb_gardnerella","col":"bb","group":"Vagina","name":"Gardnerella vaginalis","sub":"","how":"The bacterium most associated with bacterial vaginosis, where it forms a sticky film on the vaginal wall that other bacteria join. It can also be found in women with no symptoms at all, so finding it is not the same as having the condition.","evidence":"Established as the central organism of bacterial vaginosis; carriage without symptoms is common, which is why diagnosis uses the whole picture.","pos":[-0.02,0.855,0]},{"id":"bb_fannyhessea","col":"bb","group":"Vagina","name":"Fannyhessea vaginae","sub":"formerly Atopobium vaginae","how":"Turns up with Gardnerella in the film on the vaginal wall in bacterial vaginosis, and its presence goes with the condition coming back after treatment.","evidence":"Consistently found with Gardnerella in bacterial vaginosis (association).","pos":[0.02,0.855,0]},{"id":"bb_prevotella_bivia","col":"bb","group":"Vagina","name":"Prevotella bivia","sub":"","how":"One of the mixed anaerobic bacteria that expand when vaginal lactobacilli thin out. It breaks down proteins into the amines responsible for the smell of bacterial vaginosis.","evidence":"Part of the recognised bacterial vaginosis community (association).","pos":[0,0.85,-0.004]},{"id":"bb_gbs","col":"bb","group":"Vagina","name":"Group B streptococcus (carriage)","sub":"Streptococcus agalactiae","how":"Lives in the bowel and vagina of a large minority of women without causing anything. It matters only around birth, when a baby can pick it up and, rarely, become seriously ill, which is why it is screened for or treated in labour.","evidence":"Carriage in pregnancy is common; pooled studies put it near one in five. Preventing newborn infection in labour is standard practice.","pos":[0.025,0.86,0.006]},{"id":"bb_upec","col":"bb","group":"Urinary tract","name":"Uropathogenic E. coli","sub":"UPEC strains","how":"E. coli strains from the person's own bowel that carry hooks for sticking to the bladder lining. They travel the short distance from the back passage to the urethra and up into the bladder, which is why most urine infections come from one's own gut bacteria.","evidence":"Established as the cause of most urine infections, in the community and in hospital.","pos":[0.02,0.84,0.05]},{"id":"bb_staph_saprophyticus","col":"bb","group":"Urinary tract","name":"Staphylococcus saprophyticus","sub":"","how":"A skin and genital staphylococcus that is the second commonest cause of simple bladder infection in young women, after E. coli.","evidence":"Textbook as a cause of uncomplicated urine infection.","pos":[-0.02,0.84,0.05]},{"id":"bb_proteus","col":"bb","group":"Urinary tract","name":"Proteus mirabilis","sub":"","how":"A gut bacterium that, in the urinary tract, splits urea and makes the urine alkaline. That is how struvite stones form, and the stones then shelter the bacteria from treatment. It is common with long-term catheters.","evidence":"Textbook: the link with urine-splitting stones is well established.","pos":[0.03,0.885,0.045]},{"id":"staph_aureus","col":"bb","group":"Skin & wounds","name":"Staphylococcus aureus","sub":"staph","how":"Carried harmlessly in the nose or on the skin of about a third of people; it causes infection when it gets past the skin through cuts, surgery, catheters or injecting. Boils, impetigo, cellulitis and wound infections; when it reaches the blood it can seed heart valves, bones, joints and spine. Some strains make toxins (food poisoning, toxic shock). Risk is higher with diabetes, dialysis, injecting drug use and implanted devices.","evidence":"Established (textbook): one of the commonest causes of serious bloodstream infection.","pos":[-0.25,1,0.05]},{"id":"mrsa","col":"bb","group":"Skin & wounds","name":"MRSA","sub":"meticillin-resistant Staphylococcus aureus","how":"Staph aureus that has become resistant to the main penicillin-type antibiotics, so infections are harder to treat. Spread on hands and surfaces in hospitals and care homes, and also in the community (sports teams, prisons). Antibiotic overuse selects for resistant strains; hand hygiene and screening limit spread.","evidence":"Established (textbook): a leading example of antibiotic resistance.","pos":[-0.27,0.95,0.05]},{"id":"meningococcus","col":"bb","group":"Brain & meninges","name":"Meningococcus","sub":"Neisseria meningitidis","how":"Carried harmlessly in the throat by about one in ten people and spread by close contact and kissing (students, military recruits, the African meningitis belt). Rarely it invades the blood and causes meningitis and sepsis that can kill within hours, with a rash that does not fade when pressed. Without a spleen, or with complement deficiency, risk is higher.","evidence":"Established (textbook). Vaccines exist for groups A, B, C, W and Y.","pos":[0,1.73,0]},{"id":"gbs","col":"bb","group":"Mother & newborn","name":"Group B streptococcus","sub":"Streptococcus agalactiae","how":"Lives harmlessly in the gut and vagina of about a quarter of women, but can pass to the baby during birth and cause sepsis, pneumonia and meningitis in the first weeks of life. It also causes infections in older adults with diabetes.","evidence":"Established (textbook): a leading cause of newborn sepsis and meningitis.","pos":[0,0.87,0.03]},{"id":"ebv","col":"v","group":"Herpes family","name":"Epstein–Barr virus","sub":"glandular fever","how":"Infects most people for life, hiding in B cells. In a cohort of 10 million US military personnel, multiple sclerosis risk rose about 32-fold after EBV infection (Bjornevik 2022), the strongest evidence that it is the main trigger of MS.","evidence":"","pos":[0.015,1.53,0.01]},{"id":"hsv1","col":"v","group":"Herpes family","name":"Herpes simplex 1","sub":"cold sores","how":"Lives silently in nerve cells and reactivates. Linked with Alzheimer's in cohort studies; an antiviral trial (valacyclovir, VALAD) did not slow decline.","evidence":"","pos":[0.03,1.62,0.02]},{"id":"vzv","col":"v","group":"Herpes family","name":"Varicella-zoster","sub":"chickenpox, shingles","how":"Causes chickenpox, then sleeps in nerve roots and can reactivate as shingles. Shingles vaccination was linked with less dementia in a natural experiment (Eyting 2025).","evidence":"","pos":[0.03,1.3,-0.08]},{"id":"cmv","col":"v","group":"Herpes family","name":"Cytomegalovirus","sub":"CMV","how":"A herpes virus most adults carry for life, hiding in white blood cells and the salivary glands. Harmless in most people, but dangerous to unborn babies and people with weak immunity.","evidence":"Established: infection in pregnancy is the leading infectious cause of brain damage and hearing loss at birth. Links with dementia are inconsistent (null in Framingham).","pos":[-0.05,1.57,0.01]},{"id":"hhv6","col":"v","group":"Herpes family","name":"Human herpesvirus 6","sub":"HHV-6A/B, roseola","how":"Almost everyone catches HHV-6B as a toddler (roseola: high fever then rash). It stays for life in salivary glands and the brain.","evidence":"Established: a common cause of febrile seizures in small children. Association: stronger HHV-6A antibody responses go with higher MS risk (Engdahl 2019).","pos":[0.05,1.57,0.01]},{"id":"hsv2","col":"v","group":"Herpes family","name":"Herpes simplex 2","sub":"genital herpes","how":"Spread by sexual skin contact (also from mother to baby at birth). Causes painful genital sores, then sleeps for life in the sacral nerve roots at the base of the spine and can flare again. It can also cause a viral meningitis.","evidence":"Established (textbook). Condoms lower but do not remove the risk of passing it on.","pos":[0,0.83,0.07]},{"id":"hhv8","col":"v","group":"Herpes family","name":"Human herpesvirus 8","sub":"Kaposi sarcoma herpesvirus","how":"A herpes virus spread mainly in saliva and sex that stays for life in white blood cells. In people with weakened immunity, above all untreated HIV or after transplant, it can cause Kaposi sarcoma (purple skin and lymph-node tumours) and some lymphomas. Placed at the lower-leg skin where Kaposi lesions often start.","evidence":"Established (textbook): the necessary cause of Kaposi sarcoma.","pos":[0.1,0.4,0.05]},{"id":"flu","col":"v","group":"Respiratory","name":"Influenza","sub":"","how":"Severe influenza has been linked with later Parkinson's in some cohort studies (weak, inconsistent). The 1918 pandemic era was followed by post-encephalitic parkinsonism.","evidence":"","pos":[-0.07,1.33,0]},{"id":"sarscov2","col":"v","group":"Respiratory","name":"SARS-CoV-2","sub":"COVID-19","how":"Damages support cells in the smell lining (loss of smell), and is linked with long-lasting fatigue and \"brain fog\" (long COVID).","evidence":"","pos":[0,1.62,0.08]},{"id":"measles","col":"v","group":"Respiratory","name":"Measles","sub":"","how":"A highly contagious airborne virus. Besides the acute illness it erases the immune system's memory of other germs, and in rare cases persists in the brain and causes a fatal brain disease years later (SSPE).","evidence":"Established: SSPE causes jerks, seizures and mental decline. Association: wiped out 11-73% of existing antibodies in children (Mina 2019).","pos":[0,1.42,0.02]},{"id":"flu_b","col":"v","group":"Respiratory","name":"Influenza B","sub":"flu B","how":"A flu virus that circulates only in people (influenza A also lives in birds and pigs, which is why A causes pandemics). Spread by droplets and hands, it infects the airway lining, causing fever, aches and cough; it hits children especially hard. Seasonal flu vaccines cover it.","evidence":"Established (textbook). Flu vaccines reduce confirmed influenza in trials.","pos":[-0.06,1.36,0.01]},{"id":"rsv","col":"v","group":"Respiratory","name":"Respiratory syncytial virus (RSV)","sub":"bronchiolitis","how":"Spread by droplets and contaminated hands and surfaces. Infects the small airways (bronchioles), which swell and fill with mucus: the main cause of bronchiolitis and hospital stays in babies, and a cause of pneumonia in older adults.","evidence":"Established (textbook). Vaccines for older adults and in pregnancy (to protect the baby) work in trials.","pos":[-0.05,1.3,0]},{"id":"rhinovirus","col":"v","group":"Respiratory","name":"Rhinovirus","sub":"common cold","how":"The commonest cause of the common cold. Spread mainly by hands touching the nose and eyes and by droplets; it infects the lining of the nose and throat, causing runny nose, sneezing and sore throat. It is the most common trigger of asthma attacks.","evidence":"Established (textbook). Over a hundred types, so there is no vaccine.","pos":[0,1.62,0.1]},{"id":"adenovirus","col":"v","group":"Respiratory","name":"Adenovirus","sub":"colds, pink eye, child diarrhoea","how":"A tough virus that survives on surfaces and in poorly chlorinated pools. Different types cause sore throat with fever, conjunctivitis (pink eye), bronchitis, and, in young children, diarrhoea. It can be serious after transplant.","evidence":"Established (textbook).","pos":[0,1.53,0.04]},{"id":"parainfluenza","col":"v","group":"Respiratory","name":"Parainfluenza viruses","sub":"croup","how":"Droplet-spread viruses that infect the voice box and windpipe of young children, causing croup: a barking cough and noisy breathing in, usually at night. They also cause colds in adults.","evidence":"Established (textbook).","pos":[0,1.48,0.04]},{"id":"hmpv","col":"v","group":"Respiratory","name":"Human metapneumovirus","sub":"hMPV","how":"A relative of RSV that causes colds, bronchiolitis and pneumonia, mostly in young children, older adults and people with weak immunity. Spread by droplets and contact.","evidence":"Established (textbook).","pos":[0.06,1.3,0.01]},{"id":"seasonal_cov","col":"v","group":"Respiratory","name":"Common-cold coronaviruses","sub":"OC43, 229E, NL63, HKU1","how":"Four coronaviruses, relatives of SARS-CoV-2, that have circulated for decades and cause ordinary colds, mostly in winter. Most people catch them repeatedly through life.","evidence":"Established (textbook).","pos":[0.01,1.61,0.1]},{"id":"hiv","col":"v","group":"Blood-borne","name":"HIV","sub":"human immunodeficiency virus","how":"A virus carried in blood and body fluids that infects and destroys CD4 T cells, the immune system's coordinators. It also enters the brain early. Placed at the heart to stand for the blood.","evidence":"Established: untreated it leads to AIDS; modern treatment keeps it suppressed. Linked thinking problems and nerve pain are much rarer on treatment.","pos":[0,1.28,0.03]},{"id":"htlv1","col":"v","group":"Blood-borne","name":"HTLV-1","sub":"human T-cell leukaemia virus type 1","how":"A virus related to HIV, spread by breastfeeding, sex and blood, that lives in T cells for life. Most carriers stay well, but a few develop adult T-cell leukaemia/lymphoma or a slow inflammation of the spinal cord (HAM/TSP) causing stiff, weak legs and bladder problems. Common in parts of Japan, the Caribbean, South America, Africa and central Australia.","evidence":"Established (textbook): a small minority of carriers develop leukaemia or spinal cord disease, decades after infection.","pos":[-0.02,1.26,0.03]},{"id":"hbv","col":"v","group":"Liver (hepatitis viruses)","name":"Hepatitis B","sub":"HBV","how":"A blood-borne virus that infects liver cells; long-term infection can scar the liver (cirrhosis) and cause liver cancer.","evidence":"Association with Parkinson's is inconsistent: higher in England (Pakpoor 2017), not in Taiwan (Tsai 2016).","pos":[-0.08,1.17,0.03]},{"id":"hcv","col":"v","group":"Liver (hepatitis viruses)","name":"Hepatitis C","sub":"HCV","how":"A blood-borne virus that infects the liver and often goes unnoticed for decades; now curable with antiviral pills.","evidence":"Association: linked with higher Parkinson's risk in national cohorts (Tsai 2016; Pakpoor 2017); those treated with antivirals had lower risk (Lin 2019).","pos":[-0.1,1.15,0.02]},{"id":"hav","col":"v","group":"Liver (hepatitis viruses)","name":"Hepatitis A","sub":"HAV","how":"A gut-spread virus (food or water contaminated by stool, close contact) that infects liver cells and causes a short illness with fever, nausea and jaundice. It never becomes long-lasting; adults get sicker than children.","evidence":"Established (textbook). A vaccine prevents it in a placebo-controlled trial.","pos":[-0.09,1.18,0.04]},{"id":"hdv","col":"v","group":"Liver (hepatitis viruses)","name":"Hepatitis D","sub":"delta virus","how":"An incomplete virus that can only multiply in people who already have hepatitis B, because it borrows hepatitis B's coat. Spread like hepatitis B (blood, sex, birth). Together they damage the liver faster than hepatitis B alone.","evidence":"Established (textbook): the most severe form of chronic viral hepatitis; hepatitis B vaccination also prevents it.","pos":[-0.07,1.16,0.03]},{"id":"hev","col":"v","group":"Liver (hepatitis viruses)","name":"Hepatitis E","sub":"HEV","how":"Spread through stool-contaminated water (large outbreaks in South Asia and Africa) or undercooked pork, boar and deer. Usually a short liver infection, but dangerous in late pregnancy, and it can become chronic in people on transplant anti-rejection drugs.","evidence":"Established (textbook).","pos":[-0.1,1.16,0.03]},{"id":"jc_virus","col":"v","group":"Dormant in kidney","name":"JC virus","sub":"PML","how":"A virus carried silently in the kidneys of most adults. When the immune system is badly weakened it can reach the brain and destroy the white-matter insulation (progressive multifocal leukoencephalopathy, PML).","evidence":"Established: PML occurs mainly in advanced HIV, after transplants, and with some immune-suppressing drugs, including natalizumab for MS.","pos":[0.06,1.12,-0.06]},{"id":"bk_virus","col":"v","group":"Dormant in kidney","name":"BK virus","sub":"BK polyomavirus","how":"Caught silently in childhood, it then sleeps in the kidney and urinary tract lining. On strong anti-rejection drugs, especially after a kidney transplant, it can wake up and damage the new kidney, or cause bleeding from the bladder after a bone-marrow transplant.","evidence":"Established (textbook): a leading cause of transplanted-kidney damage.","pos":[0.065,1.1,-0.06]},{"id":"hpv","col":"v","group":"Skin & mucosa","name":"Human papillomavirus","sub":"HPV","how":"A family of viruses spread by skin and sexual contact, infecting the lining of the cervix, genitals, anus and throat. Most infections clear; a few high-risk types persist and can turn cells cancerous.","evidence":"Established: causes nearly all cervical cancers and most throat (oropharyngeal) cancers in many countries; vaccination prevents infection.","pos":[0,0.87,0]},{"id":"hpv_high_risk","col":"v","group":"Skin & mucosa","name":"High-risk HPV types","sub":"HPV 16, 18 and others","how":"A dozen or so HPV types (16 and 18 cause most cancers) that infect the lining of the cervix, anus, throat, penis, vulva and vagina, spread by sexual contact. Most infections clear within two years; persistent ones can turn cells precancerous and then cancerous over years.","evidence":"Established (textbook): cause nearly all cervical cancers and most anal and HPV-positive throat cancers. Vaccination prevents precancer in trials.","pos":[0,0.885,0]},{"id":"hpv_low_risk","col":"v","group":"Skin & mucosa","name":"Low-risk HPV types","sub":"HPV 6, 11 and wart types","how":"HPV types that cause harmless but troublesome growths: genital warts (types 6 and 11, spread by sexual contact), common and plantar warts on hands and feet (other types, spread by skin contact), and rarely warts in the voice box of children and adults.","evidence":"Established (textbook): not linked to cancer. HPV vaccines that cover types 6 and 11 prevent genital warts in trials.","pos":[0,0.82,0.08]},{"id":"mpox","col":"v","group":"Skin & mucosa","name":"Mpox virus","sub":"monkeypox","how":"A pox virus spread by close skin contact (including sex), contaminated bedding and from animals in Central and West Africa. It causes fever, swollen nodes and a blistering rash that can be on the genitals, anus, mouth or whole body.","evidence":"Established (textbook).","pos":[0.03,0.84,0.08]},{"id":"molluscum","col":"v","group":"Skin & mucosa","name":"Molluscum contagiosum virus","sub":"","how":"A pox virus spread by skin contact, towels and swimming, mostly in children. It causes small, pearly, dimpled bumps that are harmless and go away by themselves, usually within months.","evidence":"Established (textbook).","pos":[0.1,1.2,0.12]},{"id":"enterovirus","col":"v","group":"Gut-spread","name":"Enteroviruses & polio","sub":"poliovirus, EV-A71, EV-D68","how":"Viruses that spread by the faecal-oral or respiratory route and multiply in the throat and gut. Some, especially poliovirus, can invade the spinal cord and kill motor nerve cells.","evidence":"Established: polio causes permanent paralysis and decades later post-polio weakness and fatigue; EV-D68 is linked with polio-like paralysis in children.","pos":[0.04,1,0.06]},{"id":"norovirus","col":"v","group":"Gut-spread","name":"Norovirus","sub":"winter vomiting bug","how":"Very infectious: a few virus particles are enough. Spread by the faecal-oral route (hands, food, surfaces, shellfish) and by vomit droplets; outbreaks are common on cruise ships, in care homes and in hospitals. It infects the small intestine, causing sudden vomiting and diarrhoea for one to three days. Alcohol hand gel works poorly against it; soap and water work better.","evidence":"Established (textbook): the commonest cause of gastroenteritis in all ages.","pos":[0,1.02,0.06]},{"id":"rotavirus","col":"v","group":"Gut-spread","name":"Rotavirus","sub":"baby diarrhoea","how":"Spread by the faecal-oral route; it infects the lining of the small intestine in babies and young children, causing vomiting and watery diarrhoea that can dehydrate a child dangerously fast. Before vaccines nearly every child caught it.","evidence":"Established (textbook). Vaccines prevent it in randomised trials.","pos":[-0.01,1,0.065]},{"id":"astrovirus","col":"v","group":"Gut-spread","name":"Astrovirus","sub":"","how":"A faecal-oral virus that causes milder watery diarrhoea, mostly in young children and older people in care homes.","evidence":"Established (textbook).","pos":[0.02,1.01,0.06]},{"id":"poliovirus","col":"v","group":"Gut-spread","name":"Poliovirus","sub":"polio","how":"Spread by the faecal-oral route; it multiplies in the gut and, in about 1 in 200 infections, enters the spinal cord and kills the motor nerve cells, leaving permanent paralysis, usually of the legs. Years later some survivors develop new weakness (post-polio syndrome). Wild polio survives only in a few areas.","evidence":"Established (textbook). Vaccines prevent it; placebo-controlled field trials began in 1954.","pos":[0,1.05,-0.08]},{"id":"coxsackie","col":"v","group":"Gut-spread","name":"Coxsackie viruses","sub":"hand, foot and mouth disease","how":"Enteroviruses spread by stool, saliva and blister fluid, mostly in young children and nurseries. They cause hand, foot and mouth disease (mouth ulcers and spots on hands and feet), and some types inflame the heart muscle (myocarditis) or the brain's coverings.","evidence":"Established (textbook).","pos":[0,1.555,0.07]},{"id":"zika","col":"v","group":"Mosquito-borne","name":"Zika virus","sub":"","how":"Spread by Aedes mosquitoes (and from mother to baby). Usually a mild rash illness in adults; placed at the heart to stand for the blood.","evidence":"Established: infection in pregnancy causes microcephaly (Rasmussen 2016). Association: linked with Guillain-Barré syndrome (Cao-Lormeau 2016).","pos":[0.04,1.28,0.03]},{"id":"westnile","col":"v","group":"Mosquito-borne","name":"West Nile virus","sub":"","how":"Spread by Culex mosquitoes; most infections are silent, but about 1 in 150 reach the brain and spinal cord, mostly in older people. Placed at the brainstem.","evidence":"Case series: tremor, parkinsonism and polio-like paralysis were common in nervous-system infection (Sejvar 2003).","pos":[0,1.59,-0.02]},{"id":"dengue","col":"v","group":"Mosquito-borne","name":"Dengue virus","sub":"breakbone fever","how":"Spread by daytime-biting Aedes mosquitoes in the tropics and increasingly further north. High fever, severe headache, eye, muscle and bone pain and a rash. A second infection with a different dengue type can cause severe dengue, with leaky blood vessels, very low platelets and bleeding.","evidence":"Established (textbook). The commonest mosquito-borne virus in people.","pos":[0.02,1.25,0.03]},{"id":"chikungunya","col":"v","group":"Mosquito-borne","name":"Chikungunya virus","sub":"","how":"Spread by Aedes mosquitoes. Sudden high fever with severe joint pain in the hands, wrists, ankles and knees; the joint pain can last months or years. Placed at the knee.","evidence":"Established (textbook).","pos":[0.1,0.5,0.03]},{"id":"yellow_fever","col":"v","group":"Mosquito-borne","name":"Yellow fever virus","sub":"","how":"Spread by Aedes and forest mosquitoes in tropical Africa and South America. Most cases are a short fever; some go on to attack the liver (jaundice, hence the name), kidneys and blood clotting, which is often fatal.","evidence":"Established (textbook). A single vaccine dose gives long protection.","pos":[-0.09,1.19,0.03]},{"id":"jev","col":"v","group":"Mosquito-borne","name":"Japanese encephalitis virus","sub":"","how":"Spread by Culex mosquitoes from pigs and wading birds in rural Asia and the western Pacific. Most infections are silent, but in about 1 in 250 the virus inflames the brain, especially the thalamus and basal ganglia, causing seizures, coma, and lasting movement problems such as stiffness and tremor in survivors.","evidence":"Established (textbook). A vaccine is available.","pos":[0,1.64,0.01]},{"id":"mumps","col":"v","group":"Childhood rash & gland viruses","name":"Mumps","sub":"","how":"Spread by saliva and droplets. It infects the salivary glands, most visibly the parotid glands in front of the ears, which swell painfully. It can also inflame the testicles after puberty, the ovaries, the pancreas and the brain's coverings (meningitis), and occasionally causes deafness.","evidence":"Established (textbook). MMR vaccine protects in cohort studies.","pos":[0.06,1.57,0.02]},{"id":"rubella","col":"v","group":"Childhood rash & gland viruses","name":"Rubella","sub":"German measles","how":"A mild droplet-spread illness with a pink rash and swollen nodes behind the ears. Its danger is in early pregnancy: the virus crosses the placenta and can cause deafness, cataracts, heart defects and brain damage in the baby (congenital rubella syndrome).","evidence":"Established (textbook). Vaccination has eliminated it in many countries.","pos":[-0.06,1.58,-0.03]},{"id":"parvovirus_b19","col":"v","group":"Blood & marrow","name":"Parvovirus B19","sub":"slapped cheek (fifth disease)","how":"Droplet-spread; it infects the bone marrow cells that make red blood cells, briefly stopping their production. Children get bright red cheeks and a lacy rash; adults often get sore joints. Dangerous for people with sickle cell disease (sudden severe anaemia), weak immunity, and unborn babies (fetal anaemia). Placed in the pelvic bone marrow.","evidence":"Established (textbook).","pos":[0.08,0.98,-0.05]},{"id":"ev_d68","col":"v","group":"Brain & nerves","name":"Enterovirus D68","sub":"acute flaccid myelitis","how":"A droplet-spread enterovirus that usually causes a cold with wheeze, worse in children with asthma. Rarely it damages motor nerve cells in the spinal cord and causes sudden polio-like weakness of an arm or leg (acute flaccid myelitis), in late-summer outbreaks.","evidence":"Established: the main cause of acute flaccid myelitis outbreaks, though the condition is rare.","pos":[0,1.45,-0.05]},{"id":"tbev","col":"v","group":"Brain & nerves","name":"Tick-borne encephalitis virus","sub":"","how":"Spread by tick bites (and rarely raw milk) in forests across Europe and northern Asia. A flu-like illness, sometimes followed a week later by meningitis or encephalitis.","evidence":"Established (textbook). A vaccine is available.","pos":[-0.02,1.68,0]},{"id":"rabies","col":"v","group":"Brain & nerves","name":"Rabies virus","sub":"","how":"Spread in the saliva of infected animals (mostly dogs; bats in the Americas) through bites and scratches. The virus travels slowly up the nerves to the brain; once symptoms start (fear of water, agitation, paralysis) it is almost always fatal. Prompt wound washing and vaccine after a bite prevent it.","evidence":"Established (textbook): nearly 100% fatal once symptoms begin; post-bite vaccination is highly effective.","pos":[0,1.56,-0.02]},{"id":"ebola","col":"v","group":"Bleeding fevers & rodent-borne","name":"Ebola virus","sub":"","how":"Spread from wild animals (fruit bats) and then person to person through blood and body fluids, so carers and funeral contact spread it. It damages blood vessel linings, the liver and clotting, causing fever, vomiting, diarrhoea and sometimes bleeding.","evidence":"Established (textbook): death rates in outbreaks have often been between a quarter and two-thirds of cases.","pos":[-0.04,1.22,0.04]},{"id":"hantavirus","col":"v","group":"Bleeding fevers & rodent-borne","name":"Hantaviruses","sub":"","how":"Caught by breathing in dust contaminated by infected rodent urine and droppings (cleaning sheds and barns). European and Asian types attack the kidneys (fever with kidney failure); American types attack the lungs, which fill with fluid.","evidence":"Established (textbook).","pos":[-0.065,1.13,-0.055]},{"id":"taenia","col":"p","group":"Worms","name":"Pork tapeworm","sub":"cysticercosis","how":"Eating undercooked infected pork gives a person an intestinal tapeworm. That person then sheds tapeworm eggs; when they or people around them swallow the eggs (via unwashed hands or contaminated food), larvae hatch and lodge as cysts in muscle and the brain (neurocysticercosis), which can cause seizures.","evidence":"Association, strong and consistent: cysticercosis roughly triples the odds of epilepsy in tropical regions (Debacq 2017), and about a quarter of people with epileptic seizures in endemic areas have neurocysticercosis, a share that has fallen since 2008 (Jalal 2026).","pos":[0.04,1.69,0.02]},{"id":"hookworm","col":"p","group":"Worms","name":"Hookworm","sub":"","how":"A small worm whose larvae enter through bare skin from soil, travel via the lungs, and attach to the small-intestine wall to feed on blood, which over time drains the body's iron. It also pushes the immune system toward a calmer, 'regulatory' state, the basis of the 'old friends' idea that losing worms may have left modern immune systems more prone to allergy and autoimmunity.","evidence":"Established: heavy infection causes iron-deficiency anaemia. Association: natural hookworm infection is linked with less asthma in population studies (Leonardi-Bee 2006). Failed so far: in small placebo-controlled trials, deliberate hookworm infection did not improve asthma (Feary 2010), did not stop gluten damage in coeliac disease (Daveson 2011), and missed its main brain-scan goal in relapsing MS, although calming T cells rose (Tanasescu 2020).","pos":[0.03,1.06,0.05]},{"id":"toxocara","col":"p","group":"Worms","name":"Toxocara","sub":"dog/cat roundworm","how":"Roundworm eggs from dog and cat droppings get into soil, sandpits and on hands. In people the larvae hatch but never grow into adult worms: they wander through the liver, lungs, eyes and sometimes the brain until they die, and the immune system reacts around them with allergy-type white cells (eosinophils).","evidence":"Established: larvae migrate through the liver, lungs, eyes and brain (Lopez-Alamillo 2025). Association: antibodies to Toxocara are more common in people with epilepsy, and pooled observational studies also link them with ADHD, Alzheimer's disease and essential tremor, without showing cause (Boozhmehrani 2026). Some US population studies tie infection to lower scores on certain thinking tests, but an Iranian study of older adults found no clear link. Two small case-control studies found no link with Parkinson's disease (Celik 2013; Khatir 2025).","pos":[-0.06,1.19,0.04]},{"id":"schistosoma","col":"p","group":"Worms","name":"Schistosoma","sub":"bilharzia","how":"Flukes caught through skin from fresh water; adults live in veins around the gut (and the bladder for S. haematobium), and their eggs cause scarring.","evidence":"Established: causes bladder and liver scarring; eggs can rarely inflame the spinal cord.","pos":[-0.03,1.12,0.04]},{"id":"strongyloides","col":"p","group":"Worms","name":"Strongyloides","sub":"threadworm","how":"A tiny worm that enters through skin, lives in the small intestine and can re-infect the same person for decades. Steroid treatment can trigger a massive spread (hyperinfection).","evidence":"Established: in hyperinfection, larvae carry gut bacteria into the blood, causing sepsis and meningitis.","pos":[0,1.05,0.06]},{"id":"ascaris","col":"p","group":"Worms","name":"Large roundworm (Ascaris)","sub":"Ascaris lumbricoides; ascariasis","how":"Eggs from soil contaminated with human faeces are swallowed on unwashed food or hands. The larvae hatch, travel through the liver and lungs (which can cause cough, wheeze and fever), are coughed up and swallowed, and grow into long worms in the small intestine. Heavy infections in children can block the gut or bile duct and add to poor nutrition.","evidence":"Established life cycle and complications. Association: unlike hookworm, current Ascaris infection is linked with more asthma, not less (Leonardi-Bee 2006). Proven: common deworming medicines cure most infections (Conterno 2020).","pos":[0,1.03,0.07]},{"id":"filaria","col":"p","group":"Worms","name":"Filarial worms (lymphatic filariasis)","sub":"Wuchereria bancrofti, Brugia","how":"Thread-like worms spread by mosquito bites in tropical countries. The larvae travel to the lymph vessels, mostly of the legs, groin and genitals, and grow into adults that live there for years, releasing tiny microfilariae into the blood at night. The adult worms and the body's reaction to them damage and widen the lymph vessels so their valves fail; with repeated skin infections this leads to lymphoedema, and in advanced cases the hugely thickened skin of elephantiasis, or fluid around the testes (hydrocele).","evidence":"Textbook medicine. Mass drug treatment of whole communities is the basis of the WHO elimination programme.","pos":[0.085,0.86,0.05]},{"id":"pinworm","col":"p","group":"Worms","name":"Pinworm (Enterobius)","sub":"threadworm","how":"Tiny white worms living in the lower bowel. At night the females crawl out to lay eggs around the anus, causing itch; scratching puts eggs under the nails, and they are swallowed again or spread to family on hands, bedding and toys. Very common in school-age children everywhere.","evidence":"Established (textbook): harmless apart from itch and disturbed sleep; hand washing and short nails break the cycle.","pos":[0,0.84,-0.05]},{"id":"whipworm","col":"p","group":"Worms","name":"Whipworm (Trichuris)","sub":"","how":"Spread by swallowing eggs from soil contaminated by human stool, in warm places without sanitation. The worms thread their heads into the wall of the caecum and colon. Heavy infections in children cause bloody diarrhoea, anaemia, slowed growth and rectal prolapse.","evidence":"Established (textbook): one of the three main soil-transmitted worms with Ascaris and hookworm.","pos":[-0.1,0.98,0.06]},{"id":"echinococcus","col":"p","group":"Worms","name":"Echinococcus","sub":"hydatid disease","how":"A tiny dog tapeworm. People swallow its eggs from dog faeces (sheep-farming areas), and the larvae grow for years into fluid-filled cysts, most often in the liver and lungs. A burst cyst can cause a severe allergic reaction.","evidence":"Established (textbook).","pos":[-0.06,1.19,0.05]},{"id":"taenia_saginata","col":"p","group":"Worms","name":"Beef tapeworm (Taenia saginata)","sub":"","how":"Caught by eating raw or undercooked beef containing larval cysts. The adult worm, metres long, lives in the small intestine; segments pass in stool. Unlike the pork tapeworm, its eggs do not cause cysts in people.","evidence":"Established (textbook): usually causes few symptoms.","pos":[0.02,1,0.06]},{"id":"fish_tapeworm","col":"p","group":"Worms","name":"Fish tapeworm (Diphyllobothrium)","sub":"","how":"Caught from raw or lightly cured freshwater and some sea fish. The very long adult worm lives in the small intestine and can absorb vitamin B12 from food, sometimes causing B12-deficiency anaemia.","evidence":"Established (textbook).","pos":[0,0.99,0.07]},{"id":"liver_fluke","col":"p","group":"Worms","name":"Asian liver flukes (Clonorchis, Opisthorchis)","sub":"","how":"Caught by eating raw or undercooked freshwater fish in East and South-East Asia. The flukes live for decades in the bile ducts, causing inflammation, stones and scarring, and long infection causes bile-duct cancer (cholangiocarcinoma).","evidence":"Established: classed as definite causes of bile-duct cancer (IARC Group 1).","pos":[-0.05,1.15,0.03]},{"id":"fasciola","col":"p","group":"Worms","name":"Sheep liver fluke (Fasciola)","sub":"fascioliasis","how":"Caught by eating watercress or other water plants carrying larval cysts, in sheep- and cattle-farming areas. The young flukes burrow through the liver to the bile ducts, causing fever, pain under the right ribs and later blocked bile ducts.","evidence":"Established (textbook).","pos":[-0.08,1.16,0.05]},{"id":"paragonimus","col":"p","group":"Worms","name":"Lung fluke (Paragonimus)","sub":"","how":"Caught by eating raw or undercooked freshwater crabs or crayfish (Asia, Africa, the Americas). The flukes travel to the lungs and form cysts, causing chronic cough with blood-stained phlegm that is often mistaken for tuberculosis.","evidence":"Established (textbook).","pos":[0.09,1.33,0]},{"id":"trichinella","col":"p","group":"Worms","name":"Trichinella","sub":"trichinosis","how":"Caught by eating undercooked pork, wild boar, bear or horse meat containing larval cysts. After a gut upset, the larvae spread through the blood and burrow into muscles, causing muscle pain, fever and swelling around the eyes. Placed in the thigh muscles.","evidence":"Established (textbook).","pos":[0.1,0.65,0.03]},{"id":"onchocerca","col":"p","group":"Worms","name":"Onchocerca volvulus","sub":"river blindness","how":"A filarial worm spread by blackflies that breed in fast rivers, mostly in Africa. Adult worms live in skin nodules and release millions of microscopic young worms that move through the skin (severe itch) and into the eye, where their death causes inflammation and blindness.","evidence":"Established (textbook): a leading infectious cause of blindness; mass treatment programmes have cut it sharply.","pos":[-0.03,1.63,0.08]},{"id":"loa_loa","col":"p","group":"Worms","name":"Loa loa","sub":"African eye worm","how":"A filarial worm spread by deer flies in Central and West African rainforests. The adult worm wanders under the skin, causing itchy passing swellings, and is sometimes seen crossing the white of the eye.","evidence":"Established (textbook).","pos":[0.04,1.635,0.08]},{"id":"anisakis","col":"p","group":"Worms","name":"Anisakis","sub":"herring worm","how":"Larvae in raw or undercooked sea fish (sushi, ceviche, pickled herring) burrow into the stomach or bowel wall within hours, causing sudden severe stomach pain and vomiting. Some people develop allergy to the worm. Freezing or thorough cooking kills the larvae.","evidence":"Established (textbook).","pos":[0.06,1.16,0.06]},{"id":"angiostrongylus","col":"p","group":"Worms","name":"Rat lungworm (Angiostrongylus)","sub":"","how":"Caught by eating raw snails or slugs, or produce contaminated by them (tropics, Hawaii). The larvae migrate to the brain and cause eosinophilic meningitis: severe headache, stiff neck and tingling or burning skin.","evidence":"Established (textbook): the commonest cause of eosinophilic meningitis.","pos":[0.01,1.7,0]},{"id":"toxo","col":"p","group":"Protozoa","name":"Toxoplasma gondii","sub":"from cats and undercooked meat","how":"A single-celled parasite that forms cysts in brain and muscle for life. Infection is linked with OCD and schizophrenia in meta-analyses (association only).","evidence":"","pos":[-0.03,1.67,0]},{"id":"giardia","col":"p","group":"Protozoa","name":"Giardia","sub":"","how":"Infects the small intestine and can leave lasting gut problems (post-infectious irritable bowel) and fatigue.","evidence":"","pos":[-0.02,1.1,0.04]},{"id":"plasmodium","col":"p","group":"Protozoa","name":"Plasmodium","sub":"malaria","how":"Mosquito-borne parasites that multiply first in the liver and then inside red blood cells. P. falciparum makes infected cells stick in small brain vessels (cerebral malaria). Placed at the spleen, which filters infected cells.","evidence":"Established: cerebral malaria causes coma and seizures. Association: survivors have more epilepsy and disability (Christensen 2015).","pos":[0.1,1.18,-0.04]},{"id":"trypanosoma","col":"p","group":"Protozoa","name":"Trypanosomes","sub":"sleeping sickness, Chagas disease","how":"Two different diseases. African trypanosomes (tsetse fly) live in blood and later the brain, scrambling the sleep-wake cycle. T. cruzi (Chagas, kissing bugs, the Americas) settles in heart muscle and gut nerves.","evidence":"Established: sleeping sickness disrupts sleep and mood; chronic Chagas damages the heart and gut nerves, causing an enlarged colon and severe constipation.","pos":[0.05,1.31,0.03]},{"id":"entamoeba","col":"p","group":"Protozoa","name":"Entamoeba histolytica","sub":"amoebic dysentery","how":"An amoeba swallowed in contaminated water that can invade the colon wall (bloody diarrhoea) and spread to the liver (abscess).","evidence":"Established cause of amoebic dysentery and liver abscess.","pos":[-0.1,0.95,0.04]},{"id":"crypto","col":"p","group":"Protozoa","name":"Cryptosporidium","sub":"","how":"A chlorine-resistant parasite from water and animals that lives in the lining of the small intestine and causes watery diarrhoea; severe and long-lasting in people with weak immunity (such as advanced HIV).","evidence":"Established cause of diarrhoea outbreaks and of chronic diarrhoea in AIDS.","pos":[-0.02,0.95,0.06]},{"id":"p_falciparum","col":"p","group":"Protozoa","name":"Plasmodium falciparum","sub":"the deadliest malaria","how":"The malaria species behind most malaria deaths, mainly in sub-Saharan Africa. Spread by night-biting Anopheles mosquitoes; after a silent week in the liver it multiplies in red blood cells, which burst in waves of fever. Infected cells stick to small vessel walls in the brain, kidneys and placenta. Young children and pregnant women are most at risk. Placed at the brain, where cerebral malaria happens.","evidence":"Established (textbook). Bed nets and malaria vaccines reduce it in randomised trials.","pos":[0.02,1.67,0.01]},{"id":"p_vivax","col":"p","group":"Protozoa","name":"Plasmodium vivax","sub":"relapsing malaria","how":"The commonest malaria outside Africa (Asia, Latin America). Like other malaria it is spread by Anopheles mosquitoes and infects red blood cells, but it can also leave dormant forms in the liver that wake up months or years later and cause relapses. Placed at the liver, where the dormant forms hide.","evidence":"Established (textbook). Less often fatal than falciparum, but causes repeated illness and anaemia.","pos":[-0.07,1.18,0.02]},{"id":"babesia","col":"p","group":"Protozoa","name":"Babesia","sub":"babesiosis","how":"A malaria-like parasite of red blood cells spread by the same ticks that carry Lyme disease (north-east and upper mid-west USA, parts of Europe), and by blood transfusion. Usually mild, but severe in people without a spleen, older people and those with weak immunity.","evidence":"Established (textbook).","pos":[0.03,1.3,0.06]},{"id":"trichomonas","col":"p","group":"Protozoa","name":"Trichomonas vaginalis","sub":"trichomoniasis","how":"A single-celled parasite spread by sex that lives in the vagina and urethra (and prostate in men). Women may have frothy discharge, itch and pain passing urine; most men and many women have no symptoms. It raises the risk of catching and passing on HIV.","evidence":"Established (textbook): the commonest curable sexually transmitted infection worldwide.","pos":[0,0.86,0.04]},{"id":"leishmania_visceral","col":"p","group":"Protozoa","name":"Visceral leishmaniasis","sub":"kala-azar","how":"Leishmania parasites spread by sandfly bites (South Asia, East Africa, Brazil, the Mediterranean) infect immune cells of the spleen, liver and bone marrow, causing months of fever, weight loss, a huge spleen and anaemia. Fatal without treatment; HIV makes it far worse.","evidence":"Established (textbook).","pos":[0.09,1.17,-0.02]},{"id":"leishmania_cutaneous","col":"p","group":"Protozoa","name":"Cutaneous leishmaniasis","sub":"skin leishmaniasis","how":"Other Leishmania species, also spread by sandflies, infect skin at the bite and leave a slow-healing painless ulcer that scars, often on the face, arms or legs. Some American species later spread to the nose and mouth lining.","evidence":"Established (textbook).","pos":[0.25,1,0.05]},{"id":"cyclospora","col":"p","group":"Protozoa","name":"Cyclospora","sub":"","how":"A protozoan spread by fresh produce (berries, herbs, salad) or water contaminated with stool. It infects the small intestine, causing long-lasting watery diarrhoea, bloating and tiredness; outbreaks follow imported produce.","evidence":"Established (textbook).","pos":[0.01,1.03,0.065]},{"id":"naegleria","col":"p","group":"Protozoa","name":"Naegleria fowleri","sub":"\"brain-eating amoeba\"","how":"An amoeba living in warm fresh water. When water goes up the nose (swimming, diving, nasal rinsing with unboiled tap water) it travels along the smell nerve into the brain, causing a rapidly fatal meningoencephalitis. It cannot infect by drinking.","evidence":"Established (textbook): very rare but nearly always fatal.","pos":[0,1.62,0.05]},{"id":"acanthamoeba","col":"p","group":"Protozoa","name":"Acanthamoeba","sub":"contact-lens eye infection","how":"A free-living amoeba in tap water, pools, hot tubs and soil. In contact-lens wearers who rinse lenses in tap water or swim in them it can infect the cornea, causing a painful, sight-threatening keratitis. In people with weak immunity it can rarely infect the brain.","evidence":"Established (textbook).","pos":[0.03,1.63,0.09]},{"id":"scabies","col":"p","group":"Ectoparasites (skin & hair)","name":"Scabies mite","sub":"Sarcoptes scabiei","how":"A tiny mite that burrows into the top layer of skin, spread by prolonged skin contact (families, care homes, crowded housing). The immune reaction to mites and their droppings causes intense itch, worse at night, between the fingers, wrists, waist and genitals. Scratched skin can get bacterial infection, which in poor settings leads to kidney and heart complications.","evidence":"Established (textbook). Placed at the web of the fingers.","pos":[0.33,0.85,0.03]},{"id":"head_lice","col":"p","group":"Ectoparasites (skin & hair)","name":"Head lice","sub":"Pediculus capitis","how":"Small insects living on the scalp that feed on blood and glue their eggs (nits) to hairs. Spread by head-to-head contact, mostly between children. They cause itch but do not spread disease.","evidence":"Established (textbook): not a sign of poor hygiene.","pos":[0,1.76,0]},{"id":"body_lice","col":"p","group":"Ectoparasites (skin & hair)","name":"Body lice","sub":"Pediculus humanus","how":"Lice that live in the seams of clothing and feed on the skin, in people without access to washing and clean clothes (homelessness, war, refugee camps). Unlike head lice they spread diseases: epidemic typhus, trench fever and relapsing fever.","evidence":"Established (textbook).","pos":[0.1,1.25,0.12]},{"id":"pubic_lice","col":"p","group":"Ectoparasites (skin & hair)","name":"Pubic lice","sub":"crabs","how":"Lice that cling to coarse body hair, mainly in the pubic area, spread by sexual and close contact. They cause itch.","evidence":"Established (textbook).","pos":[0.03,0.83,0.09]},{"id":"essential_tremor","col":"x","group":"Conditions","name":"Essential tremor","sub":"","how":"The most common tremor disorder: shaking of the hands (sometimes head or voice) during action. Runs in families; the cerebellum and its loops with the thalamus are involved. Not Parkinson's, and usually doesn't respond to levodopa.","evidence":"Proven: medicines such as propranolol and primidone, and deep brain stimulation or focused ultrasound for severe cases. No food or supplement is proven; alcohol temporarily reduces it but is not a treatment.","timeline":[{"label":"Onset: action tremor of both hands","from":0,"to":5,"affects":["tremor","bp_wrists_hands","br_cerebellum","br_thalamus","s_cerebellum"],"note":"Essential tremor starts as a shake of both hands and arms when using them (writing, drinking), most often in later life though a smaller, often family-linked group starts young.","sources":[{"id":"pmid:29193359","citation":"Bhatia KP et al., Mov Disord","year":2018,"design":"review","finding":"Consensus classification: essential tremor is an isolated action tremor of both arms for at least 3 years, possibly with head or voice tremor; added soft signs make it \"essential tremor plus\"."},{"id":"pmid:18043006","citation":"Louis ED & Dogu O, Neuroepidemiology","year":2007,"design":"cohort","finding":"In the general population most essential tremor starts in later life, with only a small young-onset group that is often familial."}]},{"label":"Slow, uneven worsening over decades","from":0,"to":30,"affects":["tremor","bp_wrists_hands","isolation","anxiety"],"note":"Tremor usually grows slowly over many years, but in a third to a half of people it changes in jumps or plateaus rather than steadily; embarrassment and anxiety can lead to avoiding social eating and writing.","sources":[{"id":"pmid:35711255","citation":"McGurn MM et al., Front Neurol","year":2022,"design":"cohort","finding":"Over about 10 years, tremor generally worsened, but in a third to a half of people it rose in jumps or even improved for a time rather than steadily."}]},{"label":"Spread to head and voice, mostly in older age","from":5,"to":30,"affects":["tremor","bp_cervical_spine","bp_head_brain","speech"],"note":"A \"yes-yes\" or \"no-no\" head tremor develops in roughly 30–60% over time and a shaky voice can also appear; head tremor seems to depend more on reaching older age than on how long the tremor has lasted.","sources":[{"id":"pmid:23860504","citation":"Louis ED, Neuroepidemiology","year":2013,"design":"cross-sectional","finding":"Head tremor was seen in 39% and depended on age rather than how long the tremor had lasted; it was rare before about 40."},{"id":"pmid:29193359","citation":"Bhatia KP et al., Mov Disord","year":2018,"design":"review","finding":"Consensus classification: essential tremor is an isolated action tremor of both arms for at least 3 years, possibly with head or voice tremor; added soft signs make it \"essential tremor plus\"."}]},{"label":"Later life: balance and thinking (debated)","from":15,"to":35,"affects":["falls","cognition"],"note":"Some older people with essential tremor have trouble with heel-to-toe walking and a higher risk of dementia, especially when tremor started after 65; whether this is part of the disease or a separate process is still argued.","sources":[{"id":"pmid:20629168","citation":"Louis ED et al., Mov Disord","year":2010,"design":"cross-sectional","finding":"In 122 people with essential tremor, heel-to-toe walking errors increased with age, later onset and neck, jaw or voice tremor, but not with arm tremor severity."},{"id":"pmid:17516478","citation":"Bermejo-Pareja F et al., Mov Disord","year":2007,"design":"cohort","finding":"People whose tremor began after 65 were about twice as likely to develop dementia over 3 years as people without tremor."}]}]},{"id":"restless_legs","col":"x","group":"Conditions","name":"Restless legs syndrome","sub":"","how":"An urge to move the legs at rest and in the evening, often with unpleasant sensations, relieved by moving. Linked to low brain iron and dopamine signalling; more common in pregnancy, kidney failure and low iron.","evidence":"Proven: iron when stores are low; other medicines (some dopamine medicines carry a risk of worsening over time). Regular exercise helped in a small trial.","timeline":[{"label":"Onset: earlier familial or later sporadic","from":0,"to":5,"affects":["rls","insomnia","s_spinal","s_bg"],"note":"An evening urge to move the legs starts either earlier in life, often running in families, or in middle to older age; counting is from first symptoms because the age of onset varies so much.","sources":[{"id":"pmid:15592737","citation":"Hanson M et al., J Neurol","year":2004,"design":"cross-sectional","finding":"Familial RLS starts younger than sporadic RLS, supporting an earlier-onset genetic form and a later-onset form."},{"id":"pmid:34732752","citation":"Manconi M et al., Nat Rev Dis Primers","year":2021,"design":"review","finding":"RLS varies widely in age at onset, frequency and severity; long-term dopamine-type treatment can cause a serious worsening called augmentation."}]},{"label":"Symptoms come and go","from":0,"to":20,"affects":["rls","insomnia"],"note":"For many people RLS waxes and wanes: in population studies fewer than half still had symptoms a few years later, and mild cases often went into remission for a year or more.","sources":[{"id":"pmid:22063473","citation":"Szentkiralyi A et al., Sleep Med","year":2011,"design":"cohort","finding":"In two German population cohorts new RLS became steadily more common with age, but only about 41–47% still had symptoms at follow-up."},{"id":"pmid:26773977","citation":"Lee CS et al., Am J Med","year":2016,"design":"cohort","finding":"About a third of clinic patients had at least a year free of RLS within about 4 years; remission was less likely with severe symptoms, a family history or older age."}]},{"label":"Persistent and more frequent in some, especially with age","from":5,"to":30,"affects":["rls","insomnia","sleepy","fatigue","depression","s_bg"],"note":"RLS becomes more common with age, and people with severe symptoms, a family history or later age at diagnosis are less likely to remit, so for them nightly symptoms can steadily disturb sleep, energy and mood; this is a population pattern, not a fixed path.","sources":[{"id":"pmid:22063473","citation":"Szentkiralyi A et al., Sleep Med","year":2011,"design":"cohort","finding":"In two German population cohorts new RLS became steadily more common with age, but only about 41–47% still had symptoms at follow-up."},{"id":"pmid:26773977","citation":"Lee CS et al., Am J Med","year":2016,"design":"cohort","finding":"About a third of clinic patients had at least a year free of RLS within about 4 years; remission was less likely with severe symptoms, a family history or older age."},{"id":"pmid:15956009","citation":"Allen RP et al., Arch Intern Med","year":2005,"design":"cross-sectional","finding":"About 2.7% of adults had RLS at least twice a week with moderate distress, with sleep and quality of life as poor as in other chronic illnesses."},{"id":"pmid:34732752","citation":"Manconi M et al., Nat Rev Dis Primers","year":2021,"design":"review","finding":"RLS varies widely in age at onset, frequency and severity; long-term dopamine-type treatment can cause a serious worsening called augmentation."}]}]},{"id":"lewy","col":"x","group":"Conditions","name":"Dementia with Lewy bodies","sub":"","how":"The same α-synuclein clumps as Parkinson's, but spreading early to the cortex. Thinking problems come first or within a year of movement signs; visual hallucinations, fluctuating alertness and dream enactment are typical.","evidence":"Treatments ease symptoms (cholinesterase inhibitors); none slows it.","timeline":[{"label":"Prodrome: dream enactment, smell, gut and blood pressure","from":-15,"to":-2,"affects":["rbd","br_sld","smell","br_olfactory_bulb","constipation","oh","s_autonomic"],"note":"Acting out dreams, loss of smell, constipation and dizziness on standing can begin years to decades before the dementia; this is best documented in people first seen for dream enactment, so the timeline may differ for those who never have it.","sources":[{"id":"pmid:31111143","citation":"Fereshtehnejad SM et al., Brain","year":2019,"design":"cohort","finding":"In people with RBD followed until they developed Parkinson's or Lewy body dementia, smell loss began over 20 years before, constipation 10–16 years before, and subtle motor signs 5–7 years before."},{"id":"pmid:30789229","citation":"Postuma RB et al., Brain","year":2019,"design":"cohort","finding":"Of 1280 people with isolated RBD, about 6% a year developed Parkinson's, Lewy body dementia or MSA, and about 74% had converted after 12 years."},{"id":"pmid:22722638","citation":"Chiba Y et al., Dement Geriatr Cogn Disord","year":2012,"design":"case-control","finding":"At the onset of memory loss, people with Lewy body dementia already had more smell loss, constipation, drooling and dream enactment than those with Alzheimer's."},{"id":"pmid:25690399","citation":"Fujishiro H et al., Geriatr Gerontol Int","year":2015,"design":"review","finding":"Autonomic problems, smell loss, RBD and psychiatric symptoms precede dementia in Lewy body dementia by years or even decades."}]},{"label":"Prodromal Lewy body disease: mild impairment, delirium or late-life psychiatric onset","from":-4,"to":0,"affects":["cognition","hallucinations","depression","anxiety","sleepy"],"note":"Before full dementia, people may have mild problems with attention and visual-spatial skills, an unexplained bout of confusion, or new depression or hallucinations; these research criteria are still being tested.","sources":[{"id":"pmid:32241955","citation":"McKeith IG et al., Neurology","year":2020,"design":"review","finding":"Prodromal Lewy body dementia can start as mild cognitive impairment, as delirium, or as a late-life psychiatric illness."}]},{"label":"Diagnosis: fluctuating thinking, visual hallucinations, parkinsonism","from":0,"to":4,"affects":["cognition","hallucinations","movement","tremor","s_cortex","br_visual","br_nbm","br_amygdala","br_snc","sleepy"],"note":"Unlike Alzheimer's, attention and alertness swing from day to day, detailed visual hallucinations come early and slowness or stiffness usually develops, because Lewy changes involve the cortex and brainstem together rather than in Braak's tidy order.","sources":[{"id":"pmid:28592453","citation":"McKeith IG et al., Neurology","year":2017,"design":"review","finding":"Consensus criteria: core features are fluctuating thinking, visual hallucinations, REM sleep behaviour disorder and parkinsonism, with dementia as the essential feature."},{"id":"pmid:19067353","citation":"Burke RE et al., Ann Neurol","year":2008,"design":"review","finding":"Many older people without symptoms have Braak stage 4–6 pathology, the pattern often fails in dementia with Lewy bodies, and Braak stage does not track clinical severity."}]},{"label":"Later: falls, swallowing and a shorter course","from":2,"to":8,"affects":["falls","fracture","swallow","pneumonia","nutrition","oh","s_throat"],"note":"Falls, dizziness on standing and swallowing problems build up, and on average people live about 4 years after diagnosis, around a year and a half less than with Alzheimer's, though individual courses vary a great deal.","sources":[{"id":"pmid:30625375","citation":"Mueller C et al., Ageing Res Rev","year":2019,"design":"meta-analysis","finding":"Average survival after diagnosis was about 4.1 years in Lewy body dementia versus 5.7 years in Alzheimer's."}]}]},{"id":"msa","col":"x","group":"Conditions","name":"Multiple system atrophy","sub":"","how":"A rare, faster disease with α-synuclein in the brain's support cells (oligodendrocytes). Severe autonomic failure (blood pressure, bladder), parkinsonism and/or unsteadiness from the cerebellum.","evidence":"Treatments ease symptoms; none slows it. EGCG and other candidates failed in trials.","timeline":[{"label":"Prodrome: dream enactment, bladder and sexual changes","from":-5,"to":0,"affects":["rbd","br_sld","bladder","s_bladder","bp_sexual_function","s_autonomic"],"note":"Months to a few years before movement problems (counting from first symptom), many people develop dream enactment, erectile problems or bladder urgency; unlike Parkinson's, smell and thinking usually stay normal, but this stage is described in only small studies.","sources":[{"id":"pmid:22441197","citation":"Jecmenica-Lukic M et al., Lancet Neurol","year":2012,"design":"review","finding":"Autonomic failure, sleep problems and breathing disturbances often precede ataxia or parkinsonism by months to years."},{"id":"pmid:35094998","citation":"Postuma RB et al., J Parkinsons Dis","year":2022,"design":"cohort","finding":"People with RBD who developed MSA progressed quickly, with genitourinary problems first and with smell and thinking preserved, unlike Lewy body disease."}]},{"label":"Early: autonomic failure with parkinsonism or ataxia","from":0,"to":3,"affects":["oh","bladder","movement","falls","speech","s_autonomic","s_bg","br_putamen","s_cerebellum","br_cerebellum"],"note":"Within about 2 years most people have both body-automatic failure (fainting on standing, bladder problems) and either Parkinson-like slowness or unsteady, clumsy cerebellar walking and speech.","sources":[{"id":"pmid:11960896","citation":"Watanabe H et al., Brain","year":2002,"design":"cohort","finding":"In 230 patients, median time from first symptom to combined motor and autonomic problems was 2 years, to needing walking aid 3, wheelchair 5, bedbound 8 and death 9 years."},{"id":"pmid:23391524","citation":"Wenning GK et al., Lancet Neurol","year":2013,"design":"cohort","finding":"In a European cohort, median survival from first symptom was 9.8 years; the parkinsonian type and incomplete bladder emptying predicted shorter survival."}]},{"label":"Rapid loss of mobility","from":3,"to":8,"affects":["falls","fracture","speech","swallow","insomnia","s_brainstem","br_snc"],"note":"MSA moves much faster than Parkinson's: typically a walking aid is needed around year 3 and a wheelchair around year 5, with speech and swallowing getting harder.","sources":[{"id":"pmid:11960896","citation":"Watanabe H et al., Brain","year":2002,"design":"cohort","finding":"In 230 patients, median time from first symptom to combined motor and autonomic problems was 2 years, to needing walking aid 3, wheelchair 5, bedbound 8 and death 9 years."}]},{"label":"Late: bedbound, swallowing and breathing problems","from":7,"to":10,"affects":["swallow","pneumonia","nutrition","s_throat","s_brainstem"],"note":"Most people become bedbound around year 8, and median survival from the first symptom is just under 10 years, shorter when autonomic failure is severe early, though some live much longer.","sources":[{"id":"pmid:11960896","citation":"Watanabe H et al., Brain","year":2002,"design":"cohort","finding":"In 230 patients, median time from first symptom to combined motor and autonomic problems was 2 years, to needing walking aid 3, wheelchair 5, bedbound 8 and death 9 years."},{"id":"pmid:23391524","citation":"Wenning GK et al., Lancet Neurol","year":2013,"design":"cohort","finding":"In a European cohort, median survival from first symptom was 9.8 years; the parkinsonian type and incomplete bladder emptying predicted shorter survival."},{"id":"pmid:26025783","citation":"Low PA et al., Lancet Neurol","year":2015,"design":"cohort","finding":"In a US cohort, median survival from symptom onset was 9.8 years, shorter with severe early autonomic failure."}]}]},{"id":"huntingtons","col":"x","group":"Conditions","name":"Huntington's disease","sub":"","how":"An inherited disease caused by an expanded CAG repeat in the huntingtin gene; each child of a carrier has a 50% chance. Striatal neurons die first, giving chorea, then thinking and mood problems.","evidence":"Medicines ease chorea and mood; no treatment yet slows it.","timeline":[{"label":"Premanifest: caudate starts shrinking","from":-20,"to":-10,"affects":["br_caudate","br_putamen","s_bg"],"note":"In people who carry the gene, the caudate and putamen are already measurably smaller 10–20 years before any movement signs, while they feel and function normally; exact timing depends on the length of the gene repeat.","sources":[{"id":"pmid:15249612","citation":"Aylward EH et al., Neurology","year":2004,"design":"cohort","finding":"Caudate and putamen were already smaller 9–20 years before expected onset; caudate shrinkage became measurable about 11 years before onset and was one-third to one-half gone at diagnosis."},{"id":"pmid:24614516","citation":"Ross CA et al., Nat Rev Neurol","year":2014,"design":"review","finding":"Brain atrophy in Huntington's begins many years before diagnosable signs and continues steadily through the symptomatic period."}]},{"label":"Prodromal: subtle thinking and mood changes","from":-12,"to":0,"affects":["br_caudate","br_putamen","s_bg","s_prefrontal","cognition","depression","anxiety","apathy","rage"],"note":"In the decade before diagnosis, processing speed and planning slip and irritability, low mood or apathy often appear, changes that family members notice more than the person; striatal shrinkage speeds up.","sources":[{"id":"pmid:20919768","citation":"Stout JC et al., Neuropsychology","year":2011,"design":"cohort","finding":"Gene carriers 9–15 years from expected diagnosis already did worse on about half of thinking tests, and those within 9 years on nearly all."},{"id":"pmid:26472629","citation":"Epping EA et al., Am J Psychiatry","year":2016,"design":"cohort","finding":"Over 10 years of PREDICT-HD, psychiatric symptoms were higher and rising in gene carriers before motor diagnosis, most clearly near diagnosis."},{"id":"pmid:23664844","citation":"Tabrizi SJ et al., Lancet Neurol","year":2013,"design":"cohort","finding":"In TRACK-HD, gene carriers within about 11 years of predicted onset showed measurable decline in movement and thinking tests over 3 years."},{"id":"pmid:15249612","citation":"Aylward EH et al., Neurology","year":2004,"design":"cohort","finding":"Caudate and putamen were already smaller 9–20 years before expected onset; caudate shrinkage became measurable about 11 years before onset and was one-third to one-half gone at diagnosis."}]},{"label":"Motor diagnosis: chorea","from":0,"to":10,"affects":["chorea","s_bg","br_putamen","br_caudate","falls","cognition","depression","ocd"],"note":"Diagnosis is made when unmistakable involuntary jerky, dance-like movements (chorea) appear, usually in mid-adult life; thinking and behaviour problems keep progressing alongside them.","sources":[{"id":"pmid:27188817","citation":"Bates GP et al., Nat Rev Dis Primers","year":2015,"design":"review","finding":"Huntington's is caused by an expanded CAG repeat, usually starts in mid-adult life and progressively combines movement, thinking and behaviour problems."},{"id":"pmid:24614516","citation":"Ross CA et al., Nat Rev Neurol","year":2014,"design":"review","finding":"Brain atrophy in Huntington's begins many years before diagnosable signs and continues steadily through the symptomatic period."}]},{"label":"Late stage: swallowing, weight loss and dependence","from":10,"to":20,"affects":["swallow","pneumonia","nutrition","speech","falls","cognition","s_cortex","s_throat"],"note":"Later, speech and swallowing fail, weight falls and full care is needed; respiratory illness such as pneumonia is the most common immediate cause of death, on average about 13 years earlier than the general population.","sources":[{"id":"pmid:29480207","citation":"Solberg OK et al., J Huntingtons Dis","year":2018,"design":"cohort","finding":"In Norway, people with Huntington's died about 13 years younger than average, most often from respiratory illness, and suicide was more common."},{"id":"pmid:24614516","citation":"Ross CA et al., Nat Rev Neurol","year":2014,"design":"review","finding":"Brain atrophy in Huntington's begins many years before diagnosable signs and continues steadily through the symptomatic period."}]}]},{"id":"alzheimers","col":"x","group":"Conditions","name":"Alzheimer's disease","sub":"","how":"The most common dementia. Amyloid plaques and tau tangles spread from memory regions (hippocampus) across the cortex; recent memory goes first.","evidence":"Anti-amyloid antibodies modestly slow early disease, with risks. Exercise, blood-pressure control and hearing aids are linked with lower risk; dementia prevention evidence is mostly observational.","timeline":[{"label":"Silent amyloid build-up","from":-25,"to":-5,"affects":["s_cortex","br_ofc","br_acc","bp_head_brain"],"note":"Sticky amyloid plaques start collecting in the outer cortex 15–25 years before dementia with no symptoms; this timing is clearest in families with inherited Alzheimer's, and in the general population many older people carry amyloid without ever developing dementia.","sources":[{"id":"pmid:22784036","citation":"Bateman RJ et al., N Engl J Med","year":2012,"design":"cohort","finding":"In inherited Alzheimer's, spinal-fluid amyloid fell about 25 years before expected symptoms, amyloid on scans and shrinkage were seen about 15 years before, and memory changes about 10 years before."},{"id":"pmid:25988462","citation":"Jansen WJ et al., JAMA","year":2015,"design":"meta-analysis","finding":"Amyloid build-up is found in 10% of cognitively normal people at 50 and 44% at 90, supporting a decades-long silent phase."},{"id":"pmid:23477989","citation":"Villemagne VL et al., Lancet Neurol","year":2013,"design":"cohort","finding":"Amyloid was estimated to take about 19 years to build from the positive threshold to the levels seen in Alzheimer's dementia."}]},{"label":"Early tau: locus coeruleus and entorhinal cortex (Braak I–II)","from":-20,"to":-5,"affects":["br_lc","br_entorhinal","s_brainstem"],"note":"Tangles of tau protein first appear in a small brainstem nucleus and in the entorhinal cortex, the gateway to memory, often in middle age and without symptoms; whether this alone counts as \"Alzheimer's\" is debated because it is so common.","sources":[{"id":"pmid:1759558","citation":"Braak H & Braak E, Acta Neuropathol","year":1991,"design":"lab","finding":"Tangles follow a six-stage pattern: transentorhinal (I–II), limbic including the entorhinal cortex and hippocampus (III–IV), then the neocortex (V–VI)."},{"id":"pmid:22002422","citation":"Braak H et al., J Neuropathol Exp Neurol","year":2011,"design":"lab","finding":"In 2332 brains, early tau was often found in the locus coeruleus in young adults before any cortex was involved; amyloid plaques appeared later, from the 40s onward."}]},{"label":"Hippocampus and limbic system: mild cognitive impairment (Braak III–IV)","from":-6,"to":0,"affects":["br_hippocampus","br_amygdala","s_limbic","memory","cognition","br_nbm"],"note":"As tau spreads into the hippocampus and nearby limbic areas, new memories become harder to form but daily life is mostly intact (mild cognitive impairment), a stage lasting about 4 years on average; only about 5–10% of people with mild impairment progress each year and many never do.","sources":[{"id":"pmid:1759558","citation":"Braak H & Braak E, Acta Neuropathol","year":1991,"design":"lab","finding":"Tangles follow a six-stage pattern: transentorhinal (I–II), limbic including the entorhinal cortex and hippocampus (III–IV), then the neocortex (V–VI)."},{"id":"pmid:31164314","citation":"Vermunt L et al., Alzheimers Dement","year":2019,"design":"cohort","finding":"For someone aged 70 with preclinical Alzheimer's, the silent stage lasted about 10 years, the mild-impairment stage about 4 years and dementia about 6 years, all shorter at older ages."},{"id":"pmid:19236314","citation":"Mitchell AJ & Shiri-Feshki M, Acta Psychiatr Scand","year":2009,"design":"meta-analysis","finding":"About 5–10% of people with mild cognitive impairment progress to dementia each year, and most do not progress even after 10 years."},{"id":"pmid:22784036","citation":"Bateman RJ et al., N Engl J Med","year":2012,"design":"cohort","finding":"In inherited Alzheimer's, spinal-fluid amyloid fell about 25 years before expected symptoms, amyloid on scans and shrinkage were seen about 15 years before, and memory changes about 10 years before."}]},{"label":"Neocortex: dementia (Braak V–VI)","from":0,"to":6,"affects":["s_cortex","br_dlpfc","br_visual","memory","cognition","apathy","depression","anxiety","insomnia","isolation"],"note":"When tau reaches most of the outer cortex, language, planning, finding the way and everyday tasks are affected and dementia is diagnosed; the dementia stage averages around 6 years but varies widely, and some people follow other spreading patterns that start with vision or language.","sources":[{"id":"pmid:1759558","citation":"Braak H & Braak E, Acta Neuropathol","year":1991,"design":"lab","finding":"Tangles follow a six-stage pattern: transentorhinal (I–II), limbic including the entorhinal cortex and hippocampus (III–IV), then the neocortex (V–VI)."},{"id":"pmid:31164314","citation":"Vermunt L et al., Alzheimers Dement","year":2019,"design":"cohort","finding":"For someone aged 70 with preclinical Alzheimer's, the silent stage lasted about 10 years, the mild-impairment stage about 4 years and dementia about 6 years, all shorter at older ages."},{"id":"pmid:33927414","citation":"Vogel JW et al., Nat Med","year":2021,"design":"cohort","finding":"Tau PET in 1612 people showed four different spreading patterns, so the classic Braak order is only one of several."}]},{"label":"Advanced dementia: eating, swallowing and infections","from":5,"to":10,"affects":["swallow","nutrition","pneumonia","falls","hallucinations","s_throat"],"note":"In the late stage most people have trouble eating and swallowing, and pneumonia and fevers become frequent and are common causes of death.","sources":[{"id":"pmid:19828530","citation":"Mitchell SL et al., N Engl J Med","year":2009,"design":"cohort","finding":"In advanced dementia, eating problems (86%), fever and pneumonia were common over 18 months and each carried a high short-term risk of death."}]}]},{"id":"ms","col":"x","group":"Conditions","name":"Multiple sclerosis","sub":"","how":"The immune system attacks myelin in the brain and spinal cord, causing patches of damage. Epstein–Barr virus appears to be the main trigger; low vitamin D and smoking raise risk.","evidence":"Proven: disease-modifying immune treatments greatly reduce relapses. Vitamin D: linked with lower risk; trials of supplements are mixed.","timeline":[{"label":"Possible prodrome","from":-5,"to":0,"affects":["fatigue","pain","depression","bladder"],"note":"People later diagnosed with MS see doctors more often in the 5 years before their first attack, hinting at a vague early phase; it is not specific enough to diagnose anyone.","sources":[{"id":"pmid:28434855","citation":"Wijnands JMA et al., Lancet Neurol","year":2017,"design":"cohort","finding":"People later diagnosed with MS used more hospital, doctor and prescription care in each of the 5 years before their first demyelinating event."}]},{"label":"First attack: optic nerve, brainstem or spinal cord","from":0,"to":1,"affects":["s_eyes","bp_eyes","s_brainstem","s_spinal","neuropathy"],"note":"MS usually announces itself in a young adult as blurred painful vision in one eye, double vision or dizziness, or numbness and weakness from a spinal cord patch, and most people recover well from that first attack.","sources":[{"id":"pmid:22265211","citation":"Miller DH et al., Lancet Neurol","year":2012,"design":"review","finding":"A first MS-like attack usually hits the optic nerve, brainstem or spinal cord in young adults; after 15–20 years about a third have a benign course and half have secondary progressive MS."}]},{"label":"Relapsing-remitting phase","from":0,"to":15,"affects":["s_spinal","s_brainstem","s_cerebellum","s_cortex","s_immune","neuropathy","fatigue","bladder","tremor"],"note":"New inflamed patches cause attacks lasting days to weeks, separated by months or years of recovery; fatigue and some leftover numbness or bladder urgency often persist between attacks.","sources":[{"id":"pmid:11078767","citation":"Confavreux C et al., N Engl J Med","year":2000,"design":"cohort","finding":"In 1844 people, relapsing-onset MS took a median 11 years to limited walking and 23 years to needing a stick, and once disability started, relapses did not change its pace."},{"id":"pmid:24871874","citation":"Lublin FD et al., Neurology","year":2014,"design":"review","finding":"Consensus definitions of MS courses: relapsing-remitting, secondary progressive and primary progressive, each described as active or not and progressing or not."}]},{"label":"Silent worsening between relapses","from":2,"to":20,"affects":["s_spinal","s_cortex","falls","cognition"],"note":"In a quarter of people, disability creeps up even without new attacks, sometimes within the first 5 years, which suggests the slow degenerative side of MS runs alongside the inflammatory one from early on.","sources":[{"id":"pmid:36534392","citation":"Tur C et al., JAMA Neurol","year":2023,"design":"cohort","finding":"A quarter of people developed disability worsening without relapses, about a third of them within the first 5 years."}]},{"label":"Secondary progressive phase","from":10,"to":30,"affects":["falls","bladder","constipation","cognition","speech","swallow","tremor","s_spinal","s_cerebellum","bp_sexual_function"],"note":"In older untreated cohorts about half (up to 80% within two decades) moved into steady worsening of walking, balance, bladder and thinking, while about a third stayed mild; people on modern treatments convert less often.","sources":[{"id":"pmid:22265211","citation":"Miller DH et al., Lancet Neurol","year":2012,"design":"review","finding":"A first MS-like attack usually hits the optic nerve, brainstem or spinal cord in young adults; after 15–20 years about a third have a benign course and half have secondary progressive MS."},{"id":"pmid:23486991","citation":"Scalfari A et al., J Neurol Neurosurg Psychiatry","year":2014,"design":"cohort","finding":"Risk of entering the secondary progressive phase rose with each year of disease; onset of that phase was the main driver of long-term disability."},{"id":"pmid:30644981","citation":"Brown JWL et al., JAMA","year":2019,"design":"cohort","finding":"Untreated, about 80% of relapsing MS converts to secondary progressive within two decades; people on disease-modifying treatments converted less often."},{"id":"pmid:11078767","citation":"Confavreux C et al., N Engl J Med","year":2000,"design":"cohort","finding":"In 1844 people, relapsing-onset MS took a median 11 years to limited walking and 23 years to needing a stick, and once disability started, relapses did not change its pace."}]}]},{"id":"epilepsy","col":"x","group":"Conditions","name":"Epilepsy","sub":"","how":"A tendency to repeated seizures. Causes include genes, brain injury, stroke, tumours and infections such as neurocysticercosis.","evidence":"Proven: anti-seizure medicines (about two-thirds become seizure-free), ketogenic diet for drug-resistant cases, surgery for some."},{"id":"adhd_c","col":"x","group":"Conditions","name":"ADHD","sub":"","how":"A neurodevelopmental condition of attention, activity and impulse control, starting in childhood and often lasting into adulthood. Frontal-striatal networks running on dopamine and noradrenaline are involved; strongly genetic.","evidence":"Proven: stimulant and non-stimulant medicines, parent training and behavioural support. Omega-3: small, mixed effects. Exercise: short-term benefit for attention in small trials."},{"id":"ocd_c","col":"x","group":"Conditions","name":"Obsessive-compulsive disorder","sub":"OCD","how":"Intrusive, unwanted thoughts (obsessions) and repeated actions or mental rituals (compulsions) done to relieve the distress. Loops between the orbitofrontal cortex, striatum and thalamus are overactive.","evidence":"Proven: exposure and response prevention therapy, SSRI medicines. N-acetylcysteine: mixed small trials."},{"id":"depression_c","col":"x","group":"Conditions","name":"Major depression","sub":"","how":"Persistent low mood or loss of interest with changes in sleep, appetite, energy and thinking. Involves stress-hormone, monoamine and inflammatory pathways, and reduced plasticity in limbic and prefrontal circuits.","evidence":"Proven: psychotherapy, antidepressants, exercise; bright light for seasonal depression. Mediterranean-style diet improved depression in one trial (SMILES 2017). Omega-3 (EPA): mixed.","timeline":[{"label":"First episode","from":0,"to":1,"affects":["depression","apathy","insomnia","fatigue","nutrition","cognition","anxiety","isolation","s_limbic","s_prefrontal","br_acc","s_hypo"],"note":"A first episode of low mood, loss of interest, poor sleep and low energy typically lasts about 3–4 months; three quarters recover within a year, but about one in five is still unwell 2 years later.","sources":[{"id":"pmid:12204924","citation":"Spijker J et al., Br J Psychiatry","year":2002,"design":"cohort","finding":"In the general population the median depressive episode lasted 3 months; 76% had recovered by 12 months but nearly 20% had not recovered at 2 years."},{"id":"pmid:12813115","citation":"Kessler RC et al., JAMA","year":2003,"design":"cross-sectional","finding":"Lifetime major depression affected 16% of US adults, with a mean episode length of 16 weeks."}]},{"label":"Recovery: about half never have another episode","from":0.5,"to":25,"affects":["bp_psyche"],"note":"In the general population around half of people recover from a first episode and never have another, which is a more hopeful picture than clinic studies suggest.","sources":[{"id":"pmid:18458203","citation":"Eaton WW et al., Arch Gen Psychiatry","year":2008,"design":"cohort","finding":"Over 23 years, about half of people with a first episode recovered with no further episodes, 35% had recurrences and 15% never had a year free of depression."},{"id":"pmid:20003092","citation":"Hardeveld F et al., Acta Psychiatr Scand","year":2010,"design":"review","finding":"Recurrence is high in specialist care (85% by 15 years) but lower in the general population (35% by 15 years); past episodes and leftover symptoms predict it."}]},{"label":"Recurrent episodes","from":2,"to":25,"affects":["depression","insomnia","anxiety","fatigue","s_limbic","s_prefrontal","br_hippocampus","s_hypo"],"note":"For others episodes return, and each extra episode raises the chance of the next while stress plays a smaller triggering role, but the longer someone stays well the lower the risk becomes.","sources":[{"id":"pmid:10671391","citation":"Solomon DA et al., Am J Psychiatry","year":2000,"design":"cohort","finding":"In clinical patients followed 10 years, nearly two-thirds had a recurrence; the risk rose about 16% with each episode and fell the longer someone stayed well."},{"id":"pmid:10910786","citation":"Kendler KS et al., Am J Psychiatry","year":2000,"design":"cohort","finding":"In women twins, stressful life events triggered first episodes more strongly than later ones, consistent with a \"kindling\" effect up to about nine episodes."},{"id":"pmid:20003092","citation":"Hardeveld F et al., Acta Psychiatr Scand","year":2010,"design":"review","finding":"Recurrence is high in specialist care (85% by 15 years) but lower in the general population (35% by 15 years); past episodes and leftover symptoms predict it."}]},{"label":"Chronic course in a minority","from":1,"to":25,"affects":["depression","fatigue","isolation","cognition","pain","s_limbic"],"note":"About 15% never get a full year free of depression over two decades, with more severe episodes and long-standing milder depression making this more likely.","sources":[{"id":"pmid:18458203","citation":"Eaton WW et al., Arch Gen Psychiatry","year":2008,"design":"cohort","finding":"Over 23 years, about half of people with a first episode recovered with no further episodes, 35% had recurrences and 15% never had a year free of depression."},{"id":"pmid:12204924","citation":"Spijker J et al., Br J Psychiatry","year":2002,"design":"cohort","finding":"In the general population the median depressive episode lasted 3 months; 76% had recovered by 12 months but nearly 20% had not recovered at 2 years."}]}]},{"id":"chronic_rhinosinusitis","col":"x","group":"Conditions","name":"Chronic rhinosinusitis","sub":"long-lasting sinusitis, with or without nasal polyps","how":"Swelling of the lining of the nose and sinuses that lasts more than about twelve weeks, causing a blocked nose, thick discharge, facial pressure and reduced smell. In some people soft growths (nasal polyps) form and block the nose further. Short-lived sinusitis after a cold is different and usually clears on its own.","evidence":"Established description. Smoking is associated with higher odds of it (Tan 2024). Salty-water rinses help symptoms in small trials; steroid sprays and, for some, surgery are standard ENT care."},{"id":"otitis_media","col":"x","group":"Conditions","name":"Middle-ear infection & glue ear","sub":"otitis media, with or without fluid","how":"Germs from a cold travel up the Eustachian tube and infect the middle ear, causing earache and fever; afterwards sticky fluid can linger (glue ear) and muffle hearing for weeks. Young children are most affected because their tubes are short and level and their adenoids are large.","evidence":"Established. Most infections settle by themselves within days; glue ear often clears in months. Persistent cases may need ventilation tubes."},{"id":"bppv","col":"x","group":"Conditions","name":"Benign paroxysmal positional vertigo (BPPV)","sub":"loose ear crystals","how":"Tiny crystals come loose from the utricle and drift into a semicircular canal, so turning over in bed, looking up or bending down sets off seconds of intense spinning. It is the commonest cause of vertigo, more common with age and after head injury.","evidence":"Established. Simple repositioning manoeuvres move the crystals back and cure most attacks (Hilton 2014 Cochrane); it often comes back."},{"id":"menieres","col":"x","group":"Conditions","name":"Ménière's disease","sub":"vertigo attacks, fluctuating hearing loss, ringing, ear fullness","how":"Attacks of spinning vertigo lasting minutes to hours, with hearing loss, ringing and a full feeling in one ear. It is linked to excess fluid pressure in the inner ear (endolymphatic hydrops). Over years, hearing in the affected ear tends to worsen.","evidence":"Cause not fully known. No medicine has been shown to change its course: in the largest placebo-controlled trial betahistine did not reduce attacks (BEMED 2016), and a Cochrane review found only low-certainty evidence for oral medicines (Webster 2023)."},{"id":"presbycusis","col":"x","group":"Conditions","name":"Age-related hearing loss","sub":"presbycusis","how":"Slow loss of hearing in both ears with age, mostly from wear of cochlear hair cells and their nerve, starting at high pitches. Consonants get hard to catch, so speech sounds mumbled, especially in noise. Noise exposure over life, smoking, diabetes and genes add to it.","evidence":"Very common: a large share of people over seventy have it. Not reversible; hearing aids and, for severe loss, cochlear implants restore much of the ability to hear speech."},{"id":"osa","col":"x","group":"Conditions","name":"Obstructive sleep apnoea","sub":"snoring with pauses in breathing","how":"During sleep the muscles holding the throat open relax, and in some people the airway narrows or closes over and over. Each pause drops oxygen and briefly wakes the brain, so sleep is broken without the person knowing; loud snoring, gasping, morning headache and daytime sleepiness follow. Excess weight, a narrow jaw, large tonsils, alcohol and lying on the back make it worse.","evidence":"Common and under-diagnosed. Diagnosed with a sleep study. CPAP reduces sleepiness in randomised trials (Giles 2006 Cochrane)."},{"id":"head_neck_cancer","col":"x","group":"Conditions","name":"Head and neck cancer","sub":"mouth, throat (pharynx) and voice-box (larynx) cancers","how":"Cancers of the lining of the mouth, throat and voice box. Warning signs lasting over three weeks include a mouth ulcer or red/white patch that won't heal, hoarseness, a sore throat or trouble swallowing, ear pain on one side, or a lump in the neck. Tobacco and alcohol cause most cases; HPV causes a growing share of throat cancers, often in non-smokers.","evidence":"Established causes (tobacco, alcohol, HPV). Combined tobacco and alcohol multiply risk (Hashibe 2009). Treated by surgery, radiotherapy and drug therapy; earlier detection improves outcomes."},{"id":"uti","col":"x","group":"Conditions","name":"Urinary tract infection","sub":"cystitis, kidney infection","how":"Bacteria, usually E. coli from the bowel, climb the urethra into the bladder (cystitis: burning, urgency, frequency) and sometimes up to the kidneys (fever, back pain). Risks: a short female urethra, urine left in the bladder (enlarged prostate, nerve damage as in Parkinson's and MS), catheters, stones and diabetes. In men, a UTI often involves the prostate. In older or frail people an infection may show up mainly as sudden confusion or falls rather than urinary symptoms.","evidence":"Established. Antibiotics treat it; cranberry products and extra water reduce repeat infections in some groups (see links)."},{"id":"bph","col":"x","group":"Conditions","name":"Enlarged prostate (BPH)","sub":"benign prostatic hyperplasia","how":"A non-cancerous growth of the inner prostate that starts in mid-life and is very common in older men. It needs male hormones (DHT) to develop. Because the gland surrounds the urethra, it can narrow the outlet: a weak stream, hesitancy, urgency and getting up at night. The bladder muscle works harder and over years may thicken or fail to empty fully. Size and symptoms do not match well. In Parkinson's, urgency and night urination often come from the brain's bladder control rather than the prostate, and the two can overlap.","evidence":"Established: very common with age; it does not turn into cancer. Medicines that relax the prostate muscle or block DHT, and operations to widen the channel, are proven to ease symptoms in trials; watchful waiting is reasonable for mild symptoms."},{"id":"prostate_cancer","col":"x","group":"Conditions","name":"Prostate cancer","sub":"","how":"One of the most common cancers in men. Most grow slowly and many never cause harm in a man's lifetime; a minority are aggressive and spread, most often to the bones. Early cancer usually causes no symptoms (urinary symptoms are more often from a benign enlarged prostate). Risk rises with age, a close family history (and BRCA gene changes), and is higher in men of Black African ancestry. Advanced cancer depends on male hormones, which is why hormone-lowering treatment is used.","evidence":"Established epidemiology. Treatments for localised cancer (surgery, radiotherapy) commonly cause leakage of urine and erection problems; active monitoring of low-risk cancer is a standard option because many tumours never progress."},{"id":"male_hypogonadism","col":"x","group":"Conditions","name":"Low testosterone (male hypogonadism)","sub":"testes or pituitary not making enough","how":"The testes make too little testosterone, either because they are damaged (genetic conditions such as Klinefelter syndrome, injury, mumps, chemotherapy) or because the pituitary is not signalling them (pituitary disease, high prolactin, opioids, obesity, serious illness). Symptoms: low sex drive, erection problems, tiredness, loss of muscle and bone, mild anaemia, low fertility. Levels also drift down with age, which is not by itself a disease.","evidence":"Established: diagnosis needs both symptoms and repeatedly low morning blood levels. In men with clear deficiency, testosterone treatment improves sex drive, anaemia and bone density in trials, but it shuts down sperm production and is not for men trying to conceive."},{"id":"mononucleosis","col":"x","group":"Conditions","name":"Glandular fever (mononucleosis)","sub":"infectious mononucleosis, usually from EBV","how":"An illness, most common in teenagers and young adults, when a first EBV infection triggers a huge immune response. The virus enters through the throat and infects B cells in the tonsils; killer T cells multiply to control it, which causes the symptoms: very sore throat with swollen tonsils, fever, swollen neck nodes, tiredness that can last weeks, and an enlarged spleen. The swollen spleen can rupture, rarely, especially after a blow in the first weeks, which is why contact sport is avoided until a doctor clears it. Spread mainly by saliva.","evidence":"Textbook medicine (Luzuriaga 2010). Spleen rupture is rare but can be fatal (Toti 2023)."},{"id":"gallstones","col":"x","group":"Conditions","name":"Gallstones","sub":"cholelithiasis","how":"Hard stones form in the gallbladder when bile has too much cholesterol or pigment. Many never cause trouble; others block the outlet and cause attacks of upper-right belly pain, inflammation (cholecystitis), jaundice or pancreatitis.","evidence":"Very common, especially in women, with age, obesity and rapid weight loss. Most stones found by chance cause no symptoms and are usually left alone.","pos":[-0.07,1.12,0.07]},{"id":"appendicitis","col":"x","group":"Conditions","name":"Appendicitis","sub":"","how":"The appendix becomes blocked (often by a hard pellet of stool) and inflamed. Pain usually starts around the navel and moves to the lower right belly, with fever and loss of appetite. If it bursts, infection spreads through the belly (peritonitis).","evidence":"One of the commonest causes of emergency belly surgery, most often in teens and young adults.","pos":[-0.066,0.905,0.038]},{"id":"opsi","col":"x","group":"Conditions","name":"Severe infection after spleen loss","sub":"OPSI (overwhelming post-splenectomy infection)","how":"Without a spleen, bacteria with a sugar coat can multiply in the blood very fast. A flu-like illness can become blood poisoning (sepsis) within hours.","evidence":"Rare, but often fatal when it happens; the risk is highest in the first years after surgery and in children, and never fully goes away."},{"id":"pancreatic_insufficiency","col":"x","group":"Conditions","name":"Exocrine pancreatic insufficiency","sub":"too few digestive enzymes","how":"The pancreas does not deliver enough digestive enzymes, so fat (and some protein) passes undigested: pale, oily, floating stools, wind, cramps, weight loss, and low fat-soluble vitamins (A, D, E, K).","evidence":"Common after pancreas surgery, in chronic pancreatitis and cystic fibrosis. Enzyme capsules taken with meals replace what is missing.","pos":[0.03,1.12,0]},{"id":"obesity","col":"x","group":"Conditions","name":"Obesity","sub":"excess body fat that harms health","how":"Long-term energy intake above use stores fat; genes, sleep, stress, medicines, hormones and food environment all shape it. Excess fat, especially around the belly organs, drives insulin resistance, high blood pressure, fatty liver, sleep apnoea and joint wear.","evidence":"Very common worldwide. Lifestyle change, newer medicines and weight-loss surgery all help; surgery gives the largest and most lasting loss in severe obesity."},{"id":"type2_diabetes","col":"x","group":"Conditions","name":"Type 2 diabetes","sub":"high blood sugar from insulin resistance","how":"Muscle, liver and fat respond poorly to insulin and the pancreas cannot keep up, so blood sugar stays high and slowly damages blood vessels, nerves, eyes and kidneys.","evidence":"Very common, closely tied to excess weight and inactivity; it can go into remission with large weight loss."},{"id":"dystonia","col":"x","group":"Conditions","name":"Dystonia","sub":"sustained twisting muscle contractions","how":"The basal ganglia and their links to the cerebellum and cortex fail to switch off unwanted muscles, so opposing muscles contract together, causing twisting postures, pulling or tremor. It can affect one area (neck, eyelids, hand) or the whole body, and can be genetic, follow brain injury or medicines, or occur in Parkinson's (often during OFF).","evidence":"Treated with botulinum toxin injections for focal forms, medicines, and deep brain stimulation for severe generalised or segmental forms."},{"id":"copd","col":"x","group":"Conditions","name":"COPD (emphysema & chronic bronchitis)","sub":"chronic obstructive pulmonary disease","how":"Years of breathing in smoke or dust inflame the airways and destroy the walls between air sacs. Small airways narrow and floppy, damaged lungs trap air, so breathing out takes longer and effort rises. Long-term cough with phlegm, breathlessness on exertion and chest infections that flare it up ('exacerbations') are typical. Diagnosed by blowing into a spirometer; the damage does not reverse, but its speed can be slowed.","evidence":"Established: tobacco smoke is the main cause in most countries; stopping smoking slows the yearly loss of lung function (Fletcher & Peto 1977; Lung Health Study randomised trial). Workplace dusts, fumes and gases account for roughly one in seven cases (Blanc 2019, ATS/ERS statement), and indoor smoke from cooking fires is a major cause worldwide. Air pollution is associated with flare-ups."},{"id":"pulmonary_embolism","col":"x","group":"Conditions","name":"Pulmonary embolism (blood clot in the lung)","sub":"PE","how":"A blood clot, usually formed in a deep leg or pelvic vein (deep-vein thrombosis), breaks off, travels through the right side of the heart and lodges in a lung artery. The part of the lung beyond it gets air but no blood flow, so oxygen falls; a large clot strains or stops the right side of the heart. Sudden breathlessness, sharp chest pain on breathing in, fast heartbeat, coughing blood or collapse are warning signs and need emergency care.","evidence":"Established physiology. Risk is raised by surgery, injury, being confined to bed or a care home, cancer, pregnancy and the weeks after birth, oestrogen-containing pills, a past clot and inherited clotting traits (Heit 2000; Heit 2005). Diagnosed with a CT scan of the lung arteries; treated with blood-thinning medicines under medical care."},{"id":"hypertension","col":"x","group":"Conditions","name":"High blood pressure","sub":"hypertension","how":"Blood pressure is the push of blood on artery walls. When it stays high, the left ventricle has to pump against it and thickens, artery walls stiffen and build plaque faster, and the small vessels of the brain, kidneys and eyes are damaged. It usually causes no symptoms, so it is found by measuring. In Parkinson's and related conditions, high pressure lying down can sit alongside low pressure on standing, because the autonomic nerves that adjust it are failing.","evidence":"Association: in a million adults, higher usual blood pressure went with steadily more stroke and heart deaths (Lewington 2002). Proven: lowering it with medicines cuts strokes, heart attacks and heart failure (Ettehad 2016 meta-analysis of 123 trials); cutting salt, cutting heavy drinking and exercise each lower it in trials."},{"id":"stroke","col":"x","group":"Conditions","name":"Stroke","sub":"brain attack: blocked or burst artery","how":"Brain cells die within minutes when their blood supply stops. About eight in ten strokes are a blocked artery (a clot from the heart, often from atrial fibrillation, or plaque in the neck or brain arteries); the rest are a burst vessel bleeding into the brain, usually from high blood pressure. Signs come on suddenly: face drooping, arm weakness, slurred or lost speech (FAST), and it is an emergency because clot-dissolving or clot-removing treatment works only in the first hours. A mini-stroke (TIA) clears within a day but is a warning. Many small strokes deep in the brain can cause vascular parkinsonism (stiff, shuffling legs with little tremor) that responds poorly to levodopa.","evidence":"Textbook neurology and cardiology. Association: about 90% of stroke risk worldwide is tied to ten modifiable factors, led by high blood pressure (INTERSTROKE 2016). Proven: lowering blood pressure and LDL cholesterol prevent strokes in randomised trials."},{"id":"pneumothorax","col":"x","group":"Conditions","name":"Collapsed lung (pneumothorax)","sub":"air in the space around the lung","how":"Air leaks into the thin space between the two layers of pleura, usually from a small blister on the lung surface bursting, or after a chest injury. The lung loses its grip on the chest wall and partly collapses. Sudden one-sided sharp chest pain and breathlessness follow; a large or 'tension' pneumothorax squeezes the heart and is an emergency.","evidence":"Established anatomy. 'Primary' cases occur mostly in tall, thin young men and are strongly linked to smoking (Bense 1987); 'secondary' cases complicate lung disease such as COPD. Small ones may settle on their own; larger ones need air drained by a doctor."},{"id":"atrial_fibrillation","col":"x","group":"Conditions","name":"Atrial fibrillation","sub":"AF, irregular heartbeat","how":"Instead of the sinus node setting an orderly beat, chaotic electrical waves (often starting from the lung-vein openings in the left atrium) make the atria quiver. The AV node lets through an irregular, often fast stream of beats. People may feel palpitations, breathlessness or tiredness, or nothing. Blood stagnating in the left atrium's pouch can clot and travel to the brain, so AF raises stroke risk about fivefold. It becomes more common with age, high blood pressure, heart failure, valve disease, sleep apnoea and heavy drinking.","evidence":"Association: Framingham found AF raises stroke risk nearly fivefold (Wolf 1991). Proven: blood thinners cut that stroke risk by about two-thirds (Hart 2007); stopping alcohol reduced AF recurrence in regular drinkers (Voskoboinik 2020)."},{"id":"heart_failure","col":"x","group":"Conditions","name":"Heart failure","sub":"the heart can't pump or fill well enough","how":"The heart cannot keep up with the body's needs, either because the left ventricle squeezes weakly (after heart attacks, or a diseased muscle) or because it is stiff and fills poorly (common with long-standing high blood pressure, age and diabetes). Blood backs up into the lungs (breathlessness, especially lying flat) and the body holds salt and water (swollen ankles, weight gain), and tiredness limits activity.","evidence":"Textbook cardiology. Proven: exercise-based rehabilitation reduces hospital admissions (Long 2019 Cochrane); implanted defibrillators lower deaths when the heart is weak (SCD-HeFT). Failed: a low-salt diet did not reduce deaths or hospital stays in a randomised trial (SODIUM-HF 2022)."},{"id":"aortic_stenosis","col":"x","group":"Conditions","name":"Aortic stenosis","sub":"narrowed aortic valve","how":"With age the aortic valve's cusps thicken and stiffen with calcium (earlier if the valve was born with two cusps instead of three), so the opening narrows and the left ventricle must push harder, thickening its wall. It can be silent for years; once breathlessness on effort, chest pain or fainting appear, outlook worsens quickly without a valve replacement. Heard as a murmur and measured by an ultrasound scan of the heart.","evidence":"Textbook cardiology. Proven: in severe aortic stenosis in people unfit for open surgery, a catheter-placed valve cut deaths at one year (PARTNER 2010)."},{"id":"coronary_artery_disease","col":"x","group":"Conditions","name":"Coronary artery disease","sub":"narrowed heart arteries, angina","how":"Fatty, inflamed plaque (atherosclerosis) builds up for decades inside the coronary arteries, driven by LDL cholesterol, high blood pressure, smoking and diabetes. As a plaque narrows an artery, the heart muscle beyond it runs short of oxygen during effort, felt as angina. The bigger danger is a plaque cracking, when a clot forms on it and blocks the artery (a heart attack).","evidence":"Association: smoking, diabetes and inactivity are linked to more disease in large cohort meta-analyses. Proven: statins, blood-pressure lowering and cardiac rehabilitation reduce heart attacks in randomised trials; bypass surgery lowers heart deaths when the heart is also weak (STICH)."},{"id":"heart_attack","col":"x","group":"Conditions","name":"Heart attack","sub":"myocardial infarction","how":"A coronary artery is suddenly blocked, almost always by a clot on a cracked plaque, and the heart muscle it feeds starts dying within about 20 to 30 minutes. Typical signs are crushing chest pain spreading to the arm, neck or jaw with sweating and breathlessness, but older people and people with diabetes may have little pain. Opening the artery fast saves muscle; the dead area heals as a scar, which can weaken the pump (heart failure) or trigger dangerous rhythms.","evidence":"Textbook cardiology. Proven: opening the artery with angioplasty in a major heart attack lowers deaths (Keeley 2003); statins and cardiac rehabilitation reduce further heart attacks."},{"id":"dvt","col":"x","group":"Conditions","name":"Deep vein thrombosis","sub":"a blood clot in a deep leg vein","how":"Blood clots inside a deep vein, usually in the calf or thigh, when three things combine: slow flow (bed rest, long journeys, paralysis), blood that clots more easily (pregnancy, oestrogen medicines, cancer, inherited tendencies) and vein-wall injury (surgery, especially hip and knee). The leg may swell, ache and look red, or there may be no signs. The danger is a piece breaking off and lodging in the lungs (pulmonary embolism). It is treated with blood thinners.","evidence":"Textbook medicine. Association: long journeys roughly double the risk (Chandra 2009); pregnancy and just after birth raise it about fourfold (Heit 2005). Proven: oestrogen plus progestin doubled clots in a randomised trial (WHI, Cushman 2004); compression stockings cut symptomless clots on long flights (Clarke 2021 Cochrane)."},{"id":"low_back_disc","col":"x","group":"Work-related conditions","name":"Low back strain, disc herniation & sciatica","sub":"lumbar radiculopathy","how":"Most work back injuries are muscle or ligament strains that settle within weeks. In a disc herniation the soft centre of a disc pushes through its outer ring and presses on a nerve root, causing sciatica: pain, numbness or weakness running down the leg.","evidence":"Most acute low back pain improves within weeks; exercise therapy has moderate evidence for chronic back pain."},{"id":"cervical_radiculopathy","col":"x","group":"Work-related conditions","name":"Neck strain & cervical radiculopathy","sub":"whiplash, pinched nerve in the neck","how":"Neck strain (including whiplash) stretches or tears muscles and ligaments. Cervical radiculopathy is a pinched nerve root from a herniated disc or bony wear, causing pain, tingling or weakness down one arm.","evidence":"Most neck strains improve over weeks to months; a minority develop long-lasting pain."},{"id":"knee_meniscus_oa","col":"x","group":"Work-related conditions","name":"Knee meniscus tear & osteoarthritis","sub":"","how":"A meniscus (cartilage pad) can tear with a twist on a bent knee; over years, kneeling, squatting, climbing and heavy lifting wear down joint cartilage (osteoarthritis), causing pain, stiffness and swelling.","evidence":"Physically demanding jobs are linked with more knee osteoarthritis (moderate-quality observational evidence)."},{"id":"inguinal_hernia","col":"x","group":"Work-related conditions","name":"Inguinal (groin) hernia","sub":"","how":"Part of the gut or its fatty apron pushes through a weak spot in the groin wall, making a bulge that aches with straining. Surgery closes the gap.","evidence":"Whether specific work loads cause hernias is not settled: a review found the evidence too weak; a large Danish cohort linked long standing/walking with more repairs."},{"id":"carpal_tunnel","col":"x","group":"Work-related conditions","name":"Carpal tunnel syndrome","sub":"median nerve compression at the wrist","how":"Swelling inside the narrow carpal tunnel squeezes the median nerve: numbness and tingling in the thumb, index and middle fingers, often at night, then weak grip.","evidence":"Linked with vibration, hand force and repetition at work. Splints and steroid injections help in the short term; surgery releases the tunnel."},{"id":"rotator_cuff","col":"x","group":"Work-related conditions","name":"Rotator cuff tendinopathy & tear","sub":"shoulder impingement","how":"The cuff tendons get irritated and frayed where they pass under the top of the shoulder blade, especially with overhead work; worn tendons can tear with a fall or heavy lift. Causes pain lifting the arm and night pain.","evidence":"Repetitive, forceful and overhead work is associated with shoulder impingement. Degenerative tears are common with age even without symptoms."},{"id":"epicondylitis","col":"x","group":"Work-related conditions","name":"Epicondylitis (tennis & golfer's elbow)","sub":"","how":"Overload of the tendons that attach gripping and wrist muscles to the bony points of the elbow, causing pain with gripping and lifting.","evidence":"Associated with forceful gripping, heavy handling, repetitive movement and vibrating tools. Most cases settle within a year."},{"id":"havs","col":"x","group":"Work-related conditions","name":"Hand-arm vibration syndrome","sub":"vibration white finger","how":"Years of vibrating tools damage finger blood vessels (attacks of white, then blue and red, fingers in the cold) and nerves (numbness, poor dexterity). Damage can be permanent.","evidence":"Strongly linked with vibration dose. Reducing exposure and keeping hands warm is the main management."},{"id":"tbi","col":"x","group":"Work-related conditions","name":"Traumatic brain injury (TBI) & concussion","sub":"","how":"A blow or jolt disrupts brain function. Concussion (mild TBI) brings confusion, headache, dizziness and slowed thinking, usually clearing in days to weeks; moderate to severe TBI involves bleeding or bruising of the brain and longer-lasting deficits.","evidence":"Observational studies link TBI with later Parkinson's, dementia and depression, rising with severity and number of injuries; whether TBI causes these is not proven."},{"id":"post_concussion","col":"x","group":"Work-related conditions","name":"Post-concussion syndrome","sub":"persistent post-concussive symptoms","how":"Headache, dizziness, poor concentration, memory lapses, irritability, light and noise sensitivity and poor sleep that persist for months after a concussion.","evidence":"In a large prospective study most people with mild TBI still had at least one symptom at a year. Graded return to activity is standard care."},{"id":"ptsd","col":"x","group":"Work-related conditions","name":"Post-traumatic stress disorder (PTSD)","sub":"","how":"After a traumatic event, intrusive memories and nightmares, avoidance of reminders, negative mood and constant alertness persist for more than a month. Fear circuits (amygdala) stay over-active and the prefrontal brakes are weaker.","evidence":"Trauma-focused psychotherapies are proven treatments; some antidepressants help."},{"id":"chronic_pain","col":"x","group":"Work-related conditions","name":"Chronic pain after injury","sub":"pain lasting more than 3 months","how":"Pain that outlasts healing: nerves and the spinal cord become sensitised (central sensitisation), so normal signals hurt. Sleep loss, low mood, fear of movement and inactivity feed it.","evidence":"Exercise and psychological therapies give modest benefit; long-term opioids carry risks without clear long-term benefit."},{"id":"crps","col":"x","group":"Work-related conditions","name":"Complex regional pain syndrome (CRPS)","sub":"","how":"After an often minor injury or fracture, usually of a hand or foot, pain becomes far worse than expected, with swelling, colour and temperature change, sweating and stiffness. Inflammation and changes in nerve and brain pain processing are involved.","evidence":"Uncommon: about 0.2% of wrist fractures are diagnosed with CRPS in registers, though stricter prospective screening finds many more early cases. Early movement and physiotherapy are standard care."},{"id":"manganism","col":"x","group":"Work-related conditions","name":"Manganese parkinsonism (manganism)","sub":"","how":"A movement disorder from manganese build-up in the basal ganglia: slowness, stiffness, soft speech, an odd 'cock-walk' gait and falls, often with mood changes. Unlike Parkinson's, the dopamine neurons themselves are largely spared, so levodopa helps little.","evidence":"Established toxicology at high exposure; lower welding exposure is linked with dose-related parkinsonism."},{"id":"contact_dermatitis","col":"x","group":"Work-related conditions","name":"Contact dermatitis (work-related hand eczema)","sub":"","how":"An itchy, red, cracked rash where the skin has touched something. Two kinds: (1) irritant dermatitis, the commoner one, where water, soap, detergents, solvents or friction strip the skin's fats and damage the barrier directly; anyone can get it with enough exposure; (2) allergic dermatitis, where a small chemical (nickel, fragrance chemicals such as oxidised limonene and linalool, rubber-glove additives, hair dye, preservatives, epoxy and acrylates) soaks into the skin, binds skin proteins and is remembered by T cells. On later contact the T cells cause a rash that appears one to three days after exposure and can spread beyond the contact spot. It is a delayed T-cell reaction, not an IgE allergy. Hands are affected most, especially in hairdressing, cleaning, health care, food work and construction.","evidence":"Established. Avoiding the cause, gloves with cotton liners and moisturisers are standard care; patch testing by a dermatologist identifies allergic triggers. Association: wet work and atopic eczema both raise the risk of hand dermatitis at work."},{"id":"nihl","col":"x","group":"Work-related conditions","name":"Noise-induced hearing loss","sub":"","how":"Permanent hearing loss, first at high pitches (a 'notch' around 4 kHz on a hearing test), making speech in noise hard to follow, often with ringing in the ears.","evidence":"Preventable; not reversible. Hearing aids help."},{"id":"heat_illness","col":"x","group":"Work-related conditions","name":"Heat illness","sub":"heat exhaustion to heat stroke","how":"From cramps and exhaustion (heavy sweating, weakness, nausea) to heat stroke, where core temperature passes about 40 °C and the brain and organs fail: an emergency.","evidence":"Rest, shade, water and acclimatisation prevent most cases; rapid cooling treats heat stroke."},{"id":"occ_asthma","col":"x","group":"Work-related conditions","name":"Occupational asthma","sub":"","how":"Asthma caused by something at work: wheeze, cough and tight chest that are worse on work days and better on holidays.","evidence":"Removing exposure early gives the best chance of recovery."},{"id":"asbestos_disease","col":"x","group":"Work-related conditions","name":"Mesothelioma & asbestosis","sub":"","how":"Asbestosis is scarring of the lungs that stiffens them and causes breathlessness. Mesothelioma is a cancer of the lining of the chest or abdomen, almost always from asbestos, appearing decades after exposure.","evidence":"Established cause-effect. Mesothelioma has poor survival."},{"id":"silicosis","col":"x","group":"Work-related conditions","name":"Silicosis","sub":"","how":"Scar nodules from silica dust build up in the lungs, causing cough and breathlessness; it can progress after exposure stops, and raises the risk of tuberculosis.","evidence":"No cure; prevention is dust control. Outbreaks are rising among engineered-stone workers."},{"id":"food_allergy","col":"x","group":"Allergies & intolerances","name":"Food allergy (IgE)","sub":"peanut, tree nuts, milk, egg, fish, shellfish, sesame, wheat, soy","how":"The immune system makes IgE against a food protein, so even a small amount causes hives, swelling, vomiting, wheeze or anaphylaxis, usually within minutes to two hours. It is diagnosed from the story plus skin-prick or blood tests and, when unclear, a supervised food challenge; a positive test alone does not prove allergy.","evidence":"Established. Milk and egg allergy are often outgrown in childhood; peanut, tree nut, fish and shellfish allergy usually last. Eating peanut regularly from infancy prevents most peanut allergy in high-risk babies (LEAP trial, Du Toit 2015). Oral immunotherapy can raise the amount tolerated (PALISADE 2018) but increases allergic reactions and anaphylaxis during treatment (PACE meta-analysis, Chu 2019); it is done only by specialists."},{"id":"anaphylaxis","col":"x","group":"Allergies & intolerances","name":"Anaphylaxis","sub":"severe whole-body allergic reaction","how":"A sudden, severe allergic reaction affecting more than one body system: swelling of the throat or tongue, wheeze, a drop in blood pressure, collapse, often with hives and vomiting. It can be fatal within minutes. Common triggers are foods, insect stings and medicines.","evidence":"Established: adrenaline (epinephrine) by auto-injector is the first treatment, followed by emergency care; antihistamines alone do not treat it. People at risk are taught to carry and use an auto-injector by their doctor. Reactions are more likely or more severe with 'cofactors' in people already allergic: exercise and alcohol around the trigger (European Anaphylaxis Registry, Dolle-Bierke 2023), aspirin and other anti-inflammatory painkillers (Globig 2025), a current infection, poorly controlled asthma, and in older people heart disease and some heart medicines. Asthma and delay in giving adrenaline are linked with deaths."},{"id":"coeliac_disease","col":"x","group":"Allergies & intolerances","name":"Coeliac disease (not an allergy)","sub":"autoimmune reaction to gluten","how":"An autoimmune disease, not an allergy: in people with certain immune genes (HLA-DQ2/DQ8), gluten from wheat, barley and rye triggers T cells that attack the lining of the small intestine, flattening the finger-like villi that absorb food. This causes diarrhoea, bloating, weight loss, low iron and other nutrient shortages, or sometimes few gut symptoms at all.","evidence":"Established. Diagnosed with blood antibody tests (tTG) and a small-bowel biopsy while still eating gluten. Treatment is a strict lifelong gluten-free diet, which lets the lining heal. Unlike wheat allergy, tiny amounts matter over time even without an immediate reaction, and it is not outgrown."},{"id":"lactose_intolerance","col":"x","group":"Allergies & intolerances","name":"Lactose intolerance (not an allergy)","sub":"low lactase enzyme","how":"Not an immune reaction: the small intestine makes too little lactase, the enzyme that splits milk sugar (lactose). Undigested lactose reaches the colon, where bacteria ferment it into gas and draw in water, causing bloating, cramps and loose stools a few hours after milk. It is the normal pattern in most adults worldwide, and can also follow gut infections or coeliac disease.","evidence":"Established. Unlike milk allergy it never causes hives, swelling or anaphylaxis, and most people can manage small amounts of milk, hard cheese or yoghurt. Milk allergy (to milk protein) is a different condition."},{"id":"eoe","col":"x","group":"Allergies & intolerances","name":"Eosinophilic oesophagitis (EoE)","sub":"non-IgE food reaction in the food pipe","how":"A long-lasting allergic-type inflammation of the oesophagus in which white blood cells called eosinophils build up in its lining, usually in response to foods (most often milk, then wheat, egg and soy). The food pipe stiffens and narrows, so food sticks; children may have vomiting, pain and poor feeding. It is a delayed, non-IgE reaction, so standard allergy tests are poor at finding the trigger.","evidence":"Established: diagnosed by endoscopy with biopsies. Treatment options include acid-suppressing medicine, swallowed steroids, removing trigger foods under a dietitian, and newer biologic medicines, chosen by a specialist."},{"id":"fpies","col":"x","group":"Allergies & intolerances","name":"FPIES","sub":"food protein-induced enterocolitis syndrome","how":"A non-IgE food reaction, mostly in babies: one to four hours after eating the trigger food (often milk, soy, rice, oats, egg or fish) the baby has repeated, heavy vomiting, becomes pale and floppy and may become dehydrated, sometimes with diarrhoea later. There are no hives or wheeze, and skin and blood allergy tests are usually negative.","evidence":"Established. Diagnosed from the typical story; most children outgrow it in the first few years, which a specialist checks with a supervised feeding test."},{"id":"atopic_eczema","col":"x","group":"Allergies & intolerances","name":"Atopic eczema (atopic dermatitis)","sub":"","how":"A long-lasting itchy, dry, inflamed skin condition that usually starts in babies, in the creases of elbows and knees or on the face. A weak skin barrier (often from changes in the filaggrin gene) lets water out and irritants, microbes and allergens in, and an allergic-type (type 2) immune response keeps it inflamed. Food allergy, hay fever and asthma often follow, a pattern called the 'atopic march'.","evidence":"Established: moisturisers, avoiding irritants, and anti-inflammatory creams prescribed by a doctor are the basis of care; moisturisers reduce flares when used for treatment, but did not prevent eczema when started from birth (BEEP and PreventADALL trials). Proven: anti-IL-4 receptor biologic medicine improved moderate-to-severe eczema in trials (SOLO 1 and 2). Food allergy rarely causes eczema on its own, and strict food avoidance for eczema can raise the risk of true food allergy. The 'atopic march' (eczema, then food allergy, asthma and hay fever) is a common pattern, not a rule: in two UK birth cohorts only about 7% of children with symptoms followed it (Belgrave 2014); eczema raises the chance of the others, especially when it is early, severe or persistent."},{"id":"urticaria","col":"x","group":"Allergies & intolerances","name":"Urticaria (hives)","sub":"acute or chronic","how":"Recurrent hives, sometimes with swelling (angioedema), from mast cells releasing histamine in the skin. Acute urticaria (under six weeks) is often triggered by infections, foods, stings or medicines. Chronic urticaria (over six weeks) is usually not caused by any allergy; in many people it is autoimmune, with antibodies that activate mast cells.","evidence":"Established. Testing for food allergy is rarely helpful in chronic urticaria; non-drowsy antihistamines are the first treatment, prescribed by a doctor."},{"id":"allergic_rhinitis","col":"x","group":"Allergies & intolerances","name":"Hay fever (allergic rhinitis)","sub":"seasonal or year-round","how":"An IgE reaction in the lining of the nose (and often the eyes) to breathed-in allergens: sneezing, runny or blocked nose, itchy nose, palate and eyes. Seasonal hay fever comes from pollen; year-round rhinitis from dust mites, pets, mould or cockroaches. It disturbs sleep and concentration and often occurs with asthma.","evidence":"Established. Proven: allergen immunotherapy (injections or under-the-tongue tablets or drops, given for about three years under specialist care) reduces hay-fever symptoms and medicine use in placebo-controlled trials (Cochrane review, Calderon 2007), and its benefit can last after stopping. Nasal steroid sprays and antihistamines relieve symptoms."},{"id":"allergic_asthma","col":"x","group":"Allergies & intolerances","name":"Allergic asthma","sub":"asthma driven by breathed-in allergens","how":"The most common type of asthma, especially when it starts in childhood: breathing in an allergen (dust mite, pet dander, pollen, mould, cockroach) makes IgE-armed mast cells in the airways release chemicals that tighten the airway muscles and cause swelling and mucus, giving wheeze, cough, tight chest and breathlessness. Occupational asthma from sensitisers at work (flour, latex, lab animals, isocyanates) is the same process acquired on the job.","evidence":"Established. Asthma is treated with inhaled medicines prescribed by a doctor; avoiding triggers and allergen immunotherapy (for suitable mite- or pollen-driven asthma) are added under specialist care. Severe allergic reactions are more dangerous in people whose asthma is poorly controlled."},{"id":"allergic_conjunctivitis","col":"x","group":"Allergies & intolerances","name":"Allergic conjunctivitis","sub":"itchy, red, watery eyes from allergens","how":"Pollen, pet dander or dust-mite particles land on the thin clear lining of the eye and eyelids (the conjunctiva); IgE-armed mast cells there release histamine within minutes, so the eyes itch, redden, water and the lids puff up. It usually comes with hay fever ('rhinoconjunctivitis') and is seasonal with pollen or year-round with indoor allergens. Rubbing makes it worse. Itch is the key sign: red eyes without itch point to other causes.","evidence":"Established. Antihistamine or mast-cell-stabilising eye drops, cool compresses and treating the hay fever relieve it; allergen immunotherapy reduces eye symptoms along with nose symptoms. Rare severe forms (vernal and atopic keratoconjunctivitis) can scar the cornea and need an eye specialist."},{"id":"drug_allergy","col":"x","group":"Allergies & intolerances","name":"Drug allergy","sub":"immune reactions to medicines","how":"An immune reaction to a medicine, as opposed to an expected side effect. Immediate reactions (within about an hour) are usually IgE-driven: hives, swelling, wheeze or anaphylaxis. Delayed reactions (days later) are T-cell driven: most are a harmless measles-like rash, but rare severe forms blister and peel the skin (Stevens-Johnson syndrome, toxic epidermal necrolysis) or inflame organs (DRESS). Antibiotics, especially penicillins, are the commonest cause; anti-inflammatory painkillers (NSAIDs) and anaesthetic drugs follow. Some reactions, such as aspirin and NSAID-triggered hives or asthma, are not allergies at all but a change in how the body makes leukotrienes.","evidence":"Established. About one in ten people carry a penicillin allergy label, but most of them are not allergic when properly assessed, tested and re-challenged (Blumenthal 2019); the label pushes doctors to broader antibiotics with more side effects and resistance. Specialist testing and supervised drug challenges can remove a wrong label."},{"id":"venom_allergy","col":"x","group":"Allergies & intolerances","name":"Insect venom allergy","sub":"bee, wasp, hornet and fire-ant stings","how":"After an earlier sting, some people make IgE against venom proteins. A later sting can then cause a large local swelling (more than about 10 cm, lasting days) or a whole-body reaction: hives, throat swelling, wheeze, dizziness and collapse. Venom also contains peptides that trigger mast cells directly. People with mastocytosis (too many mast cells) are at risk of the most severe reactions.","evidence":"Established. Proven: venom immunotherapy (a long course of venom injections under a specialist) cut the chance of a whole-body reaction to a later sting from about four in ten to under three in a hundred in pooled trials (Boyle 2012, Cochrane). An adrenaline auto-injector is the emergency treatment."},{"id":"alpha_gal_syndrome","col":"x","group":"Allergies & intolerances","name":"Alpha-gal syndrome (red-meat allergy)","sub":"tick bite, then allergy to mammal meat","how":"A bite from certain ticks (the lone star tick in the USA, Ixodes ticks in Europe and Australia) makes the body produce IgE against a sugar called alpha-gal, which sits on the meat and organs of mammals (beef, pork, lamb, venison) and in some medicines and gelatin. Unusually, reactions come three to six hours after eating, because the sugar is absorbed slowly with fat: hives, belly pain, diarrhoea or anaphylaxis, often at night. Poultry and fish do not carry alpha-gal. Repeat tick bites raise the IgE; avoiding bites can let it fall over years.","evidence":"Established description: delayed anaphylaxis, hives and swelling after red meat in people with alpha-gal IgE (Commins 2009), and tick bites raise alpha-gal IgE (Commins 2011). It is easily missed because of the delay. The cancer drug cetuximab can cause immediate anaphylaxis in sensitised people."},{"id":"caries","col":"x","group":"Mouth & teeth","name":"Tooth decay (dental caries)","sub":"cavities","how":"Plaque bacteria (such as Streptococcus mutans) ferment sugars into acid, which dissolves enamel and then dentine. Early white spots can re-harden with saliva and fluoride; once a hole (cavity) forms it does not heal and can spread to the pulp, causing toothache and abscess. Anything that lowers saliva flow, such as many medicines, raises the risk.","evidence":"Established: the most common disease in the world. Association: more frequent and larger amounts of free sugars go with more decay in children and adults (systematic reviews informing WHO). Proven: fluoride toothpaste and fluoride varnish prevent decay in trials. In Parkinson's, a 2026 meta-analysis of small cross-sectional studies found no clear difference in decay compared with people without Parkinson's, with very low certainty."},{"id":"gingivitis","col":"x","group":"Mouth & teeth","name":"Gingivitis","sub":"inflamed, bleeding gums","how":"When plaque is left on teeth along the gum line, the gums become red, swollen and bleed on brushing within days to weeks. It is fully reversible once the plaque is removed regularly.","evidence":"Established: a classic experiment in volunteers who stopped cleaning their teeth showed plaque build-up leads to gingivitis, which reverses when cleaning resumes (Löe 1965). Very common in adults."},{"id":"periodontitis","col":"x","group":"Mouth & teeth","name":"Periodontitis","sub":"chronic gum disease","how":"In some people long-standing gingivitis spreads deeper: the body's inflammatory reaction to bacteria in pockets beside the teeth destroys the ligament and socket bone. Gums recede, pockets deepen, teeth loosen and may be lost. Severe periodontitis affects roughly one in ten adults and keeps a low-grade inflammation going in the rest of the body.","evidence":"Established: driven by plaque bacteria such as P. gingivalis plus the person's own inflammatory response; a leading cause of tooth loss in adults. Association: smoking and diabetes raise the risk. Association: periodontitis is linked with heart and blood-vessel disease and with dementia, but these links are not shown to be causal. Proven (moderate certainty): in people with both diabetes and periodontitis, professional deep cleaning under the gums improved blood-sugar control in a Cochrane review (Simpson 2022)."},{"id":"bruxism","col":"x","group":"Mouth & teeth","name":"Bruxism (teeth grinding & clenching)","sub":"awake or during sleep","how":"Repeated clenching or grinding of the teeth, either while awake (often clenching under stress or concentration) or during sleep (rhythmic grinding linked with brief arousals). It can wear and crack teeth, tire and ache the jaw muscles, and cause morning headache. Some medicines, notably SSRI antidepressants, are reported to trigger it.","evidence":"Established: grinding wears tooth surfaces. Association: linked with jaw-joint disorders and with stress, anxiety and depression in observational studies. SSRI-linked bruxism is known mainly from case reports. Night guards (occlusal splints) protect teeth from wear, but evidence that they stop bruxism itself is weak."},{"id":"tmd","col":"x","group":"Mouth & teeth","name":"Jaw joint disorder (TMD)","sub":"temporomandibular disorder","how":"Pain in the jaw joints and chewing muscles, often with clicking, limited opening or the jaw locking. Most cases are muscle pain rather than joint damage, and many settle on their own.","evidence":"Association: more common with bruxism, stress and other chronic pain conditions. Proven but heterogeneous: in a meta-analysis of randomised trials, self-managed care such as home jaw exercises and education reduced TMD pain, with a non-significant trend to better mouth opening (Mohr 2026)."},{"id":"oral_cancer","col":"x","group":"Mouth & teeth","name":"Mouth cancer","sub":"oral cavity cancer: tongue, gums, floor of mouth, cheek, lips","how":"Most mouth cancers start in the thin lining (squamous cells) after years of exposure to tobacco, alcohol or betel quid, often after a white or red patch that does not heal. A mouth ulcer or lump lasting more than about three weeks is the classic warning sign. It spreads first to the lymph nodes in the neck.","evidence":"Established: tobacco (smoked and chewed), alcohol and betel quid/areca nut cause mouth cancer, and tobacco plus alcohol together multiply the risk (Hashibe 2009 pooled analysis). Throat (oropharyngeal) cancer behind the mouth is largely caused by HPV, but HPV plays a much smaller role inside the mouth itself."},{"id":"amd","col":"x","group":"Eye conditions","name":"Age-related macular degeneration","sub":"loss of central vision","how":"Wear of the macula's support layer (the retinal pigment epithelium) with yellow deposits (drusen) beneath it. The 'dry' form slowly thins the macula; in the 'wet' form fragile new vessels grow from the choroid and leak, which can take central vision quickly. Side vision is kept. Risk rises with age, smoking and family genes.","evidence":"Proven: for people who already have intermediate AMD, the AREDS vitamin-and-mineral formula modestly slows progression to late AMD; injections into the eye treat wet AMD. Supplements do not prevent AMD in people who do not have it. Association: smoking raises risk."},{"id":"diabetic_retinopathy","col":"x","group":"Eye conditions","name":"Diabetic retinopathy","sub":"diabetes damage to retinal vessels","how":"Years of high blood sugar damage the small vessels of the retina: they leak (swelling the macula) or close off, and the starved retina grows fragile new vessels that can bleed. Often silent until late, so people with diabetes need regular eye screening.","evidence":"Proven: in the DCCT trial, tight blood-sugar control in type 1 diabetes cut new retinopathy by about three-quarters and slowed existing retinopathy by about half. Laser and eye injections treat advanced disease."},{"id":"cataract","col":"x","group":"Eye conditions","name":"Cataract","sub":"clouding of the lens","how":"The lens slowly clouds as its lifelong proteins clump, scattering light: blurred or dim vision, glare from headlights, faded colours. Very common with age; also more likely with smoking, diabetes, long-term steroid use, strong sunlight and eye injury. Surgery replaces the cloudy lens with a clear artificial one.","evidence":"Established: cataract surgery restores sight reliably. Association: smoking raises risk. No supplement has been shown to prevent it."},{"id":"glaucoma","col":"x","group":"Eye conditions","name":"Glaucoma","sub":"optic nerve damage, side vision first","how":"Slow death of retinal ganglion cells and their fibres in the optic nerve, usually with eye pressure too high for that nerve. Side vision goes first and unnoticed; central vision is lost late, and the loss is permanent. Risk rises with age, family history, African ancestry and short- or long-sightedness. Found by checking eye pressure, the optic disc and the visual field.","evidence":"Proven: lowering eye pressure (drops, laser or surgery) slows worsening and delays onset in people at high risk."},{"id":"breast_cancer","col":"x","group":"Cancers","name":"Breast cancer","sub":"","how":"Cancer that starts in the milk ducts or lobules of the breast. It is the most common cancer in women and rare in men. It often shows as a painless lump or a change in the skin or nipple, and usually spreads first to the armpit lymph nodes. Most breast cancers are fuelled by oestrogen. Risk rises with age, inherited genes such as BRCA1 and BRCA2, alcohol, combined hormone therapy after menopause and weight gain after menopause; breastfeeding and physical activity are linked with lower risk.","evidence":"Established risk factors. Outcomes have improved greatly with modern treatment; screening finds some cancers earlier but also finds some that would never have caused harm (overdiagnosis)."},{"id":"lymphoma","col":"x","group":"Cancers","name":"Lymphoma","sub":"cancer of lymphocytes (Hodgkin and non-Hodgkin)","how":"A cancer that starts when B or T lymphocytes grow out of control, usually in lymph nodes but also in the spleen, marrow, gut (MALT lymphoma) or skin. Hodgkin lymphoma has large abnormal cells (Reed–Sternberg cells) among many normal immune cells and often begins in the neck or chest nodes of young adults; non-Hodgkin lymphomas are a large family, from slow-growing types that may need no treatment for years to fast-growing ones. Typical signs: painless swollen nodes that keep growing, fevers, drenching night sweats, weight loss and itching. Risk is higher with a weakened immune system (HIV, transplant drugs), some infections (EBV, H. pylori, hepatitis C) and some autoimmune diseases.","evidence":"Textbook medicine. Many types are curable with modern treatment, especially Hodgkin lymphoma."},{"id":"lung_cancer","col":"x","group":"Cancers","name":"Lung cancer","sub":"","how":"Cells lining the airways or air sacs pick up DNA damage, most often from chemicals in tobacco smoke, and grow out of control. It rarely causes symptoms early; later signs include a cough that will not go away, coughing blood, breathlessness, chest pain, weight loss and repeated chest infections. It spreads readily to lymph nodes in the chest, the brain, bones, liver and adrenal glands.","evidence":"Established: tobacco smoke causes most lung cancers; asbestos, radon, silica, diesel exhaust and outdoor air pollution are recognised causes, and asbestos and smoking together multiply the risk. About one in ten to one in five cases occur in people who never smoked. Screening with low-dose CT lowers lung-cancer deaths in people with heavy smoking histories (NLST 2011; NELSON 2020)."},{"id":"liver_cancer","col":"x","group":"Cancers","name":"Liver cancer","sub":"hepatocellular carcinoma","how":"Cancer of the liver's own cells, nearly always arising in a liver already scarred by cirrhosis or chronically infected with hepatitis B, where constant injury and repair lets gene changes build up.","evidence":"Established. Hepatitis B vaccination and hepatitis treatment prevent many cases.","pos":[-0.09,1.18,0.02]},{"id":"pancreatic_cancer","col":"x","group":"Cancers","name":"Pancreatic cancer","sub":"pancreatic ductal adenocarcinoma","how":"Cancer growing from the cells lining the pancreatic ducts. Because the gland lies deep behind the stomach it usually causes no early symptoms; a tumour in the head of the pancreas may first show itself by blocking the bile duct, causing painless jaundice. Risk is raised by smoking, chronic pancreatitis, diabetes, obesity and family history.","evidence":"Established. Surgery (often a Whipple operation) is the only potentially curative treatment, possible in a minority.","pos":[0,1.09,0]},{"id":"colorectal_cancer","col":"x","group":"Cancers","name":"Bowel cancer","sub":"colorectal (colon and rectal) cancer","how":"Most bowel cancers grow slowly over about ten years from small growths (polyps, adenomas) in the lining of the colon or rectum, which pick up gene changes one after another. Finding and removing polyps, or finding cancer early, is why screening works. Risk rises with age, family history, long-standing colitis, processed and red meat, alcohol, smoking, obesity and inactivity; fibre and physical activity are linked with lower risk.","evidence":"Established. Screening with stool blood tests, sigmoidoscopy or colonoscopy reduced bowel cancer deaths in randomised trials. Blood in the stool, a lasting change in bowel habit, or unexplained anaemia or weight loss need checking.","pos":[0.06,0.93,0.03]},{"id":"gastric_cancer","col":"x","group":"Cancers","name":"Stomach cancer","sub":"gastric cancer","how":"Most stomach cancers develop over decades from long-term H. pylori inflammation, which thins the lining (atrophic gastritis), changes it to an intestine-like lining, and then to precancerous change. Smoking, salt-preserved foods and family history add risk. Early cancer usually causes no symptoms; later it causes indigestion, early fullness, weight loss or anaemia.","evidence":"Established: H. pylori is classed as a definite cause. Rates have fallen in countries where H. pylori has become less common.","pos":[0.05,1.15,0.04]},{"id":"cervical_cancer","col":"x","group":"Cancers","name":"Cervical cancer","sub":"cancer of the neck of the womb","how":"Cancer of the cervix, the neck of the womb, which grows slowly over years from precancerous changes caused by persistent high-risk HPV. Screening (smear or HPV tests) finds and removes precancer before it becomes cancer.","evidence":"Established: nearly all cases are caused by HPV. Smoking and weakened immunity (HIV) raise risk.","pos":[0,0.885,0]},{"id":"anal_cancer","col":"x","group":"Cancers","name":"Anal cancer","sub":"cancer of the anal canal","how":"A cancer of the skin-like lining of the anal canal, most often caused by long-lasting high-risk HPV infection. Risk is higher with HIV, after organ transplant and in people who have had cervical precancer.","evidence":"Established: around nine in ten cases are linked to HPV.","pos":[0,0.84,-0.05]},{"id":"kaposi_sarcoma","col":"x","group":"Cancers","name":"Kaposi sarcoma","sub":"tumour of blood and lymph vessel cells","how":"A cancer of the cells lining small blood and lymph vessels, caused by human herpesvirus 8 when immunity is weak. It shows as purple-brown patches or lumps on the skin, often the legs, and can affect lymph nodes, the gut and the lungs.","evidence":"Established: needs HHV-8; was a defining illness of AIDS and often shrinks when HIV is treated.","pos":[0.1,0.4,0.05]},{"id":"cholangiocarcinoma","col":"x","group":"Cancers","name":"Bile duct cancer","sub":"cholangiocarcinoma","how":"Cancer of the bile ducts inside or outside the liver. Usually found late, often when a blocked duct causes painless jaundice, itch and pale stools. Long-term liver fluke infection is the main cause in parts of South-East Asia; elsewhere, chronic bile-duct inflammation raises risk.","evidence":"Established: liver flukes (Opisthorchis, Clonorchis) are definite causes (IARC Group 1)."},{"id":"menopause","col":"x","group":"Women's health","name":"Menopause","sub":"a life stage, not a disease","how":"The last period, confirmed after a year without one, usually around 51 (earlier after surgery to remove both ovaries or some cancer treatments). The ovaries run out of eggs and stop making most of their oestrogen and progesterone. The years around it (perimenopause) can bring irregular periods, hot flushes and night sweats, poorer sleep, low mood, joint aches and vaginal dryness. Afterwards bone loss speeds up and heart risk slowly catches up with men's.","evidence":"Established physiology. Symptoms vary widely; many women need no treatment. Menopause before 45 is linked with more heart disease (Muka 2016)."},{"id":"pcos","col":"x","group":"Women's health","name":"Polycystic ovary syndrome (PCOS)","sub":"","how":"A common hormone condition, diagnosed when at least two of three are present: irregular or absent ovulation (infrequent periods), higher androgens such as testosterone (shown by acne, extra facial or body hair, or blood tests), and many small egg follicles on the ovaries. Insulin resistance is common, even in slim women: the extra insulin pushes the ovaries to make more testosterone and disturbs ovulation. It raises the risk of type 2 diabetes and is a leading cause of trouble getting pregnant because eggs are not released regularly.","evidence":"Established (2023 international guideline, Teede 2023). Diet and activity changes lowered androgen levels and weight a little in small, low-quality trials (Lim 2019); medicines can regulate periods, treat skin symptoms and help ovulation."},{"id":"pregnancy","col":"x","group":"Women's health","name":"Pregnancy","sub":"a state, not a disease","how":"About 40 weeks from the last period to birth. The placenta makes large amounts of progesterone and other hormones; blood volume rises by about half, the heart pumps more, and the womb grows from fist-size to hold the baby. Needs for folate and iron rise sharply. Common effects include nausea early on, constipation, heartburn, back and pelvic pain, and leaking urine.","evidence":"Established physiology. Proven: folic acid before and in early pregnancy prevents most neural-tube defects; iron supplements in pregnancy reduce anaemia in the mother (Finkelstein 2024); low-dose aspirin lowered early (preterm) pre-eclampsia in women at high risk (Rolnik 2017)."},{"id":"pre_eclampsia","col":"x","group":"Women's health","name":"Pre-eclampsia","sub":"high blood pressure of pregnancy with organ strain","how":"A pregnancy condition, usually after 20 weeks, in which a poorly attached placenta releases factors that damage the lining of the mother's blood vessels. This raises blood pressure and can strain the kidneys (protein in the urine), liver, brain (headaches, vision changes, and in eclampsia, seizures) and blood clotting, and can starve the baby of growth. It ends only when the placenta is delivered, though it can flare just after birth.","evidence":"Established mechanism (Chappell 2021). A major cause of illness and death in mothers and babies worldwide. Women who had it carry a higher lifelong risk of high blood pressure and heart disease (Bellamy 2007)."},{"id":"fibroids","col":"x","group":"Women's health","name":"Fibroids","sub":"uterine leiomyomas","how":"Non-cancerous lumps of womb muscle and fibrous tissue, from pea-sized to melon-sized, that grow under oestrogen and progesterone. They are very common by the age of 50 and appear earlier and more severely in Black women. Many cause no symptoms; others cause heavy or long periods, pelvic pressure or bloating, needing to pass urine often, and sometimes trouble getting or staying pregnant. They usually shrink after menopause.","evidence":"Established (Stewart 2016). They account for a third to half of hysterectomies; options range from watching, hormone medicines and procedures that cut their blood supply to surgery that removes only the fibroid or the womb."},{"id":"endometriosis","col":"x","group":"Women's health","name":"Endometriosis","sub":"","how":"Tissue like the womb lining grows outside the womb, mainly on the ovaries, the lining of the pelvis, the ligaments behind the womb and sometimes the bowel or bladder. It responds to the monthly hormones and causes inflammation, scarring and adhesions. Typical symptoms are severe period pain, pain between periods, pain during sex or bowel movements, tiredness, and trouble getting pregnant. Diagnosis is often delayed by years.","evidence":"Established: affects about 5 to 10% of women of reproductive age (Zondervan 2018). Diagnosis is confirmed by surgery, though some forms show on scans. Treatments (painkillers, hormone medicines, surgery) ease symptoms but rarely give lasting relief, and no cure is known."},{"id":"bacterial_vaginosis","col":"x","group":"Women's health","name":"Bacterial vaginosis","sub":"BV","how":"Not an infection caught from outside, but a change of community: the protective lactic-acid bacteria thin out, the vaginal pH rises, and a mixed group of other bacteria takes over, giving a thin grey discharge and a fishy smell. It often comes back after treatment because the lactobacilli do not always re-establish.","evidence":"Well established as a community shift rather than a single-germ infection. It is linked with preterm birth and with catching sexually transmitted infections more easily; those links are associations.","pos":[0,0.856,0.002]},{"id":"ckd","col":"x","group":"Kidney & electrolytes","name":"Chronic kidney disease","sub":"CKD, kidney failure","how":"Kidney damage or reduced filtering (measured as eGFR from a blood test, and protein in the urine) lasting more than three months. The commonest causes are diabetes and high blood pressure; others include glomerulonephritis, inherited cysts and long-term blockage. Nephrons are lost slowly and do not grow back, so it usually causes no symptoms until late. As it advances, waste, potassium, acid and fluid build up, the kidneys make less calcitriol and less of the red-cell hormone erythropoietin (causing anaemia), and bones and blood vessels suffer. At the last stage (kidney failure) dialysis or a transplant is needed.","evidence":"Established definition and course (KDIGO staging by eGFR and urine albumin). Reduced eGFR is independently linked with more cardiovascular events and death in large cohorts (Go 2004). Medicines that slow it have trial evidence (see treatment links).","pos":[0.056,1.11,-0.035]},{"id":"hyponatraemia","col":"x","group":"Kidney & electrolytes","name":"Low blood sodium (hyponatraemia)","sub":"too much water for the salt","how":"The blood has too little sodium for its water, usually because the kidneys are holding back water rather than because of too little salt in the diet. Common causes are excess vasopressin (the SIADH pattern, after surgery, with lung or brain disease, or from medicines such as SSRI antidepressants and some anti-seizure drugs), water pills (thiazide diuretics), heart, liver or kidney failure, and drinking large amounts of water with little food. Mild, long-standing cases cause unsteadiness and poor attention; a fast drop makes brain cells swell (headache, confusion, seizures). Correcting it too fast can also injure the brain, so it is treated carefully.","evidence":"Established physiology. Even mild chronic hyponatraemia is associated with falls, fractures and attention problems (Corona 2018 meta-analysis; Renneboog 2006)."},{"id":"aki","col":"x","group":"Kidney & electrolytes","name":"Acute kidney injury","sub":"AKI, sudden kidney failure","how":"A drop in kidney function over hours to days, seen as rising creatinine in the blood or much less urine. Causes are grouped as before the kidney (too little blood flow: dehydration, bleeding, heart failure, low blood pressure, sepsis), in the kidney (tubule cells injured by low flow or by toxins and some medicines, inflammation), and after the kidney (a blockage such as an enlarged prostate). Older people, people with diabetes or CKD, and people taking several kidney-affecting medicines at once are most at risk. Many recover, but not always fully.","evidence":"Established (KDIGO definition). AKI is independently linked with later chronic kidney disease (Coca 2012 meta-analysis).","pos":[0.056,1.11,-0.035]},{"id":"hyperkalaemia","col":"x","group":"Kidney & electrolytes","name":"High blood potassium (hyperkalaemia)","sub":"potassium the kidneys can't clear","how":"Too much potassium in the blood, almost always because the kidneys can't get rid of it: advanced chronic kidney disease, acute kidney injury, low aldosterone, or medicines that make the kidney keep potassium (such as ACE inhibitors, angiotensin blockers, potassium-sparing water pills). It often causes no symptoms, then muscle weakness and dangerous heart rhythms, so it is found with blood tests.","evidence":"Established physiology.","pos":[0.056,1.11,-0.035]},{"id":"ibs","col":"x","group":"Digestive & liver","name":"Irritable bowel syndrome (IBS)","sub":"a disorder of gut-brain interaction","how":"Repeated belly pain linked to bowel movements, with diarrhoea, constipation or both, and bloating, without visible damage on tests. The gut's nerves are over-sensitive (normal amounts of gas or stretch hurt), its muscle waves are irregular, and signalling between the gut and brain is altered. Stress, a past gut infection, some foods (especially fermentable sugars, FODMAPs) and changes in gut bacteria all play a part.","evidence":"Diagnosed on symptoms after ruling out other diseases (Rome criteria). Several treatments beat placebo in trials, but none cures it; symptoms often come and go for years.","pos":[0,1,0.07]},{"id":"crohns","col":"x","group":"Digestive & liver","name":"Crohn's disease","sub":"inflammatory bowel disease (IBD)","how":"A lifelong immune disease in which the gut's immune system over-reacts to gut bacteria in people with certain genes. Inflammation goes through the whole thickness of the gut wall, in patches, anywhere from mouth to anus, most often the end of the small intestine (ileum) and the colon. It can narrow the gut, make tunnels (fistulas) between loops of bowel or to the skin, and reduce absorption of B12 and other nutrients.","evidence":"Established immune disease with no cure; medicines (including anti-TNF and other biologics) control inflammation in trials, and surgery treats complications.","pos":[-0.05,0.97,0.05]},{"id":"ulcerative_colitis","col":"x","group":"Digestive & liver","name":"Ulcerative colitis","sub":"inflammatory bowel disease (IBD)","how":"A lifelong immune disease that inflames only the inner lining of the large intestine, always starting at the rectum and spreading continuously upward for a varying distance. The inflamed lining ulcerates and bleeds, causing bloody diarrhoea and urgency. After many years of widespread colitis, the risk of bowel cancer rises, so people are offered surveillance colonoscopy.","evidence":"Established immune disease. Medicines control it in most people; removing the colon and rectum ends the bowel disease.","pos":[0,0.95,0.03]},{"id":"masld","col":"x","group":"Digestive & liver","name":"Fatty liver disease (MASLD)","sub":"metabolic dysfunction-associated steatotic liver disease, formerly NAFLD","how":"Fat builds up inside liver cells when the body takes in more energy than it burns and insulin works poorly, as in obesity and type 2 diabetes. In some people the fat inflames the liver (MASH), which slowly lays down scar tissue (fibrosis) and can end in cirrhosis. It usually causes no symptoms until late.","evidence":"Established: the commonest liver disease. Weight loss and exercise reduce liver fat in trials; heavy drinking on top worsens it.","pos":[-0.06,1.17,0.03]},{"id":"cirrhosis","col":"x","group":"Digestive & liver","name":"Cirrhosis","sub":"advanced liver scarring","how":"After years of injury (alcohol, fatty liver, hepatitis B or C), scar tissue replaces healthy liver and breaks it into nodules. Blood from the gut struggles through, so pressure in the portal vein rises, the spleen swells and fragile veins form in the gullet. The failing liver makes fewer blood proteins and clotting factors and clears fewer toxins, causing fluid in the belly, jaundice, bleeding and confusion (hepatic encephalopathy).","evidence":"Established. Removing the cause (stopping alcohol, curing hepatitis C) can halt and partly reverse scarring; it raises liver cancer risk, so people are offered regular scans.","pos":[-0.07,1.17,0.03]},{"id":"gerd","col":"x","group":"Digestive & liver","name":"Reflux disease (GERD)","sub":"gastro-oesophageal reflux disease, acid reflux","how":"Stomach contents, mainly acid, flow back up into the oesophagus often enough to cause symptoms or damage. The lower oesophageal sphincter relaxes too often or is weak, a hiatus hernia lets the stomach top slip above the diaphragm, and belly pressure (excess weight, pregnancy) pushes contents up. Acid inflames the lining (oesophagitis); over years it can cause narrowing or Barrett's oesophagus.","evidence":"Very common. Acid-suppressing medicines heal inflammation and relieve heartburn in trials; weight loss and raising the head of the bed help some people. Trouble swallowing, weight loss, vomiting blood or black stools need prompt assessment.","pos":[0.02,1.25,-0.01]},{"id":"barretts","col":"x","group":"Digestive & liver","name":"Barrett's oesophagus","sub":"acid-adapted lining of the lower gullet","how":"After years of reflux, the normal flat lining of the lower oesophagus is replaced by a gland-type lining like the intestine's, which resists acid better. It causes no symptoms itself but is the main precursor of oesophageal adenocarcinoma, so it is watched with periodic endoscopy.","evidence":"Established: found in a minority of people with long-standing reflux. Most people with Barrett's never develop cancer; the yearly risk is low.","pos":[0.02,1.24,-0.015]},{"id":"pancreatitis","col":"x","group":"Digestive & liver","name":"Pancreatitis","sub":"acute and chronic","how":"Digestive enzymes that should only switch on in the gut become active inside the pancreas and start digesting it, causing inflammation. Acute attacks are most often set off by a gallstone blocking the shared bile and pancreatic duct opening, or by heavy drinking, and cause severe upper belly pain going through to the back. Repeated injury (mostly alcohol and smoking) leads to chronic pancreatitis, which scars the gland and slowly destroys its enzyme- and insulin-making cells.","evidence":"Established. Most acute attacks settle with hospital care; removing the gallbladder after gallstone pancreatitis prevents further attacks.","pos":[0.025,1.09,0]},{"id":"diverticular_disease","col":"x","group":"Digestive & liver","name":"Diverticular disease","sub":"diverticulosis and diverticulitis","how":"Small pouches (diverticula) bulge out through weak spots in the wall of the colon, most often the S-shaped sigmoid colon low on the left, and become common with age. Most people never notice them. If one becomes inflamed or infected (diverticulitis) it causes pain low on the left, fever and sometimes an abscess, bleeding or a hole.","evidence":"Established. Higher fibre intake is linked with less diverticular disease needing hospital care in cohort studies.","pos":[0.08,0.92,0.02]},{"id":"peptic_ulcer","col":"x","group":"Digestive & liver","name":"Peptic ulcer","sub":"stomach and duodenal ulcers","how":"An open sore in the lining of the stomach or duodenum where acid and digestive enzymes eat through the protective mucus layer. Most are caused by H. pylori infection or by anti-inflammatory painkillers (NSAIDs such as ibuprofen, and aspirin), which weaken the lining's defences. Ulcers can bleed (black stools, vomiting blood) or, rarely, perforate.","evidence":"Established. Clearing H. pylori heals ulcers and stops most from coming back; acid-suppressing medicines heal them.","pos":[-0.02,1.12,0.03]},{"id":"trigeminal_neuralgia","col":"x","group":"Nerve conditions","name":"Trigeminal neuralgia","sub":"electric-shock face pain","how":"Brief, severe, electric-shock-like stabs of pain in one side of the face, in the area of one or two trigeminal nerve branches, set off by light touch, chewing, talking, brushing teeth or a breeze. Usually from an artery pressing on the nerve root where it leaves the brainstem, wearing away its insulation; sometimes from multiple sclerosis or a tumour. Between attacks the face is normal.","evidence":"The 2019 European guideline recommends an MRI scan to find the cause, anti-seizure medicines (carbamazepine or oxcarbazepine) as first treatment, and surgery to move the pressing artery for suitable people whose pain is not controlled."},{"id":"bells_palsy","col":"x","group":"Nerve conditions","name":"Bell's palsy","sub":"sudden one-sided facial weakness","how":"Sudden weakness of all the muscles on one side of the face over a day or two, from swelling of the facial nerve inside its narrow bony canal (often thought to follow a viral infection). The eye cannot close, the mouth droops, and there may be pain behind the ear, altered taste and sensitivity to loud sound. Most people recover fully within weeks to months. Weakness that spares the forehead, other new symptoms, or a slow onset point to another cause such as a stroke and need urgent care.","evidence":"A short course of steroid tablets started within three days improves the chance of full recovery in randomised trials; adding antiviral medicines has uncertain extra benefit. Protecting the eye while it cannot close matters."},{"id":"shingles","col":"x","group":"Nerve conditions","name":"Shingles (herpes zoster)","sub":"reactivated chickenpox virus in a nerve","how":"The chickenpox virus, asleep for decades in a sensory nerve ganglion, wakes up (more often with age or weakened immunity) and travels down that one nerve to the skin: burning pain, then a band of blisters on one side in one or two dermatomes, most often around the chest (intercostal nerves) or over the forehead and eye (the trigeminal nerve, which can threaten sight). In the ear it can paralyse the facial nerve (Ramsay Hunt syndrome). Pain lasting months after the rash has healed is postherpetic neuralgia.","evidence":"Vaccination prevents most shingles in randomised trials, including in older adults."},{"id":"cubital_tunnel","col":"x","group":"Nerve conditions","name":"Cubital tunnel syndrome","sub":"ulnar nerve squeezed at the elbow","how":"The ulnar nerve is pressed or stretched where it runs behind the inner elbow, especially when the elbow is bent for long periods (phones, sleeping with arms bent, leaning on the elbow). Tingling and numbness in the little and ring fingers, then clumsy, weak hand muscles.","evidence":"The second most common nerve entrapment after carpal tunnel. A 2025 Cochrane review of 15 trials found simple surgical release works about as well as moving the nerve (transposition) and endoscopic as well as open surgery; evidence on splints and other non-surgical treatments was limited."},{"id":"guillain_barre","col":"x","group":"Nerve conditions","name":"Guillain–Barré syndrome","sub":"immune attack on the nerves after an infection","how":"An uncommon condition in which the immune system, often a few weeks after a gut or chest infection, attacks the peripheral nerves and their roots. Tingling in the feet and hands is followed over days to a few weeks by rising weakness of the legs, arms, face and sometimes the breathing and swallowing muscles, with swings in heart rate and blood pressure. It can need intensive care. Most people recover over months, but some are left with weakness or fatigue.","evidence":"Plasma exchange and intravenous immunoglobulin each speed recovery in randomised trials and work about equally well; steroids alone do not help. Infection with Campylobacter (a cause of food poisoning) is a well-documented trigger."},{"id":"acne","col":"x","group":"Skin conditions","name":"Acne","sub":"acne vulgaris","how":"Blocked, inflamed hair follicles on the face, chest and upper back. Oil production rises at puberty, the follicle opening plugs with skin cells and oil, the bacteria normally living in the follicle multiply in that oily plug, and the wall inflames.","evidence":"The follicle bacteria are part of the picture, but everyone carries them; which strains and how the skin reacts matter more, so the microbe link is an association rather than a cause.","pos":[0,1.69,0.075]},{"id":"seborrhoeic_dermatitis","col":"x","group":"Skin conditions","name":"Dandruff & seborrhoeic dermatitis","sub":"","how":"Flaking, itching and redness on the scalp, eyebrows and sides of the nose, where the skin is oiliest. The yeast Malassezia lives on those oils and its breakdown products irritate the skin of susceptible people.","evidence":"Malassezia is found on everyone, so it is a susceptibility problem rather than an infection; antifungal treatment helping is the main argument for its role.","pos":[0,1.73,0.02]},{"id":"pneumonia_infection","col":"x","group":"Infections","name":"Pneumonia (lung infection)","sub":"community-acquired pneumonia","how":"An infection of the air sacs (alveoli), which fill with fluid and pus so less oxygen gets in. Caused by bacteria (pneumococcus most often), viruses (flu, RSV, SARS-CoV-2) and, with weak immunity, fungi. Fever, cough, breathlessness and chest pain; in older people sometimes only confusion. Risk rises with age, smoking, lung and heart disease, diabetes and weak immunity.","evidence":"Established (textbook). A leading cause of death worldwide at both ends of life."},{"id":"gastroenteritis","col":"x","group":"Infections","name":"Gastroenteritis (stomach bug)","sub":"infectious diarrhoea and vomiting","how":"An infection of the stomach and intestine lining by viruses (norovirus, rotavirus), bacteria (Campylobacter, Salmonella, E. coli) or parasites (Giardia, Cryptosporidium), usually spread by the faecal-oral route through hands, food and water. The main danger is losing water and salts (dehydration), especially in babies and older people.","evidence":"Established (textbook). Hand washing and safe water prevent many cases in trials."},{"id":"meningitis","col":"x","group":"Infections","name":"Meningitis","sub":"infection of the brain and spinal cord coverings","how":"Inflammation of the membranes (meninges) around the brain and spinal cord. Viral meningitis (enteroviruses, herpes viruses) is usually mild; bacterial meningitis (meningococcus, pneumococcus, Hib, Listeria) can kill within hours. Signs: fever, severe headache, stiff neck, light sensitivity, drowsiness; with meningococcus a rash that does not fade when pressed.","evidence":"Established (textbook). Vaccines have greatly reduced bacterial meningitis.","pos":[0,1.72,0]},{"id":"encephalitis","col":"x","group":"Infections","name":"Encephalitis","sub":"inflammation of the brain itself","how":"Inflammation of the brain tissue, most often from viruses (herpes simplex, mosquito- and tick-borne viruses, rabies) or from the immune system attacking the brain. Fever, confusion, behaviour change, seizures and drowsiness; survivors may have lasting memory problems.","evidence":"Established (textbook). Association: viral encephalitis was the exposure most strongly linked with later Alzheimer's disease in national biobanks (Levine 2023).","pos":[0,1.66,0]},{"id":"congenital_infection","col":"x","group":"Infections","name":"Infections passed to the unborn baby","sub":"TORCH and Zika","how":"Some infections cross the placenta and harm the developing baby: toxoplasma, rubella, cytomegalovirus, herpes, syphilis, Zika and parvovirus. Effects range from miscarriage to deafness, eye damage, small head (microcephaly) and learning disability.","evidence":"Established (textbook). Congenital cytomegalovirus is the commonest infectious cause of childhood deafness."},{"id":"sepsis","col":"x","group":"Infections","name":"Sepsis","sub":"blood poisoning","how":"A life-threatening reaction in which the body's response to an infection (often lung, urine, gut or skin) starts damaging its own organs: blood pressure falls, the kidneys, lungs and brain fail, and blood clotting goes wrong. Signs include fever or low temperature, fast breathing and heart rate, confusion, mottled skin and passing little urine. Risk is highest at the extremes of age, with diabetes, cancer, weak immunity and without a spleen.","evidence":"Established (textbook). Association: survivors often have lasting memory and thinking problems (Iwashyna 2010)."},{"id":"neurocysticercosis","col":"x","group":"Infections","name":"Neurocysticercosis","sub":"pork tapeworm cysts in the brain","how":"When a person swallows pork tapeworm eggs (from food, water or hands contaminated by a tapeworm carrier's stool, not from eating pork itself), the larvae form cysts in the brain. As the cysts die they inflame the surrounding brain and can cause seizures, headache and raised brain pressure.","evidence":"Established: the leading preventable cause of adult-onset epilepsy worldwide (WHO)."}],"edges":[{"from":"levodopa","to":"m_dopa","level":"established","effect":"helps","note":"Converted to dopamine by AADC in the brain."},{"from":"caffeine","to":"m_aden","level":"established","effect":"helps","note":"Blocks A1 and A2A adenosine receptors."},{"from":"sulforaphane","to":"m_nrf2","level":"mixed","effect":"helps","note":"Turns on protective genes in some small human trials but not in the largest placebo-controlled one; no Parkinson's outcome yet.","sources":[{"id":"pmid:27832073","citation":"Wise RA et al., PLoS One","year":2016,"design":"RCT","finding":"In 89 people with COPD, four weeks of oral sulforaphane at two doses did not raise Nrf2 target genes (NQO1, HO-1, AKR1C1/3) in lung cells versus placebo, though it was absorbed."},{"id":"pmid:19028145","citation":"Riedl MA et al., Clin Immunol","year":2009,"design":"RCT","finding":"In a small placebo-controlled dose-escalation study, broccoli sprout sulforaphane raised Phase II enzyme RNA (NQO1, HO-1, GSTs) in nasal cells; alfalfa sprouts did not."},{"id":"pmid:38772511","citation":"Ribeiro M et al., Free Radic Biol Med","year":2024,"design":"RCT","finding":"In non-dialysis kidney-disease patients, one month of sulforaphane raised NRF2 and NQO1 mRNA versus placebo."}]},{"from":"quercetin","to":"m_nrf2","level":"lab","effect":"helps","note":"Weak Nrf2 activation in cells."},{"from":"quercetin","to":"m_inflam","level":"lab","effect":"helps","note":"Inhibits inflammatory kinases in cells."},{"from":"anthocyanins","to":"m_micro","level":"lab","effect":"helps","note":"Fermented by gut bacteria into phenolic acids; shifts microbes."},{"from":"anthocyanins","to":"m_inflam","level":"lab","effect":"helps","note":"Anti-inflammatory in cells and animals."},{"from":"fibre","to":"m_micro","level":"established","effect":"helps","note":"Fermented into butyrate and other short-chain fatty acids."},{"from":"fibre","to":"m_motility","level":"proven","effect":"helps","note":"Fibre holds water and bulks stool; fibre supplements, psyllium most of all, eased chronic constipation in pooled trials.","sources":[{"id":"pmid:35816465","citation":"van der Schoot A et al., Am J Clin Nutr","year":2022,"design":"meta-analysis","finding":"Meta-analysis of RCTs in adults with chronic constipation: fibre supplements improved treatment response, stool frequency and consistency, with psyllium most effective."}]},{"from":"kiwi","to":"m_motility","level":"proven","effect":"helps","note":"Kiwifruit and prunes eased constipation in trials in people without Parkinson's; a review rated the kiwifruit evidence only low to moderate certainty.","sources":[{"id":"pmid:34074830","citation":"Chey SW et al., American Journal of Gastroenterology","year":2021,"design":"RCT","finding":"In 79 US adults with chronic constipation, 4 weeks of green kiwifruit, prunes or psyllium each increased complete bowel movements; kiwifruit and prunes also improved stool consistency and straining."},{"id":"pmid:36247043","citation":"Eltorki M et al., Canadian Journal of Gastroenterology and Hepatology","year":2022,"design":"meta-analysis","finding":"Across 7 randomised trials (399 people), kiwifruit may increase bowel movements versus placebo or psyllium, but overall certainty of evidence was low."}]},{"from":"omega3","to":"m_inflam","level":"lab","effect":"helps","note":"Converted to resolvins that end inflammation."},{"from":"omega3","to":"m_nurr1","level":"lab","effect":"helps","note":"DHA binds the Nurr1 pocket in lab experiments."},{"from":"omega3","to":"m_reward","level":"mixed","effect":"helps","note":"Depression trials mixed; one small positive Parkinson's trial."},{"from":"ergothioneine","to":"m_oxid","level":"lab","effect":"helps","note":"Antioxidant taken up by OCTN1; lower in Parkinson's blood (association)."},{"from":"egcg","to":"m_asyn","level":"failed","effect":"helps","note":"Redirects clumping in a dish; no benefit in the PROMESA trial (MSA).","sources":[{"id":"pmid:31278067","citation":"Levin J et al. (PROMESA), Lancet Neurology","year":2019,"design":"RCT","finding":"In 92 people with multiple system atrophy, 48 weeks of EGCG did not slow worsening of movement scores versus placebo, and some had liver toxicity."}]},{"from":"curcumin","to":"m_asyn","level":"lab","effect":"helps","note":"Binds clumps in a dish; barely reaches spinal fluid."},{"from":"curcumin","to":"m_inflam","level":"proven","effect":"helps","note":"Turmeric and curcumin supplements lowered blood markers of inflammation (CRP, TNF, IL-6) in pooled trials; so little reaches the brain that effects on brain inflammation are untested.","sources":[{"id":"pmid:36804260","citation":"Dehzad MJ et al., Cytokine","year":2023,"design":"meta-analysis","finding":"Across 66 randomised trials, turmeric/curcumin supplements lowered CRP, TNF-alpha and IL-6 (but not IL-1beta) and improved blood antioxidant markers."},{"id":"pmid:38561618","citation":"Hosseini H et al., Current Medicinal Chemistry","year":2025,"design":"meta-analysis","finding":"Across 13 randomised trials, curcumin taken with piperine lowered TNF-alpha, IL-6 and the oxidation marker MDA and raised SOD and glutathione."}]},{"from":"resveratrol","to":"m_oxid","level":"lab","effect":"helps","note":"SIRT1/AMPK and antioxidant effects in cells."},{"from":"olive","to":"m_inflam","level":"lab","effect":"helps","note":"Oleocanthal weakly blocks COX enzymes."},{"from":"olive","to":"m_oxid","level":"lab","effect":"helps","note":"Hydroxytyrosol scavenges radicals."},{"from":"nightshade","to":"m_dopa","level":"failed","effect":"helps","note":"Nicotine boosts dopamine release, but nicotine patches did not slow Parkinson's (NIC-PD). Peppers and risk: association only.","sources":[{"id":"pmid:38320207","citation":"Oertel WH et al. (NIC-PD), NEJM Evidence","year":2023,"design":"RCT","finding":"In 163 people with early Parkinson's, one year of nicotine patches did not slow progression compared with placebo."}]},{"from":"protein","to":"m_absorb","level":"established","effect":"harms","note":"A protein-rich meal close to a levodopa dose can slow and blunt it; moving protein away from doses helped some people, but controlled tests disagree, and total protein should not be cut.","scope":["parkinsons"],"sources":[{"id":"pmid:20669318","citation":"Cereda E et al., Mov Disord","year":2010,"design":"review","finding":"Systematic review of 16 heterogeneous, mostly uncontrolled studies: no support for low-protein diets; protein redistribution improved motor function on average but with complications and declining adherence."},{"id":"pmid:37355689","citation":"Rusch C et al., NPJ Parkinsons Dis","year":2023,"design":"review","finding":"Low-protein and redistribution diets are often recommended, but there is a paucity of high-level evidence and no standard definition of the diets."},{"id":"pmid:2049250","citation":"Robertson DR et al., Br J Clin Pharmacol","year":1991,"design":"pharmacokinetic study (8 healthy volunteers)","finding":"In eight healthy volunteers, a 30.5 g protein meal did not impair the rate or extent of levodopa absorption compared with fasting."},{"id":"pmid:36786430","citation":"Pinelli G et al., Int J Neurosci","year":2024,"design":"RCT","finding":"In a randomised single-blind study of 51 people with Parkinson's, twice-daily whey protein for 28 days did not worsen motor scores or levodopa response compared with magnesium."},{"id":"pmid:6694694","citation":"Nutt JG et al., N Engl J Med","year":1984,"design":"small human experiment","finding":"In people with Parkinson's and on-off swings, meals cut peak plasma levodopa by 29% and delayed its absorption; large neutral amino acids blunted the response to levodopa."}]},{"from":"melatonin","to":"m_clock","level":"established","effect":"helps","note":"Acts on MT1/MT2 clock receptors."},{"from":"magnesium","to":"m_motility","level":"proven","effect":"helps","note":"Magnesium taken as a laxative draws water into the bowel and eased constipation in trials; the amount in food does not act as a laxative.","dose":"excess","sources":[{"id":"pmid:31587548","citation":"Mori S et al., Journal of Neurogastroenterology and Motility","year":2019,"design":"RCT","finding":"In 34 women with mild to moderate chronic constipation, magnesium oxide for 4 weeks improved overall symptoms (71% vs 25%), bowel-movement frequency, stool form and colon transit time versus placebo."},{"id":"pmid:32969946","citation":"Morishita D et al., American Journal of Gastroenterology","year":2021,"design":"RCT","finding":"In 90 people with chronic constipation, magnesium oxide (like senna) improved overall symptoms (68% vs 12% on placebo), bowel-movement frequency and quality of life over 28 days."}]},{"from":"b12","to":"m_methyl","level":"established","effect":"helps","note":"Recycles homocysteine to methionine.","dose":"deficiency"},{"from":"vitd","to":"m_bone","level":"established","effect":"helps","note":"Raises calcium absorption; supports bone and muscle when deficient.","dose":"deficiency"},{"from":"probiotics","to":"m_motility","level":"proven","effect":"helps","note":"More complete bowel movements in two Parkinson's trials.","sources":[{"id":"pmid:27543643","citation":"Barichella M et al., Neurology","year":2016,"design":"RCT","finding":"In 120 people with Parkinson's and constipation, fermented milk with probiotics and prebiotic fibre increased complete bowel movements versus placebo over 4 weeks."},{"id":"pmid:33046607","citation":"Tan AH et al., Neurology","year":2021,"design":"RCT","finding":"In 72 people with Parkinson's, multistrain probiotic capsules increased spontaneous bowel movements and improved stool consistency versus placebo over 4 weeks."}]},{"from":"probiotics","to":"m_micro","level":"association","effect":"helps","note":"Temporarily shifts the gut community."},{"from":"exercise","to":"m_plastic","level":"proven","effect":"helps","note":"Exercise programmes improved movement scores in Parkinson's trials, most with dance and gait and balance training; the brain changes behind this are less certain.","sources":[{"id":"pmid:38588457","citation":"Ernst M et al., Cochrane Database Syst Rev","year":2024,"design":"meta-analysis","finding":"Network meta-analysis of 154 RCTs in Parkinson's: dance and gait/balance/functional training probably improve motor signs moderately (moderate confidence); most other exercise types small benefit."}]},{"from":"exercise","to":"m_reward","level":"proven","effect":"helps","note":"Exercise lowered depression symptoms in many trials, about as much as talking therapy, though most trials were small and of low quality.","sources":[{"id":"pmid:41500513","citation":"Clegg AJ et al., Cochrane Database Syst Rev","year":2026,"design":"meta-analysis","finding":"73 RCTs in adults with depression: exercise may reduce depressive symptoms versus control (low certainty) and probably works about as well as psychological therapy (moderate certainty)."},{"id":"pmid:38355154","citation":"Noetel M et al., BMJ","year":2024,"design":"meta-analysis","finding":"Network meta-analysis of 218 RCTs in major depression: walking or jogging, yoga and strength training reduced depression compared with active controls."}]},{"from":"exercise","to":"m_motility","level":"association","effect":"helps","note":"Movement stimulates gut transit."},{"from":"exercise","to":"m_bp","level":"association","effect":"helps","note":"Leg muscle pump and blood volume."},{"from":"exercise","to":"m_clock","level":"association","effect":"helps","note":"Daytime activity strengthens the rhythm and sleep pressure."},{"from":"exercise","to":"m_bone","level":"established","effect":"helps","note":"Load builds bone and muscle."},{"from":"fluids","to":"m_bp","level":"established","effect":"helps","note":"Raises blood volume and standing pressure."},{"from":"fluids","to":"m_motility","level":"established","effect":"helps","note":"Softer stool."},{"from":"light","to":"m_clock","level":"established","effect":"helps","note":"Bright light reaching the eyes is the main signal that sets the body clock each day (textbook physiology); whether light therapy improves sleep in Parkinson's is less certain.","sources":[{"id":"pmid:28241159","citation":"Videnovic A et al., JAMA Neurology","year":2017,"design":"RCT","finding":"In 31 people with Parkinson's and daytime sleepiness, bright light therapy for 2 weeks lowered Epworth sleepiness scores compared with dim red light."},{"id":"pmid:40913446","citation":"Videnovic A et al. (ENLITE-PD), Movement Disorders","year":2025,"design":"RCT","finding":"In 150 people with Parkinson's, twice-daily bright light improved sleep scores, but the gain over dim red light was too small to justify a phase 3 trial."}]},{"from":"voice","to":"m_plastic","level":"proven","effect":"helps","note":"Recalibrates movement size and loudness.","sources":[{"id":"pmid:30264896","citation":"Ramig L et al., Movement Disorders","year":2018,"design":"RCT","finding":"In Parkinson's, LSVT LOUD raised speech loudness more than articulation therapy or no treatment at 1 and 7 months."}]},{"from":"social","to":"m_reward","level":"association","effect":"helps","note":"Company and conversation engage mood circuits."},{"from":"social","to":"m_plastic","level":"association","effect":"helps","note":"Daily speech practice."},{"from":"m_nrf2","to":"m_oxid","level":"established","effect":"helps","note":"Nrf2 genes make glutathione and detox enzymes."},{"from":"m_micro","to":"m_barrier","level":"established","effect":"helps","note":"Butyrate fuels the lining and tight junctions."},{"from":"m_barrier","to":"m_inflam","level":"association","effect":"helps","note":"Leaky gut lets bacterial products reach immune cells."},{"from":"m_motility","to":"m_absorb","level":"established","effect":"helps","note":"A slow tract delays levodopa reaching the small intestine."},{"from":"m_dopa","to":"movement","level":"proven","effect":"helps","note":"Levodopa restores movement.","scope":["parkinsons","lewy","msa"],"sources":[{"id":"pmid:15590952","citation":"Fahn S et al. (ELLDOPA), N Engl J Med","year":2004,"design":"RCT","finding":"In early Parkinson's, parkinsonism (UPDRS) worsened 7.8 points on placebo over 42 weeks versus 1.9 to -1.4 points on levodopa, dose-dependently."}]},{"from":"m_dopa","to":"off","level":"proven","effect":"helps","note":"Dose timing and steady delivery (including pumps) shorten OFF time.","scope":["parkinsons"],"sources":[{"id":"pmid:24361112","citation":"Olanow CW et al., Lancet Neurology","year":2014,"design":"RCT","finding":"Double-blind, double-dummy trial: continuous levodopa-carbidopa intestinal gel cut OFF time by about 1.9 hours a day more than oral immediate-release levodopa."},{"id":"pmid:36402160","citation":"Soileau MJ et al., Lancet Neurology","year":2022,"design":"RCT","finding":"Double-blind phase 3 trial: continuous subcutaneous foslevodopa-foscarbidopa cut OFF time by about 1.8 hours a day more than oral levodopa-carbidopa."}]},{"from":"m_dopa","to":"insomnia","level":"established","effect":"helps","note":"Night-time dopamine helps turning over in bed.","scope":["parkinsons"]},{"from":"m_dopa","to":"apathy","level":"mixed","effect":"helps","note":"Sometimes improves with dopamine treatment.","scope":["parkinsons"]},{"from":"m_dopa","to":"oh","level":"established","effect":"harms","note":"Levodopa can lower blood pressure.","scope":["parkinsons","lewy"]},{"from":"m_absorb","to":"off","level":"established","effect":"helps","note":"Late or blocked absorption causes delayed ON and dose failure.","scope":["parkinsons"]},{"from":"m_aden","to":"movement","level":"mixed","effect":"helps","note":"Prescription A2A blocker helps as add-on; caffeine itself no lasting benefit.","scope":["parkinsons"]},{"from":"m_aden","to":"sleepy","level":"mixed","effect":"helps","note":"Caffeine eased sleepiness modestly at best in trials."},{"from":"m_aden","to":"insomnia","level":"established","effect":"harms","note":"Caffeine late in the day disrupts night sleep."},{"from":"m_aden","to":"progression","level":"association","effect":"helps","note":"Coffee drinkers have lower risk; cause not shown."},{"from":"m_oxid","to":"progression","level":"lab","effect":"helps","note":"Antioxidant supplements (e.g. CoQ10, vitamin E) failed to slow it in trials."},{"from":"m_asyn","to":"progression","level":"lab","effect":"helps","note":"Clumping drives spread in models; no food compound has changed it in people."},{"from":"m_inflam","to":"progression","level":"lab","effect":"helps","note":"Inflammation is present; slowing by anti-inflammatories not shown."},{"from":"m_inflam","to":"fatigue","level":"association","effect":"helps","note":"Cytokines signal fatigue to the brain."},{"from":"m_inflam","to":"depression","level":"association","effect":"helps","note":"Inflammation is linked to low mood."},{"from":"m_nurr1","to":"progression","level":"lab","effect":"helps","note":"Nurr1 activation protects neurons in animals."},{"from":"m_micro","to":"constipation","level":"association","effect":"helps","note":"Microbe changes go with constipation; cause and effect run both ways."},{"from":"m_motility","to":"constipation","level":"proven","effect":"helps","note":"Faster, softer transit relieves constipation.","sources":[{"id":"pmid:27543643","citation":"Barichella M et al., Neurology","year":2016,"design":"RCT","finding":"In 120 people with Parkinson's and constipation, fermented milk with probiotics and prebiotic fibre increased complete bowel movements versus placebo over 4 weeks."},{"id":"pmid:33046607","citation":"Tan AH et al., Neurology","year":2021,"design":"RCT","finding":"In 72 people with Parkinson's, multistrain probiotic capsules increased spontaneous bowel movements and improved stool consistency versus placebo over 4 weeks."}]},{"from":"m_clock","to":"insomnia","level":"mixed","effect":"helps","note":"Clock signals help sleep onset modestly."},{"from":"m_clock","to":"rbd","level":"mixed","effect":"helps","note":"Melatonin for dream enactment: conflicting trials.","scope":["parkinsons","lewy","msa"]},{"from":"m_clock","to":"sleepy","level":"mixed","effect":"helps","note":"Light therapy reduced daytime sleepiness in two small Parkinson's trials, but a larger trial did not show a clear difference.","scope":["parkinsons"],"sources":[{"id":"pmid:28241159","citation":"Videnovic A et al., JAMA Neurology","year":2017,"design":"RCT","finding":"In 31 people with Parkinson's and daytime sleepiness, bright light therapy for 2 weeks lowered Epworth sleepiness scores compared with dim red light."},{"id":"pmid:40903343","citation":"Wyman BT et al., Neurotherapeutics","year":2025,"design":"RCT","finding":"In 92 people with Parkinson's, 6 months of evening circadian light therapy gave a non-significant trend on the main symptom score and on daytime sleepiness (Epworth, p=0.054), and no difference in disturbed sleep."},{"id":"pmid:40913446","citation":"Videnovic A et al. (ENLITE-PD), Movement Disorders","year":2025,"design":"RCT","finding":"In 150 people with Parkinson's, twice-daily bright light improved sleep scores, but the gain over dim red light was too small to justify a phase 3 trial."},{"id":"pmid:42558005","citation":"Smilowska K et al., Journal of Parkinson's Disease","year":2026,"design":"RCT","finding":"In a 30-person single-blind pilot, blue light through LED glasses twice daily for 2 weeks improved sleep quality and daytime sleepiness versus red light."}]},{"from":"m_methyl","to":"neuropathy","level":"established","effect":"helps","note":"Low B12 and high homocysteine damage nerves."},{"from":"m_methyl","to":"cognition","level":"association","effect":"helps","note":"High homocysteine is linked to worse cognition."},{"from":"m_bp","to":"oh","level":"established","effect":"helps","note":"More volume and muscle pump support standing pressure."},{"from":"m_bp","to":"falls","level":"association","effect":"helps","note":"Fewer faints and near-falls."},{"from":"m_plastic","to":"movement","level":"proven","effect":"helps","note":"Training improves walking speed and movement size.","sources":[{"id":"pmid:38588457","citation":"Ernst M et al., Cochrane Database Syst Rev","year":2024,"design":"meta-analysis","finding":"Network meta-analysis of 154 RCTs in Parkinson's: dance and gait/balance/functional training probably improve motor signs moderately (moderate confidence); most other exercise types small benefit."}]},{"from":"m_plastic","to":"falls","level":"proven","effect":"helps","note":"Balance training reduces falls.","sources":[{"id":"pmid:35665915","citation":"Allen NE et al., Cochrane Database of Systematic Reviews","year":2022,"design":"meta-analysis","finding":"Across 12 trials in mild to moderate Parkinson's, exercise probably reduces the rate of falls by about a quarter (moderate-certainty evidence)."}]},{"from":"m_plastic","to":"speech","level":"proven","effect":"helps","note":"Voice therapy raises loudness.","sources":[{"id":"pmid:30264896","citation":"Ramig L et al., Movement Disorders","year":2018,"design":"RCT","finding":"In people with Parkinson's, one month of LSVT LOUD voice therapy raised speech loudness more than articulation therapy or no treatment, with gains lasting to 7 months."}]},{"from":"m_plastic","to":"swallow","level":"association","effect":"helps","note":"Swallowing exercises; smaller evidence."},{"from":"m_plastic","to":"cognition","level":"association","effect":"helps","note":"Activity is linked to better thinking."},{"from":"m_reward","to":"depression","level":"association","effect":"helps","note":"Mood circuits engaged by activity and company."},{"from":"m_reward","to":"apathy","level":"association","effect":"helps","note":"Engagement counters loss of drive."},{"from":"m_bone","to":"fracture","level":"established","effect":"helps","note":"Stronger bone and muscle, fewer fractures."},{"from":"progression","to":"movement","level":"established","effect":"harms","note":"Dopamine loss in the striatum."},{"from":"progression","to":"off","level":"established","effect":"harms","note":"Fewer terminals to buffer dopamine."},{"from":"progression","to":"constipation","level":"established","effect":"harms","note":"Pathology in gut nerves and the vagus."},{"from":"progression","to":"smell","level":"established","effect":"harms","note":"Pathology in the olfactory bulb."},{"from":"progression","to":"rbd","level":"established","effect":"harms","note":"Pathology in REM-atonia circuits."},{"from":"progression","to":"oh","level":"established","effect":"harms","note":"Sympathetic nerve loss."},{"from":"progression","to":"depression","level":"established","effect":"harms","note":"Serotonin and noradrenaline nuclei degenerate."},{"from":"progression","to":"cognition","level":"established","effect":"harms","note":"Cholinergic and cortical pathology."},{"from":"progression","to":"bladder","level":"established","effect":"harms","note":"Lost basal-ganglia control of the bladder reflex."},{"from":"movement","to":"speech","level":"established","effect":"harms","note":"The same shrinking of movement."},{"from":"movement","to":"swallow","level":"established","effect":"harms","note":"Slower, weaker swallowing movements."},{"from":"movement","to":"falls","level":"association","effect":"harms","note":"Shuffling and freezing."},{"from":"stomach","to":"off","level":"established","effect":"harms","note":"A dose stuck in the stomach arrives late."},{"from":"constipation","to":"off","level":"association","effect":"harms","note":"A slow gut means erratic levodopa.","scope":["parkinsons"]},{"from":"constipation","to":"nutrition","level":"association","effect":"harms","note":"Fullness and discomfort reduce eating."},{"from":"off","to":"anxiety","level":"association","effect":"harms","note":"Unpredictable OFF periods are frightening."},{"from":"anxiety","to":"off","level":"association","effect":"harms","note":"Stress worsens tremor and freezing.","scope":["parkinsons"]},{"from":"off","to":"falls","level":"association","effect":"harms","note":"Falls cluster in OFF time."},{"from":"off","to":"pain","level":"established","effect":"harms","note":"OFF dystonia and cramps."},{"from":"off","to":"insomnia","level":"established","effect":"harms","note":"Unable to turn over at night."},{"from":"pain","to":"insomnia","level":"association","effect":"harms","note":"Pain wakes people."},{"from":"bladder","to":"insomnia","level":"established","effect":"harms","note":"Getting up to urinate."},{"from":"bladder","to":"dehydration","level":"association","effect":"harms","note":"People drink less to avoid urgency."},{"from":"dehydration","to":"constipation","level":"established","effect":"harms","note":"Less water, harder stool."},{"from":"dehydration","to":"oh","level":"established","effect":"harms","note":"Less blood volume."},{"from":"oh","to":"falls","level":"established","effect":"harms","note":"Fainting and dizziness."},{"from":"oh","to":"fatigue","level":"association","effect":"harms","note":"Low brain blood flow when upright."},{"from":"oh","to":"cognition","level":"association","effect":"harms","note":"Thinking dips when pressure falls."},{"from":"insomnia","to":"sleepy","level":"established","effect":"harms","note":"Sleep debt."},{"from":"insomnia","to":"fatigue","level":"association","effect":"harms","note":"Unrefreshing nights."},{"from":"insomnia","to":"depression","level":"association","effect":"harms","note":"Poor sleep and low mood feed each other."},{"from":"insomnia","to":"cognition","level":"association","effect":"harms","note":"Sleep is needed for attention and memory."},{"from":"rbd","to":"insomnia","level":"association","effect":"harms","note":"Injury and broken sleep for both partners."},{"from":"fatigue","to":"inactivity","level":"association","effect":"harms","note":"Too tired to move."},{"from":"depression","to":"inactivity","level":"association","effect":"harms","note":"Low drive."},{"from":"depression","to":"insomnia","level":"association","effect":"harms","note":"Early waking, fragmented sleep."},{"from":"depression","to":"fatigue","level":"association","effect":"harms","note":"Low energy."},{"from":"depression","to":"isolation","level":"association","effect":"harms","note":"Withdrawal."},{"from":"apathy","to":"inactivity","level":"association","effect":"harms","note":"Loss of drive."},{"from":"falls","to":"inactivity","level":"association","effect":"harms","note":"Fear of falling."},{"from":"falls","to":"fracture","level":"established","effect":"harms","note":"Hip and wrist fractures."},{"from":"inactivity","to":"movement","level":"association","effect":"harms","note":"Deconditioning worsens slowness and stiffness."},{"from":"inactivity","to":"constipation","level":"association","effect":"harms","note":"Less movement, slower gut."},{"from":"inactivity","to":"depression","level":"association","effect":"harms","note":"Less activity, lower mood."},{"from":"inactivity","to":"fracture","level":"established","effect":"harms","note":"Unloaded bone thins."},{"from":"inactivity","to":"oh","level":"association","effect":"harms","note":"Deconditioning weakens the muscle pump."},{"from":"inactivity","to":"insomnia","level":"association","effect":"harms","note":"Less sleep pressure by night."},{"from":"speech","to":"isolation","level":"association","effect":"harms","note":"Hard to be heard in a group."},{"from":"isolation","to":"depression","level":"association","effect":"harms","note":"Loneliness lowers mood."},{"from":"isolation","to":"inactivity","level":"association","effect":"harms","note":"Fewer reasons to go out."},{"from":"swallow","to":"pneumonia","level":"established","effect":"harms","note":"Food or saliva entering the airway."},{"from":"swallow","to":"nutrition","level":"association","effect":"harms","note":"Eating becomes slow and tiring."},{"from":"smell","to":"nutrition","level":"association","effect":"harms","note":"Food loses its appeal."},{"from":"nutrition","to":"fracture","level":"association","effect":"harms","note":"Low weight and nutrients thin bone."},{"from":"cognition","to":"falls","level":"association","effect":"harms","note":"Divided attention while walking."},{"from":"neuropathy","to":"falls","level":"association","effect":"harms","note":"Poor sense of foot position."},{"from":"broccsprouts","to":"sulforaphane","level":"established","effect":"contains","note":"Richest source of glucoraphanin, many times more than mature broccoli. Chew raw or lightly cooked."},{"from":"brassicas","to":"sulforaphane","level":"established","effect":"contains","note":"Less than sprouts; heavy cooking destroys the enzyme that makes it."},{"from":"brassicas","to":"fibre","level":"established","effect":"contains","note":"Fibre."},{"from":"brassicas","to":"quercetin","level":"established","effect":"contains","note":"Kale carries quercetin."},{"from":"redcabbage","to":"anthocyanins","level":"established","effect":"contains","note":"The red-purple pigment."},{"from":"redcabbage","to":"sulforaphane","level":"established","effect":"contains","note":"A crucifer: some glucoraphanin."},{"from":"onions","to":"quercetin","level":"established","effect":"contains","note":"Among the richest sources; capers are higher still."},{"from":"onions","to":"fibre","level":"established","effect":"contains","note":"Inulin-type fibre."},{"from":"greens","to":"magnesium","level":"established","effect":"contains","note":"Magnesium sits at the centre of chlorophyll."},{"from":"greens","to":"fibre","level":"established","effect":"contains","note":"Fibre."},{"from":"mushrooms","to":"ergothioneine","level":"established","effect":"contains","note":"The richest dietary source."},{"from":"mushrooms","to":"vitd","level":"established","effect":"contains","note":"Only if grown or left under UV light."},{"from":"peppers","to":"nightshade","level":"established","effect":"contains","note":"Trace nicotine."},{"from":"tomatoes","to":"nightshade","level":"established","effect":"contains","note":"Trace nicotine."},{"from":"potatoes","to":"nightshade","level":"established","effect":"contains","note":"Trace nicotine."},{"from":"potatoes","to":"b6","level":"established","effect":"contains","note":"A main B6 source in many diets."},{"from":"eggplant","to":"nightshade","level":"established","effect":"contains","note":"Highest nicotine of common vegetables, still tiny."},{"from":"eggplant","to":"anthocyanins","level":"established","effect":"contains","note":"In the purple skin."},{"from":"berries","to":"anthocyanins","level":"established","effect":"contains","note":"Among the richest sources."},{"from":"berries","to":"fibre","level":"established","effect":"contains","note":"Fibre and seeds."},{"from":"cherries","to":"anthocyanins","level":"established","effect":"contains","note":"Dark red pigment."},{"from":"cherries","to":"melatonin","level":"established","effect":"contains","note":"Small amounts."},{"from":"grapes","to":"resveratrol","level":"established","effect":"contains","note":"In the skin; small amounts."},{"from":"grapes","to":"anthocyanins","level":"established","effect":"contains","note":"In the skin."},{"from":"grapes","to":"quercetin","level":"established","effect":"contains","note":"In the skin."},{"from":"apples","to":"quercetin","level":"established","effect":"contains","note":"Quercetin is mostly in the skin; peeled apples carry much less.","sources":[{"id":"pmid:32744555","citation":"Bondonno CP et al., Food & Function","year":2020,"design":"lab","finding":"Across 91 apple varieties, quercetin, epicatechin, procyanidin B2, phloridzin and anthocyanins were more concentrated in the skin than the flesh."}]},{"from":"apples","to":"fibre","level":"established","effect":"contains","note":"Apples carry pectin, a soluble fibre that gut bacteria ferment; clear apple juice has had it filtered out.","sources":[{"id":"pmid:23271615","citation":"Ravn-Haren G et al., European Journal of Nutrition","year":2013,"design":"RCT","finding":"Whole apples and apple pomace tended to lower LDL cholesterol while clear (pectin-free) juice raised it, pointing to the fibre as the active part."}]},{"from":"apples","to":"kiwi","level":"established","effect":"contains","note":"Apples contain sorbitol and extra fructose, both of which draw water into the bowel; less sorbitol than prunes."},{"from":"prunes","to":"kiwi","level":"established","effect":"contains","note":"Sorbitol."},{"from":"prunes","to":"fibre","level":"established","effect":"contains","note":"Fibre."},{"from":"kiwifruit","to":"kiwi","level":"established","effect":"contains","note":"Actinidin and water-holding fibre."},{"from":"kiwifruit","to":"fibre","level":"established","effect":"contains","note":"Fibre."},{"from":"bananas","to":"b6","level":"established","effect":"contains","note":"B6."},{"from":"bananas","to":"fibre","level":"established","effect":"contains","note":"Resistant starch when less ripe."},{"from":"olives","to":"olive","level":"established","effect":"contains","note":"Hydroxytyrosol and oleocanthal, highest in fresh extra-virgin oil."},{"from":"fava","to":"levodopa","level":"established","effect":"contains","note":"Variable amounts; adds to prescribed levodopa."},{"from":"fava","to":"fibre","level":"established","effect":"contains","note":"Fibre."},{"from":"fava","to":"protein","level":"established","effect":"contains","note":"Protein."},{"from":"mucuna","to":"levodopa","level":"established","effect":"contains","note":"Concentrated; behaves like the medicine without carbidopa."},{"from":"legumes","to":"fibre","level":"established","effect":"contains","note":"One of the best fibre sources."},{"from":"legumes","to":"protein","level":"established","effect":"contains","note":"Protein."},{"from":"legumes","to":"b6","level":"established","effect":"contains","note":"Chickpeas especially."},{"from":"legumes","to":"magnesium","level":"established","effect":"contains","note":"Magnesium."},{"from":"oats","to":"fibre","level":"established","effect":"contains","note":"Beta-glucan."},{"from":"oats","to":"magnesium","level":"established","effect":"contains","note":"Magnesium."},{"from":"nuts","to":"magnesium","level":"established","effect":"contains","note":"Pumpkin seeds and almonds especially."},{"from":"nuts","to":"omega3","level":"established","effect":"contains","note":"ALA in walnuts and flax; the body converts only a few percent to DHA."},{"from":"nuts","to":"protein","level":"established","effect":"contains","note":"Protein."},{"from":"peanuts","to":"resveratrol","level":"established","effect":"contains","note":"Small amounts."},{"from":"peanuts","to":"protein","level":"established","effect":"contains","note":"Protein."},{"from":"coffee","to":"caffeine","level":"established","effect":"contains","note":"The main dietary source."},{"from":"greentea","to":"caffeine","level":"established","effect":"contains","note":"Less than coffee."},{"from":"greentea","to":"egcg","level":"established","effect":"contains","note":"The main catechin."},{"from":"cocoa","to":"caffeine","level":"established","effect":"contains","note":"Small amounts, plus theobromine."},{"from":"cocoa","to":"magnesium","level":"established","effect":"contains","note":"Magnesium."},{"from":"turmeric","to":"curcumin","level":"established","effect":"contains","note":"A few percent of the spice by weight."},{"from":"algae","to":"omega3","level":"established","effect":"contains","note":"Algal oil is the plant source of DHA and EPA (fish get it from algae)."},{"from":"fermented","to":"probiotics","level":"established","effect":"contains","note":"Live cultures, if not pasteurised after fermenting."},{"from":"cannabis","to":"cannabinoids","level":"established","effect":"contains","note":"THC and CBD; legal status varies."},{"from":"fortified","to":"b12","level":"established","effect":"contains","note":"The reliable plant-based source of B12."},{"from":"b6","to":"m_excit","level":"mixed","effect":"helps","note":"Cofactor for making GABA; tried with magnesium for tics."},{"from":"magnesium","to":"m_excit","level":"mixed","effect":"helps","note":"Blocks NMDA glutamate channels; tried with B6 for tics."},{"from":"nac","to":"m_excit","level":"failed","effect":"helps","note":"Adjusts glutamate; no benefit for tics in a trial.","sources":[{"id":"pmid:27027204","citation":"Bloch MH et al., J Child Adolesc Psychopharmacol","year":2016,"design":"RCT","finding":"In 31 children with Tourette syndrome, 12 weeks of N-acetylcysteine did not reduce tic severity more than placebo."}]},{"from":"cannabinoids","to":"m_cb","level":"established","effect":"helps","note":"THC activates CB1 receptors."},{"from":"cbit","to":"m_cstc","level":"proven","effect":"helps","note":"Competing-response training strengthens control (randomised trials).","sources":[{"id":"pmid:20483969","citation":"Piacentini J et al., JAMA","year":2010,"design":"RCT","finding":"In 126 children with Tourette or chronic tic disorder, behaviour therapy (CBIT) reduced tic severity more than supportive therapy and education."},{"id":"pmid:22868933","citation":"Wilhelm S et al., Archives of General Psychiatry","year":2012,"design":"RCT","finding":"In 122 adults with Tourette or chronic tic disorder, behaviour therapy reduced tic severity more than supportive treatment."}]},{"from":"exercise","to":"m_cstc","level":"association","effect":"helps","note":"Tics drop during and after exercise in small studies."},{"from":"m_cstc","to":"tics","level":"proven","effect":"helps","note":"Training inhibitory control reduces tics (CBIT trials).","sources":[{"id":"pmid:20483969","citation":"Piacentini J et al., JAMA","year":2010,"design":"RCT","finding":"In 126 children with Tourette or chronic tic disorder, behaviour therapy (CBIT) reduced tic severity more than supportive therapy and education."},{"id":"pmid:22868933","citation":"Wilhelm S et al., Archives of General Psychiatry","year":2012,"design":"RCT","finding":"In 122 adults with Tourette or chronic tic disorder, behaviour therapy reduced tic severity more than supportive treatment."}]},{"from":"m_cstc","to":"urge","level":"association","effect":"helps","note":"The urge habituates when it passes without a tic."},{"from":"m_dopa","to":"tics","level":"mixed","effect":"harms","note":"Dopamine blockers reduce tics (proven), but raising dopamine doesn't reliably worsen them; ADHD stimulants usually don't.","scope":["tourette"]},{"from":"m_aden","to":"tics","level":"association","effect":"harms","note":"Some people report caffeine worsens their tics (surveys)."},{"from":"m_excit","to":"tics","level":"mixed","effect":"helps","note":"One small positive magnesium + B6 trial; not replicated."},{"from":"m_cb","to":"tics","level":"mixed","effect":"helps","note":"Small THC trials positive; CANNA-TICS missed its main goal."},{"from":"urge","to":"tics","level":"established","effect":"harms","note":"The tic relieves the urge, which reinforces the tic."},{"from":"tics","to":"pain","level":"association","effect":"harms","note":"Forceful neck and limb tics cause pain and injury."},{"from":"tics","to":"isolation","level":"association","effect":"harms","note":"Stigma and bullying."},{"from":"tics","to":"anxiety","level":"association","effect":"harms","note":"Worry about tics in public."},{"from":"anxiety","to":"tics","level":"association","effect":"harms","note":"Stress and anticipation make tics worse.","scope":["tourette"]},{"from":"fatigue","to":"tics","level":"association","effect":"harms","note":"Tics rise when tired.","scope":["tourette"]},{"from":"tics","to":"insomnia","level":"association","effect":"harms","note":"Tics can delay falling asleep."},{"from":"adhd","to":"isolation","level":"association","effect":"harms","note":"Social difficulties."},{"from":"adhd","to":"rage","level":"association","effect":"harms","note":"Outbursts are more common with ADHD."},{"from":"adhd","to":"insomnia","level":"association","effect":"harms","note":"Trouble settling to sleep."},{"from":"ocd","to":"anxiety","level":"association","effect":"harms","note":"Compulsions are driven by anxiety and feed it."},{"from":"rage","to":"isolation","level":"association","effect":"harms","note":"Strained relationships."},{"from":"parkinsons","to":"progression","level":"established","effect":"harms","note":"The core of the disease."},{"from":"parkinsons","to":"movement","level":"established","effect":"harms","note":"Defining movement signs."},{"from":"parkinsons","to":"off","level":"established","effect":"harms","note":"Appear with treatment as the disease progresses."},{"from":"parkinsons","to":"falls","level":"established","effect":"harms","note":"Especially in later stages."},{"from":"parkinsons","to":"speech","level":"established","effect":"harms","note":"Common."},{"from":"parkinsons","to":"swallow","level":"established","effect":"harms","note":"More common later."},{"from":"parkinsons","to":"constipation","level":"established","effect":"harms","note":"Often years before diagnosis."},{"from":"parkinsons","to":"stomach","level":"established","effect":"harms","note":"Common."},{"from":"parkinsons","to":"insomnia","level":"established","effect":"harms","note":"Very common."},{"from":"parkinsons","to":"rbd","level":"established","effect":"harms","note":"Often years before diagnosis."},{"from":"parkinsons","to":"sleepy","level":"established","effect":"harms","note":"Common."},{"from":"parkinsons","to":"fatigue","level":"established","effect":"harms","note":"Common."},{"from":"parkinsons","to":"depression","level":"established","effect":"harms","note":"In about a third or more."},{"from":"parkinsons","to":"anxiety","level":"established","effect":"harms","note":"Common."},{"from":"parkinsons","to":"apathy","level":"established","effect":"harms","note":"Common."},{"from":"parkinsons","to":"cognition","level":"established","effect":"harms","note":"Mild changes early; dementia in many after years."},{"from":"parkinsons","to":"oh","level":"established","effect":"harms","note":"Common."},{"from":"parkinsons","to":"bladder","level":"established","effect":"harms","note":"Common."},{"from":"parkinsons","to":"smell","level":"established","effect":"harms","note":"In most people, often years before diagnosis."},{"from":"parkinsons","to":"pain","level":"established","effect":"harms","note":"Common."},{"from":"parkinsons","to":"neuropathy","level":"association","effect":"harms","note":"More common with long-term levodopa."},{"from":"parkinsons","to":"inactivity","level":"association","effect":"harms","note":"Follows from the other problems."},{"from":"parkinsons","to":"dehydration","level":"association","effect":"harms","note":"Follows from urgency and swallowing."},{"from":"parkinsons","to":"isolation","level":"association","effect":"harms","note":"Follows from voice, mobility and stigma."},{"from":"parkinsons","to":"nutrition","level":"association","effect":"harms","note":"Weight loss is common."},{"from":"parkinsons","to":"fracture","level":"association","effect":"harms","note":"Higher hip-fracture rate."},{"from":"parkinsons","to":"pneumonia","level":"established","effect":"harms","note":"In advanced disease."},{"from":"tourette","to":"tics","level":"established","effect":"harms","note":"The defining feature."},{"from":"tourette","to":"urge","level":"established","effect":"harms","note":"Felt by most people with tics."},{"from":"tourette","to":"adhd","level":"established","effect":"harms","note":"In about half."},{"from":"tourette","to":"ocd","level":"established","effect":"harms","note":"In about a third to half."},{"from":"tourette","to":"rage","level":"association","effect":"harms","note":"Common, especially with ADHD or OCD."},{"from":"tourette","to":"anxiety","level":"association","effect":"harms","note":"Common."},{"from":"tourette","to":"depression","level":"association","effect":"harms","note":"More common than in the general population."},{"from":"tourette","to":"insomnia","level":"association","effect":"harms","note":"Sleep problems are common."},{"from":"tourette","to":"isolation","level":"association","effect":"harms","note":"Stigma and bullying."},{"from":"tourette","to":"pain","level":"association","effect":"harms","note":"From forceful tics."},{"from":"progression","to":"s_bg","level":"established","effect":"located","note":"Arises here."},{"from":"movement","to":"s_bg","level":"established","effect":"located","note":"Arises here."},{"from":"tremor","to":"s_bg","level":"established","effect":"located","note":"Arises here."},{"from":"tremor","to":"s_cerebellum","level":"established","effect":"located","note":"Arises here."},{"from":"off","to":"s_bg","level":"established","effect":"located","note":"Arises here."},{"from":"chorea","to":"s_bg","level":"established","effect":"located","note":"Arises here."},{"from":"falls","to":"s_bg","level":"established","effect":"located","note":"Arises here."},{"from":"falls","to":"s_brainstem","level":"established","effect":"located","note":"Arises here."},{"from":"falls","to":"s_muscle","level":"established","effect":"located","note":"Arises here."},{"from":"speech","to":"s_throat","level":"established","effect":"located","note":"Arises here."},{"from":"swallow","to":"s_throat","level":"established","effect":"located","note":"Arises here."},{"from":"swallow","to":"s_brainstem","level":"established","effect":"located","note":"Arises here."},{"from":"tics","to":"s_bg","level":"established","effect":"located","note":"Arises here."},{"from":"urge","to":"s_cortex","level":"established","effect":"located","note":"Arises here."},{"from":"rls","to":"s_bg","level":"established","effect":"located","note":"Arises here."},{"from":"rls","to":"s_spinal","level":"established","effect":"located","note":"Arises here."},{"from":"seizures","to":"s_cortex","level":"established","effect":"located","note":"Arises here."},{"from":"constipation","to":"s_gut","level":"established","effect":"located","note":"Arises here."},{"from":"stomach","to":"s_gut","level":"established","effect":"located","note":"Arises here."},{"from":"insomnia","to":"s_hypo","level":"established","effect":"located","note":"Arises here."},{"from":"insomnia","to":"s_brainstem","level":"established","effect":"located","note":"Arises here."},{"from":"rbd","to":"s_brainstem","level":"established","effect":"located","note":"Arises here."},{"from":"sleepy","to":"s_hypo","level":"established","effect":"located","note":"Arises here."},{"from":"sleepy","to":"s_brainstem","level":"established","effect":"located","note":"Arises here."},{"from":"fatigue","to":"s_limbic","level":"established","effect":"located","note":"Arises here."},{"from":"fatigue","to":"s_immune","level":"established","effect":"located","note":"Arises here."},{"from":"depression","to":"s_limbic","level":"established","effect":"located","note":"Arises here."},{"from":"anxiety","to":"s_limbic","level":"established","effect":"located","note":"Arises here."},{"from":"apathy","to":"s_limbic","level":"established","effect":"located","note":"Arises here."},{"from":"apathy","to":"s_prefrontal","level":"established","effect":"located","note":"Arises here."},{"from":"cognition","to":"s_cortex","level":"established","effect":"located","note":"Arises here."},{"from":"cognition","to":"s_prefrontal","level":"established","effect":"located","note":"Arises here."},{"from":"memory","to":"s_limbic","level":"established","effect":"located","note":"Arises here."},{"from":"memory","to":"s_cortex","level":"established","effect":"located","note":"Arises here."},{"from":"hallucinations","to":"s_cortex","level":"established","effect":"located","note":"Arises here."},{"from":"adhd","to":"s_prefrontal","level":"established","effect":"located","note":"Arises here."},{"from":"adhd","to":"s_bg","level":"established","effect":"located","note":"Arises here."},{"from":"ocd","to":"s_prefrontal","level":"established","effect":"located","note":"Arises here."},{"from":"ocd","to":"s_bg","level":"established","effect":"located","note":"Arises here."},{"from":"rage","to":"s_prefrontal","level":"established","effect":"located","note":"Arises here."},{"from":"rage","to":"s_limbic","level":"established","effect":"located","note":"Arises here."},{"from":"oh","to":"s_autonomic","level":"established","effect":"located","note":"Arises here."},{"from":"bladder","to":"s_bladder","level":"established","effect":"located","note":"Arises here."},{"from":"bladder","to":"s_autonomic","level":"established","effect":"located","note":"Arises here."},{"from":"smell","to":"s_smell","level":"established","effect":"located","note":"Arises here."},{"from":"pain","to":"s_muscle","level":"established","effect":"located","note":"Arises here."},{"from":"pain","to":"s_spinal","level":"established","effect":"located","note":"Arises here."},{"from":"neuropathy","to":"s_peripheral","level":"established","effect":"located","note":"Arises here."},{"from":"inactivity","to":"s_muscle","level":"established","effect":"located","note":"Arises here."},{"from":"dehydration","to":"s_autonomic","level":"established","effect":"located","note":"Arises here."},{"from":"nutrition","to":"s_gut","level":"established","effect":"located","note":"Arises here."},{"from":"pneumonia","to":"s_throat","level":"established","effect":"located","note":"Arises here."},{"from":"pneumonia","to":"s_immune","level":"established","effect":"located","note":"Arises here."},{"from":"iron","to":"m_iron","level":"established","effect":"helps","note":"Cofactor for making dopamine."},{"from":"iron","to":"m_absorb","level":"established","effect":"harms","note":"Binds levodopa in the gut; take apart.","dose":"timing"},{"from":"m_iron","to":"rls","level":"proven","effect":"helps","note":"Iron treatment helps restless legs when stores are low.","scope":["restless_legs"],"sources":[{"id":"pmid:30609006","citation":"Trotti LM & Becker LA, Cochrane Database Syst Rev","year":2019,"design":"meta-analysis","finding":"Across 7 placebo-controlled trials, iron improved restless legs severity (IRLS mean difference -3.78); GRADE certainty moderate."}]},{"from":"keto","to":"m_excit","level":"proven","effect":"helps","note":"Shifts the brain toward inhibition; more children with drug-resistant epilepsy had fewer seizures in trials, though the trials were unblinded and certainty is low.","sources":[{"id":"pmid:32588435","citation":"Martin-McGill KJ et al., Cochrane Database Syst Rev","year":2020,"design":"meta-analysis","finding":"In 13 RCTs (932 people), ketogenic diets raised seizure freedom and 50% seizure reduction in children with drug-resistant epilepsy versus usual care; evidence low to very low certainty."}]},{"from":"m_excit","to":"seizures","level":"established","effect":"helps","note":"The excitation–inhibition balance sets the seizure threshold."},{"from":"m_excit","to":"rls","level":"mixed","effect":"helps","note":"Magnesium is often suggested for restless legs; trials are inconclusive."},{"from":"m_dopa","to":"tremor","level":"mixed","effect":"helps","note":"Parkinson's rest tremor responds to levodopa less reliably than slowness.","scope":["parkinsons"]},{"from":"m_dopa","to":"chorea","level":"established","effect":"harms","note":"Levodopa peaks cause dyskinesia in Parkinson's.","scope":["parkinsons"]},{"from":"m_dopa","to":"hallucinations","level":"established","effect":"harms","note":"Dopamine medicines can trigger hallucinations.","scope":["parkinsons","lewy"]},{"from":"m_dopa","to":"rls","level":"proven","effect":"helps","note":"Dopamine medicines ease restless legs in short trials, but over time they can make it worse (augmentation), so a 2025 sleep-medicine guideline advises against them as standard treatment.","scope":["restless_legs"],"sources":[{"id":"pmid:21412893","citation":"Scholz H et al., Cochrane Database Syst Rev","year":2011,"design":"meta-analysis","finding":"35 placebo-controlled RCTs: dopamine agonists reduced restless legs severity short-term; augmentation, the main long-term harm, was not reliably assessed."},{"id":"pmid:39324694","citation":"Winkelman JW et al., J Clin Sleep Med (AASM guideline)","year":2025,"design":"review","finding":"Guideline suggests against standard use of levodopa, pramipexole and rotigotine for restless legs because of long-term adverse effects, particularly augmentation."}]},{"from":"m_plastic","to":"memory","level":"association","effect":"helps","note":"Physical and mental activity go with slower memory decline."},{"from":"m_methyl","to":"memory","level":"association","effect":"helps","note":"High homocysteine is linked with Alzheimer's; B-vitamin trials are mixed."},{"from":"m_clock","to":"depression","level":"mixed","effect":"helps","note":"Bright light therapy helps seasonal depression; less clear otherwise."},{"from":"greens","to":"iron","level":"established","effect":"contains","note":"Non-haem iron, better absorbed with vitamin C."},{"from":"legumes","to":"iron","level":"established","effect":"contains","note":"Non-haem iron."},{"from":"rls","to":"insomnia","level":"established","effect":"harms","note":"Symptoms peak at night and stop sleep."},{"from":"insomnia","to":"seizures","level":"established","effect":"harms","note":"In people with epilepsy, sleep loss lowers the seizure threshold.","scope":["epilepsy"]},{"from":"seizures","to":"falls","level":"association","effect":"harms","note":"Falls and injuries during seizures."},{"from":"seizures","to":"cognition","level":"association","effect":"harms","note":"Frequent seizures and medicines slow thinking."},{"from":"memory","to":"isolation","level":"association","effect":"harms","note":"Conversations and outings get harder."},{"from":"memory","to":"nutrition","level":"association","effect":"harms","note":"Meals forgotten."},{"from":"cognition","to":"hallucinations","level":"association","effect":"harms","note":"Hallucinations are more likely as thinking declines."},{"from":"hallucinations","to":"anxiety","level":"association","effect":"harms","note":"Frightening experiences."},{"from":"chorea","to":"falls","level":"association","effect":"harms","note":"Unsteady, unpredictable movement."},{"from":"chorea","to":"nutrition","level":"association","effect":"harms","note":"Constant movement burns energy; weight loss."},{"from":"anxiety","to":"tremor","level":"established","effect":"harms","note":"Adrenaline makes tremor larger."},{"from":"tremor","to":"isolation","level":"association","effect":"harms","note":"Embarrassment eating and writing in public."},{"from":"fibre","to":"faecali","level":"established","effect":"helps","note":"Its main food."},{"from":"fibre","to":"roseburia","level":"established","effect":"helps","note":"Ferments fibre and resistant starch."},{"from":"fibre","to":"prevotella","level":"established","effect":"helps","note":"Thrives on plant fibre."},{"from":"fibre","to":"bifido","level":"established","effect":"helps","note":"Inulin-type fibre (onions, chicory) raises Bifidobacterium."},{"from":"probiotics","to":"bifido","level":"established","effect":"helps","note":"Many probiotics contain it."},{"from":"probiotics","to":"lacto","level":"established","effect":"helps","note":"Many probiotics contain it."},{"from":"fermented","to":"lacto","level":"established","effect":"contains","note":"Live lactic-acid bacteria."},{"from":"anthocyanins","to":"akk","level":"association","effect":"helps","note":"Polyphenol-rich diets raise Akkermansia in human studies."},{"from":"anthocyanins","to":"bifido","level":"association","effect":"helps","note":"Berry polyphenols raise Bifidobacterium in small human studies."},{"from":"faecali","to":"m_micro","level":"established","effect":"helps","note":"Makes butyrate."},{"from":"roseburia","to":"m_micro","level":"established","effect":"helps","note":"Makes butyrate."},{"from":"prevotella","to":"m_micro","level":"established","effect":"helps","note":"Makes short-chain fatty acids."},{"from":"bifido","to":"faecali","level":"lab","effect":"helps","note":"Its acetate and lactate feed butyrate makers."},{"from":"akk","to":"m_barrier","level":"mixed","effect":"helps","note":"Supports the lining in metabolic studies, but may thin mucus on low-fibre diets."},{"from":"lacto","to":"m_motility","level":"mixed","effect":"helps","note":"Part of probiotic mixes that improved constipation; genus-level effect unclear."},{"from":"lacto","to":"hpylori","level":"mixed","effect":"helps","note":"As an add-on, probiotics modestly improve eradication rates."},{"from":"faecali","to":"entero","level":"lab","effect":"helps","note":"Butyrate keeps the gut wall low in oxygen, which E. coli-type bacteria dislike."},{"from":"hpylori","to":"m_absorb","level":"mixed","effect":"harms","note":"Linked with erratic levodopa response; eradication trial negative."},{"from":"sibo","to":"m_absorb","level":"association","effect":"harms","note":"Linked with more motor fluctuations."},{"from":"desulfo","to":"m_barrier","level":"lab","effect":"harms","note":"Hydrogen sulfide damages the lining in the lab."},{"from":"entero","to":"m_inflam","level":"lab","effect":"harms","note":"Outer-wall LPS triggers inflammation."},{"from":"entero","to":"m_barrier","level":"lab","effect":"harms","note":"Thrives when the barrier leaks, and adds to it."},{"from":"m_motility","to":"sibo","level":"association","effect":"helps","note":"Good transit keeps the small intestine clear."},{"from":"constipation","to":"sibo","level":"association","effect":"harms","note":"Slow transit lets bacteria build up."},{"from":"giardia","to":"m_barrier","level":"association","effect":"harms","note":"Damages the small-intestine lining."},{"from":"hookworm","to":"m_inflam","level":"mixed","effect":"helps","note":"Hookworm infection raises calming 'regulatory' T cells in people, but whether this eases any disease is unproven.","sources":[{"id":"pmid:32539079","citation":"Tanasescu et al., JAMA Neurol","year":2020,"design":"RCT","finding":"Hookworm infection increased the proportion of regulatory T cells in blood compared with placebo in relapsing MS."},{"id":"pmid:27977856","citation":"Elliott & Weinstock, Parasite Immunol","year":2017,"design":"review","finding":"Therapeutic Trichuris suis or low-number Necator americanus exposure is safe; efficacy has been suggested in some small trials but is absent in others."}]},{"from":"toxo","to":"m_inflam","level":"lab","effect":"harms","note":"Keeps the brain's immune cells active around cysts."},{"from":"vaccine","to":"vzv","level":"proven","effect":"helps","note":"The non-live shingles vaccine cut shingles by about 97% in adults over 50 in a large randomised trial.","sources":[{"id":"pmid:25916341","citation":"Lal et al., N Engl J Med","year":2015,"design":"RCT","finding":"In 15,411 adults aged 50 or older, the adjuvanted zoster subunit vaccine reduced herpes zoster by 97.2% versus placebo over 3.2 years."}]},{"from":"sarscov2","to":"smell","level":"established","effect":"harms","note":"Loss of smell during and after infection."},{"from":"sarscov2","to":"fatigue","level":"association","effect":"harms","note":"Long COVID fatigue."},{"from":"sarscov2","to":"cognition","level":"association","effect":"harms","note":"\"Brain fog\"."},{"from":"strep","to":"tics","level":"mixed","effect":"harms","note":"PANDAS: sudden-onset tics after strep, debated."},{"from":"strep","to":"ocd","level":"mixed","effect":"harms","note":"PANDAS: sudden-onset OCD after strep, debated."},{"from":"taenia","to":"seizures","level":"established","effect":"harms","note":"Brain cysts cause seizures."},{"from":"giardia","to":"fatigue","level":"association","effect":"harms","note":"Lasting fatigue after infection."},{"from":"hpylori","to":"stomach","level":"association","effect":"harms","note":"Gastritis and slow emptying."},{"from":"entero","to":"falls","level":"association","effect":"harms","note":"Higher levels went with more balance problems in Parkinson's.","scope":["parkinsons"],"sources":[{"id":"pmid:25476529","citation":"Scheperjans F et al., Movement Disorders","year":2015,"design":"case-control","finding":"In 72 people with Parkinson's and 72 controls, the relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty."}]},{"from":"parkinsons","to":"s_bg","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"parkinsons","to":"s_brainstem","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"parkinsons","to":"s_gut","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"parkinsons","to":"s_autonomic","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"parkinsons","to":"s_smell","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"parkinsons","to":"s_limbic","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"parkinsons","to":"s_cortex","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"parkinsons","to":"s_bladder","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"parkinsons","to":"s_hypo","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"parkinsons","to":"s_throat","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"tourette","to":"s_bg","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"tourette","to":"s_prefrontal","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"tourette","to":"s_cortex","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"essential_tremor","to":"tremor","level":"established","effect":"harms","note":"A recognised feature."},{"from":"essential_tremor","to":"isolation","level":"established","effect":"harms","note":"A recognised feature."},{"from":"essential_tremor","to":"anxiety","level":"established","effect":"harms","note":"A recognised feature."},{"from":"essential_tremor","to":"s_cerebellum","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"restless_legs","to":"rls","level":"established","effect":"harms","note":"A recognised feature."},{"from":"restless_legs","to":"insomnia","level":"established","effect":"harms","note":"A recognised feature."},{"from":"restless_legs","to":"sleepy","level":"established","effect":"harms","note":"A recognised feature."},{"from":"restless_legs","to":"fatigue","level":"established","effect":"harms","note":"A recognised feature."},{"from":"restless_legs","to":"depression","level":"established","effect":"harms","note":"A recognised feature."},{"from":"restless_legs","to":"s_bg","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"restless_legs","to":"s_spinal","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"lewy","to":"cognition","level":"established","effect":"harms","note":"A recognised feature."},{"from":"lewy","to":"hallucinations","level":"established","effect":"harms","note":"A recognised feature."},{"from":"lewy","to":"rbd","level":"established","effect":"harms","note":"A recognised feature."},{"from":"lewy","to":"movement","level":"established","effect":"harms","note":"A recognised feature."},{"from":"lewy","to":"tremor","level":"established","effect":"harms","note":"A recognised feature."},{"from":"lewy","to":"oh","level":"established","effect":"harms","note":"A recognised feature."},{"from":"lewy","to":"sleepy","level":"established","effect":"harms","note":"A recognised feature."},{"from":"lewy","to":"depression","level":"established","effect":"harms","note":"A recognised feature."},{"from":"lewy","to":"falls","level":"established","effect":"harms","note":"A recognised feature."},{"from":"lewy","to":"constipation","level":"established","effect":"harms","note":"A recognised feature."},{"from":"lewy","to":"smell","level":"established","effect":"harms","note":"A recognised feature."},{"from":"lewy","to":"s_cortex","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"lewy","to":"s_bg","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"lewy","to":"s_brainstem","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"lewy","to":"s_autonomic","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"lewy","to":"s_limbic","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"msa","to":"oh","level":"established","effect":"harms","note":"A recognised feature."},{"from":"msa","to":"bladder","level":"established","effect":"harms","note":"A recognised feature."},{"from":"msa","to":"movement","level":"established","effect":"harms","note":"A recognised feature."},{"from":"msa","to":"falls","level":"established","effect":"harms","note":"A recognised feature."},{"from":"msa","to":"speech","level":"established","effect":"harms","note":"A recognised feature."},{"from":"msa","to":"swallow","level":"established","effect":"harms","note":"A recognised feature."},{"from":"msa","to":"rbd","level":"established","effect":"harms","note":"A recognised feature."},{"from":"msa","to":"constipation","level":"established","effect":"harms","note":"A recognised feature."},{"from":"msa","to":"insomnia","level":"established","effect":"harms","note":"A recognised feature."},{"from":"msa","to":"s_autonomic","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"msa","to":"s_bg","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"msa","to":"s_cerebellum","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"msa","to":"s_brainstem","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"msa","to":"s_bladder","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"huntingtons","to":"chorea","level":"established","effect":"harms","note":"A recognised feature."},{"from":"huntingtons","to":"cognition","level":"established","effect":"harms","note":"A recognised feature."},{"from":"huntingtons","to":"depression","level":"established","effect":"harms","note":"A recognised feature."},{"from":"huntingtons","to":"apathy","level":"established","effect":"harms","note":"A recognised feature."},{"from":"huntingtons","to":"rage","level":"established","effect":"harms","note":"A recognised feature."},{"from":"huntingtons","to":"swallow","level":"established","effect":"harms","note":"A recognised feature."},{"from":"huntingtons","to":"nutrition","level":"established","effect":"harms","note":"A recognised feature."},{"from":"huntingtons","to":"falls","level":"established","effect":"harms","note":"A recognised feature."},{"from":"huntingtons","to":"insomnia","level":"established","effect":"harms","note":"A recognised feature."},{"from":"huntingtons","to":"anxiety","level":"established","effect":"harms","note":"A recognised feature."},{"from":"huntingtons","to":"ocd","level":"established","effect":"harms","note":"A recognised feature."},{"from":"huntingtons","to":"s_bg","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"huntingtons","to":"s_cortex","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"huntingtons","to":"s_limbic","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"alzheimers","to":"memory","level":"established","effect":"harms","note":"A recognised feature."},{"from":"alzheimers","to":"cognition","level":"established","effect":"harms","note":"A recognised feature."},{"from":"alzheimers","to":"apathy","level":"established","effect":"harms","note":"A recognised feature."},{"from":"alzheimers","to":"depression","level":"established","effect":"harms","note":"A recognised feature."},{"from":"alzheimers","to":"insomnia","level":"established","effect":"harms","note":"A recognised feature."},{"from":"alzheimers","to":"hallucinations","level":"established","effect":"harms","note":"A recognised feature."},{"from":"alzheimers","to":"isolation","level":"established","effect":"harms","note":"A recognised feature."},{"from":"alzheimers","to":"nutrition","level":"established","effect":"harms","note":"A recognised feature."},{"from":"alzheimers","to":"falls","level":"established","effect":"harms","note":"A recognised feature."},{"from":"alzheimers","to":"anxiety","level":"established","effect":"harms","note":"A recognised feature."},{"from":"alzheimers","to":"s_cortex","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"alzheimers","to":"s_limbic","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"alzheimers","to":"s_hypo","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"ms","to":"fatigue","level":"established","effect":"harms","note":"A recognised feature."},{"from":"ms","to":"neuropathy","level":"established","effect":"harms","note":"A recognised feature."},{"from":"ms","to":"pain","level":"established","effect":"harms","note":"A recognised feature."},{"from":"ms","to":"bladder","level":"established","effect":"harms","note":"A recognised feature."},{"from":"ms","to":"falls","level":"established","effect":"harms","note":"A recognised feature."},{"from":"ms","to":"cognition","level":"established","effect":"harms","note":"A recognised feature."},{"from":"ms","to":"depression","level":"established","effect":"harms","note":"A recognised feature."},{"from":"ms","to":"constipation","level":"established","effect":"harms","note":"A recognised feature."},{"from":"ms","to":"speech","level":"established","effect":"harms","note":"A recognised feature."},{"from":"ms","to":"swallow","level":"established","effect":"harms","note":"A recognised feature."},{"from":"ms","to":"tremor","level":"established","effect":"harms","note":"A recognised feature."},{"from":"ms","to":"s_spinal","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"ms","to":"s_cortex","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"ms","to":"s_cerebellum","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"ms","to":"s_immune","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"ms","to":"s_bladder","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"ms","to":"s_peripheral","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"epilepsy","to":"seizures","level":"established","effect":"harms","note":"A recognised feature."},{"from":"epilepsy","to":"cognition","level":"established","effect":"harms","note":"A recognised feature."},{"from":"epilepsy","to":"depression","level":"established","effect":"harms","note":"A recognised feature."},{"from":"epilepsy","to":"anxiety","level":"established","effect":"harms","note":"A recognised feature."},{"from":"epilepsy","to":"fatigue","level":"established","effect":"harms","note":"A recognised feature."},{"from":"epilepsy","to":"isolation","level":"established","effect":"harms","note":"A recognised feature."},{"from":"epilepsy","to":"insomnia","level":"established","effect":"harms","note":"A recognised feature."},{"from":"epilepsy","to":"s_cortex","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"adhd_c","to":"adhd","level":"established","effect":"harms","note":"A recognised feature."},{"from":"adhd_c","to":"insomnia","level":"established","effect":"harms","note":"A recognised feature."},{"from":"adhd_c","to":"rage","level":"established","effect":"harms","note":"A recognised feature."},{"from":"adhd_c","to":"anxiety","level":"established","effect":"harms","note":"A recognised feature."},{"from":"adhd_c","to":"isolation","level":"established","effect":"harms","note":"A recognised feature."},{"from":"adhd_c","to":"depression","level":"established","effect":"harms","note":"A recognised feature."},{"from":"adhd_c","to":"s_prefrontal","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"adhd_c","to":"s_bg","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"ocd_c","to":"ocd","level":"established","effect":"harms","note":"A recognised feature."},{"from":"ocd_c","to":"anxiety","level":"established","effect":"harms","note":"A recognised feature."},{"from":"ocd_c","to":"depression","level":"established","effect":"harms","note":"A recognised feature."},{"from":"ocd_c","to":"s_prefrontal","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"ocd_c","to":"s_bg","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"depression_c","to":"depression","level":"established","effect":"harms","note":"A recognised feature."},{"from":"depression_c","to":"insomnia","level":"established","effect":"harms","note":"A recognised feature."},{"from":"depression_c","to":"fatigue","level":"established","effect":"harms","note":"A recognised feature."},{"from":"depression_c","to":"apathy","level":"established","effect":"harms","note":"A recognised feature."},{"from":"depression_c","to":"cognition","level":"established","effect":"harms","note":"A recognised feature."},{"from":"depression_c","to":"nutrition","level":"established","effect":"harms","note":"A recognised feature."},{"from":"depression_c","to":"isolation","level":"established","effect":"harms","note":"A recognised feature."},{"from":"depression_c","to":"anxiety","level":"established","effect":"harms","note":"A recognised feature."},{"from":"depression_c","to":"pain","level":"established","effect":"harms","note":"A recognised feature."},{"from":"depression_c","to":"s_limbic","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"depression_c","to":"s_prefrontal","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"depression_c","to":"s_hypo","level":"established","effect":"affects","note":"Affected in this condition."},{"from":"parkinsons","to":"tremor","level":"established","effect":"harms","note":"Rest tremor in most people."},{"from":"parkinsons","to":"chorea","level":"established","effect":"harms","note":"Dyskinesia with long-term levodopa."},{"from":"parkinsons","to":"hallucinations","level":"established","effect":"harms","note":"In later disease, often with medicines."},{"from":"parkinsons","to":"memory","level":"association","effect":"harms","note":"Memory may decline with dementia later on."},{"from":"parkinsons","to":"rls","level":"association","effect":"harms","note":"More common than in the general population."},{"from":"hpylori","to":"parkinsons","level":"association","effect":"harms","note":"Slightly more common before and in Parkinson's; a large Swedish study found only a small excess risk, so it is unlikely to be a major cause.","sources":[{"id":"pmid:42455020","citation":"Licaj S et al., J Parkinsons Dis","year":2026,"design":"cohort","finding":"In a Swedish nationwide cohort, H. pylori infection (HR 1.14) and gastritis were linked to marginally higher Parkinson's risk; peptic ulcer was not; authors judge it unlikely to be a major contributor."}]},{"from":"desulfo","to":"parkinsons","level":"association","effect":"harms","note":"Higher levels in Parkinson's in several studies."},{"from":"entero","to":"parkinsons","level":"association","effect":"harms","note":"Higher levels in Parkinson's."},{"from":"flu","to":"parkinsons","level":"association","effect":"harms","note":"Weak, inconsistent link after severe flu."},{"from":"strep","to":"tourette","level":"mixed","effect":"harms","note":"PANDAS hypothesis, debated."},{"from":"ebv","to":"ms","level":"association","effect":"harms","note":"About 32-fold higher risk after infection; widely seen as the main trigger.","sources":[{"id":"pmid:35025605","citation":"Bjornevik K et al., Science","year":2022,"design":"cohort","finding":"In over 10 million US military personnel, MS risk rose 32-fold after EBV infection but not after other viruses such as cytomegalovirus."}]},{"from":"hsv1","to":"alzheimers","level":"association","effect":"harms","note":"Linked with Alzheimer's in cohort studies, but an antiviral drug did not help people with early Alzheimer's in a randomised trial.","sources":[{"id":"pmid:41405855","citation":"Devanand DP et al. (VALAD), JAMA","year":2026,"design":"RCT","finding":"In 120 people with early Alzheimer's and HSV antibodies, 78 weeks of valacyclovir did not help and cognitive scores worsened more than on placebo."}]},{"from":"vzv","to":"alzheimers","level":"association","effect":"harms","note":"In Wales, people just young enough to get the shingles vaccine had fewer new dementia diagnoses over 7 years (a natural experiment); which dementias, and why, is not settled.","sources":[{"id":"pmid:40175543","citation":"Eyting M et al., Nature","year":2025,"design":"cohort","finding":"Using a birth-date eligibility cut-off in Wales, receiving the live zoster vaccine reduced new dementia diagnoses over 7 years by 3.5 percentage points (about 20% relative)."}]},{"from":"toxo","to":"ocd_c","level":"association","effect":"harms","note":"Linked in meta-analyses."},{"from":"taenia","to":"epilepsy","level":"established","effect":"harms","note":"A leading cause of acquired epilepsy worldwide.","sources":[{"id":"pmid:28267746","citation":"Debacq et al., PLoS Negl Trop Dis","year":2017,"design":"meta-analysis","finding":"Across 37 studies from 23 tropical countries, cysticercosis was associated with epilepsy with a common odds ratio of about 2.7."},{"id":"pmid:42717381","citation":"Jalal et al., Infect Dis Poverty","year":2026,"design":"meta-analysis","finding":"In 35 well-defined studies, the pooled proportion of neurocysticercosis among people with epileptic seizures in endemic regions was about 25%, declining after 2008."}]},{"from":"hookworm","to":"ms","level":"failed","effect":"helps","note":"In the one placebo-controlled trial, deliberate hookworm infection in relapsing MS did not significantly reduce new brain-scan lesions, though calming T cells rose.","sources":[{"id":"pmid:32539079","citation":"Tanasescu et al., JAMA Neurol","year":2020,"design":"RCT","finding":"In 71 people with relapsing MS, hookworm infection did not significantly reduce cumulative new or enlarging MRI lesions at 9 months versus placebo (primary endpoint missed); regulatory T cells increased."}]},{"from":"faecali","to":"parkinsons","level":"association","effect":"helps","note":"Lower levels in Parkinson's."},{"from":"faecali","to":"depression_c","level":"association","effect":"helps","note":"Lower levels in depression."},{"from":"prevotella","to":"parkinsons","level":"association","effect":"helps","note":"Lower levels in Parkinson's."},{"from":"m_catechol","to":"adhd","level":"proven","effect":"helps","note":"Raising these signals improves attention: how ADHD medicines work (many trials).","sources":[{"id":"pmid:30097390","citation":"Cortese S et al., Lancet Psychiatry","year":2018,"design":"meta-analysis","finding":"In 133 double-blind RCTs, all ADHD medicines studied (stimulants, atomoxetine, guanfacine and others) reduced core ADHD symptoms more than placebo in children."}]},{"from":"exercise","to":"m_catechol","level":"mixed","effect":"helps","note":"Exercise improves attention in ADHD in small, mostly short-term trials."},{"from":"omega3","to":"m_catechol","level":"mixed","effect":"helps","note":"Small average benefit for ADHD symptoms in meta-analyses; how is unclear."},{"from":"m_iron","to":"adhd","level":"mixed","effect":"helps","note":"Low ferritin is linked with ADHD; iron helped iron-deficient children in a small trial (Konofal 2008).","scope":["adhd_c","tourette"]},{"from":"sugar","to":"m_catechol","level":"failed","effect":"harms","note":"Blinded trials: sugar does not cause hyperactivity (Wolraich 1995).","sources":[{"id":"pmid:7474248","citation":"Wolraich ML et al., JAMA","year":1995,"design":"meta-analysis","finding":"Across 23 blinded placebo-controlled studies, sugar did not affect children's behaviour or thinking."},{"id":"pmid:8277950","citation":"Wolraich ML et al., New England Journal of Medicine","year":1994,"design":"RCT","finding":"In a double-blind diet trial, including children whose parents called them sugar-sensitive, high-sugar diets did not change behaviour or thinking."}]},{"from":"colours","to":"m_catechol","level":"mixed","effect":"harms","note":"Small increase in hyperactivity in some children (McCann 2007)."},{"from":"fewfoods","to":"m_catechol","level":"mixed","effect":"helps","note":"One trial found large improvement (INCA 2011); not widely replicated."},{"from":"insomnia","to":"adhd","level":"association","effect":"harms","note":"Poor sleep worsens attention and impulsivity."},{"from":"sweets","to":"sugar","level":"established","effect":"contains","note":"Added sugar."},{"from":"sweets","to":"colours","level":"established","effect":"contains","note":"Often coloured with synthetic dyes."},{"from":"m_stress","to":"anxiety","level":"established","effect":"helps","note":"A calmer stress system means less anxiety."},{"from":"m_stress","to":"rage","level":"association","effect":"helps","note":"Lower stress, fewer outbursts."},{"from":"m_stress","to":"insomnia","level":"association","effect":"helps","note":"Lower arousal at night helps sleep."},{"from":"m_catechol","to":"rage","level":"association","effect":"helps","note":"Better prefrontal control, fewer outbursts."},{"from":"exercise","to":"m_stress","level":"proven","effect":"helps","note":"Strength and mind-body exercise eased anxiety in trials; aerobic exercise alone did no better than comparison activities in an earlier pooled analysis.","sources":[{"id":"pmid:41574022","citation":"Lei EF et al., BMJ Open Sport Exerc Med","year":2026,"design":"meta-analysis","finding":"Network meta-analysis of 30 RCTs in adults with anxiety: resistance training and mind-body exercise reduced anxiety (moderate certainty)."},{"id":"pmid:23643675","citation":"Bartley CA et al., Prog Neuropsychopharmacol Biol Psychiatry","year":2013,"design":"meta-analysis","finding":"Seven RCTs in anxiety disorders: aerobic exercise showed no significant effect versus control conditions; only waitlist-controlled trials showed large effects."}]},{"from":"cbt","to":"m_stress","level":"proven","effect":"helps","note":"CBT reduced anxiety more than placebo treatments in many trials, a moderate effect.","sources":[{"id":"pmid:29451967","citation":"Carpenter JK et al., Depression and Anxiety","year":2018,"design":"meta-analysis","finding":"41 placebo-controlled RCTs: CBT had a moderate effect on anxiety-disorder symptoms versus psychological or pill placebo."}]},{"from":"social","to":"m_stress","level":"association","effect":"helps","note":"Support buffers stress."},{"from":"m_aden","to":"anxiety","level":"established","effect":"harms","note":"High caffeine intake can trigger anxiety and jitteriness."},{"from":"m_bladderctl","to":"bladder","level":"established","effect":"helps","note":"Better control, less urgency."},{"from":"pelvic","to":"m_bladderctl","level":"proven","effect":"helps","note":"Pelvic-floor training cured or improved urine leaking in women in many trials; bladder training for urgency (overactive bladder) helps too, but that evidence is weaker.","sources":[{"id":"pmid:30288727","citation":"Dumoulin C et al., Cochrane Database Syst Rev","year":2018,"design":"meta-analysis","finding":"31 trials in women: pelvic floor muscle training cured or improved stress and all types of urinary incontinence versus no treatment (high to moderate quality)."},{"id":"pmid:37811598","citation":"Funada S et al., Cochrane Database Syst Rev","year":2023,"design":"meta-analysis","finding":"15 trials of bladder training for overactive bladder: may help, but certainty was low to very low and no study was at low risk of bias."}]},{"from":"caffeine","to":"m_bladderctl","level":"established","effect":"harms","note":"Caffeine irritates the bladder and adds urgency."},{"from":"m_painproc","to":"pain","level":"established","effect":"helps","note":"Quieter pain signalling, less pain."},{"from":"exercise","to":"m_painproc","level":"proven","effect":"helps","note":"Exercise therapy eased chronic low back pain in many trials; for other long-lasting pain the trial results are less consistent.","sources":[{"id":"pmid:34580864","citation":"Hayden JA et al., Cochrane Database Syst Rev","year":2021,"design":"meta-analysis","finding":"249 trials: moderate-certainty evidence that exercise treatment reduces chronic low back pain versus no treatment, usual care or placebo."},{"id":"pmid:28436583","citation":"Geneen LJ et al., Cochrane Database Syst Rev","year":2017,"design":"meta-analysis","finding":"Overview of 21 Cochrane reviews of chronic pain: exercise improved physical function, but pain results were inconsistent and evidence quality low."}]},{"from":"curcumin","to":"m_painproc","level":"mixed","effect":"helps","note":"Small trials in knee osteoarthritis pain; quality is limited."},{"from":"insomnia","to":"pain","level":"association","effect":"harms","note":"Poor sleep makes pain feel worse."},{"from":"depression","to":"pain","level":"association","effect":"harms","note":"Low mood amplifies pain."},{"from":"exercise","to":"inactivity","level":"established","effect":"helps","note":"Doing it is the remedy; structured programmes keep people active."},{"from":"fluids","to":"dehydration","level":"established","effect":"helps","note":"Drinking enough, spread through the day."},{"from":"social","to":"isolation","level":"established","effect":"helps","note":"Contact is the opposite of withdrawal."},{"from":"m_motility","to":"stomach","level":"established","effect":"helps","note":"When the stomach's muscle waves slow down, food and pills sit in the stomach longer.","sources":[{"id":"pmid:19451015","citation":"Krygowska-Wajs A et al., Parkinsonism Relat Disord","year":2009,"design":"case-control","finding":"Solid-meal scintigraphy showed delayed gastric emptying in 60% of people with Parkinson's, including some at an early stage, compared with age-matched controls."},{"id":"pmid:27941374","citation":"Bestetti A et al., Clin Nucl Med","year":2017,"design":"cohort","finding":"In 51 consecutive Parkinson's patients, gastric emptying was delayed in about 42% of those with motor complications."}]},{"from":"epilepsy","to":"memory","level":"established","effect":"harms","note":"A recognised feature, especially when seizures start in the temporal lobe.","sources":[{"id":"pmid:39136620","citation":"Pugh R et al., Epilepsia Open","year":2024,"design":"case-control","finding":"Adults with new-onset epilepsy performed worse than matched controls on all memory measures, with 44% impaired at baseline testing."},{"id":"pmid:40893696","citation":"Olejnik A et al., Front Hum Neurosci","year":2025,"design":"case-control","finding":"People with left mesial temporal lobe epilepsy had reduced short- and long-term verbal and visual memory and working memory compared with healthy controls."}]},{"from":"m_cstc","to":"ocd","level":"association","effect":"helps","note":"OCD is tied to overactive cortex-striatum-thalamus loops, and calming this circuit eases symptoms in small trials.","sources":[{"id":"pmid:40994079","citation":"Zhu F et al., Psychiatry Clin Neurosci","year":2025,"design":"meta-analysis","finding":"Across 55 MRS studies, people with OCD had lower striatal NAA and higher thalamic choline than controls, with striatal choline tracking symptom severity, indicating cortico-striatal-thalamo-cortical circuit dysregulation."},{"id":"pmid:40579425","citation":"Cohen SE et al., Mol Psychiatry","year":2025,"design":"meta-analysis","finding":"Individual-participant meta-analysis of 9 sham-controlled RCTs (91 patients): deep brain stimulation of the circuit lowered Y-BOCS by 5.1 points versus sham, but GRADE quality was low."}]},{"from":"fracture","to":"s_bones","level":"established","effect":"located","note":"A fracture is a break in a bone, most often the hip or wrist after a fall."},{"from":"inactivity","to":"s_bones","level":"established","effect":"located","note":"Bones need regular load to stay dense, so moving less thins them."},{"from":"pain","to":"s_bones","level":"established","effect":"located","note":"Some pain is felt in the joints, such as a stiff, painful shoulder."},{"from":"s_marrow","to":"s_bones","level":"established","effect":"located","note":"Part of the bones: it fills their inner space."},{"from":"s_marrow","to":"s_immune","level":"established","effect":"located","note":"Part of the immune system: it makes the white blood cells."},{"from":"s_mouth","to":"s_gut","level":"established","effect":"located","note":"Part of the digestive tract: where digestion begins."},{"from":"s_oesophagus","to":"s_gut","level":"established","effect":"located","note":"Part of the digestive tract: carries food from throat to stomach."},{"from":"s_oesophagus","to":"s_throat","level":"established","effect":"located","note":"Part of the swallowing pathway."},{"from":"s_stomach","to":"s_gut","level":"established","effect":"located","note":"Part of the digestive tract."},{"from":"s_small_intestine","to":"s_gut","level":"established","effect":"located","note":"Part of the digestive tract."},{"from":"s_colon","to":"s_gut","level":"established","effect":"located","note":"Part of the digestive tract: its last section."},{"from":"s_liver","to":"s_gut","level":"established","effect":"located","note":"Part of the digestive system: it makes bile that flows into the small intestine."},{"from":"s_gallbladder","to":"s_gut","level":"established","effect":"located","note":"Part of the digestive system: it stores bile for the small intestine."},{"from":"stomach","to":"s_stomach","level":"established","effect":"located","note":"Slow emptying happens in the stomach itself."},{"from":"constipation","to":"s_colon","level":"established","effect":"located","note":"Stool moves too slowly through the large intestine."},{"from":"swallow","to":"s_oesophagus","level":"established","effect":"located","note":"Food can move slowly down the oesophagus."},{"from":"swallow","to":"s_mouth","level":"established","effect":"located","note":"Drooling is saliva pooling in the mouth because it is swallowed less often."},{"from":"s_heart","to":"s_autonomic","level":"established","effect":"located","note":"Part of the circulation; the autonomic nerves set how fast it beats."},{"from":"s_blood","to":"s_autonomic","level":"established","effect":"located","note":"Part of the circulation; the autonomic nerves tighten vessels to hold blood pressure."},{"from":"oh","to":"s_blood","level":"established","effect":"located","note":"Blood vessels in the legs and belly fail to tighten on standing, so blood pressure drops."},{"from":"oh","to":"s_heart","level":"established","effect":"located","note":"The heart does not speed up enough to make up for the drop in pressure."},{"from":"dehydration","to":"s_blood","level":"established","effect":"located","note":"Drinking less lowers the amount of blood, which lowers blood pressure."},{"from":"pneumonia","to":"s_lungs","level":"established","effect":"located","note":"Food, drink or saliva going down the wrong way infects the lungs."},{"from":"dehydration","to":"s_kidneys","level":"established","effect":"located","note":"The kidneys hold back water when the body is short of it, making urine darker and smaller in amount."},{"from":"s_lymph","to":"s_immune","level":"established","effect":"located","note":"Part of the immune system: where immune cells gather and meet microbes."},{"from":"dairy","to":"protein","level":"established","effect":"contains","note":"Milk protein (casein and whey)."},{"from":"dairy","to":"b12","level":"established","effect":"contains","note":"B12; one of the main sources for people who eat no meat."},{"from":"dairy","to":"parkinsons","level":"association","effect":"harms","note":"Large cohort studies and a 2026 meta-analysis link high dairy intake, especially low-fat milk, to a somewhat higher chance of Parkinson's, but a big European study found no link and no cause is proven.","sources":[{"id":"pmid:41252180","citation":"Akhlaghi M et al., Nutr Rev","year":2026,"design":"meta-analysis","finding":"Across 29 prospective cohorts, the highest intakes of dairy, low-fat dairy and milk were linked to 26%, 30% and 23% higher Parkinson's risk than the lowest intakes, with a dose-response trend."},{"id":"pmid:28596209","citation":"Hughes KC et al., Neurology","year":2017,"design":"cohort","finding":"In two US cohorts (about 129,000 people), total dairy was not linked to Parkinson's, but 3 or more servings a day of low-fat dairy was (pooled HR 1.34)."},{"id":"pmid:39625618","citation":"Gröninger M et al., Eur J Epidemiol","year":2024,"design":"cohort","finding":"In the European EPIC4ND cohort (183,225 people), dairy and individual dairy products were not linked to Parkinson's risk; higher calcium intake was, weakly."}]},{"from":"eggs","to":"protein","level":"established","effect":"contains","note":"Protein, mostly in the white."},{"from":"eggs","to":"b12","level":"established","effect":"contains","note":"B12 in the yolk."},{"from":"eggs","to":"vitd","level":"established","effect":"contains","note":"A modest amount of vitamin D in the yolk."},{"from":"oilyfish","to":"omega3","level":"established","effect":"contains","note":"The richest food source of ready-made DHA and EPA (the fish get it from algae)."},{"from":"oilyfish","to":"vitd","level":"established","effect":"contains","note":"One of the few foods with a useful amount of vitamin D."},{"from":"oilyfish","to":"protein","level":"established","effect":"contains","note":"Protein."},{"from":"whitefish","to":"protein","level":"established","effect":"contains","note":"Lean protein."},{"from":"shellfish","to":"b12","level":"established","effect":"contains","note":"Clams, oysters and mussels are very rich in B12."},{"from":"shellfish","to":"iron","level":"established","effect":"contains","note":"Clams and mussels contain iron."},{"from":"redmeat","to":"iron","level":"established","effect":"contains","note":"Haem iron, absorbed far better than iron from plants."},{"from":"redmeat","to":"b12","level":"established","effect":"contains","note":"B12."},{"from":"redmeat","to":"protein","level":"established","effect":"contains","note":"Protein."},{"from":"poultry","to":"protein","level":"established","effect":"contains","note":"Lean protein."},{"from":"liver","to":"b12","level":"established","effect":"contains","note":"Liver is the richest food source of B12."},{"from":"br_snc","to":"s_bg","level":"established","effect":"located","note":"Part of the basal ganglia; its dopamine tunes the whole circuit."},{"from":"br_putamen","to":"s_bg","level":"established","effect":"located","note":"Part of the basal ganglia (the striatum, their input stage)."},{"from":"br_gp","to":"s_bg","level":"established","effect":"located","note":"Part of the basal ganglia (their main output station)."},{"from":"progression","to":"br_snc","level":"established","effect":"located","note":"Parkinson's movement symptoms appear when many of the dopamine neurons in the substantia nigra have been lost."},{"from":"movement","to":"br_putamen","level":"established","effect":"located","note":"Slowness and stiffness come from the putamen losing its dopamine supply."},{"from":"movement","to":"br_gp","level":"established","effect":"located","note":"The globus pallidus output becomes too strong and holds movement back."},{"from":"off","to":"br_putamen","level":"established","effect":"located","note":"OFF periods happen when dopamine in the putamen falls between medicine doses."},{"from":"tics","to":"br_putamen","level":"established","effect":"located","note":"Tics are thought to come from unwanted movement plans slipping through the putamen's filter."},{"from":"parkinsons","to":"br_snc","level":"established","effect":"affects","note":"Parkinson's movement symptoms come from losing dopamine neurons in the substantia nigra."},{"from":"parkinsons","to":"br_putamen","level":"established","effect":"affects","note":"The putamen loses most of its dopamine supply in Parkinson's."},{"from":"lewy","to":"br_snc","level":"established","effect":"affects","note":"Dementia with Lewy bodies damages the substantia nigra, causing parkinsonism."},{"from":"msa","to":"br_putamen","level":"established","effect":"affects","note":"Multiple system atrophy shrinks the putamen, so dopamine medicine helps less."},{"from":"msa","to":"br_snc","level":"established","effect":"affects","note":"Multiple system atrophy also damages the substantia nigra."},{"from":"huntingtons","to":"br_putamen","level":"established","effect":"affects","note":"Huntington's also destroys neurons in the putamen."},{"from":"tourette","to":"br_putamen","level":"established","effect":"affects","note":"The putamen is the movement part of the tic circuit."},{"from":"adhd_c","to":"br_putamen","level":"association","effect":"affects","note":"Large brain-scan studies find the putamen slightly smaller in ADHD, mostly in children.","sources":[{"id":"pmid:28219628","citation":"Hoogman M et al., Lancet Psychiatry","year":2017,"design":"case-control","finding":"In 1713 people with ADHD vs 1529 controls, the accumbens, amygdala, caudate, hippocampus and putamen were slightly smaller, most clearly in children."}]},{"from":"ocd_c","to":"br_gp","level":"association","effect":"affects","note":"A large brain-scan study found a slightly larger globus pallidus in adults with OCD.","sources":[{"id":"pmid:27609241","citation":"Boedhoe PS et al., Am J Psychiatry","year":2017,"design":"case-control","finding":"In 1830 OCD patients vs 1759 controls, adults with OCD had larger pallidum and smaller hippocampus volumes."}]},{"from":"br_lc","to":"s_brainstem","level":"established","effect":"located","note":"Part of the brainstem (an arousal centre)."},{"from":"br_raphe","to":"s_brainstem","level":"established","effect":"located","note":"Part of the brainstem (the serotonin centre)."},{"from":"br_dmnv","to":"s_brainstem","level":"established","effect":"located","note":"Part of the brainstem (lower medulla)."},{"from":"br_dmnv","to":"s_autonomic","level":"established","effect":"located","note":"Part of the autonomic nervous system (it sends the vagus nerve's signals to the gut)."},{"from":"constipation","to":"br_dmnv","level":"established","effect":"located","note":"When the vagus nucleus is affected, signals that keep the gut moving get weaker."},{"from":"stomach","to":"br_dmnv","level":"established","effect":"located","note":"The vagus nucleus drives the stomach to empty."},{"from":"sleepy","to":"br_lc","level":"established","effect":"located","note":"The locus coeruleus helps keep us awake and alert."},{"from":"anxiety","to":"br_lc","level":"established","effect":"located","note":"Noradrenaline from the locus coeruleus drives the alarm and stress response."},{"from":"depression","to":"br_raphe","level":"established","effect":"located","note":"Serotonin from the raphe nuclei helps set mood."},{"from":"depression","to":"br_lc","level":"established","effect":"located","note":"Noradrenaline from the locus coeruleus helps set energy and mood."},{"from":"cognition","to":"br_lc","level":"established","effect":"located","note":"Noradrenaline from the locus coeruleus focuses attention."},{"from":"pain","to":"br_raphe","level":"established","effect":"located","note":"The lower raphe nuclei turn down pain signals in the spinal cord."},{"from":"parkinsons","to":"br_dmnv","level":"established","effect":"affects","note":"The vagus nucleus is one of the first brain sites affected, linked to early constipation."},{"from":"parkinsons","to":"br_lc","level":"established","effect":"affects","note":"The locus coeruleus loses many neurons in Parkinson's, often before the substantia nigra."},{"from":"parkinsons","to":"br_raphe","level":"established","effect":"affects","note":"The raphe nuclei are affected in Parkinson's, reducing serotonin."},{"from":"lewy","to":"br_lc","level":"established","effect":"affects","note":"The locus coeruleus loses neurons in dementia with Lewy bodies."},{"from":"alzheimers","to":"br_lc","level":"established","effect":"affects","note":"The locus coeruleus is one of the earliest places Alzheimer's tau changes appear."},{"from":"br_hippocampus","to":"s_limbic","level":"established","effect":"located","note":"Part of the limbic system."},{"from":"br_amygdala","to":"s_limbic","level":"established","effect":"located","note":"Part of the limbic system."},{"from":"br_acc","to":"s_limbic","level":"established","effect":"located","note":"Part of the limbic system (its cortex part)."},{"from":"br_acc","to":"s_cortex","level":"established","effect":"located","note":"Part of the cerebral cortex (on the inner surface)."},{"from":"memory","to":"br_hippocampus","level":"established","effect":"located","note":"The hippocampus is where new memories are formed, so damage here makes it hard to remember recent things."},{"from":"seizures","to":"br_hippocampus","level":"established","effect":"located","note":"The hippocampus is the most common starting point of focal seizures in adults."},{"from":"anxiety","to":"br_amygdala","level":"established","effect":"located","note":"The amygdala triggers fear; when it is overactive, anxiety follows."},{"from":"rage","to":"br_amygdala","level":"established","effect":"located","note":"The amygdala fires up anger and fight responses."},{"from":"depression","to":"br_amygdala","level":"established","effect":"located","note":"The amygdala colours experiences with negative emotion and is overactive in depression."},{"from":"depression","to":"br_acc","level":"established","effect":"located","note":"The lower part of the anterior cingulate helps set mood."},{"from":"apathy","to":"br_acc","level":"established","effect":"located","note":"The anterior cingulate decides whether something is worth the effort, so loss here causes apathy."},{"from":"pain","to":"br_acc","level":"established","effect":"located","note":"The anterior cingulate carries how unpleasant pain feels."},{"from":"ocd","to":"br_acc","level":"established","effect":"located","note":"The anterior cingulate signals that something is wrong, a feeling that keeps going in OCD."},{"from":"cognition","to":"br_acc","level":"established","effect":"located","note":"The anterior cingulate keeps attention on the task and notices mistakes."},{"from":"lewy","to":"br_amygdala","level":"established","effect":"affects","note":"The amygdala carries many Lewy bodies in this dementia."},{"from":"alzheimers","to":"br_hippocampus","level":"established","effect":"affects","note":"Alzheimer's damages the hippocampus early, causing memory loss."},{"from":"epilepsy","to":"br_hippocampus","level":"established","effect":"affects","note":"Scarring of the hippocampus is the commonest cause of focal epilepsy in adults."},{"from":"depression_c","to":"br_hippocampus","level":"association","effect":"affects","note":"Large brain-scan studies find a slightly smaller hippocampus in people with repeated depression.","sources":[{"id":"pmid:26122586","citation":"Schmaal L et al., Mol Psychiatry","year":2016,"design":"meta-analysis","finding":"In 1728 people with major depression vs 7199 controls, the hippocampus was smaller, driven by recurrent depression."}]},{"from":"depression_c","to":"br_acc","level":"association","effect":"affects","note":"The lower part of the anterior cingulate works differently in depression, though size findings are mixed.","sources":[{"id":"pmid:9126739","citation":"Drevets WC et al., Nature","year":1997,"design":"case-control","finding":"Depressed patients had lower activity and less grey matter in the prefrontal cortex below the front of the corpus callosum (subgenual cingulate)."},{"id":"pmid:41916951","citation":"Demchenko I et al., Transl Psychiatry","year":2026,"design":"meta-analysis","finding":"Across 42 MRI studies of medication-free depression, subgenual cingulate volume and activity findings were split, but its network connections were consistently weaker."}]},{"from":"br_ppn","to":"s_brainstem","level":"established","effect":"located","note":"Part of the brainstem (a walking and arousal centre)."},{"from":"br_sld","to":"s_brainstem","level":"established","effect":"located","note":"Part of the brainstem (the dream-sleep switches)."},{"from":"rbd","to":"br_sld","level":"established","effect":"located","note":"Dream enactment happens when this switch fails to relax the muscles during dream sleep."},{"from":"falls","to":"br_ppn","level":"established","effect":"located","note":"The pedunculopontine nucleus helps keep balance and walking going; problems here are linked to freezing and falls."},{"from":"br_cerebellum","to":"s_cerebellum","level":"established","effect":"located","note":"Part of the cerebellum."},{"from":"br_dentate","to":"s_cerebellum","level":"established","effect":"located","note":"Part of the cerebellum (its main output nucleus)."},{"from":"br_olfactory_bulb","to":"s_smell","level":"established","effect":"located","note":"Part of the smell system."},{"from":"tremor","to":"br_cerebellum","level":"established","effect":"located","note":"The cerebellum's timing loops help set the rhythm of tremor, especially tremor during action."},{"from":"tremor","to":"br_dentate","level":"established","effect":"located","note":"Tremor rhythms run through the dentate nucleus on the way to the thalamus."},{"from":"falls","to":"br_cerebellum","level":"established","effect":"located","note":"The cerebellum keeps balance, so problems here make falls more likely."},{"from":"smell","to":"br_olfactory_bulb","level":"established","effect":"located","note":"Loss of smell happens when the olfactory bulb is damaged."},{"from":"parkinsons","to":"br_olfactory_bulb","level":"established","effect":"affects","note":"The olfactory bulb is one of the first places Parkinson's changes appear, which is why smell often goes early."},{"from":"parkinsons","to":"br_ppn","level":"established","effect":"affects","note":"The pedunculopontine nucleus loses neurons in Parkinson's, linked to gait and balance problems."},{"from":"msa","to":"br_cerebellum","level":"established","effect":"affects","note":"Multiple system atrophy can shrink the cerebellum, causing unsteadiness."},{"from":"essential_tremor","to":"br_cerebellum","level":"established","effect":"affects","note":"Essential tremor centres on the cerebellum and its loops."},{"from":"br_m1","to":"s_cortex","level":"established","effect":"located","note":"Part of the cerebral cortex (the movement strip)."},{"from":"br_sma","to":"s_cortex","level":"established","effect":"located","note":"Part of the cerebral cortex (a movement-planning area)."},{"from":"br_dlpfc","to":"s_prefrontal","level":"established","effect":"located","note":"Part of the prefrontal cortex."},{"from":"br_ofc","to":"s_prefrontal","level":"established","effect":"located","note":"Part of the prefrontal cortex."},{"from":"br_insula","to":"s_cortex","level":"established","effect":"located","note":"Part of the cerebral cortex (a deep fold of it)."},{"from":"br_visual","to":"s_cortex","level":"established","effect":"located","note":"Part of the cerebral cortex (the back, seeing part)."},{"from":"movement","to":"br_sma","level":"established","effect":"located","note":"With too little dopamine the supplementary motor area gets weaker drive, so self-started movements are slow to begin."},{"from":"tics","to":"br_sma","level":"established","effect":"located","note":"The supplementary motor area is part of the circuit that starts tics."},{"from":"urge","to":"br_sma","level":"established","effect":"located","note":"The supplementary motor area is active just before a tic, when the urge is felt."},{"from":"urge","to":"br_insula","level":"established","effect":"located","note":"The insula is where the body feeling of the urge before a tic is sensed."},{"from":"cognition","to":"br_dlpfc","level":"established","effect":"located","note":"The dorsolateral prefrontal cortex holds information in mind and plans, so problems here slow thinking and attention."},{"from":"adhd","to":"br_dlpfc","level":"established","effect":"located","note":"The dorsolateral prefrontal cortex controls attention and holding back impulses."},{"from":"ocd","to":"br_ofc","level":"established","effect":"located","note":"The orbitofrontal cortex is the front part of the loop that keeps repeating in obsessions and compulsions."},{"from":"rage","to":"br_ofc","level":"established","effect":"located","note":"The orbitofrontal cortex normally holds back anger, so weak control here lets outbursts through."},{"from":"hallucinations","to":"br_visual","level":"established","effect":"located","note":"Seeing things that are not there involves the visual cortex and its nearby areas."},{"from":"pain","to":"br_insula","level":"established","effect":"located","note":"The insula is one of the main places where pain is felt."},{"from":"anxiety","to":"br_insula","level":"established","effect":"located","note":"The insula senses a racing heart and tight gut, which feed the feeling of anxiety."},{"from":"tourette","to":"br_sma","level":"established","effect":"affects","note":"The supplementary motor area is part of the circuit that starts tics and the urge before them."},{"from":"ocd_c","to":"br_ofc","level":"association","effect":"affects","note":"Brain-scan studies consistently find the orbitofrontal cortex working differently in OCD.","sources":[{"id":"pmid:15546704","citation":"Whiteside SP et al., Psychiatry Res","year":2004,"design":"meta-analysis","finding":"Across PET and SPECT studies, brain activity differed consistently between OCD and controls in the orbital gyrus and the head of the caudate."},{"id":"pmid:18061263","citation":"Menzies L et al., Neurosci Biobehav Rev","year":2008,"design":"meta-analysis","finding":"A voxel-level meta-analysis of functional MRI found consistent abnormalities in orbitofronto-striatal areas in OCD."}]},{"from":"br_caudate","to":"s_bg","level":"established","effect":"located","note":"Part of the basal ganglia (the striatum, their input stage)."},{"from":"br_accumbens","to":"s_bg","level":"established","effect":"located","note":"Part of the basal ganglia (the lower, reward part of the striatum)."},{"from":"br_accumbens","to":"s_limbic","level":"established","effect":"located","note":"Part of the reward circuit, where dopamine turns wanting into effort."},{"from":"br_stn","to":"s_bg","level":"established","effect":"located","note":"Part of the basal ganglia (the circuit's brake)."},{"from":"movement","to":"br_stn","level":"established","effect":"located","note":"With too little dopamine the subthalamic nucleus over-brakes movement, adding to slowness."},{"from":"chorea","to":"br_caudate","level":"established","effect":"located","note":"Writhing movements in Huntington's come from loss of neurons in the caudate and putamen."},{"from":"chorea","to":"br_stn","level":"established","effect":"located","note":"Damage to the subthalamic nucleus removes the brake and causes flinging, writhing movements."},{"from":"tics","to":"br_caudate","level":"established","effect":"located","note":"The caudate is part of the loop that normally holds back unwanted movements and sounds."},{"from":"ocd","to":"br_caudate","level":"established","effect":"located","note":"The caudate is part of the front-of-brain loop that keeps repeating in obsessions and compulsions."},{"from":"adhd","to":"br_caudate","level":"established","effect":"located","note":"The caudate helps hold attention and stop impulses, and works with the prefrontal cortex."},{"from":"apathy","to":"br_accumbens","level":"established","effect":"located","note":"The accumbens turns wanting into effort, so low dopamine here can leave people unmotivated."},{"from":"huntingtons","to":"br_caudate","level":"established","effect":"affects","note":"Huntington's destroys neurons in the caudate first."},{"from":"tourette","to":"br_caudate","level":"established","effect":"affects","note":"Tics are thought to come from the loop between the cortex and the striatum, including the caudate."},{"from":"adhd_c","to":"br_caudate","level":"association","effect":"affects","note":"Large brain-scan studies find the caudate slightly smaller in ADHD, mostly in children.","sources":[{"id":"pmid:28219628","citation":"Hoogman M et al., Lancet Psychiatry","year":2017,"design":"case-control","finding":"In 1713 people with ADHD vs 1529 controls, the accumbens, amygdala, caudate, hippocampus and putamen were slightly smaller, most clearly in children."}]},{"from":"adhd_c","to":"br_accumbens","level":"association","effect":"affects","note":"Large brain-scan studies find the accumbens, a reward area, slightly smaller in ADHD.","sources":[{"id":"pmid:28219628","citation":"Hoogman M et al., Lancet Psychiatry","year":2017,"design":"case-control","finding":"In 1713 people with ADHD vs 1529 controls, the accumbens, amygdala, caudate, hippocampus and putamen were slightly smaller, most clearly in children."}]},{"from":"ocd_c","to":"br_caudate","level":"association","effect":"affects","note":"Brain-scan studies consistently find the caudate working differently in OCD.","sources":[{"id":"pmid:15546704","citation":"Whiteside SP et al., Psychiatry Res","year":2004,"design":"meta-analysis","finding":"Across PET and SPECT studies, brain activity differed consistently between OCD and controls in the orbital gyrus and the head of the caudate."},{"id":"pmid:18061263","citation":"Menzies L et al., Neurosci Biobehav Rev","year":2008,"design":"meta-analysis","finding":"A voxel-level meta-analysis of functional MRI found consistent abnormalities in orbitofronto-striatal areas in OCD."}]},{"from":"br_thalamus","to":"s_bg","level":"established","effect":"located","note":"Part of the basal ganglia–thalamus–cortex movement loop (its relay station)."},{"from":"br_thalamus","to":"s_cortex","level":"established","effect":"located","note":"Part of the thalamus–cortex system that feeds the cortex its input."},{"from":"br_hypothalamus","to":"s_hypo","level":"established","effect":"located","note":"Part of the hypothalamus and body clock system."},{"from":"br_scn","to":"s_hypo","level":"established","effect":"located","note":"Part of the hypothalamus (it is the body's master clock)."},{"from":"br_nbm","to":"s_cortex","level":"established","effect":"located","note":"Part of the basal forebrain system that supplies the cortex with acetylcholine."},{"from":"tremor","to":"br_thalamus","level":"established","effect":"located","note":"Tremor signals pass through the thalamus's tremor relay on the way to the motor cortex."},{"from":"insomnia","to":"br_scn","level":"established","effect":"located","note":"When the body clock is weak or shifted, night sleep breaks up."},{"from":"insomnia","to":"br_hypothalamus","level":"established","effect":"located","note":"The hypothalamus holds the sleep and wake switches."},{"from":"sleepy","to":"br_hypothalamus","level":"established","effect":"located","note":"Orexin cells in the hypothalamus keep us awake; when they fail, daytime sleepiness follows."},{"from":"nutrition","to":"br_hypothalamus","level":"established","effect":"located","note":"The hypothalamus sets hunger and fullness."},{"from":"dehydration","to":"br_hypothalamus","level":"established","effect":"located","note":"The hypothalamus creates thirst; a weaker thirst signal leads to drinking less."},{"from":"memory","to":"br_nbm","level":"established","effect":"located","note":"Acetylcholine from the nucleus basalis helps the cortex and hippocampus store memories."},{"from":"cognition","to":"br_nbm","level":"established","effect":"located","note":"Acetylcholine from the nucleus basalis keeps attention sharp."},{"from":"pain","to":"br_thalamus","level":"established","effect":"located","note":"Pain signals pass through the thalamus on their way to the cortex."},{"from":"parkinsons","to":"br_nbm","level":"established","effect":"affects","note":"The nucleus basalis loses neurons in Parkinson's, linked to thinking problems."},{"from":"lewy","to":"br_nbm","level":"established","effect":"affects","note":"Dementia with Lewy bodies causes heavy loss of acetylcholine neurons in the nucleus basalis."},{"from":"alzheimers","to":"br_nbm","level":"established","effect":"affects","note":"Alzheimer's destroys acetylcholine neurons in the nucleus basalis."},{"from":"essential_tremor","to":"br_thalamus","level":"established","effect":"affects","note":"The thalamus relays the tremor signal and is the main surgical target for essential tremor."},{"from":"hm_cortisol","to":"s_adrenal","level":"established","effect":"located","note":"Made in the outer layer of the adrenal glands."},{"from":"hm_adrenaline","to":"s_adrenal","level":"established","effect":"located","note":"Made in the inner core of the adrenal glands."},{"from":"hm_cortisol","to":"m_inflam","level":"established","effect":"helps","note":"Cortisol is the body's own brake on inflammation."},{"from":"hm_cortisol","to":"m_bone","level":"established","effect":"harms","note":"Cortisol that stays high for a long time thins bone and wastes muscle."},{"from":"hm_cortisol","to":"memory","level":"association","effect":"harms","note":"Older people whose cortisol stays high for years tend to have a smaller memory centre and poorer memory.","sources":[{"id":"pmid:10195112","citation":"Lupien SJ et al., Nat Neurosci","year":1998,"design":"cohort","finding":"Older people whose cortisol stayed high over years had a smaller hippocampus and worse memory than those with normal cortisol."},{"id":"pmid:30881301","citation":"Ouanes S, Popp J, Front Aging Neurosci","year":2019,"design":"review","finding":"Higher cortisol is linked with poorer memory and thinking and a higher risk of later cognitive decline and Alzheimer's."}]},{"from":"depression_c","to":"hm_cortisol","level":"association","effect":"affects","note":"Depression often goes with raised cortisol, especially severe and melancholic forms.","sources":[{"id":"pmid:21257974","citation":"Stetler C, Miller GE, Psychosom Med","year":2011,"design":"meta-analysis","finding":"Across 361 studies, people with depression tended to have higher cortisol, about half as large in the best-designed studies."}]},{"from":"hm_adrenaline","to":"tremor","level":"established","effect":"harms","note":"Adrenaline makes every kind of tremor larger."},{"from":"hm_adrenaline","to":"anxiety","level":"established","effect":"harms","note":"Adrenaline produces the racing heart, shaking and sweating felt in anxiety."},{"from":"hm_adrenaline","to":"m_bp","level":"established","effect":"helps","note":"Adrenaline and noradrenaline tighten blood vessels and hold blood pressure up."},{"from":"hm_thyroid","to":"s_thyroid","level":"established","effect":"located","note":"Made in the thyroid gland in the neck."},{"from":"hm_thyroid","to":"fatigue","level":"established","effect":"helps","note":"Too little thyroid hormone causes tiredness; bringing a low level back to normal relieves it, but extra does not add energy.","dose":"deficiency"},{"from":"hm_thyroid","to":"depression","level":"established","effect":"helps","note":"Low thyroid hormone can cause low mood, which lifts when the level is corrected."},{"from":"hm_thyroid","to":"cognition","level":"established","effect":"helps","note":"Low thyroid hormone slows thinking and memory; it is a reversible cause checked in anyone with new memory problems."},{"from":"hm_thyroid","to":"constipation","level":"established","effect":"helps","note":"Low thyroid hormone slows the gut and causes constipation."},{"from":"hm_oestrogen","to":"s_ovaries","level":"established","effect":"located","note":"Made mainly in the ovaries before menopause."},{"from":"hm_progesterone","to":"s_ovaries","level":"established","effect":"located","note":"Made in the ovaries after an egg is released."},{"from":"hm_testosterone","to":"s_testes","level":"established","effect":"located","note":"Made mainly in the testes."},{"from":"hm_oestrogen","to":"m_bone","level":"established","effect":"helps","note":"Oestrogen slows bone breakdown; bone loss speeds up when it falls at menopause."},{"from":"hm_testosterone","to":"m_bone","level":"established","effect":"helps","note":"Testosterone builds muscle and bone density, and low levels lead to loss of both; but raising it with treatment has not been shown to prevent fractures."},{"from":"hm_oestrogen","to":"cognition","level":"failed","effect":"helps","note":"Hormone therapy (oestrogen plus progestin) started at 65 or older did not protect thinking and raised dementia risk in a large trial.","sources":[{"id":"pmid:12771112","citation":"Shumaker SA et al., JAMA","year":2003,"design":"RCT","finding":"In women aged 65 or older, oestrogen plus progestin did not prevent mild cognitive impairment and doubled the rate of probable dementia compared with placebo."}]},{"from":"hm_testosterone","to":"depression","level":"mixed","effect":"helps","note":"In men with low testosterone, treatment lifted mood a little in large trials, but the effect is small and was not seen in every group.","sources":[{"id":"pmid:30427999","citation":"Walther A et al., JAMA Psychiatry","year":2019,"design":"meta-analysis","finding":"Across 27 randomised trials in 1,890 men, testosterone treatment reduced depressive symptoms slightly more than placebo, with large differences between trials."},{"id":"pmid:26886521","citation":"Snyder PJ et al., N Engl J Med","year":2016,"design":"RCT","finding":"In 790 men aged 65+ with low testosterone, a year of testosterone gel moderately improved sexual function and slightly improved mood, but not vitality or walking distance."},{"id":"pmid:38205962","citation":"Bhasin S et al., J Clin Endocrinol Metab","year":2024,"design":"RCT","finding":"In the TRAVERSE trial of 5,204 men with low testosterone, treatment gave modest improvements in mood and energy but not in thinking or sleep quality; in the few men with long-lasting low-grade depression there was no clear difference."}]},{"from":"hm_testosterone","to":"fatigue","level":"failed","effect":"helps","note":"In a small trial in men with Parkinson's and low testosterone, testosterone did not reduce fatigue or other symptoms.","scope":["parkinsons"],"sources":[{"id":"pmid:16682542","citation":"Okun MS et al., Arch Neurol","year":2006,"design":"RCT","finding":"In a small 8-week placebo-controlled trial in men with Parkinson's and low testosterone, testosterone did not improve fatigue, mood or other non-movement or movement symptoms."}]},{"from":"hm_insulin","to":"s_pancreas","level":"established","effect":"located","note":"Made in the islets of the pancreas."},{"from":"hm_glucagon","to":"s_pancreas","level":"established","effect":"located","note":"Made in the islets of the pancreas."},{"from":"hm_leptin","to":"s_fat","level":"established","effect":"located","note":"Made by fat cells."},{"from":"hm_ghrelin","to":"s_gut","level":"established","effect":"located","note":"Made mainly in the stomach lining."},{"from":"hm_ghrelin","to":"m_motility","level":"established","effect":"helps","note":"Ghrelin speeds up stomach emptying."},{"from":"exercise","to":"hm_insulin","level":"proven","effect":"harms","note":"Regular exercise makes the body respond better to insulin, so it needs less and blood insulin falls.","sources":[{"id":"pmid:27535644","citation":"Way KL et al., Diabetes Metab J","year":2016,"design":"meta-analysis","finding":"Pooled randomised trials in adults with type 2 diabetes showed regular exercise clearly improved insulin sensitivity, lasting beyond 72 hours after the last session."}]},{"from":"hm_insulin","to":"alzheimers","level":"association","effect":"harms","note":"Persistently high insulin, a sign the body resists it, is linked to more Alzheimer's plaques in the brain years later.","sources":[{"id":"pmid:20739649","citation":"Matsuzaki T et al., Neurology","year":2010,"design":"cohort","finding":"In 135 autopsies from the Hisayama town study, higher fasting insulin and insulin resistance measured years earlier went with more Alzheimer's plaques (but not tangles)."}]},{"from":"hm_melatonin","to":"s_pineal","level":"established","effect":"located","note":"Made in the pineal gland at night."},{"from":"melatonin","to":"hm_melatonin","level":"established","effect":"helps","note":"Taking melatonin raises blood levels of it for a few hours."},{"from":"hm_melatonin","to":"m_clock","level":"established","effect":"helps","note":"Melatonin is the night signal that keeps the body clock in time."},{"from":"light","to":"hm_melatonin","level":"established","effect":"helps","note":"Daylight sets when the night-time melatonin rise happens; bright light at night switches it off."},{"from":"parkinsons","to":"hm_melatonin","level":"association","effect":"affects","note":"People with Parkinson's have a flatter, lower 24-hour melatonin rhythm.","sources":[{"id":"pmid:24566763","citation":"Videnovic A et al., JAMA Neurol","year":2014,"design":"case-control","finding":"People with Parkinson's had a flatter 24-hour melatonin rhythm with lower total melatonin than controls, and the lowest levels went with the most daytime sleepiness."}]},{"from":"hm_melatonin","to":"sleepy","level":"association","effect":"helps","note":"In Parkinson's, a weaker melatonin rhythm goes with more daytime sleepiness.","scope":["parkinsons"],"sources":[{"id":"pmid:24566763","citation":"Videnovic A et al., JAMA Neurol","year":2014,"design":"case-control","finding":"People with Parkinson's had a flatter 24-hour melatonin rhythm with lower total melatonin than controls, and the lowest levels went with the most daytime sleepiness."}]},{"from":"hm_oxytocin","to":"s_hypo","level":"established","effect":"located","note":"Made in the hypothalamus, then released from the back of the pituitary."},{"from":"hm_vasopressin","to":"s_hypo","level":"established","effect":"located","note":"Made in the hypothalamus, then released from the back of the pituitary."},{"from":"social","to":"hm_oxytocin","level":"mixed","effect":"helps","note":"Close company is weakly linked with higher oxytocin, but experiments adding social contact often do not raise it.","sources":[{"id":"pmid:38713749","citation":"Burenkova OV et al., Psychol Bull","year":2023,"design":"meta-analysis","finding":"Across 51 studies, social contact correlated weakly with oxytocin levels, but experiments that added social interaction did not reliably raise it."}]},{"from":"hm_vasopressin","to":"m_bp","level":"established","effect":"helps","note":"Vasopressin keeps water in the blood and tightens vessels, holding blood pressure up."},{"from":"hm_vasopressin","to":"bladder","level":"established","effect":"helps","note":"Vasopressin cuts how much urine the kidneys make, especially at night."},{"from":"vitd","to":"hm_calcitriol","level":"established","effect":"helps","note":"The liver and kidneys turn vitamin D into calcitriol; extra vitamin D beyond normal levels does not raise it much because the kidneys control the final step.","dose":"deficiency"},{"from":"hm_calcitriol","to":"m_bone","level":"established","effect":"helps","note":"Calcitriol makes the gut absorb calcium, which bone needs."},{"from":"hm_gh","to":"s_pituitary","level":"established","effect":"located","note":"Made in the front of the pituitary gland."},{"from":"hm_prolactin","to":"s_pituitary","level":"established","effect":"located","note":"Made in the front of the pituitary gland."},{"from":"hm_gh","to":"m_bone","level":"established","effect":"helps","note":"Growth hormone (through IGF-1) builds and maintains bone and muscle."},{"from":"insomnia","to":"hm_gh","level":"established","effect":"harms","note":"Most growth hormone is released in deep sleep, so broken sleep lowers it."},{"from":"levodopa","to":"hm_prolactin","level":"established","effect":"harms","note":"Dopamine is the brake on prolactin, so levodopa lowers prolactin levels."},{"from":"hm_prolactin","to":"m_bone","level":"established","effect":"harms","note":"Prolactin that stays high switches off sex hormones, which thins bone."},{"from":"zinc","to":"s_immune","level":"established","effect":"helps","note":"Needed by immune cells; lack raises infections. Extra isn't shown to help people who aren't low.","dose":"deficiency"},{"from":"zinc","to":"s_smell","level":"established","effect":"helps","note":"Needed for normal taste and smell, and lack dulls them; but zinc sprayed into the nose has caused lasting smell loss.","sources":[{"id":"pmid:16467707","citation":"Alexander TH, Davidson TM, Laryngoscope","year":2006,"design":"case series","finding":"Seventeen people lost their sense of smell after using intranasal zinc gluconate gel for colds."}]},{"from":"zinc","to":"s_skin","level":"established","effect":"helps","note":"Needed for skin repair and wound healing."},{"from":"zinc","to":"copper","level":"established","effect":"harms","note":"Long-term high zinc intake blocks copper absorption and can cause copper deficiency.","dose":"excess","sources":[{"id":"pmid:17036563","citation":"Kumar N, Mayo Clin Proc","year":2006,"design":"review","finding":"Acquired copper deficiency causes a spinal cord disease (spastic, unsteady gait) like B12 deficiency, plus anaemia; known causes include gastric surgery, malabsorption and excessive zinc intake."}]},{"from":"shellfish","to":"zinc","level":"established","effect":"contains","note":"Oysters are by far the richest zinc source."},{"from":"redmeat","to":"zinc","level":"established","effect":"contains","note":"Red meat is a main zinc source."},{"from":"legumes","to":"zinc","level":"established","effect":"contains","note":"Beans and lentils contain zinc, less well absorbed than from meat."},{"from":"nuts","to":"zinc","level":"established","effect":"contains","note":"Pumpkin seeds and cashews contain zinc."},{"from":"oats","to":"zinc","level":"established","effect":"contains","note":"Whole grains contain zinc."},{"from":"copper","to":"s_spinal","level":"established","effect":"helps","note":"Needed to keep spinal-cord myelin; deficiency causes a stiff, unsteady walk like B12 deficiency.","sources":[{"id":"pmid:17036563","citation":"Kumar N, Mayo Clin Proc","year":2006,"design":"review","finding":"Acquired copper deficiency causes a spinal cord disease (spastic, unsteady gait) like B12 deficiency, plus anaemia; known causes include gastric surgery, malabsorption and excessive zinc intake."}]},{"from":"copper","to":"s_marrow","level":"established","effect":"helps","note":"Needed to make red and white blood cells; lack causes anaemia."},{"from":"copper","to":"m_catechol","level":"established","effect":"helps","note":"The enzyme that turns dopamine into noradrenaline needs copper.","dose":"deficiency"},{"from":"shellfish","to":"copper","level":"established","effect":"contains","note":"Oysters and other shellfish are rich in copper."},{"from":"liver","to":"copper","level":"established","effect":"contains","note":"Liver is the richest food source of copper."},{"from":"nuts","to":"copper","level":"established","effect":"contains","note":"Nuts and seeds contain copper."},{"from":"cocoa","to":"copper","level":"established","effect":"contains","note":"Dark chocolate and cocoa contain copper."},{"from":"manganese","to":"m_oxid","level":"established","effect":"helps","note":"Needed for the main antioxidant enzyme inside mitochondria (MnSOD).","dose":"deficiency"},{"from":"manganese","to":"movement","level":"established","effect":"harms","note":"Heavy exposure (welding fumes, mining, contaminated water) or poor liver clearance builds manganese up in the basal ganglia and causes parkinsonism that levodopa helps little.","dose":"excess","sources":[{"id":"pmid:37627255","citation":"Lucchini R, Tieu K, Biomolecules","year":2023,"design":"review","finding":"High manganese exposure causes manganism by damaging the globus pallidus, and long-term lower exposure is linked in epidemiological studies to parkinsonism and Parkinson's."},{"id":"pmid:40496384","citation":"Khindri NM, Maj MC, Degener Neurol Neuromuscul Dis","year":2025,"design":"review","finding":"Reviews the causes, mechanisms and treatments of manganese-induced parkinsonism, a neurotoxic effect of high manganese exposure."}]},{"from":"oats","to":"manganese","level":"established","effect":"contains","note":"Whole grains are a main manganese source."},{"from":"nuts","to":"manganese","level":"established","effect":"contains","note":"Nuts are rich in manganese."},{"from":"greentea","to":"manganese","level":"established","effect":"contains","note":"Tea is one of the main sources of manganese in many diets."},{"from":"thiamine","to":"m_oxid","level":"established","effect":"helps","note":"Needed for mitochondria to turn sugar into energy; extra isn't shown to protect them.","dose":"deficiency"},{"from":"thiamine","to":"memory","level":"established","effect":"helps","note":"Deficiency causes Wernicke–Korsakoff syndrome with lasting memory loss; replacing thiamine prevents it, extra in well-fed people does not help memory.","dose":"deficiency"},{"from":"thiamine","to":"neuropathy","level":"established","effect":"helps","note":"Deficiency (beriberi) damages leg nerves; replacing it helps only when low.","dose":"deficiency"},{"from":"oats","to":"thiamine","level":"established","effect":"contains","note":"Whole grains are a main thiamine source; white flour loses most of it unless fortified."},{"from":"legumes","to":"thiamine","level":"established","effect":"contains","note":"Beans and lentils contain thiamine."},{"from":"redmeat","to":"thiamine","level":"established","effect":"contains","note":"Pork is especially rich in thiamine."},{"from":"riboflavin","to":"m_oxid","level":"established","effect":"helps","note":"Built into FAD and FMN, which mitochondria need to make energy.","dose":"deficiency"},{"from":"riboflavin","to":"m_methyl","level":"established","effect":"helps","note":"Needed by the enzyme (MTHFR) that recycles folate, and to activate B6.","dose":"deficiency"},{"from":"dairy","to":"riboflavin","level":"established","effect":"contains","note":"Milk and yoghurt are main riboflavin sources."},{"from":"eggs","to":"riboflavin","level":"established","effect":"contains","note":"Eggs contain riboflavin."},{"from":"mushrooms","to":"riboflavin","level":"established","effect":"contains","note":"Mushrooms are a good plant source of riboflavin."},{"from":"niacin","to":"m_oxid","level":"established","effect":"helps","note":"Made into NAD, which mitochondria need to make energy and cells need to repair DNA.","dose":"deficiency"},{"from":"niacin","to":"cognition","level":"established","effect":"helps","note":"Severe deficiency (pellagra) causes confusion and dementia that reverse with niacin; extra in well-fed people isn't shown to help thinking.","dose":"deficiency"},{"from":"poultry","to":"niacin","level":"established","effect":"contains","note":"Chicken and turkey are rich in niacin."},{"from":"peanuts","to":"niacin","level":"established","effect":"contains","note":"Peanuts are among the richest plant sources of niacin."},{"from":"pantothenic","to":"m_oxid","level":"established","effect":"helps","note":"Built into coenzyme A, needed to burn fat and sugar in mitochondria.","dose":"deficiency"},{"from":"mushrooms","to":"pantothenic","level":"established","effect":"contains","note":"Mushrooms are rich in pantothenic acid."},{"from":"eggs","to":"biotin","level":"established","effect":"contains","note":"Cooked egg yolk is a good biotin source (raw white blocks it)."},{"from":"biotin","to":"ms","level":"failed","effect":"helps","note":"High-dose biotin did not improve disability in progressive multiple sclerosis in a large placebo-controlled trial.","sources":[{"id":"pmid:33222767","citation":"Cree BAC et al., Lancet Neurol","year":2020,"design":"RCT","finding":"In the phase 3 SPI2 trial in progressive MS, high-dose biotin (MD1003) did not improve disability or walking versus placebo."}]},{"from":"b6","to":"neuropathy","level":"established","effect":"harms","note":"Long-term high-dose B6 supplements can themselves damage sensory nerves, causing numbness and unsteadiness that usually improve after stopping (normal dietary B6 is needed by nerves).","dose":"excess","sources":[{"id":"pmid:6308447","citation":"Schaumburg H et al., N Engl J Med","year":1983,"design":"case-control","finding":"Seven adults developed ataxia and severe sensory neuropathy after taking high daily doses of pyridoxine (B6); all improved after stopping."},{"id":"pmid:1620347","citation":"Berger AR et al., Neurology","year":1992,"design":"lab","finding":"A prospective dosing study in healthy volunteers showed pyridoxine causes sensory nerve damage in a dose-dependent way, with symptoms that can keep worsening for weeks after stopping."}]},{"from":"greens","to":"folate","level":"established","effect":"contains","note":"Leafy greens are a main folate source (the name comes from 'foliage')."},{"from":"legumes","to":"folate","level":"established","effect":"contains","note":"Lentils, beans and chickpeas are rich in folate."},{"from":"brassicas","to":"folate","level":"established","effect":"contains","note":"Broccoli and other cabbage-family vegetables contain folate."},{"from":"fortified","to":"folate","level":"established","effect":"contains","note":"Folic acid is added to many breakfast cereals, flours and nutritional yeast."},{"from":"liver","to":"folate","level":"established","effect":"contains","note":"Liver is very rich in folate."},{"from":"eggs","to":"choline","level":"established","effect":"contains","note":"Egg yolk is one of the richest everyday sources of choline."},{"from":"liver","to":"choline","level":"established","effect":"contains","note":"Liver is very rich in choline."},{"from":"redmeat","to":"choline","level":"established","effect":"contains","note":"Meat supplies choline."},{"from":"legumes","to":"choline","level":"established","effect":"contains","note":"Beans and especially soy contain some choline."},{"from":"brassicas","to":"choline","level":"established","effect":"contains","note":"Broccoli and Brussels sprouts contain modest choline."},{"from":"folate","to":"m_methyl","level":"established","effect":"helps","note":"Needed, with B12, to recycle homocysteine; extra beyond a normal diet isn't shown to protect the brain.","dose":"deficiency"},{"from":"folate","to":"s_marrow","level":"established","effect":"helps","note":"Needed to make red blood cells in the bone marrow; too little causes anaemia."},{"from":"folate","to":"s_spinal","level":"proven","effect":"helps","note":"Folic acid taken before and in early pregnancy prevents most spina bifida and other neural-tube defects in the baby.","scope":["pregnancy"],"sources":[{"id":"pmid:1677062","citation":"MRC Vitamin Study Research Group, Lancet","year":1991,"design":"RCT","finding":"In 1,817 women at high risk, folic acid around conception cut neural-tube defects by 72% (RR 0.28); a mix of seven other vitamins had no significant effect."}]},{"from":"b12","to":"neuropathy","level":"established","effect":"helps","note":"Low B12 strips nerve insulation and causes numb feet; correcting a low level helps, extra above normal doesn't.","dose":"deficiency"},{"from":"b12","to":"s_marrow","level":"established","effect":"helps","note":"Needed to make red blood cells; low B12 causes anaemia."},{"from":"choline","to":"m_methyl","level":"established","effect":"helps","note":"Its breakdown product betaine donates methyl groups to recycle homocysteine.","dose":"deficiency"},{"from":"choline","to":"s_liver","level":"established","effect":"helps","note":"Needed to carry fat out of the liver; too little causes fatty liver."},{"from":"calcium","to":"m_bone","level":"established","effect":"helps","note":"The main mineral of bone; needed, absorbed with vitamin D. Extra beyond a normal diet does little for fractures.","dose":"deficiency"},{"from":"calcium","to":"s_muscle","level":"established","effect":"helps","note":"Every muscle contraction is triggered by calcium."},{"from":"dairy","to":"calcium","level":"established","effect":"contains","note":"Milk, yoghurt and cheese are the main calcium source in many diets."},{"from":"brassicas","to":"calcium","level":"established","effect":"contains","note":"Kale, bok choy and broccoli contain well-absorbed calcium."},{"from":"greens","to":"calcium","level":"established","effect":"contains","note":"Spinach and chard contain calcium, but oxalate in them blocks most of its absorption."},{"from":"fortified","to":"calcium","level":"established","effect":"contains","note":"Many plant milks and some tofu have calcium added."},{"from":"oilyfish","to":"calcium","level":"established","effect":"contains","note":"Tinned sardines and salmon eaten with their soft bones are rich in calcium."},{"from":"phosphorus","to":"m_bone","level":"established","effect":"helps","note":"Joins calcium to form bone mineral; most diets have plenty.","dose":"deficiency"},{"from":"dairy","to":"phosphorus","level":"established","effect":"contains","note":"Milk and cheese are rich in phosphorus."},{"from":"redmeat","to":"phosphorus","level":"established","effect":"contains","note":"Meat is rich in phosphorus."},{"from":"potassium","to":"m_excit","level":"established","effect":"helps","note":"Nerves and muscles fire by moving potassium and sodium across their membranes.","dose":"deficiency"},{"from":"potassium","to":"s_heart","level":"established","effect":"helps","note":"Needed for a steady heartbeat; both too little and too much cause dangerous rhythms."},{"from":"bananas","to":"potassium","level":"established","effect":"contains","note":"Bananas are a well-known potassium source."},{"from":"potatoes","to":"potassium","level":"established","effect":"contains","note":"Potatoes are one of the richest everyday potassium sources."},{"from":"legumes","to":"potassium","level":"established","effect":"contains","note":"Beans and lentils are rich in potassium."},{"from":"prunes","to":"potassium","level":"established","effect":"contains","note":"Prunes and other dried fruit are rich in potassium."},{"from":"sodium","to":"m_bp","level":"established","effect":"helps","note":"Salt holds water in the bloodstream, keeping blood volume up, which helps when pressure drops on standing; too much raises blood pressure in most people."},{"from":"fermented","to":"sodium","level":"established","effect":"contains","note":"Pickles, sauerkraut, miso and soy sauce are very salty."},{"from":"olives","to":"sodium","level":"established","effect":"contains","note":"Brined olives are salty (olive oil is not)."},{"from":"dairy","to":"sodium","level":"established","effect":"contains","note":"Cheese is often salty."},{"from":"redmeat","to":"sodium","level":"established","effect":"contains","note":"Processed meats (ham, bacon, sausages) are high in salt."},{"from":"vite","to":"m_oxid","level":"established","effect":"helps","note":"The main antioxidant in cell membranes; needed, but extra hasn't been shown to protect brain cells in people.","dose":"deficiency"},{"from":"vite","to":"neuropathy","level":"established","effect":"helps","note":"Deficiency (usually from poor fat absorption) damages nerves; replacing it helps only when low.","dose":"deficiency"},{"from":"vite","to":"progression","level":"failed","effect":"helps","note":"High-dose vitamin E (tocopherol) did not delay disability in early Parkinson's in the large DATATOP trial.","sources":[{"id":"pmid:8417384","citation":"Parkinson Study Group, N Engl J Med","year":1993,"design":"RCT","finding":"In 800 people with early Parkinson's, tocopherol had no benefit on time until levodopa was needed, alone or with deprenyl."}]},{"from":"nuts","to":"vite","level":"established","effect":"contains","note":"Almonds, sunflower and other seeds are among the richest vitamin E sources."},{"from":"peanuts","to":"vite","level":"established","effect":"contains","note":"Peanuts contain vitamin E."},{"from":"olives","to":"vite","level":"established","effect":"contains","note":"Olive oil contains vitamin E."},{"from":"greens","to":"vite","level":"established","effect":"contains","note":"Spinach and other greens contain some vitamin E."},{"from":"vitk","to":"s_blood","level":"established","effect":"helps","note":"Needed to make the clotting proteins that stop bleeding; lack causes easy bleeding."},{"from":"vitk","to":"s_bones","level":"established","effect":"helps","note":"Switches on bone proteins that hold calcium; extra isn't shown to prevent fractures.","dose":"deficiency"},{"from":"greens","to":"vitk","level":"established","effect":"contains","note":"Leafy greens are the richest source of vitamin K1."},{"from":"brassicas","to":"vitk","level":"established","effect":"contains","note":"Kale, broccoli and cabbage are rich in vitamin K1."},{"from":"fermented","to":"vitk","level":"established","effect":"contains","note":"Fermented foods such as natto and some cheeses contain vitamin K2, made by bacteria."},{"from":"liver","to":"vitk","level":"established","effect":"contains","note":"Liver contains vitamin K2."},{"from":"eggs","to":"vitk","level":"established","effect":"contains","note":"Egg yolk contains some vitamin K2."},{"from":"vita","to":"s_eyes","level":"established","effect":"helps","note":"Needed to see in dim light and to keep the eye surface healthy; lack causes night blindness."},{"from":"vita","to":"s_immune","level":"established","effect":"helps","note":"Needed for immune defences and healthy linings; lack makes infections more severe. Extra beyond normal doesn't boost immunity.","dose":"deficiency"},{"from":"vita","to":"s_skin","level":"established","effect":"helps","note":"Needed to renew skin and the linings of the body."},{"from":"liver","to":"vita","level":"established","effect":"contains","note":"Liver is so rich in ready-made vitamin A that eating it often can exceed safe levels."},{"from":"dairy","to":"vita","level":"established","effect":"contains","note":"Ready-made vitamin A in whole milk, butter and cheese."},{"from":"eggs","to":"vita","level":"established","effect":"contains","note":"Ready-made vitamin A in the yolk."},{"from":"greens","to":"vita","level":"established","effect":"contains","note":"Beta-carotene, which the body turns into vitamin A as needed."},{"from":"brassicas","to":"vita","level":"established","effect":"contains","note":"Kale and other dark-green cabbages supply beta-carotene."},{"from":"peppers","to":"vita","level":"established","effect":"contains","note":"Red and orange peppers supply beta-carotene."},{"from":"vitc","to":"s_skin","level":"established","effect":"helps","note":"Needed to make collagen for skin and wound healing; extra beyond normal isn't shown to do more.","dose":"deficiency"},{"from":"vitc","to":"s_blood","level":"established","effect":"helps","note":"Needed for strong blood-vessel walls and gums; lack (scurvy) causes bleeding and bruising."},{"from":"vitc","to":"s_immune","level":"established","effect":"helps","note":"Needed by white blood cells; extra doesn't prevent colds in most people.","dose":"deficiency"},{"from":"vitc","to":"iron","level":"established","effect":"helps","note":"Taken in the same meal, it helps the gut absorb iron from plant foods."},{"from":"vitc","to":"m_oxid","level":"established","effect":"helps","note":"The main water-soluble antioxidant; extra hasn't been shown to slow brain disease.","dose":"deficiency"},{"from":"peppers","to":"vitc","level":"established","effect":"contains","note":"Peppers, especially red, are among the richest sources of vitamin C."},{"from":"kiwifruit","to":"vitc","level":"established","effect":"contains","note":"Kiwifruit are very rich in vitamin C."},{"from":"brassicas","to":"vitc","level":"established","effect":"contains","note":"Broccoli, Brussels sprouts and kale are rich in vitamin C."},{"from":"berries","to":"vitc","level":"established","effect":"contains","note":"Berries contain vitamin C."},{"from":"tomatoes","to":"vitc","level":"established","effect":"contains","note":"Tomatoes contain vitamin C."},{"from":"potatoes","to":"vitc","level":"established","effect":"contains","note":"Potatoes supply useful vitamin C in many diets."},{"from":"greens","to":"vitc","level":"established","effect":"contains","note":"Raw leafy greens contain vitamin C; cooking loses some."},{"from":"selenium","to":"m_oxid","level":"established","effect":"helps","note":"Built into antioxidant enzymes (glutathione peroxidases); needed, but extra isn't shown to protect.","dose":"deficiency"},{"from":"selenium","to":"s_immune","level":"established","effect":"helps","note":"Selenoproteins are needed by immune cells; extra isn't shown to boost immunity.","dose":"deficiency"},{"from":"nuts","to":"selenium","level":"established","effect":"contains","note":"Brazil nuts are so rich in selenium that a few a day can exceed safe amounts; other nuts have little."},{"from":"oilyfish","to":"selenium","level":"established","effect":"contains","note":"Fish are a reliable selenium source."},{"from":"whitefish","to":"selenium","level":"established","effect":"contains","note":"Sea fish are a reliable selenium source."},{"from":"shellfish","to":"selenium","level":"established","effect":"contains","note":"Shellfish are rich in selenium."},{"from":"eggs","to":"selenium","level":"established","effect":"contains","note":"Eggs contain selenium."},{"from":"poultry","to":"selenium","level":"established","effect":"contains","note":"Chicken and turkey contain selenium."},{"from":"iodine","to":"cognition","level":"established","effect":"helps","note":"Needed to make thyroid hormone; deficiency slows thinking in adults and, in pregnancy and infancy, harms brain development. Extra doesn't help.","dose":"deficiency"},{"from":"iodine","to":"fatigue","level":"established","effect":"helps","note":"Deficiency causes an underactive thyroid with tiredness; extra iodine doesn't help tiredness from other causes.","dose":"deficiency"},{"from":"algae","to":"iodine","level":"established","effect":"contains","note":"Seaweed is extremely rich in iodine; some kinds (kelp) can supply far too much."},{"from":"dairy","to":"iodine","level":"established","effect":"contains","note":"Milk is a main iodine source in many countries (from cattle feed and dairy cleaning)."},{"from":"whitefish","to":"iodine","level":"established","effect":"contains","note":"Sea fish such as cod and haddock are rich in iodine."},{"from":"eggs","to":"iodine","level":"established","effect":"contains","note":"Eggs contain iodine."},{"from":"shellfish","to":"iodine","level":"established","effect":"contains","note":"Shellfish contain iodine."},{"from":"cdiff","to":"m_barrier","level":"established","effect":"harms","note":"Its toxins damage the colon lining."},{"from":"cdiff","to":"m_inflam","level":"established","effect":"harms","note":"Causes colon inflammation (colitis)."},{"from":"cdiff","to":"s_gut","level":"established","effect":"harms","note":"Causes antibiotic-associated diarrhoea and colitis."},{"from":"probiotics","to":"cdiff","level":"mixed","effect":"helps","note":"Pooled trials found fewer C. diff cases on antibiotics, but the largest single trial found no benefit.","sources":[{"id":"pmid:29257353","citation":"Goldenberg JZ et al., Cochrane Database Syst Rev","year":2017,"design":"meta-analysis","finding":"Pooling 39 randomised trials (9,955 people on antibiotics), probiotics were linked with fewer cases of C. difficile diarrhoea (moderate-certainty evidence)."},{"id":"pmid:23932219","citation":"Allen SJ et al., Lancet (PLACIDE)","year":2013,"design":"RCT","finding":"In about 2,900 older inpatients, a lactobacilli/bifidobacteria mix did not reduce antibiotic-associated or C. difficile diarrhoea."}]},{"from":"salmonella","to":"m_barrier","level":"established","effect":"harms","note":"Invades and damages the intestinal lining."},{"from":"salmonella","to":"s_gut","level":"established","effect":"harms","note":"Causes diarrhoea and gut inflammation."},{"from":"campylobacter","to":"s_gut","level":"established","effect":"harms","note":"Causes diarrhoea and cramps."},{"from":"campylobacter","to":"s_peripheral","level":"established","effect":"harms","note":"Can trigger Guillain-Barré syndrome, an immune attack on the nerves.","sources":[{"id":"pmid:21261199","citation":"Poropatich KO et al., J Health Popul Nutr","year":2010,"design":"review","finding":"Across studies of 2,502 Guillain-Barré cases, about 31% were attributable to preceding Campylobacter infection."}]},{"from":"campylobacter","to":"neuropathy","level":"established","effect":"harms","note":"Guillain-Barré syndrome after infection causes tingling, numbness and weakness.","sources":[{"id":"pmid:21261199","citation":"Poropatich KO et al., J Health Popul Nutr","year":2010,"design":"review","finding":"Across studies of 2,502 Guillain-Barré cases, about 31% were attributable to preceding Campylobacter infection."}]},{"from":"klebsiella","to":"m_inflam","level":"lab","effect":"harms","note":"Strains from saliva drove gut inflammation in mice.","sources":[{"id":"pmid:29051379","citation":"Atarashi K et al., Science","year":2017,"design":"lab","finding":"Klebsiella strains from human saliva colonised the gut of mice, strongly induced inflammatory TH1 immune cells and caused gut inflammation in susceptible hosts."}]},{"from":"fuso","to":"m_inflam","level":"lab","effect":"harms","note":"Created an inflamed environment in colon tumours in mice.","sources":[{"id":"pmid:23954159","citation":"Kostic AD et al., Cell Host Microbe","year":2013,"design":"lab","finding":"Fusobacterium was enriched in human colon adenomas and cancers; in mice F. nucleatum recruited immune cells and created a pro-inflammatory tumour environment."},{"id":"pmid:22009989","citation":"Castellarin M et al., Genome Res","year":2012,"design":"case-control","finding":"Fusobacterium nucleatum was over-represented in human colorectal tumours compared with normal tissue."}]},{"from":"fermented","to":"sthermo","level":"established","effect":"contains","note":"Yogurt is made with live S. thermophilus."},{"from":"greens","to":"oral_nitrate","level":"established","effect":"helps","note":"Leafy greens are rich in nitrate, which these mouth bacteria use."},{"from":"oral_nitrate","to":"m_bp","level":"mixed","effect":"helps","note":"Their nitrite helps blood vessels relax; killing them with mouthwash raised blood pressure in some studies but not others.","sources":[{"id":"pmid:23183324","citation":"Kapil V et al., Free Radic Biol Med","year":2013,"design":"lab","finding":"In 19 healthy volunteers, a week of antiseptic mouthwash cut oral nitrite production by 90% and raised blood pressure by 2-3.5 mmHg."},{"id":"pmid:42754848","citation":"Singh B et al., BMC Cardiovasc Disord","year":2026,"design":"review","finding":"Of nine human studies of antibacterial mouthwash, five found higher blood pressure and four found no effect; evidence judged inconclusive."},{"id":"pmid:41820203","citation":"Toonen LSJ et al., Int J Dent Hyg","year":2026,"design":"meta-analysis","finding":"Five studies: two reported small blood pressure rises after chlorhexidine mouthwash, but the pooled analysis found no significant change in systolic or diastolic pressure."}]},{"from":"nuts","to":"gordonibacter","level":"association","effect":"helps","note":"Walnuts supply the ellagitannins these bacteria turn into urolithins.","sources":[{"id":"pmid:33135412","citation":"Cortés-Martín A et al., J Agric Food Chem","year":2020,"design":"cohort","finding":"Breastfeeding mothers who ate walnuts (an ellagitannin source) passed urolithins into milk according to their urolithin metabotype; Gordonibacter colonisation of babies tracked the mother’s metabotype."}]},{"from":"gordonibacter","to":"m_inflam","level":"lab","effect":"helps","note":"Its urolithins calmed inflammation in animal studies.","sources":[{"id":"pmid:24744017","citation":"Selma MV et al., Int J Syst Evol Microbiol","year":2014,"design":"lab","finding":"Described Gordonibacter urolithinfaciens, a human gut bacterium that turns ellagic acid into urolithins, metabolites with anti-inflammatory activity in animals."}]},{"from":"legumes","to":"equol_makers","level":"established","effect":"helps","note":"Soybeans supply daidzein, which these bacteria turn into equol.","sources":[{"id":"pmid:20519412","citation":"Setchell KD, Clerici C, J Nutr","year":2010,"design":"review","finding":"Equol is made from soy isoflavones (daidzein) by gut bacteria present in only some adults (\"equol producers\")."}]},{"from":"fibre","to":"erectale","level":"established","effect":"helps","note":"Ferments fibre and starch fragments."},{"from":"fibre","to":"ruminococcus","level":"established","effect":"helps","note":"Its specialty is resistant starch, a type of fibre.","sources":[{"id":"pmid:22343308","citation":"Ze X et al., ISME J","year":2012,"design":"lab","finding":"Ruminococcus bromii was uniquely able to start the breakdown of resistant starch and enabled E. rectale, B. thetaiotaomicron and Bifidobacterium to use it in co-culture."}]},{"from":"fibre","to":"btheta","level":"established","effect":"helps","note":"Has enzymes for many kinds of plant fibre."},{"from":"erectale","to":"m_micro","level":"established","effect":"helps","note":"Makes butyrate."},{"from":"ruminococcus","to":"m_micro","level":"established","effect":"helps","note":"Its starch breakdown feeds short-chain fatty acid production."},{"from":"btheta","to":"m_micro","level":"established","effect":"helps","note":"Makes acetate and propionate."},{"from":"ruminococcus","to":"erectale","level":"lab","effect":"helps","note":"Opens up resistant starch so E. rectale can use it.","sources":[{"id":"pmid:22343308","citation":"Ze X et al., ISME J","year":2012,"design":"lab","finding":"Ruminococcus bromii was uniquely able to start the breakdown of resistant starch and enabled E. rectale, B. thetaiotaomicron and Bifidobacterium to use it in co-culture."}]},{"from":"ruminococcus","to":"bifido","level":"lab","effect":"helps","note":"Opens up resistant starch so Bifidobacterium can use it.","sources":[{"id":"pmid:22343308","citation":"Ze X et al., ISME J","year":2012,"design":"lab","finding":"Ruminococcus bromii was uniquely able to start the breakdown of resistant starch and enabled E. rectale, B. thetaiotaomicron and Bifidobacterium to use it in co-culture."}]},{"from":"btheta","to":"m_barrier","level":"lab","effect":"helps","note":"Boosted mucus-making cells in germ-free rats.","sources":[{"id":"pmid:23692866","citation":"Wrzosek L et al., BMC Biol","year":2013,"design":"lab","finding":"In germ-free rats, B. thetaiotaomicron (an acetate maker) increased mucus-making goblet cells; F. prausnitzii (an acetate user and butyrate maker) changed this response."}]},{"from":"btheta","to":"faecali","level":"lab","effect":"helps","note":"Its acetate feeds Faecalibacterium.","sources":[{"id":"pmid:23692866","citation":"Wrzosek L et al., BMC Biol","year":2013,"design":"lab","finding":"In germ-free rats, B. thetaiotaomicron (an acetate maker) increased mucus-making goblet cells; F. prausnitzii (an acetate user and butyrate maker) changed this response."}]},{"from":"christensenella","to":"m_micro","level":"lab","effect":"helps","note":"Raised short-chain fatty acids in mice.","sources":[{"id":"pmid:41356823","citation":"Kong P et al., Front Nutr","year":2025,"design":"lab","finding":"In obese mice, Christensenella intestinihominis raised short-chain-fatty-acid makers and colon propionate and reduced weight gain."}]},{"from":"oscillospira","to":"m_micro","level":"association","effect":"helps","note":"Probably makes butyrate; known from stool DNA, not yet grown alone.","sources":[{"id":"pmid:34693878","citation":"Yang J et al., Gut Microbes","year":2021,"design":"review","finding":"Oscillospira, not yet grown in pure culture, is consistently linked with leanness and is likely a short-chain fatty acid (butyrate) producer."}]},{"from":"hiv","to":"s_immune","level":"established","effect":"harms","note":"Destroys CD4 T cells, the immune system's coordinators."},{"from":"hiv","to":"cognition","level":"established","effect":"harms","note":"Untreated HIV can cause thinking and memory problems."},{"from":"hiv","to":"neuropathy","level":"established","effect":"harms","note":"Can cause painful numbness of the feet."},{"from":"hiv","to":"mtb","level":"established","effect":"harms","note":"A weakened immune system lets TB become active far more often."},{"from":"hiv","to":"jc_virus","level":"established","effect":"harms","note":"Advanced HIV lets JC virus attack the brain (PML)."},{"from":"hiv","to":"cmv","level":"established","effect":"harms","note":"Advanced HIV lets CMV damage the eyes, gut and brain."},{"from":"hiv","to":"toxo","level":"established","effect":"harms","note":"Advanced HIV lets dormant Toxoplasma cysts reactivate in the brain."},{"from":"mtb","to":"seizures","level":"established","effect":"harms","note":"TB of the brain or its lining can cause seizures."},{"from":"mtb","to":"nutrition","level":"established","effect":"harms","note":"Active TB causes weight loss and wasting."},{"from":"mtb","to":"fatigue","level":"established","effect":"harms","note":"Active TB causes tiredness and night sweats."},{"from":"jc_virus","to":"cognition","level":"established","effect":"harms","note":"PML damages brain white matter, affecting thinking, movement and vision."},{"from":"cmv","to":"s_cortex","level":"established","effect":"harms","note":"Infection before birth can damage the developing brain."},{"from":"plasmodium","to":"seizures","level":"established","effect":"harms","note":"Cerebral malaria causes seizures."},{"from":"plasmodium","to":"epilepsy","level":"association","effect":"harms","note":"Children who survive cerebral malaria have more epilepsy later.","sources":[{"id":"pmid:25631856","citation":"Christensen SS & Eslick GD, Trans R Soc Trop Med Hyg","year":2015,"design":"meta-analysis","finding":"Cerebral malaria was linked with later epilepsy (OR 4.7), neurodisability and behavioural problems in children."}]},{"from":"plasmodium","to":"cognition","level":"association","effect":"harms","note":"Survivors of cerebral malaria have more learning and behaviour problems.","sources":[{"id":"pmid:25631856","citation":"Christensen SS & Eslick GD, Trans R Soc Trop Med Hyg","year":2015,"design":"meta-analysis","finding":"Cerebral malaria was linked with later epilepsy (OR 4.7), neurodisability and behavioural problems in children."}]},{"from":"plasmodium","to":"ebv","level":"association","effect":"harms","note":"Repeated malaria lets EBV expand, part of why Burkitt lymphoma clusters in malaria regions.","sources":[{"id":"pmid:42449688","citation":"Rochford R & Mbulaiteye SM, Cancers (Basel)","year":2026,"design":"review","finding":"Repeated malaria drives B-cell activation in which EBV expands, explaining why Burkitt lymphoma clusters in malaria regions."}]},{"from":"trypanosoma","to":"insomnia","level":"established","effect":"harms","note":"Sleeping sickness breaks up night sleep."},{"from":"trypanosoma","to":"sleepy","level":"established","effect":"harms","note":"Sleeping sickness causes daytime sleep attacks."},{"from":"trypanosoma","to":"constipation","level":"established","effect":"harms","note":"Chagas disease destroys gut nerves, causing severe constipation."},{"from":"trypanosoma","to":"s_autonomic","level":"established","effect":"harms","note":"Chagas disease damages the gut's and heart's nerve supply."},{"from":"toxocara","to":"epilepsy","level":"association","effect":"harms","note":"Infection is linked with epilepsy in pooled studies.","sources":[{"id":"pmid:30028858","citation":"Luna J et al., PLoS Negl Trop Dis","year":2018,"design":"meta-analysis","finding":"Pooling case-control studies, Toxocara seropositivity was linked with epilepsy (OR 1.69)."},{"id":"pmid:41429484","citation":"Boozhmehrani et al., Trop Med Int Health","year":2026,"design":"meta-analysis","finding":"Across 34 observational studies, Toxocara antibodies were linked with epilepsy (pooled RR about 1.6) and several other neurological disorders; causality cannot be inferred."}]},{"from":"schistosoma","to":"s_bladder","level":"established","effect":"harms","note":"S. haematobium eggs scar the bladder wall."},{"from":"schistosoma","to":"s_spinal","level":"established","effect":"harms","note":"Eggs can rarely lodge in and inflame the spinal cord."},{"from":"strongyloides","to":"s_gut","level":"established","effect":"harms","note":"Lives in and damages the small intestine."},{"from":"strongyloides","to":"entero","level":"established","effect":"harms","note":"In hyperinfection, larvae carry gut bacteria into the blood."},{"from":"entamoeba","to":"m_barrier","level":"established","effect":"harms","note":"Invades and ulcerates the colon lining."},{"from":"entamoeba","to":"s_gut","level":"established","effect":"harms","note":"Causes bloody diarrhoea (amoebic dysentery)."},{"from":"crypto","to":"m_barrier","level":"established","effect":"harms","note":"Damages the small-intestine lining."},{"from":"crypto","to":"s_gut","level":"established","effect":"harms","note":"Causes watery diarrhoea, long-lasting with weak immunity."},{"from":"hhv6","to":"ms","level":"association","effect":"harms","note":"Stronger antibody responses to HHV-6A go with higher MS risk.","sources":[{"id":"pmid:32038605","citation":"Engdahl E et al., Front Immunol","year":2019,"design":"case-control","finding":"A stronger antibody response against HHV-6A was associated with higher multiple sclerosis risk and interacted with EBV antibodies."}]},{"from":"hhv6","to":"seizures","level":"established","effect":"harms","note":"Roseola is a common cause of fever-related seizures in toddlers."},{"from":"hpv","to":"s_throat","level":"established","effect":"harms","note":"High-risk types cause most throat (oropharyngeal) cancers in many countries."},{"from":"hcv","to":"parkinsons","level":"association","effect":"harms","note":"Linked with higher Parkinson's risk; treated people had lower risk.","sources":[{"id":"pmid:26701382","citation":"Tsai HH et al., Neurology","year":2016,"design":"cohort","finding":"In a Taiwanese national cohort, hepatitis C was linked with higher Parkinson’s risk (adjusted HR 1.29), while hepatitis B was not (crude HR 0.66)."},{"id":"pmid:28356465","citation":"Pakpoor J et al., Neurology","year":2017,"design":"cohort","finding":"In English hospital records, Parkinson’s rates were higher after hepatitis B (RR 1.76) and hepatitis C (RR 1.51)."},{"id":"pmid:31168563","citation":"Lin WY et al., JAMA Neurol","year":2019,"design":"cohort","finding":"Among people with chronic hepatitis C, those given antiviral treatment had lower later Parkinson’s incidence (HR 0.71)."}]},{"from":"hbv","to":"parkinsons","level":"association","effect":"harms","note":"Linked with Parkinson's in England but not in Taiwan; inconsistent.","sources":[{"id":"pmid:28356465","citation":"Pakpoor J et al., Neurology","year":2017,"design":"cohort","finding":"In English hospital records, Parkinson’s rates were higher after hepatitis B (RR 1.76) and hepatitis C (RR 1.51)."},{"id":"pmid:26701382","citation":"Tsai HH et al., Neurology","year":2016,"design":"cohort","finding":"In a Taiwanese national cohort, hepatitis C was linked with higher Parkinson’s risk (adjusted HR 1.29), while hepatitis B was not (crude HR 0.66)."}]},{"from":"measles","to":"seizures","level":"established","effect":"harms","note":"SSPE, a late measles brain infection, causes jerks and seizures."},{"from":"measles","to":"cognition","level":"established","effect":"harms","note":"SSPE causes progressive mental decline."},{"from":"measles","to":"s_immune","level":"association","effect":"harms","note":"Wipes out existing immune memory against other germs.","sources":[{"id":"pmid:31672891","citation":"Mina MJ et al., Science","year":2019,"design":"cohort","finding":"In 77 unvaccinated children, measles wiped out 11-73% of their existing antibodies against other germs (\"immune amnesia\"); not seen after MMR vaccination."}]},{"from":"enterovirus","to":"s_spinal","level":"established","effect":"harms","note":"Polio kills motor nerve cells in the spinal cord."},{"from":"enterovirus","to":"s_muscle","level":"established","effect":"harms","note":"Causes paralysed, wasted muscles and later post-polio weakness."},{"from":"zika","to":"s_cortex","level":"established","effect":"harms","note":"Infection in pregnancy stops the baby's brain from growing (microcephaly).","sources":[{"id":"pmid:27074377","citation":"Rasmussen SA et al., N Engl J Med","year":2016,"design":"review","finding":"Reviewed the evidence and concluded that Zika virus infection in pregnancy causes microcephaly and other severe brain defects."}]},{"from":"zika","to":"s_peripheral","level":"association","effect":"harms","note":"Linked with Guillain-Barré syndrome, an immune attack on nerves.","sources":[{"id":"pmid:26948433","citation":"Cao-Lormeau VM et al., Lancet","year":2016,"design":"case-control","finding":"During the French Polynesia outbreak, nearly all 42 Guillain-Barré patients had evidence of recent Zika infection, far more than controls."}]},{"from":"westnile","to":"tremor","level":"association","effect":"harms","note":"Tremor was very common in West Nile brain infection.","sources":[{"id":"pmid:12876094","citation":"Sejvar JJ et al., JAMA","year":2003,"design":"cohort","finding":"Among 16 people with West Nile infection of the nervous system, tremor (94%), parkinsonism (69%) and polio-like paralysis were common; paralysis often did not recover."}]},{"from":"westnile","to":"movement","level":"association","effect":"harms","note":"Can cause temporary parkinson-like slowness and stiffness.","sources":[{"id":"pmid:12876094","citation":"Sejvar JJ et al., JAMA","year":2003,"design":"cohort","finding":"Among 16 people with West Nile infection of the nervous system, tremor (94%), parkinsonism (69%) and polio-like paralysis were common; paralysis often did not recover."}]},{"from":"westnile","to":"s_spinal","level":"established","effect":"harms","note":"Can cause polio-like paralysis by attacking the spinal cord.","sources":[{"id":"pmid:12876094","citation":"Sejvar JJ et al., JAMA","year":2003,"design":"cohort","finding":"Among 16 people with West Nile infection of the nervous system, tremor (94%), parkinsonism (69%) and polio-like paralysis were common; paralysis often did not recover."}]},{"from":"pging","to":"m_inflam","level":"lab","effect":"harms","note":"Keeps gums inflamed and inflamed the brain in mice.","sources":[{"id":"pmid:30746447","citation":"Dominy SS et al., Sci Adv","year":2019,"design":"lab","finding":"P. gingivalis and its enzymes (gingipains) were found in Alzheimer’s brains; in mice, mouth infection reached the brain and blocking gingipains reduced brain inflammation."}]},{"from":"pging","to":"cognition","level":"association","effect":"harms","note":"Gum disease is linked with poorer thinking in observational studies.","sources":[{"id":"pmid:34202071","citation":"Guo H et al., Int J Environ Res Public Health","year":2021,"design":"meta-analysis","finding":"In 20 observational studies, periodontitis (gum disease) was linked with cognitive impairment (OR 1.77) and dementia."}]},{"from":"pging","to":"alzheimers","level":"association","effect":"harms","note":"Gum disease is linked with dementia; causation unproven.","sources":[{"id":"pmid:34202071","citation":"Guo H et al., Int J Environ Res Public Health","year":2021,"design":"meta-analysis","finding":"In 20 observational studies, periodontitis (gum disease) was linked with cognitive impairment (OR 1.77) and dementia."},{"id":"pmid:30746447","citation":"Dominy SS et al., Sci Adv","year":2019,"design":"lab","finding":"P. gingivalis and its enzymes (gingipains) were found in Alzheimer’s brains; in mice, mouth infection reached the brain and blocking gingipains reduced brain inflammation."},{"id":"pmid:42747062","citation":"Demmer RT et al., J Periodontal Res","year":2026,"design":"meta-analysis","finding":"28 cohort studies: severe periodontitis (HR 1.16), edentulism and low tooth count associated with higher dementia/MCI risk; estimates weaker in lower risk-of-bias studies and confounder adjustment often inadequate."}]},{"from":"borrelia","to":"s_peripheral","level":"established","effect":"harms","note":"Lyme can inflame nerve roots and the facial nerve."},{"from":"borrelia","to":"neuropathy","level":"established","effect":"harms","note":"Lyme nerve inflammation can cause numbness and tingling."},{"from":"borrelia","to":"pain","level":"established","effect":"harms","note":"Lyme nerve-root inflammation causes burning, shooting pain."},{"from":"treponema","to":"memory","level":"established","effect":"harms","note":"Untreated neurosyphilis can cause dementia."},{"from":"treponema","to":"s_cortex","level":"established","effect":"harms","note":"Late syphilis can damage the brain itself (general paresis)."},{"from":"treponema","to":"s_spinal","level":"established","effect":"harms","note":"Late syphilis can damage the spinal cord (tabes dorsalis)."},{"from":"chlamydia_pn","to":"alzheimers","level":"association","effect":"harms","note":"Linked with Alzheimer's in one large cohort but not in another.","sources":[{"id":"pmid:34489674","citation":"Ou H et al., Front Aging Neurosci","year":2021,"design":"cohort","finding":"In a Taiwanese national cohort, hospitalisation for C. pneumoniae pneumonia was linked with higher Alzheimer’s risk (adjusted HR 1.6)."},{"id":"pmid:34057145","citation":"Zilli EM et al., J Alzheimers Dis (Framingham)","year":2021,"design":"cohort","finding":"In the Framingham cohorts, antibodies to C. pneumoniae, H. pylori and CMV were not associated with later dementia."}]},{"from":"apples","to":"flavanols","level":"established","effect":"contains","note":"Epicatechin and procyanidins, mostly in the skin; amounts vary a lot between varieties.","sources":[{"id":"pmid:32744555","citation":"Bondonno CP et al., Food & Function","year":2020,"design":"lab","finding":"Across 91 apple varieties, epicatechin and procyanidin B2 ranged widely and were more concentrated in the skin than the flesh."}]},{"from":"cocoa","to":"flavanols","level":"established","effect":"contains","note":"Cocoa is among the richest sources; much is lost in heavily processed chocolate."},{"from":"greentea","to":"flavanols","level":"established","effect":"contains","note":"Tea catechins, including EGCG, are flavan-3-ols."},{"from":"grapes","to":"flavanols","level":"established","effect":"contains","note":"Procyanidins in the skin and seeds."},{"from":"flavanols","to":"s_blood","level":"proven","effect":"helps","note":"Trials show modest improvements in blood pressure, cholesterol and how well arteries relax; a large cocoa-extract trial did not clearly cut heart attacks and strokes overall.","sources":[{"id":"pmid:36190328","citation":"Crowe-White KM et al., Advances in Nutrition","year":2022,"design":"review","finding":"An expert guideline based on 157 randomised trials and 15 cohort studies found moderate evidence that food flavan-3-ols improve blood pressure, cholesterol and blood-sugar markers."},{"id":"pmid:35294962","citation":"Sesso HD et al., American Journal of Clinical Nutrition","year":2022,"design":"RCT","finding":"In 21,442 older adults, cocoa extract did not significantly reduce total cardiovascular events (HR 0.90) but cardiovascular deaths were 27% lower, a secondary outcome."}]},{"from":"flavanols","to":"memory","level":"mixed","effect":"helps","note":"In a large trial, cocoa flavanols did not improve memory overall but did in older people whose usual diet was low in them.","sources":[{"id":"pmid:37252983","citation":"Brickman AM et al., PNAS","year":2023,"design":"RCT","finding":"In 3,562 older adults, cocoa flavanols for 3 years did not improve memory overall (primary endpoint) but improved hippocampus-dependent memory in those with lower diet quality or lower habitual flavanol intake."}]},{"from":"flavanols","to":"parkinsons","level":"association","effect":"helps","note":"People with Parkinson's who ate more flavan-3-ols lived longer in two large cohorts; no clear link with the chance of getting it.","sources":[{"id":"pmid:35082171","citation":"Zhang X et al., Neurology","year":2022,"design":"cohort","finding":"Among 1,251 people with Parkinson's, the highest pre-diagnosis intake of flavan-3-ols went with lower mortality (pooled HR 0.69), as did anthocyanins, berries and red wine."},{"id":"pmid:22491871","citation":"Gao X et al., Neurology","year":2012,"design":"cohort","finding":"In about 130,000 US adults, anthocyanins and berries, not other flavonoid subclasses, were linked with lower Parkinson's risk in pooled analyses; total flavonoids only in men."}]},{"from":"apples","to":"s_blood","level":"mixed","effect":"helps","note":"Eating whole apples daily modestly lowered LDL cholesterol in some small trials, mostly in people whose cholesterol was already high, but pooled results are borderline.","sources":[{"id":"pmid:31840162","citation":"Koutsos A et al., American Journal of Clinical Nutrition","year":2020,"design":"RCT","finding":"Two apples a day for 8 weeks lowered total and LDL cholesterol and triglycerides and improved small-vessel relaxation compared with a sugar-matched apple drink, without changing blood pressure."},{"id":"pmid:23271615","citation":"Ravn-Haren G et al., European Journal of Nutrition","year":2013,"design":"RCT","finding":"Whole apples and pomace tended to lower LDL cholesterol, while clear apple juice raised it relative to whole apples; no effect on blood pressure or inflammation."},{"id":"pmid:35449537","citation":"Kim SJ et al., Frontiers in Nutrition","year":2022,"design":"meta-analysis","finding":"Across 18 apple trials, total and LDL cholesterol showed only a non-significant downward trend overall (significant against placebo and in people with high cholesterol), with a small fall in HDL."},{"id":"pmid:34565081","citation":"Zhu X et al., Reviews in Cardiovascular Medicine","year":2021,"design":"meta-analysis","finding":"Apple or apple-polyphenol intake raised HDL cholesterol and lowered C-reactive protein in pooled trials, with high variability between studies."}]},{"from":"greentea","to":"theanine","level":"established","effect":"contains","note":"Tea is the main dietary source; shaded green teas such as matcha have the most."},{"from":"coffee","to":"chlorogenic_acid","level":"established","effect":"contains","note":"Coffee is the main dietary source; light roasts keep more."},{"from":"herbs_mint","to":"rosmarinic_acid","level":"established","effect":"contains","note":"Rosemary, oregano, sage and lemon balm all contain it."},{"from":"lions_mane","to":"hericenones","level":"established","effect":"contains","note":"Hericenones in the mushroom; erinacines mainly in the mycelium used in many supplements."},{"from":"theanine","to":"insomnia","level":"mixed","effect":"helps","note":"Small randomised trials found better sleep quality in stressed adults and boys with ADHD; not tested in Parkinson's.","sources":[{"id":"pmid:31623400","citation":"Hidese S et al., Nutrients","year":2019,"design":"RCT","finding":"In a randomised blinded trial in 30 healthy adults, 4 weeks of L-theanine improved self-rated sleep quality, stress and anxiety scores versus placebo."},{"id":"pmid:22214254","citation":"Lyon MR et al., Alternative Medicine Review","year":2011,"design":"RCT","finding":"In a randomised placebo-controlled trial in boys aged 8-12 with ADHD, L-theanine for 6 weeks improved sleep efficiency measured by wrist actigraphy versus placebo."}]},{"from":"theanine","to":"caffeine","level":"mixed","effect":"helps","note":"Together they sharpened attention more than caffeine alone in short trials, and theanine blunted caffeine's rise in blood pressure; this combination is how tea delivers both.","sources":[{"id":"pmid:24946991","citation":"Camfield DA et al., Nutrition Reviews","year":2014,"design":"meta-analysis","finding":"Pooled short-term trials found caffeine plus L-theanine improved alertness and accuracy when switching attention in the first 2 hours."},{"id":"pmid:17891480","citation":"Rogers PJ et al., Psychopharmacology","year":2008,"design":"RCT","finding":"In 48 adults, theanine blunted the rise in blood pressure caused by caffeine, but did not reduce caffeine's jitteriness."}]},{"from":"egcg","to":"iron","level":"established","effect":"harms","note":"Green-tea polyphenols in the same meal cut iron absorption from plant foods eaten in that meal.","sources":[{"id":"pmid:11237939","citation":"Samman S et al., American Journal of Clinical Nutrition","year":2001,"design":"crossover","finding":"In young women given iron-labelled meals in balanced crossover order, adding a green-tea or a rosemary polyphenol extract lowered non-haem iron absorption."}]},{"from":"coffee","to":"iron","level":"established","effect":"harms","note":"Coffee with a meal cut iron absorption from plant foods by about a third; coffee an hour before eating did not.","sources":[{"id":"pmid:6402915","citation":"Morck TA et al., American Journal of Clinical Nutrition","year":1983,"design":"crossover","finding":"In human iron-isotope absorption studies, a cup of coffee with a meal cut non-haem iron absorption by about 39% (tea by 64%); coffee taken an hour before the meal did not."}]},{"from":"herbs_mint","to":"iron","level":"mixed","effect":"harms","note":"In one human absorption study, a rosemary polyphenol extract added to a meal lowered iron absorption from it.","sources":[{"id":"pmid:11237939","citation":"Samman S et al., American Journal of Clinical Nutrition","year":2001,"design":"crossover","finding":"In young women given iron-labelled meals in balanced crossover order, adding a green-tea or a rosemary polyphenol extract lowered non-haem iron absorption."}]},{"from":"chlorogenic_acid","to":"s_blood","level":"mixed","effect":"helps","note":"Lowered blood pressure in five small trials, all manufacturer-funded; independent trials are needed.","sources":[{"id":"pmid:24943289","citation":"Onakpoya IJ et al., Journal of Human Hypertension","year":2015,"design":"meta-analysis","finding":"Five randomised trials (364 people) found chlorogenic acid lowered blood pressure by about 4 mmHg systolic, but all were small, Asian and manufacturer-funded."}]},{"from":"rosmarinic_acid","to":"m_inflam","level":"lab","effect":"helps","note":"Calmed brain immune cells and protected dopamine neurons in Parkinson's model mice.","sources":[{"id":"pmid:30880023","citation":"Lv R et al., Life Sciences","year":2019,"design":"lab","finding":"In Parkinson's model mice, rosmarinic acid improved movement, preserved dopamine neurons and reduced microglial inflammation."}]},{"from":"hericenones","to":"m_plastic","level":"lab","effect":"helps","note":"Lion's mane extract raised nerve growth factor in cells and mice, but the purified hericenones tested did not, so the active part is unclear.","sources":[{"id":"pmid:18758067","citation":"Mori K et al., Biological & Pharmaceutical Bulletin","year":2008,"design":"lab","finding":"Lion's mane extracts raised nerve growth factor in human brain-derived cells and in mice, but the purified hericenones C, D and E did not."}]},{"from":"hericenones","to":"cognition","level":"mixed","effect":"helps","note":"Improved thinking scores in one small trial in mild cognitive impairment; a single dose did nothing in young adults.","sources":[{"id":"pmid:18844328","citation":"Mori K et al., Phytotherapy Research","year":2009,"design":"RCT","finding":"In 30 older Japanese adults with mild cognitive impairment, 16 weeks of lion's mane powder improved cognitive scores versus placebo; the benefit faded after stopping."},{"id":"pmid:40276537","citation":"Surendran G et al., Frontiers in Nutrition","year":2025,"design":"RCT","finding":"In healthy younger adults, a single dose of lion's mane gave no overall improvement in cognition or mood versus placebo."}]},{"from":"black_pepper","to":"piperine","level":"established","effect":"contains","note":"Piperine gives black pepper its bite; a pinch of pepper holds only a few milligrams."},{"from":"ginger","to":"gingerols","level":"established","effect":"contains","note":"Fresh ginger is richest in gingerols; dried or cooked ginger has more shogaols."},{"from":"piperine","to":"curcumin","level":"mixed","effect":"helps","note":"A famous 1998 study found piperine raised blood curcumin about 20-fold, but three newer crossover trials found no real boost; whether the pair does anything for health is untested.","sources":[{"id":"pmid:9619120","citation":"Shoba G et al., Planta Medica","year":1998,"design":"crossover (rats and volunteers)","finding":"In rats and in healthy volunteers, adding piperine to curcumin greatly raised blood curcumin; in people, curcumin alone was barely detectable and absorption rose about 20-fold with piperine."},{"id":"pmid:34665507","citation":"Flory S et al., Molecular Nutrition & Food Research","year":2021,"design":"RCT","finding":"In a randomised double-blind crossover trial in 12 healthy adults, curcumin with adjuvants including piperine did not significantly raise blood curcumin; only micellar and cyclodextrin forms did."},{"id":"pmid:33877323","citation":"Fança-Berthon P et al., Journal of Nutrition","year":2021,"design":"RCT","finding":"In a randomised crossover trial in 30 healthy adults, a piperine-curcuminoid product gave no significant gain in curcuminoid absorption over a standard turmeric extract."},{"id":"pmid:40487425","citation":"Kroon MAGM et al., iScience","year":2025,"design":"crossover","finding":"In an independent crossover study in 9 healthy men, adding piperine gave no benefit; free curcumin in blood stayed minimal with every formulation."}]},{"from":"piperine","to":"egcg","level":"lab","effect":"helps","note":"Raised levels of the green-tea catechin EGCG in mice by the same enzyme-slowing effect; not tested in people.","sources":[{"id":"pmid:15284381","citation":"Lambert JD et al., Journal of Nutrition","year":2004,"design":"lab","finding":"In mice, piperine slowed the breakdown of the green-tea catechin EGCG and raised its levels in the gut and blood."}]},{"from":"piperine","to":"m_absorb","level":"lab","effect":"helps","note":"In Parkinson's model rats it suppressed gut bacteria that break down levodopa before it is absorbed, raising brain dopamine; never tested in people, and piperine also changes how some medicines are processed.","sources":[{"id":"pmid:37528534","citation":"Hu X et al., CNS Neuroscience & Therapeutics","year":2024,"design":"lab","finding":"In Parkinson's model rats, piperine cut gut Enterococcus bacteria and their levodopa-destroying enzyme (tyrosine decarboxylase), raising levodopa availability and brain dopamine."}]},{"from":"gingerols","to":"m_motility","level":"mixed","effect":"helps","note":"Ginger sped stomach emptying in two small randomised crossover trials; whether it helps levodopa reach the gut faster is untested.","sources":[{"id":"pmid:18403946","citation":"Wu KL et al., European Journal of Gastroenterology & Hepatology","year":2008,"design":"RCT","finding":"In a randomised double-blind crossover study of 24 healthy volunteers, ginger capsules sped up stomach emptying and stimulated stomach contractions versus placebo."},{"id":"pmid:21218090","citation":"Hu ML et al., World Journal of Gastroenterology","year":2011,"design":"RCT","finding":"In 11 people with functional dyspepsia (randomised, double-blind crossover), ginger sped stomach emptying but did not change symptoms."}]},{"from":"black_seed","to":"thymoquinone","level":"established","effect":"contains","note":"Thymoquinone is the main active compound in black-seed oil."},{"from":"garlic","to":"allicin","level":"established","effect":"contains","note":"Allicin forms when raw garlic is crushed; cooking straight away destroys the enzyme that makes it."},{"from":"garlic","to":"fibre","level":"established","effect":"contains","note":"Inulin-type fibre (fructans) that feeds gut bacteria."},{"from":"cinnamon","to":"cinnamaldehyde","level":"established","effect":"contains","note":"Gives cinnamon its flavour."},{"from":"thymoquinone","to":"m_dopa","level":"lab","effect":"helps","note":"Protected dopamine neurons and movement in Parkinson's model rats and mice, and pairing it with metformin or a Centella compound looked somewhat stronger in mice; none of this has been tested in people.","sources":[{"id":"pmid:40951472","citation":"Kusumawati S et al., Narra J","year":2025,"design":"lab","finding":"In rotenone Parkinson's model mice, thymoquinone improved movement, raised dopamine and reduced alpha-synuclein build-up."},{"id":"pmid:24734075","citation":"Sedaghat R et al., Iranian Journal of Pharmaceutical Research","year":2014,"design":"lab","finding":"Oral thymoquinone given before a 6-OHDA lesion in rats prevented loss of substantia nigra neurons, improved turning behaviour and lowered lipid peroxidation."},{"id":"pmid:39585743","citation":"Kavrik O et al., Journal of Receptor and Signal Transduction Research","year":2024,"design":"lab","finding":"In MPTP mice, thymoquinone and metformin each improved movement and preserved dopamine (TH-positive) neurons, and the two together appeared more effective than either alone."}]},{"from":"allicin","to":"s_blood","level":"proven","effect":"helps","note":"Garlic supplements lower high blood pressure a little in trials; in someone who gets dizzy on standing, extra lowering could add to that, which is untested.","sources":[{"id":"pmid:26764326","citation":"Ried K, Journal of Nutrition","year":2016,"design":"meta-analysis","finding":"Across 20 randomised trials (970 people), garlic preparations lowered systolic blood pressure by about 5 mmHg on average, more in people with high blood pressure."},{"id":"pmid:30619868","citation":"Ried K et al., Frontiers in Nutrition","year":2018,"design":"RCT","finding":"In a 12-week double-blind placebo-controlled trial in 49 people with uncontrolled high blood pressure, aged garlic extract lowered blood pressure and arterial stiffness."}]},{"from":"cinnamaldehyde","to":"m_asyn","level":"lab","effect":"helps","note":"Oral cinnamon and its breakdown product benzoate reduced alpha-synuclein clumps in mice; not tested in people.","sources":[{"id":"pmid:32889602","citation":"Raha S et al., Journal of Neuroimmune Pharmacology","year":2021,"design":"lab","finding":"In mice carrying a human Parkinson's alpha-synuclein mutation, oral cinnamon and its metabolite sodium benzoate reduced insoluble alpha-synuclein in the brain."}]},{"from":"soy","to":"isoflavones","level":"established","effect":"contains","note":"Soy is by far the main dietary source of isoflavones."},{"from":"soy","to":"protein","level":"established","effect":"contains","note":"A complete plant protein."},{"from":"soy","to":"fibre","level":"established","effect":"contains","note":"Whole soybeans and edamame contain fibre; tofu and soy milk have little."},{"from":"flaxseed","to":"omega3","level":"established","effect":"contains","note":"One of the richest ALA sources; the body converts only a few percent to DHA."},{"from":"flaxseed","to":"fibre","level":"established","effect":"contains","note":"Sticky soluble fibre (mucilage) plus insoluble fibre."},{"from":"flaxseed","to":"s_blood","level":"proven","effect":"helps","note":"Flaxseed lowered blood pressure slightly in pooled controlled trials; which part (ALA, lignans or fibre) does it is unclear.","sources":[{"id":"pmid:25740909","citation":"Khalesi S et al., Journal of Nutrition","year":2015,"design":"meta-analysis","finding":"Across controlled trials, flaxseed lowered systolic blood pressure by about 1.8 mmHg and diastolic by about 1.6 mmHg, more with whole seed taken over 12 weeks."}]},{"from":"chia","to":"omega3","level":"established","effect":"contains","note":"Rich in ALA, which the body converts only a little into DHA."},{"from":"chia","to":"fibre","level":"established","effect":"contains","note":"Soluble fibre that forms a gel."},{"from":"isoflavones","to":"m_bone","level":"mixed","effect":"helps","note":"One meta-analysis found slightly denser spine bone in menopausal women, another found no significant effect.","sources":[{"id":"pmid:20199985","citation":"Taku K et al., Asia Pacific Journal of Clinical Nutrition","year":2010,"design":"meta-analysis","finding":"Across randomised trials in 1240 menopausal women, soy isoflavone extracts for 6-12 months raised spine bone density by about 2%, with no effect at the hip."},{"id":"pmid:19168161","citation":"Liu J et al., Bone","year":2009,"design":"meta-analysis","finding":"Across 10 randomised trials of at least a year in 896 women, soy isoflavones did not significantly change spine or hip bone density."}]},{"from":"pomegranate","to":"ellagitannins","level":"established","effect":"contains","note":"Very rich in ellagitannins (punicalagin), especially whole-fruit juice."},{"from":"nuts","to":"ellagitannins","level":"established","effect":"contains","note":"Walnuts are rich in ellagitannins."},{"from":"strawberries","to":"ellagitannins","level":"established","effect":"contains","note":"Strawberries (and raspberries) contain ellagitannins."},{"from":"strawberries","to":"fisetin","level":"established","effect":"contains","note":"Strawberries are the richest common food source of fisetin, still in small amounts."},{"from":"strawberries","to":"anthocyanins","level":"established","effect":"contains","note":"The red pigment."},{"from":"strawberries","to":"vitc","level":"established","effect":"contains","note":"Rich in vitamin C."},{"from":"cranberries","to":"proanthocyanidins","level":"established","effect":"contains","note":"The characteristic type-A proanthocyanidins."},{"from":"cranberries","to":"anthocyanins","level":"established","effect":"contains","note":"The red pigment."},{"from":"cranberries","to":"quercetin","level":"established","effect":"contains","note":"Among the richer fruit sources of quercetin."},{"from":"ellagitannins","to":"urolithin_a","level":"established","effect":"helps","note":"Gut bacteria turn ellagitannins into urolithin A, but how much varies widely between people and shifts with age.","sources":[{"id":"pmid:30004553","citation":"Cortés-Martín A et al., Food & Function","year":2018,"design":"cohort","finding":"In 839 people aged 5-90, the gut-bacteria pattern that turns ellagic acid into urolithins (urolithin metabotype) varied between people and mainly shifted with age."}]},{"from":"urolithin_a","to":"m_oxid","level":"proven","effect":"helps","note":"Randomised trials of the purified compound improved markers of mitochondrial health in muscle; brain effects in people are untested.","sources":[{"id":"pmid:32694802","citation":"Andreux PA et al., Nature Metabolism","year":2019,"design":"RCT","finding":"In a first-in-human placebo-controlled trial in sedentary older adults, urolithin A was safe, reached the blood, and shifted muscle mitochondrial gene activity and blood markers toward healthier mitochondria."},{"id":"pmid:35050355","citation":"Liu S et al., JAMA Network Open","year":2022,"design":"RCT","finding":"In 66 older adults, 4 months of urolithin A improved hand and leg muscle endurance versus placebo, but not the main walking-distance outcome."},{"id":"pmid:35584623","citation":"Singh A et al., Cell Reports Medicine","year":2022,"design":"RCT","finding":"In middle-aged adults, 4 months of urolithin A raised muscle strength by about 12% and mitochondrial markers, but missed its main outcome (peak power)."}]},{"from":"urolithin_a","to":"m_bone","level":"mixed","effect":"helps","note":"Improved muscle endurance or strength in two randomised trials, but both missed their main outcome.","sources":[{"id":"pmid:35050355","citation":"Liu S et al., JAMA Network Open","year":2022,"design":"RCT","finding":"In 66 older adults, 4 months of urolithin A improved hand and leg muscle endurance versus placebo, but not the main walking-distance outcome."},{"id":"pmid:35584623","citation":"Singh A et al., Cell Reports Medicine","year":2022,"design":"RCT","finding":"In middle-aged adults, 4 months of urolithin A raised muscle strength by about 12% and mitochondrial markers, but missed its main outcome (peak power)."}]},{"from":"fisetin","to":"m_inflam","level":"lab","effect":"helps","note":"Cleared worn-out cells and lowered inflammation in old mice.","sources":[{"id":"pmid:30279143","citation":"Yousefzadeh MJ et al., EBioMedicine","year":2018,"design":"lab","finding":"Fisetin cleared worn-out (senescent) cells, lowered inflammation markers and extended lifespan in old mice."}]},{"from":"fisetin","to":"m_plastic","level":"lab","effect":"helps","note":"Strengthened memory-forming signals in rat brain tissue and improved memory in mice.","sources":[{"id":"pmid:17050681","citation":"Maher P et al., PNAS","year":2006,"design":"lab","finding":"Fisetin strengthened memory-forming signals in rat brain slices and improved object memory in mice."}]},{"from":"proanthocyanidins","to":"s_bladder","level":"proven","effect":"helps","note":"Cranberry products cut repeat urinary infections in some groups, but not in people whose bladders don't empty properly because of nerve problems.","sources":[{"id":"pmid:37068952","citation":"Williams G et al., Cochrane Database of Systematic Reviews","year":2023,"design":"meta-analysis","finding":"Across 50 trials (8857 people), cranberry products cut repeat urinary infections by about 30% in women with recurrent infections, children and people after procedures, but showed little or no benefit in older people in care homes or in people whose bladders don't empty properly because of nerve problems."}]},{"from":"tomatoes","to":"lycopene","level":"established","effect":"contains","note":"The main dietary source; cooked tomato with oil delivers much more than raw."},{"from":"carrots","to":"beta_carotene","level":"established","effect":"contains","note":"One of the richest everyday sources."},{"from":"carrots","to":"fibre","level":"established","effect":"contains","note":"Fibre."},{"from":"sweet_potato","to":"beta_carotene","level":"established","effect":"contains","note":"Orange-fleshed sweet potato is very rich in beta-carotene."},{"from":"sweet_potato","to":"fibre","level":"established","effect":"contains","note":"Fibre, especially with the skin."},{"from":"sweet_potato","to":"potassium","level":"established","effect":"contains","note":"A good potassium source."},{"from":"greens","to":"beta_carotene","level":"established","effect":"contains","note":"Spinach and kale carry beta-carotene hidden under the green chlorophyll."},{"from":"greens","to":"lutein","level":"established","effect":"contains","note":"Spinach and kale are among the richest lutein sources."},{"from":"avocado","to":"lutein","level":"established","effect":"contains","note":"Some lutein, in an easily absorbed fatty fruit."},{"from":"avocado","to":"fibre","level":"established","effect":"contains","note":"Fibre."},{"from":"avocado","to":"potassium","level":"established","effect":"contains","note":"Rich in potassium."},{"from":"avocado","to":"beta_carotene","level":"mixed","effect":"helps","note":"Eating avocado in the same meal raised beta-carotene absorption from carrots and tomato sauce several-fold in small single-meal studies.","sources":[{"id":"pmid:15735074","citation":"Unlu NZ et al., Journal of Nutrition","year":2005,"design":"RCT","finding":"In crossover meal studies in healthy adults, adding avocado or avocado oil to salsa or salad raised absorption of lycopene, beta-carotene and lutein several-fold."},{"id":"pmid:24899156","citation":"Kopec RE et al., Journal of Nutrition","year":2014,"design":"RCT","finding":"In two randomised crossover studies (12 adults each), eating avocado with tomato sauce or raw carrots raised beta-carotene absorption 2.4- to 6.6-fold and increased its conversion to vitamin A."}]},{"from":"avocado","to":"lycopene","level":"mixed","effect":"helps","note":"Adding avocado to tomato salsa raised lycopene absorption about four-fold in a crossover study.","sources":[{"id":"pmid:15735074","citation":"Unlu NZ et al., Journal of Nutrition","year":2005,"design":"RCT","finding":"In crossover meal studies in healthy adults, adding avocado or avocado oil to salsa or salad raised absorption of lycopene, beta-carotene and lutein several-fold."}]},{"from":"beta_carotene","to":"vita","level":"established","effect":"helps","note":"The gut turns beta-carotene into vitamin A as the body needs it."},{"from":"beta_carotene","to":"s_lungs","level":"proven","effect":"harms","note":"As high-dose pills in smokers and asbestos workers it raised lung cancer in two large trials; the amounts in carrots and other foods are not linked to this.","dose":"excess","sources":[{"id":"pmid:8127329","citation":"Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group, New England Journal of Medicine","year":1994,"design":"RCT","finding":"In 29,133 male smokers, beta-carotene supplements did not prevent lung cancer and were linked to more lung-cancer cases and 8% higher total deaths."},{"id":"pmid:8602180","citation":"Omenn GS et al., New England Journal of Medicine","year":1996,"design":"RCT","finding":"In smokers and asbestos workers, beta-carotene plus vitamin A raised lung-cancer deaths (relative risk 1.46) and the trial was stopped early."}]},{"from":"lutein","to":"s_eyes","level":"established","effect":"affects","note":"Lutein is the yellow pigment at the centre of the retina; having more of it has not been shown to protect sight in trials."},{"from":"lutein","to":"cognition","level":"mixed","effect":"helps","note":"Small trials found better attention in older adults, but a large five-year trial found no slowing of cognitive decline.","sources":[{"id":"pmid:28824416","citation":"Hammond BR et al., Frontiers in Aging Neuroscience","year":2017,"design":"RCT","finding":"In 62 randomised older adults, lutein and zeaxanthin raised macular pigment and improved some cognitive scores (such as complex attention) versus placebo."},{"id":"pmid:26305649","citation":"Chew EY et al. (AREDS2), JAMA","year":2015,"design":"RCT","finding":"In about 3,500 older adults tested over 5 years, lutein/zeaxanthin supplements did not slow cognitive decline."}]},{"from":"lycopene","to":"m_dopa","level":"lab","effect":"helps","note":"Protected dopamine neurons and movement in Parkinson's model mice; not tested in people.","sources":[{"id":"pmid:42514303","citation":"Xia J et al., Nutrients","year":2026,"design":"lab","finding":"In Parkinson's model mice, lycopene improved motor coordination and reduced dopamine-neuron damage."}]},{"from":"citrus","to":"citrus_flavanones","level":"established","effect":"contains","note":"Hesperidin in oranges and lemons, naringenin in grapefruit; most is in the pith and membranes."},{"from":"citrus","to":"vitc","level":"established","effect":"contains","note":"Citrus fruits are a classic vitamin C source."},{"from":"citrus","to":"fibre","level":"established","effect":"contains","note":"Pectin fibre, mostly lost in clear juice."},{"from":"citrus","to":"potassium","level":"established","effect":"contains","note":"Oranges supply potassium."},{"from":"parsley_celery","to":"apigenin_luteolin","level":"established","effect":"contains","note":"Parsley is among the richest apigenin sources; celery adds luteolin."},{"from":"parsley_celery","to":"vitk","level":"established","effect":"contains","note":"Parsley is very rich in vitamin K1."},{"from":"citrus_flavanones","to":"s_blood","level":"proven","effect":"helps","note":"Orange juice and hesperidin lowered blood pressure a little in randomised trials, helped by vessel-relaxing nitric oxide; whether this matters for dizziness on standing is untested.","sources":[{"id":"pmid:21068346","citation":"Morand C et al., American Journal of Clinical Nutrition","year":2011,"design":"RCT","finding":"In a randomised crossover trial in healthy overweight men, 4 weeks of orange juice or the same amount of hesperidin lowered diastolic blood pressure versus placebo."},{"id":"pmid:32661681","citation":"Valls RM et al., European Journal of Nutrition","year":2021,"design":"RCT","finding":"In 159 people with mildly high blood pressure, 12 weeks of orange juice (especially hesperidin-enriched) lowered systolic and pulse pressure versus a control drink."}]},{"from":"citrus_flavanones","to":"m_dopa","level":"lab","effect":"helps","note":"Naringenin protected dopamine neurons in a rat Parkinson's model; not tested in people.","sources":[{"id":"pmid:16298737","citation":"Zbarsky V et al., Free Radical Research","year":2005,"design":"lab","finding":"In a 6-OHDA rat Parkinson's model, naringenin (and curcumin) protected dopamine neurons, while quercetin and fisetin did not."}]},{"from":"apigenin_luteolin","to":"m_excit","level":"lab","effect":"helps","note":"Apigenin binds the calming GABA-A receptor at the same site as benzodiazepine drugs, in lab studies.","sources":[{"id":"pmid:7617761","citation":"Viola H et al., Planta Medica","year":1995,"design":"lab","finding":"Apigenin from chamomile binds the benzodiazepine site of brain GABA-A receptors and had calming effects in mice."}]},{"from":"apigenin_luteolin","to":"m_inflam","level":"lab","effect":"helps","note":"Luteolin turned inflamed brain immune cells into a calmer, protective state in cell culture.","sources":[{"id":"pmid:20074346","citation":"Dirscherl K et al., Journal of Neuroinflammation","year":2010,"design":"lab","finding":"Luteolin switched activated microglia (brain immune cells) to an anti-inflammatory, protective pattern in cell culture."}]},{"from":"apigenin_luteolin","to":"insomnia","level":"mixed","effect":"helps","note":"Chamomile improved self-rated sleep quality in pooled trials but did not help diagnosed insomnia in a small trial; apigenin alone is untested.","sources":[{"id":"pmid:31006899","citation":"Hieu TH et al., Phytotherapy Research","year":2019,"design":"meta-analysis","finding":"Across randomised trials, chamomile improved sleep quality and generalised anxiety, but the one insomnia trial found no change in insomnia severity."},{"id":"pmid:21939549","citation":"Zick SM et al., BMC Complementary and Alternative Medicine","year":2011,"design":"RCT","finding":"In 34 adults with chronic insomnia, chamomile extract for 28 days did not improve sleep diary measures versus placebo."}]},{"from":"beetroot","to":"nitrate","level":"established","effect":"contains","note":"Among the richest nitrate sources, along with rocket and spinach."},{"from":"beetroot","to":"betalains","level":"established","effect":"contains","note":"The deep red pigment."},{"from":"beetroot","to":"folate","level":"established","effect":"contains","note":"Beetroot supplies folate."},{"from":"beetroot","to":"fibre","level":"established","effect":"contains","note":"Fibre."},{"from":"greens","to":"nitrate","level":"established","effect":"contains","note":"Rocket, spinach and lettuce are rich in nitrate."},{"from":"peppers","to":"capsaicin","level":"established","effect":"contains","note":"Only hot chilli peppers; sweet bell peppers have essentially none."},{"from":"nitrate","to":"s_blood","level":"proven","effect":"helps","note":"Beetroot juice and nitrate lowered blood pressure in pooled trials, and need mouth bacteria to work (antiseptic mouthwash blocked it); in people who get dizzy on standing this lowering is untested and could add to it.","sources":[{"id":"pmid:23596162","citation":"Siervo M et al., Journal of Nutrition","year":2013,"design":"meta-analysis","finding":"Across 16 crossover trials, inorganic nitrate or beetroot juice lowered systolic blood pressure by about 4.4 mmHg."},{"id":"pmid:25359409","citation":"Bondonno CP et al., American Journal of Hypertension","year":2015,"design":"RCT","finding":"In a randomised crossover trial in 15 treated hypertensive adults, 3 days of antibacterial mouthwash blocked mouth bacteria from turning nitrate into nitrite and slightly raised blood pressure."}]},{"from":"betalains","to":"m_inflam","level":"lab","effect":"helps","note":"Beetroot's betanin calmed inflamed brain immune cells in a dish.","sources":[{"id":"pmid:32401824","citation":"Ahmadi H et al., PLoS One","year":2020,"design":"lab","finding":"Betanin purified from red beetroot reduced inflammatory signals (nitric oxide, TNF-alpha, IL-6, IL-1beta) from activated microglia in cell culture."}]},{"from":"capsaicin","to":"swallow","level":"mixed","effect":"helps","note":"Capsaicin lozenges sped up the swallowing reflex and eased symptoms in small trials in older people with swallowing difficulty; not tested in Parkinson's.","sources":[{"id":"pmid:15877558","citation":"Ebihara T et al., Journal of the American Geriatrics Society","year":2005,"design":"RCT","finding":"In 64 nursing-home residents, capsaicin lozenges before meals for 4 weeks shortened the delay of the swallowing reflex versus placebo, most in those at high aspiration risk."},{"id":"pmid:28319947","citation":"Nakato R et al., Digestion","year":2017,"design":"RCT","finding":"In a double-blind placebo-controlled crossover study in older people with throat swallowing difficulty, capsaicin improved symptoms more often than placebo."}]},{"from":"capsaicin","to":"m_painproc","level":"proven","effect":"helps","note":"High-strength capsaicin skin patches relieve nerve pain for some people by switching off pain nerve endings; eating chillies does not do this.","dose":"excess","sources":[{"id":"pmid:28085183","citation":"Derry S et al., Cochrane Database of Systematic Reviews","year":2017,"design":"meta-analysis","finding":"High-concentration capsaicin skin patches gave more people moderate or substantial relief of nerve pain than a low-concentration control, though the extra benefit was modest and evidence quality moderate to very low."}]},{"from":"hm_testosterone","to":"fracture","level":"failed","effect":"helps","note":"In a large trial of men with low testosterone, treatment did not reduce fractures; slightly more fractures happened than with placebo.","sources":[{"id":"pmid:38231621","citation":"Snyder PJ et al., N Engl J Med","year":2024,"design":"RCT","finding":"In 5,204 middle-aged and older men with low testosterone followed about 3 years, testosterone gel did not lower clinical fractures; fractures were more common than with placebo (3.5% vs 2.5%)."}]},{"from":"hm_testosterone","to":"s_marrow","level":"established","effect":"helps","note":"Testosterone spurs the bone marrow to make red blood cells, so low levels cause mild anaemia; too much can make the blood too thick.","sources":[{"id":"pmid:37889486","citation":"Pencina KM et al., JAMA Netw Open","year":2023,"design":"RCT","finding":"In men with low testosterone and anaemia, testosterone corrected the anaemia more often than placebo, and fewer men without anaemia went on to develop it."}]},{"from":"hm_testosterone","to":"s_reproductive","level":"proven","effect":"helps","note":"Testosterone drives sex drive; in men with low levels, treatment raised desire and sexual activity in trials but did not improve erections.","sources":[{"id":"pmid:26886521","citation":"Snyder PJ et al., N Engl J Med","year":2016,"design":"RCT","finding":"In 790 men aged 65+ with low testosterone, a year of testosterone gel moderately improved sexual function and slightly improved mood, but not vitality or walking distance."},{"id":"pmid:37589949","citation":"Pencina KM et al., J Clin Endocrinol Metab","year":2024,"design":"RCT","finding":"In men with low testosterone and low sex drive, two years of testosterone improved sexual activity and desire but not erectile function compared with placebo."}]},{"from":"hm_testosterone","to":"cognition","level":"failed","effect":"helps","note":"In older men with low testosterone and memory complaints, a year of testosterone did not improve memory or thinking.","sources":[{"id":"pmid:28241356","citation":"Resnick SM et al., JAMA","year":2017,"design":"RCT","finding":"In 493 older men with low testosterone and age-related memory complaints, a year of testosterone did not improve memory, executive function or spatial ability compared with placebo."},{"id":"pmid:38205962","citation":"Bhasin S et al., J Clin Endocrinol Metab","year":2024,"design":"RCT","finding":"In the TRAVERSE trial of 5,204 men with low testosterone, treatment gave modest improvements in mood and energy but not in thinking or sleep quality; in the few men with long-lasting low-grade depression there was no clear difference."}]},{"from":"hm_testosterone","to":"alzheimers","level":"association","effect":"helps","note":"Men whose testosterone is shut down to treat prostate cancer have a slightly higher risk of Alzheimer's disease; this does not show that extra testosterone protects.","dose":"deficiency","sources":[{"id":"pmid:39956977","citation":"Zhu S et al., J Alzheimers Dis","year":2025,"design":"meta-analysis","finding":"Across 21 studies of over 2 million men with prostate cancer, hormone treatment that suppresses testosterone was linked to a modestly higher risk of dementia and Alzheimer's disease."},{"id":"pmid:40603530","citation":"Jeon HL et al., Sci Rep","year":2025,"design":"cohort","finding":"In a Korean nationwide cohort, men given testosterone-suppressing treatment for prostate cancer had a higher risk of Alzheimer's disease but no higher risk of Parkinson's disease."}]},{"from":"hm_testosterone","to":"hm_oestrogen","level":"established","effect":"helps","note":"An enzyme called aromatase, found in fat and other tissues, turns some testosterone into oestrogen; this is where most of a man's oestrogen comes from."},{"from":"zinc","to":"hm_testosterone","level":"established","effect":"helps","note":"Lack of zinc lowers testosterone and correcting it raises it again; extra zinc is not shown to raise it in people who are not low.","dose":"deficiency","sources":[{"id":"pmid:8875519","citation":"Prasad AS et al., Nutrition","year":1996,"design":"small uncontrolled human studies","finding":"In small human studies, restricting dietary zinc lowered testosterone in young men, and zinc given to marginally zinc-deficient older men raised it."}]},{"from":"insomnia","to":"hm_testosterone","level":"mixed","effect":"harms","note":"A night or more without sleep lowers testosterone in men, but a few nights of shorter sleep showed no clear effect.","sources":[{"id":"pmid:34801825","citation":"Su L et al., Sleep Med","year":2021,"design":"meta-analysis","finding":"Across 18 studies in 252 healthy men, a full night or more without sleep lowered testosterone, while a few nights of shortened sleep had no significant effect."}]},{"from":"vitd","to":"hm_testosterone","level":"failed","effect":"helps","note":"In trials, vitamin D supplements did not clearly raise testosterone in men.","sources":[{"id":"pmid:42451097","citation":"Paez-Allendes L et al., Nutrients","year":2026,"design":"meta-analysis","finding":"Pooled randomised trials in adult men showed no clear effect of vitamin D supplements on total or free testosterone."}]},{"from":"isoflavones","to":"hm_testosterone","level":"failed","effect":"harms","note":"Despite a common worry, soy foods and isoflavone supplements did not lower testosterone in men in controlled studies.","sources":[{"id":"pmid:19524224","citation":"Hamilton-Reeves JM et al., Fertil Steril","year":2010,"design":"meta-analysis","finding":"Across placebo-controlled studies in men, soy protein or isoflavone intake did not change testosterone, free testosterone or SHBG."}]},{"from":"bp_cervical_spine","to":"s_bones","level":"established","effect":"located","note":"Made of bones and joints."},{"from":"bp_cervical_spine","to":"s_spinal","level":"established","effect":"located","note":"The neck bones surround and protect the spinal cord and the nerve roots to the arms."},{"from":"bp_thoracic_spine","to":"s_bones","level":"established","effect":"located","note":"Made of bones and joints."},{"from":"bp_thoracic_spine","to":"s_spinal","level":"established","effect":"located","note":"The mid-back bones surround and protect the spinal cord."},{"from":"bp_lumbar_spine","to":"s_bones","level":"established","effect":"located","note":"Made of bones and joints."},{"from":"bp_lumbar_spine","to":"s_spinal","level":"established","effect":"located","note":"The low-back bones protect the lowest end of the spinal cord and the bundle of nerve roots heading to the legs."},{"from":"bp_shoulders","to":"s_bones","level":"established","effect":"located","note":"Made of bones and joints."},{"from":"bp_shoulders","to":"s_muscle","level":"established","effect":"located","note":"The rotator cuff muscles hold the shoulder joint together."},{"from":"bp_elbows","to":"s_bones","level":"established","effect":"located","note":"Made of bones and joints."},{"from":"bp_elbows","to":"s_muscle","level":"established","effect":"located","note":"Gripping and twisting muscles attach at the elbow by tendons."},{"from":"bp_elbows","to":"s_peripheral","level":"established","effect":"located","note":"The ulnar nerve runs just behind the elbow."},{"from":"bp_wrists_hands","to":"s_bones","level":"established","effect":"located","note":"Made of bones and joints."},{"from":"bp_wrists_hands","to":"s_peripheral","level":"established","effect":"located","note":"The median nerve runs through the carpal tunnel at the wrist."},{"from":"bp_fingers","to":"s_bones","level":"established","effect":"located","note":"Made of bones and joints."},{"from":"bp_fingers","to":"s_peripheral","level":"established","effect":"located","note":"Fingers are packed with touch nerves."},{"from":"bp_hips","to":"s_bones","level":"established","effect":"located","note":"Made of bones and joints."},{"from":"bp_knees","to":"s_bones","level":"established","effect":"located","note":"Made of bones and joints."},{"from":"bp_ankles_feet","to":"s_bones","level":"established","effect":"located","note":"Made of bones and joints."},{"from":"bp_chest_ribs","to":"s_bones","level":"established","effect":"located","note":"Made of bones and joints."},{"from":"bp_chest_ribs","to":"s_muscle","level":"established","effect":"located","note":"Muscles between the ribs move them with each breath."},{"from":"bp_abdomen","to":"s_muscle","level":"established","effect":"located","note":"The belly wall is layers of muscle."},{"from":"bp_abdomen","to":"s_gut","level":"established","effect":"located","note":"A hernia lets part of the gut or its fatty apron push through the belly wall."},{"from":"bp_head_brain","to":"s_bones","level":"established","effect":"located","note":"The skull is bone."},{"from":"bp_head_brain","to":"s_cortex","level":"established","effect":"located","note":"The head holds the brain; the cortex is its outer thinking layer."},{"from":"bp_face_jaw","to":"s_bones","level":"established","effect":"located","note":"The jaw and face are bone; the jaw joint sits in front of each ear."},{"from":"bp_face_jaw","to":"s_muscle","level":"established","effect":"located","note":"Chewing muscles work the jaw joint."},{"from":"bp_eyes","to":"s_eyes","level":"established","effect":"located","note":"The eyes (textbook anatomy)."},{"from":"bp_ears","to":"s_ears","level":"established","effect":"located","note":"The ears (textbook anatomy)."},{"from":"bp_teeth","to":"s_mouth","level":"established","effect":"located","note":"Teeth are part of the mouth."},{"from":"bp_internal_organs","to":"s_gut","level":"established","effect":"located","note":"Includes the gut."},{"from":"bp_internal_organs","to":"s_liver","level":"established","effect":"located","note":"Includes the liver, which can be torn by blunt force and is harmed by some solvents."},{"from":"bp_internal_organs","to":"s_kidneys","level":"established","effect":"located","note":"Includes the kidneys, which heat stress and some metals can damage."},{"from":"bp_psyche","to":"s_limbic","level":"established","effect":"located","note":"Fear, mood and memory of trauma run through the limbic system."},{"from":"bp_psyche","to":"s_prefrontal","level":"established","effect":"located","note":"Planning, concentration and calming fear depend on the prefrontal cortex."},{"from":"bp_sleep","to":"s_hypo","level":"established","effect":"located","note":"The hypothalamus holds the body clock and sleep switch."},{"from":"bp_sleep","to":"s_brainstem","level":"established","effect":"located","note":"The brainstem switches between sleep stages."},{"from":"bp_sexual_function","to":"s_reproductive","level":"established","effect":"located","note":"Sexual organs."},{"from":"bp_sexual_function","to":"s_autonomic","level":"established","effect":"located","note":"Erection and arousal depend on autonomic nerves that pass the low spine and pelvis."},{"from":"bp_skin","to":"s_skin","level":"established","effect":"located","note":"The skin (textbook anatomy)."},{"from":"bp_lungs","to":"s_lungs","level":"established","effect":"located","note":"The lungs (textbook anatomy)."},{"from":"bp_heart_circulation","to":"s_heart","level":"established","effect":"located","note":"The heart."},{"from":"bp_heart_circulation","to":"s_blood","level":"established","effect":"located","note":"Blood vessels and blood pressure."},{"from":"wi_lifting","to":"bp_lumbar_spine","level":"established","effect":"affects","note":"Lifting loads the low-back discs, muscles and ligaments more than any other body part."},{"from":"wi_lifting","to":"bp_shoulders","level":"established","effect":"affects","note":"Lifting and carrying strain the shoulder muscles and rotator cuff."},{"from":"wi_lifting","to":"bp_abdomen","level":"established","effect":"affects","note":"Straining to lift raises pressure inside the belly against the groin wall."},{"from":"wi_vehicle","to":"bp_cervical_spine","level":"established","effect":"affects","note":"Whiplash strains the neck in crashes."},{"from":"wi_vehicle","to":"bp_head_brain","level":"established","effect":"affects","note":"The head can strike the vehicle, causing concussion."},{"from":"wi_wbv","to":"bp_lumbar_spine","level":"established","effect":"affects","note":"Seat vibration repeatedly loads the low-back discs."},{"from":"wi_prolonged_posture","to":"bp_ankles_feet","level":"established","effect":"affects","note":"Standing for hours loads the feet and pools blood in leg veins."},{"from":"wi_prolonged_posture","to":"bp_lumbar_spine","level":"established","effect":"affects","note":"Hours in one posture tire and stiffen the low back."},{"from":"low_back_disc","to":"bp_lumbar_spine","level":"established","effect":"affects","note":"A low-back condition."},{"from":"cervical_radiculopathy","to":"bp_cervical_spine","level":"established","effect":"affects","note":"A neck condition."},{"from":"knee_meniscus_oa","to":"bp_knees","level":"established","effect":"affects","note":"A knee condition."},{"from":"inguinal_hernia","to":"bp_abdomen","level":"established","effect":"affects","note":"A weakness in the groin wall."},{"from":"wi_lifting","to":"low_back_disc","level":"association","effect":"harms","note":"Heavier and more frequent lifting is linked with more low back pain.","sources":[{"id":"pmid:25165395","citation":"Coenen P et al., Occup Environ Med","year":2014,"design":"meta-analysis","finding":"In 8 longitudinal studies, low back pain rose with load (OR 1.11 per 10 kg) and lifts per day (OR 1.09 per 10 lifts)."}]},{"from":"wi_wbv","to":"low_back_disc","level":"association","effect":"harms","note":"Driving vibrating vehicles for work is linked with about twice the low back pain and sciatica.","sources":[{"id":"pmid:25142739","citation":"Burström L et al., Int Arch Occup Environ Health","year":2015,"design":"meta-analysis","finding":"Whole-body vibration at work was linked with more low back pain (OR 2.17) and sciatica (OR 1.92)."}]},{"from":"wi_vehicle","to":"cervical_radiculopathy","level":"established","effect":"harms","note":"Crashes are the classic cause of whiplash neck strain."},{"from":"wi_lifting","to":"knee_meniscus_oa","level":"association","effect":"harms","note":"Jobs with heavy lifting, kneeling and climbing are linked with more knee osteoarthritis.","sources":[{"id":"pmid:32638548","citation":"Wang X et al., Arthritis Care Res","year":2020,"design":"meta-analysis","finding":"Physically demanding jobs with lifting, kneeling, squatting, climbing and standing were linked with higher odds of knee osteoarthritis (moderate-quality evidence)."}]},{"from":"wi_prolonged_posture","to":"inguinal_hernia","level":"association","effect":"harms","note":"Standing or walking 6+ hours a day was linked with more groin hernia repairs; evidence on other work loads is weak.","sources":[{"id":"pmid:28546321","citation":"Vad MV et al., Occup Environ Med","year":2017,"design":"cohort","finding":"In 17,967 Danish men, standing/walking 6+ hours a day was linked with more lateral inguinal hernia repairs (HR 1.45)."},{"id":"pmid:22643828","citation":"Svendsen SW et al., Scand J Work Environ Health","year":2013,"design":"review","finding":"Systematic review found the evidence too weak to conclude that specific work loads cause inguinal hernia."}]},{"from":"low_back_disc","to":"pain","level":"established","effect":"harms","note":"Back strain and sciatica are painful."},{"from":"cervical_radiculopathy","to":"pain","level":"established","effect":"harms","note":"Neck pain, and arm pain from a pinched nerve."},{"from":"knee_meniscus_oa","to":"pain","level":"established","effect":"harms","note":"Knee pain, worse with kneeling and stairs."},{"from":"h_ergonomics","to":"wi_lifting","level":"established","effect":"helps","note":"Hoists and lifting aids take load off the worker directly."},{"from":"h_ergonomics","to":"low_back_disc","level":"association","effect":"helps","note":"Patient-lifting devices are linked with less back pain in care staff; lifting-technique training alone does not prevent back pain.","sources":[{"id":"pmid:37712457","citation":"Richarz HU et al., J Occup Health","year":2023,"design":"meta-analysis","finding":"Mechanical patient-lifting devices were linked with fewer musculoskeletal injuries and less low back pain in health-care staff."},{"id":"pmid:21678349","citation":"Verbeek JH et al., Cochrane Database Syst Rev","year":2011,"design":"meta-analysis","finding":"Moderate-quality evidence that lifting advice and training, with or without assistive devices, does not prevent back pain."}]},{"from":"h_early_activity","to":"low_back_disc","level":"proven","effect":"helps","note":"Exercise therapy modestly reduces chronic back pain in trials; starting physical therapy very early adds little for new back pain.","sources":[{"id":"pmid:34580864","citation":"Hayden JA et al., Cochrane Database Syst Rev","year":2021,"design":"meta-analysis","finding":"Moderate-certainty evidence that exercise therapy reduces chronic low back pain compared with no treatment or usual care; function gains were small."},{"id":"pmid:26461996","citation":"Fritz JM et al., JAMA","year":2015,"design":"RCT","finding":"Early physical therapy for new low back pain improved disability slightly at 3 months, less than a clinically important amount, and not at 1 year."}]},{"from":"wi_repetitive","to":"bp_wrists_hands","level":"established","effect":"affects","note":"Repetitive gripping loads the wrist tendons and carpal tunnel."},{"from":"wi_repetitive","to":"bp_elbows","level":"established","effect":"affects","note":"Gripping muscles pull on their elbow attachments."},{"from":"wi_repetitive","to":"bp_shoulders","level":"established","effect":"affects","note":"Repeated arm movements load the rotator cuff."},{"from":"wi_awkward_posture","to":"bp_shoulders","level":"established","effect":"affects","note":"Overhead work pinches the rotator cuff tendons."},{"from":"wi_awkward_posture","to":"bp_knees","level":"established","effect":"affects","note":"Kneeling and squatting load the knee cartilage."},{"from":"wi_awkward_posture","to":"bp_cervical_spine","level":"established","effect":"affects","note":"Long neck bending loads the neck."},{"from":"wi_awkward_posture","to":"bp_lumbar_spine","level":"established","effect":"affects","note":"Bending and twisting load the low back."},{"from":"wi_hav","to":"bp_fingers","level":"established","effect":"affects","note":"Vibration damages finger blood vessels and nerves."},{"from":"wi_hav","to":"bp_wrists_hands","level":"established","effect":"affects","note":"Vibration reaches the wrist and median nerve."},{"from":"carpal_tunnel","to":"bp_wrists_hands","level":"established","effect":"affects","note":"A wrist and hand condition."},{"from":"carpal_tunnel","to":"s_peripheral","level":"established","effect":"affects","note":"Compresses the median nerve."},{"from":"rotator_cuff","to":"bp_shoulders","level":"established","effect":"affects","note":"A shoulder condition."},{"from":"epicondylitis","to":"bp_elbows","level":"established","effect":"affects","note":"An elbow tendon condition."},{"from":"havs","to":"bp_fingers","level":"established","effect":"affects","note":"Damages finger blood vessels and nerves."},{"from":"havs","to":"s_peripheral","level":"established","effect":"affects","note":"Damages touch nerves in the fingers."},{"from":"wi_repetitive","to":"carpal_tunnel","level":"association","effect":"harms","note":"Repetition and forceful gripping are linked with 2 to 4 times the odds of carpal tunnel syndrome.","sources":[{"id":"pmid:21586523","citation":"Barcenilla A et al., Rheumatology","year":2012,"design":"meta-analysis","finding":"Carpal tunnel syndrome was linked with vibration (OR 5.4), hand force (OR 4.2) and repetition (OR 2.3) at work."}]},{"from":"wi_hav","to":"carpal_tunnel","level":"association","effect":"harms","note":"Vibrating tools are linked with roughly 3 to 5 times the odds of carpal tunnel syndrome.","sources":[{"id":"pmid:21586523","citation":"Barcenilla A et al., Rheumatology","year":2012,"design":"meta-analysis","finding":"Carpal tunnel syndrome was linked with vibration (OR 5.4), hand force (OR 4.2) and repetition (OR 2.3) at work."},{"id":"pmid:28704466","citation":"Nilsson T et al., PLoS One","year":2017,"design":"meta-analysis","finding":"Hand-arm vibration raised the risk of white finger (OR 6.9), nerve injury in the hands (OR 7.4) and carpal tunnel syndrome (OR 2.9)."}]},{"from":"wi_hav","to":"havs","level":"established","effect":"harms","note":"Vibration dose is the cause of vibration white finger; risk rises with years of use.","sources":[{"id":"pmid:28704466","citation":"Nilsson T et al., PLoS One","year":2017,"design":"meta-analysis","finding":"Hand-arm vibration raised the risk of white finger (OR 6.9), nerve injury in the hands (OR 7.4) and carpal tunnel syndrome (OR 2.9)."}]},{"from":"wi_repetitive","to":"rotator_cuff","level":"association","effect":"harms","note":"Repetitive and forceful arm work is linked with shoulder impingement.","sources":[{"id":"pmid:20094690","citation":"van Rijn RM et al., Scand J Work Environ Health","year":2010,"design":"review","finding":"Highly repetitive work, forceful exertion, awkward arm postures and high job demands were associated with shoulder impingement (rotator cuff) disorders."}]},{"from":"wi_awkward_posture","to":"rotator_cuff","level":"association","effect":"harms","note":"Working with arms raised is linked with shoulder impingement.","sources":[{"id":"pmid:20094690","citation":"van Rijn RM et al., Scand J Work Environ Health","year":2010,"design":"review","finding":"Highly repetitive work, forceful exertion, awkward arm postures and high job demands were associated with shoulder impingement (rotator cuff) disorders."}]},{"from":"wi_repetitive","to":"epicondylitis","level":"association","effect":"harms","note":"Forceful gripping and repetitive movements are linked with epicondylitis.","sources":[{"id":"pmid:19224937","citation":"van Rijn RM et al., Rheumatology","year":2009,"design":"review","finding":"Forceful gripping, heavy handling, repetitive movements and vibrating tools were associated with epicondylitis."}]},{"from":"carpal_tunnel","to":"pain","level":"established","effect":"harms","note":"Hand pain and tingling, often waking people at night."},{"from":"carpal_tunnel","to":"insomnia","level":"established","effect":"harms","note":"Numbness and pain classically wake people at night."},{"from":"rotator_cuff","to":"pain","level":"established","effect":"harms","note":"Shoulder pain, worse lifting the arm."},{"from":"epicondylitis","to":"pain","level":"established","effect":"harms","note":"Elbow pain with gripping."},{"from":"havs","to":"pain","level":"established","effect":"harms","note":"Painful finger attacks in the cold and tingling."},{"from":"headache","to":"bp_head_brain","level":"established","effect":"located","note":"Felt in the head."},{"from":"wi_slip_trip_fall","to":"bp_wrists_hands","level":"established","effect":"affects","note":"Catching a fall on an outstretched hand breaks or sprains the wrist."},{"from":"wi_slip_trip_fall","to":"bp_ankles_feet","level":"established","effect":"affects","note":"Twisted ankles and foot fractures."},{"from":"wi_slip_trip_fall","to":"bp_knees","level":"established","effect":"affects","note":"Landing on or twisting the knee."},{"from":"wi_slip_trip_fall","to":"bp_hips","level":"established","effect":"affects","note":"Hip fractures, especially in older workers."},{"from":"wi_slip_trip_fall","to":"bp_head_brain","level":"established","effect":"affects","note":"The head can strike the floor."},{"from":"wi_fall_height","to":"bp_ankles_feet","level":"established","effect":"affects","note":"Heel and ankle fractures from landing feet-first."},{"from":"wi_fall_height","to":"bp_lumbar_spine","level":"established","effect":"affects","note":"Spinal compression fractures."},{"from":"wi_fall_height","to":"bp_head_brain","level":"established","effect":"affects","note":"Serious head injury."},{"from":"wi_struck_caught","to":"bp_fingers","level":"established","effect":"affects","note":"Crush and amputation injuries in machinery."},{"from":"wi_struck_caught","to":"bp_head_brain","level":"established","effect":"affects","note":"Falling objects strike the head."},{"from":"wi_head_impacts","to":"bp_head_brain","level":"established","effect":"affects","note":"Blows and blasts jolt the brain."},{"from":"wi_assault","to":"bp_face_jaw","level":"established","effect":"affects","note":"Blows to the face and jaw."},{"from":"wi_assault","to":"bp_psyche","level":"association","effect":"affects","note":"Violence at work is linked with post-traumatic stress, rising with how often it happens.","sources":[{"id":"pmid:31233309","citation":"Pihl-Thingvad J et al., J Occup Health Psychol","year":2019,"design":"cohort","finding":"In 1,763 social educators followed 1 year, workplace violence raised PTSD risk in an exposure-response pattern (OR 4 to 6.5)."}]},{"from":"wi_slip_trip_fall","to":"fracture","level":"established","effect":"harms","note":"Falls are the main cause of fractures."},{"from":"wi_fall_height","to":"fracture","level":"established","effect":"harms","note":"Falls from height commonly break bones."},{"from":"wi_slip_trip_fall","to":"tbi","level":"established","effect":"harms","note":"Falls are a leading cause of brain injury."},{"from":"wi_fall_height","to":"tbi","level":"established","effect":"harms","note":"Falls from height cause serious brain injury."},{"from":"wi_head_impacts","to":"tbi","level":"established","effect":"harms","note":"Blows and blasts to the head cause concussion and TBI."},{"from":"wi_assault","to":"tbi","level":"established","effect":"harms","note":"Assaults cause head injuries."},{"from":"tbi","to":"bp_head_brain","level":"established","effect":"affects","note":"A brain injury."},{"from":"tbi","to":"post_concussion","level":"established","effect":"harms","note":"Symptoms can persist for months after a concussion.","sources":[{"id":"pmid:23952719","citation":"McMahon P et al., J Neurotrauma","year":2014,"design":"cohort","finding":"In the TRACK-TBI study, 82% of people with mild TBI still reported at least one post-concussion symptom at 1 year."}]},{"from":"post_concussion","to":"headache","level":"established","effect":"harms","note":"Headache is the commonest lasting symptom."},{"from":"post_concussion","to":"cognition","level":"established","effect":"harms","note":"Slowed thinking and poor concentration."},{"from":"post_concussion","to":"insomnia","level":"established","effect":"harms","note":"Sleep is often disturbed after concussion."},{"from":"tbi","to":"parkinsons","level":"association","effect":"harms","note":"Head injury is linked with about 1.4 to 1.6 times the risk of later Parkinson's, more with repeated injuries; cause is not proven.","sources":[{"id":"pmid:25726936","citation":"Gardner RC et al., Ann Neurol","year":2015,"design":"cohort","finding":"Among 165,799 people aged 55+, traumatic brain injury was linked with 44% higher Parkinson's risk over 5 to 7 years, higher with repeated injuries."},{"id":"pmid:23609436","citation":"Jafari S et al., Mov Disord","year":2013,"design":"meta-analysis","finding":"Across 22 studies, head injury with concussion was linked with higher Parkinson's risk (pooled OR 1.57)."}]},{"from":"tbi","to":"alzheimers","level":"association","effect":"harms","note":"TBI is linked with higher later dementia risk, including Alzheimer's, more with repeated or severe injuries; cause is not proven.","sources":[{"id":"pmid:29653873","citation":"Fann JR et al., Lancet Psychiatry","year":2018,"design":"cohort","finding":"In 2.8 million Danes, traumatic brain injury was linked with higher dementia risk (HR 1.24) and Alzheimer's risk (HR 1.16), rising with number of injuries."},{"id":"pmid:29801145","citation":"Barnes DE et al., JAMA Neurol","year":2018,"design":"cohort","finding":"In over 350,000 US veterans, even mild TBI without loss of consciousness was linked with more than twice the risk of dementia."}]},{"from":"tbi","to":"depression","level":"association","effect":"harms","note":"Even mild TBI is linked with about 3 times the odds of depression for years afterwards.","sources":[{"id":"pmid:32508733","citation":"Hellewell SC et al., Front Neurol","year":2020,"design":"meta-analysis","finding":"Mild traumatic brain injury was linked with about 3 times the odds of depression, persisting for years."}]},{"from":"wi_traumatic_events","to":"bp_psyche","level":"association","effect":"affects","note":"Traumatic scenes at work raise the risk of PTSD and depression.","sources":[{"id":"pmid:15285961","citation":"Fullerton CS et al., Am J Psychiatry","year":2004,"design":"cohort","finding":"Disaster and rescue workers exposed to traumatic scenes had more acute stress disorder, depression and PTSD than unexposed comparison workers."}]},{"from":"wi_job_strain","to":"bp_psyche","level":"association","effect":"affects","note":"Job strain is linked with clinical depression.","sources":[{"id":"pmid:28122650","citation":"Madsen IEH et al., Psychol Med","year":2017,"design":"meta-analysis","finding":"Job strain (high demands, low control) was linked with more clinical depression (RR 1.77 published, 1.27 unpublished data)."}]},{"from":"wi_job_strain","to":"bp_heart_circulation","level":"association","effect":"affects","note":"Job strain is linked with a modestly higher risk of heart disease.","sources":[{"id":"pmid:22981903","citation":"Kivimaki M et al., Lancet","year":2012,"design":"meta-analysis","finding":"In 197,473 workers, job strain was linked with modestly higher coronary heart disease risk (HR about 1.23)."}]},{"from":"wi_shift_work","to":"bp_sleep","level":"established","effect":"affects","note":"Night work shifts sleep against the body clock.","sources":[{"id":"pmid:27803010","citation":"Kecklund G, Axelsson J, BMJ","year":2016,"design":"review","finding":"Shift work causes sleep loss around night and early shifts and is linked with accidents, type 2 diabetes, weight gain and heart disease."}]},{"from":"wi_traumatic_events","to":"ptsd","level":"association","effect":"harms","note":"Exposure to traumatic scenes at work is linked with more PTSD.","sources":[{"id":"pmid:15285961","citation":"Fullerton CS et al., Am J Psychiatry","year":2004,"design":"cohort","finding":"Disaster and rescue workers exposed to traumatic scenes had more acute stress disorder, depression and PTSD than unexposed comparison workers."}]},{"from":"wi_job_strain","to":"depression","level":"association","effect":"harms","note":"High demands with low control are linked with more clinical depression.","sources":[{"id":"pmid:28122650","citation":"Madsen IEH et al., Psychol Med","year":2017,"design":"meta-analysis","finding":"Job strain (high demands, low control) was linked with more clinical depression (RR 1.77 published, 1.27 unpublished data)."}]},{"from":"wi_shift_work","to":"insomnia","level":"established","effect":"harms","note":"Daytime sleep after night shifts is short and broken.","sources":[{"id":"pmid:27803010","citation":"Kecklund G, Axelsson J, BMJ","year":2016,"design":"review","finding":"Shift work causes sleep loss around night and early shifts and is linked with accidents, type 2 diabetes, weight gain and heart disease."}]},{"from":"wi_shift_work","to":"sleepy","level":"established","effect":"harms","note":"Sleepiness is greatest on night and early-morning shifts.","sources":[{"id":"pmid:27803010","citation":"Kecklund G, Axelsson J, BMJ","year":2016,"design":"review","finding":"Shift work causes sleep loss around night and early shifts and is linked with accidents, type 2 diabetes, weight gain and heart disease."}]},{"from":"wi_shift_work","to":"m_clock","level":"established","effect":"harms","note":"Light and activity at night push against the body clock.","sources":[{"id":"pmid:27803010","citation":"Kecklund G, Axelsson J, BMJ","year":2016,"design":"review","finding":"Shift work causes sleep loss around night and early shifts and is linked with accidents, type 2 diabetes, weight gain and heart disease."}]},{"from":"wi_shift_work","to":"hm_insulin","level":"association","effect":"affects","note":"Shift work is linked with a slightly higher risk of type 2 diabetes, where the body stops responding well to insulin.","sources":[{"id":"pmid:25030030","citation":"Gan Y et al., Occup Environ Med","year":2015,"design":"meta-analysis","finding":"Shift work was linked with slightly higher diabetes risk (OR 1.09), more in men and rotating shifts."},{"id":"pmid:27803010","citation":"Kecklund G, Axelsson J, BMJ","year":2016,"design":"review","finding":"Shift work causes sleep loss around night and early shifts and is linked with accidents, type 2 diabetes, weight gain and heart disease."}]},{"from":"ptsd","to":"bp_psyche","level":"established","effect":"affects","note":"A psychiatric injury."},{"from":"ptsd","to":"s_limbic","level":"established","effect":"affects","note":"Fear circuits in the limbic system stay over-active."},{"from":"ptsd","to":"insomnia","level":"established","effect":"harms","note":"Nightmares and hyper-alertness break up sleep."},{"from":"ptsd","to":"anxiety","level":"established","effect":"harms","note":"Constant alertness and fear are core features."},{"from":"ptsd","to":"depression","level":"established","effect":"harms","note":"Depression commonly comes with PTSD.","sources":[{"id":"pmid:15285961","citation":"Fullerton CS et al., Am J Psychiatry","year":2004,"design":"cohort","finding":"Disaster and rescue workers exposed to traumatic scenes had more acute stress disorder, depression and PTSD than unexposed comparison workers."}]},{"from":"chronic_pain","to":"m_painproc","level":"established","effect":"affects","note":"Pain pathways in the spinal cord and brain become sensitised."},{"from":"chronic_pain","to":"pain","level":"established","effect":"harms","note":"Ongoing pain."},{"from":"chronic_pain","to":"insomnia","level":"association","effect":"harms","note":"Pain and poor sleep feed each other; poor sleep predicts more pain.","sources":[{"id":"pmid:24290442","citation":"Finan PH et al., J Pain","year":2013,"design":"review","finding":"Sleep and pain affect each other; poor sleep predicts later pain more strongly than pain predicts poor sleep."}]},{"from":"chronic_pain","to":"depression","level":"association","effect":"harms","note":"Depression is much more common with chronic pain and each worsens the other.","sources":[{"id":"pmid:14609780","citation":"Bair MJ et al., Arch Intern Med","year":2003,"design":"review","finding":"Depression is much more common in people with chronic pain, and each makes the other harder to treat."}]},{"from":"crps","to":"chronic_pain","level":"established","effect":"harms","note":"CRPS is a chronic pain condition."},{"from":"crps","to":"bp_wrists_hands","level":"established","effect":"affects","note":"Most often affects a hand or foot after injury."},{"from":"fracture","to":"crps","level":"association","effect":"harms","note":"Fractures, especially of the wrist, are the commonest trigger; reported frequency varies from 0.2% to about a third depending on how cases are found.","sources":[{"id":"pmid:41718642","citation":"Melbye P et al., Acta Orthop","year":2026,"design":"cohort","finding":"In a national register, about 0.2% of people with a wrist fracture were diagnosed with CRPS within a year."},{"id":"pmid:24080349","citation":"Jellad A et al., Arch Phys Med Rehabil","year":2014,"design":"cohort","finding":"In a prospective study of wrist fractures, 32% met criteria for CRPS type I after cast removal."}]},{"from":"wi_welding_fumes","to":"manganism","level":"established","effect":"harms","note":"Manganese in welding fume causes parkinsonism that worsens with cumulative exposure.","sources":[{"id":"pmid:22975422","citation":"Racette BA et al., Neurotoxicology","year":2012,"design":"cross-sectional","finding":"In shipyard and fabrication welders, 15.6% had parkinsonism versus 0% of unexposed workers."},{"id":"pmid:28031394","citation":"Racette BA et al., Neurology","year":2017,"design":"cohort","finding":"Parkinsonism in welders worsened faster with higher cumulative manganese exposure."}]},{"from":"wi_welding_fumes","to":"movement","level":"established","effect":"harms","note":"Welders with high manganese exposure develop slowness and stiffness.","sources":[{"id":"pmid:28031394","citation":"Racette BA et al., Neurology","year":2017,"design":"cohort","finding":"Parkinsonism in welders worsened faster with higher cumulative manganese exposure."}]},{"from":"wi_welding_fumes","to":"bp_head_brain","level":"established","effect":"affects","note":"Manganese builds up in deep movement centres of the brain.","sources":[{"id":"pmid:28031394","citation":"Racette BA et al., Neurology","year":2017,"design":"cohort","finding":"Parkinsonism in welders worsened faster with higher cumulative manganese exposure."}]},{"from":"wi_welding_fumes","to":"bp_lungs","level":"established","effect":"affects","note":"Fumes are breathed in and irritate the airways."},{"from":"manganism","to":"s_bg","level":"established","effect":"affects","note":"Damages the basal ganglia, especially the globus pallidus."},{"from":"manganism","to":"movement","level":"established","effect":"harms","note":"Slowness, stiffness and gait problems."},{"from":"manganism","to":"falls","level":"established","effect":"harms","note":"Gait and balance problems cause falls."},{"from":"wi_solvent_degreasing","to":"parkinsons","level":"association","effect":"harms","note":"Trichloroethylene exposure is linked with higher Parkinson's risk in a twin study and in Marines exposed through drinking water.","sources":[{"id":"pmid:22083847","citation":"Goldman SM et al., Annals of Neurology","year":2012,"design":"case-control","finding":"In twin pairs, past trichloroethylene exposure was linked with about 6 times the odds of Parkinson's (wide confidence interval)."},{"id":"pmid:37184848","citation":"Goldman SM et al., JAMA Neurology","year":2023,"design":"cohort","finding":"Marines stationed at Camp Lejeune, whose water was contaminated with trichloroethylene, had 70% higher odds of Parkinson's than those at Camp Pendleton."}]},{"from":"wi_solvent_degreasing","to":"bp_head_brain","level":"established","effect":"affects","note":"Solvents dissolve into the brain, causing dizziness and headache."},{"from":"wi_solvent_degreasing","to":"bp_internal_organs","level":"established","effect":"affects","note":"Some solvents harm the liver and kidneys."},{"from":"wi_solvent_degreasing","to":"contact_dermatitis","level":"established","effect":"harms","note":"Solvents strip the skin's oils and cause irritant dermatitis."},{"from":"wi_pesticide_application","to":"parkinsons","level":"association","effect":"harms","note":"Paraquat use was linked with about 2.5 times the odds of Parkinson's in farmers, but this was not confirmed in their 20-year follow-up; other pesticides were.","sources":[{"id":"pmid:21269927","citation":"Tanner CM et al., Environmental Health Perspectives","year":2011,"design":"case-control","finding":"In farmers, paraquat use was linked with about 2.5 times the odds of Parkinson's."},{"id":"pmid:32919961","citation":"Shrestha S et al., Environ Res","year":2020,"design":"cohort","finding":"In the 20-year follow-up of the same farm cohort, some pesticides were linked with Parkinson's but paraquat was not among those clearly raising risk; glove use appeared protective."}]},{"from":"wi_pesticide_application","to":"bp_skin","level":"established","effect":"affects","note":"Pesticides are absorbed through the skin during mixing and spraying."},{"from":"wi_lead_work","to":"parkinsons","level":"association","effect":"harms","note":"High bone lead (lifelong exposure) was linked with about 3 times the odds of Parkinson's.","sources":[{"id":"pmid:20807691","citation":"Weisskopf MG et al., Environ Health Perspect","year":2010,"design":"case-control","finding":"People with the highest bone lead (a marker of lifelong exposure) had about 3 times the odds of Parkinson's."}]},{"from":"wi_lead_work","to":"cognition","level":"association","effect":"harms","note":"Higher lifelong lead exposure is linked with poorer thinking in older age.","sources":[{"id":"pmid:19440496","citation":"Weuve J et al., Environ Health Perspect","year":2009,"design":"cohort","finding":"Higher bone lead was linked with worse thinking scores in older women."}]},{"from":"wi_lead_work","to":"bp_head_brain","level":"established","effect":"affects","note":"Lead is toxic to the brain."},{"from":"wi_lead_work","to":"bp_internal_organs","level":"established","effect":"affects","note":"Lead damages the kidneys."},{"from":"wi_carbon_monoxide","to":"bp_head_brain","level":"established","effect":"affects","note":"Starves the brain of oxygen."},{"from":"wi_carbon_monoxide","to":"bp_heart_circulation","level":"established","effect":"affects","note":"Starves the heart muscle of oxygen."},{"from":"wi_carbon_monoxide","to":"cognition","level":"established","effect":"harms","note":"Memory and thinking problems follow poisoning in many survivors.","sources":[{"id":"pmid:12362006","citation":"Weaver LK et al., N Engl J Med","year":2002,"design":"RCT","finding":"After carbon monoxide poisoning, 46% given normal oxygen had memory and thinking problems at 6 weeks; hyperbaric oxygen cut this to 25%."}]},{"from":"wi_wet_work","to":"bp_skin","level":"established","effect":"affects","note":"Wet work breaks down the skin barrier of the hands."},{"from":"wi_wet_work","to":"contact_dermatitis","level":"association","effect":"harms","note":"Two or more hours of wet work a day is linked with 2 to 3.5 times the odds of hand eczema.","sources":[{"id":"pmid:31956920","citation":"Lund T et al., Scand J Work Environ Health","year":2020,"design":"case-control","finding":"Two or more hours a day of wet hands or glove wear was linked with 2 to 3.5 times the odds of work-related hand eczema."}]},{"from":"contact_dermatitis","to":"bp_skin","level":"established","effect":"affects","note":"A skin condition."},{"from":"contact_dermatitis","to":"s_skin","level":"established","effect":"affects","note":"Inflames the skin barrier."},{"from":"tinnitus","to":"bp_ears","level":"established","effect":"located","note":"Heard in the ears and hearing pathways."},{"from":"tinnitus","to":"s_ears","level":"established","effect":"located","note":"Comes from damaged hearing pathways."},{"from":"breathless","to":"bp_lungs","level":"established","effect":"located","note":"Felt with lung and airway disease."},{"from":"breathless","to":"s_lungs","level":"established","effect":"located","note":"Comes from the lungs and airways."},{"from":"wi_noise","to":"bp_ears","level":"established","effect":"affects","note":"Loud noise kills inner-ear hair cells."},{"from":"wi_noise","to":"nihl","level":"established","effect":"harms","note":"Noise is the cause of noise-induced hearing loss."},{"from":"nihl","to":"tinnitus","level":"established","effect":"harms","note":"Hearing damage often brings ringing in the ears."},{"from":"nihl","to":"bp_ears","level":"established","effect":"affects","note":"Permanent inner-ear hearing loss."},{"from":"h_hearing_protection","to":"wi_noise","level":"association","effect":"helps","note":"Properly inserted earplugs reduce noise reaching the ear; proof that programmes prevent hearing loss is weak.","sources":[{"id":"pmid:28685503","citation":"Tikka C et al., Cochrane Database Syst Rev","year":2017,"design":"meta-analysis","finding":"Training workers to insert earplugs properly cuts noise exposure (moderate quality); evidence that hearing-protection programmes prevent hearing loss is very low quality."}]},{"from":"wi_heat","to":"heat_illness","level":"established","effect":"harms","note":"Heat strain causes heat exhaustion and heat stroke.","sources":[{"id":"pmid:30526938","citation":"Flouris AD et al., Lancet Planet Health","year":2018,"design":"meta-analysis","finding":"Workers under heat strain had more heat-related illness and kidney disease or acute kidney injury, and lower productivity."}]},{"from":"wi_heat","to":"dehydration","level":"established","effect":"harms","note":"Heavy sweating loses water and salt."},{"from":"wi_heat","to":"bp_internal_organs","level":"association","effect":"affects","note":"Workers under heat strain have more kidney injury.","sources":[{"id":"pmid:30526938","citation":"Flouris AD et al., Lancet Planet Health","year":2018,"design":"meta-analysis","finding":"Workers under heat strain had more heat-related illness and kidney disease or acute kidney injury, and lower productivity."}]},{"from":"heat_illness","to":"bp_heart_circulation","level":"established","effect":"affects","note":"The heart and circulation strain to cool the body."},{"from":"wi_silica_dust","to":"silicosis","level":"established","effect":"harms","note":"Crystalline silica is the cause of silicosis."},{"from":"wi_silica_dust","to":"bp_lungs","level":"established","effect":"affects","note":"Silica scars the lungs."},{"from":"wi_asbestos_work","to":"asbestos_disease","level":"established","effect":"harms","note":"Asbestos causes asbestosis and mesothelioma."},{"from":"wi_asbestos_work","to":"bp_lungs","level":"established","effect":"affects","note":"Fibres lodge in the lungs and chest lining."},{"from":"wi_isocyanates","to":"occ_asthma","level":"established","effect":"harms","note":"Isocyanates are a leading chemical cause of occupational asthma."},{"from":"wi_isocyanates","to":"bp_lungs","level":"established","effect":"affects","note":"Sensitisers inflame the airways."},{"from":"occ_asthma","to":"breathless","level":"established","effect":"harms","note":"Narrowed airways cause wheeze and breathlessness."},{"from":"silicosis","to":"breathless","level":"established","effect":"harms","note":"Scarred lungs cause breathlessness."},{"from":"asbestos_disease","to":"breathless","level":"established","effect":"harms","note":"Scarring and fluid around the lungs cause breathlessness."},{"from":"silicosis","to":"s_lungs","level":"established","effect":"affects","note":"Scars the lungs; also raises tuberculosis risk.","sources":[{"id":"pmid:34016067","citation":"Ehrlich R et al., BMC Public Health","year":2021,"design":"meta-analysis","finding":"Silicosis strongly raises tuberculosis risk; silica exposure without silicosis roughly doubles it (lower certainty)."}]},{"from":"asbestos_disease","to":"s_lungs","level":"established","effect":"affects","note":"Scars the lungs and causes cancer of the chest lining."},{"from":"occ_asthma","to":"s_lungs","level":"established","effect":"affects","note":"Inflamed, narrowed airways."},{"from":"h_respiratory_protection","to":"wi_silica_dust","level":"established","effect":"helps","note":"Wet cutting, extraction and fitted respirators cut the dust breathed in."},{"from":"h_respiratory_protection","to":"wi_asbestos_work","level":"established","effect":"helps","note":"Controls and respirators cut the fibres breathed in."},{"from":"wi_bloodborne","to":"hbv","level":"established","effect":"harms","note":"Needlesticks and splashes can transmit hepatitis B."},{"from":"wi_bloodborne","to":"hcv","level":"established","effect":"harms","note":"Needlesticks can transmit hepatitis C."},{"from":"wi_bloodborne","to":"hiv","level":"established","effect":"harms","note":"Needlesticks can transmit HIV, though the risk per injury is low."},{"from":"wi_covid19","to":"sarscov2","level":"association","effect":"harms","note":"Front-line health-care workers had about 3.4 times the community infection risk early in the pandemic.","sources":[{"id":"pmid:32745512","citation":"Nguyen LH et al., Lancet Public Health","year":2020,"design":"cohort","finding":"Front-line health-care workers had about 3.4 times the risk of a positive COVID-19 test compared with the general community early in the pandemic."}]},{"from":"wi_covid19","to":"bp_lungs","level":"established","effect":"affects","note":"COVID-19 mainly infects the airways and lungs."},{"from":"protein","to":"aa_phenylalanine","level":"established","effect":"contains","note":"Protein is digested into its amino acids, including phenylalanine."},{"from":"protein","to":"aa_tyrosine","level":"established","effect":"contains","note":"Protein is digested into its amino acids, including tyrosine."},{"from":"protein","to":"aa_tryptophan","level":"established","effect":"contains","note":"Protein is digested into its amino acids, including tryptophan."},{"from":"dairy","to":"aa_tryptophan","level":"established","effect":"contains","note":"Milk proteins, especially whey, are rich in tryptophan."},{"from":"poultry","to":"aa_tryptophan","level":"established","effect":"contains","note":"Chicken and turkey supply tryptophan, about as much as other meats."},{"from":"dairy","to":"aa_tyrosine","level":"established","effect":"contains","note":"Cheese and milk protein (casein) are rich in tyrosine."},{"from":"aa_phenylalanine","to":"aa_tyrosine","level":"established","effect":"helps","note":"The liver turns spare phenylalanine into tyrosine."},{"from":"aa_tyrosine","to":"levodopa","level":"established","effect":"helps","note":"Dopamine-making nerve cells turn tyrosine into their own L-DOPA; in Parkinson's it is these cells that are lost, which is why taking levodopa works."},{"from":"aa_tyrosine","to":"m_dopa","level":"established","effect":"helps","note":"Tyrosine is the raw material for dopamine; extra tyrosine raised a dopamine breakdown marker in Parkinson's but has not been shown to ease symptoms.","dose":"deficiency","sources":[{"id":"pmid:6175872","citation":"Growdon JH et al., Life Sci","year":1982,"design":"small human study","finding":"In 23 people with Parkinson's, oral tyrosine raised spinal-fluid tyrosine and, in those given probenecid, the dopamine breakdown product homovanillic acid; symptoms were not the outcome measured."}]},{"from":"aa_tyrosine","to":"hm_adrenaline","level":"established","effect":"helps","note":"Noradrenaline and adrenaline are made from tyrosine; extra beyond a normal diet isn't shown to do more.","dose":"deficiency"},{"from":"aa_tyrosine","to":"cognition","level":"mixed","effect":"helps","note":"Tyrosine supplements helped thinking in healthy people only during short, stressful or demanding tasks; not tested this way in Parkinson's.","sources":[{"id":"pmid:26424423","citation":"Jongkees BJ et al., J Psychiatr Res","year":2015,"design":"review","finding":"Tyrosine supplements seem to help thinking only during short, stressful or demanding situations, and show little promise for treating clinical disorders."}]},{"from":"aa_tryptophan","to":"aa_5htp","level":"established","effect":"helps","note":"The body's first step in making serotonin turns tryptophan into 5-HTP."},{"from":"aa_tryptophan","to":"m_reward","level":"established","effect":"helps","note":"Serotonin, a mood messenger, is made from tryptophan; extra beyond a normal diet isn't shown to do more.","dose":"deficiency"},{"from":"aa_tryptophan","to":"hm_melatonin","level":"established","effect":"helps","note":"The pineal gland makes melatonin from tryptophan, by way of serotonin; extra beyond a normal diet isn't shown to do more.","dose":"deficiency"},{"from":"aa_tryptophan","to":"depression","level":"mixed","effect":"helps","note":"Two small good-quality trials favoured tryptophan or 5-HTP for depression, too little to be sure; contaminated supplements once caused a serious muscle and blood illness.","sources":[{"id":"pmid:11869656","citation":"Shaw K et al., Cochrane Database Syst Rev","year":2002,"design":"meta-analysis","finding":"Of 108 trials of tryptophan or 5-HTP for depression only 2 (64 patients) were good enough to include; they favoured the supplements over placebo, but the evidence was too weak to be conclusive and safety was unresolved."},{"id":"pmid:8895184","citation":"Kilbourne EM et al., J Rheumatol Suppl","year":1996,"design":"review of case-control studies","finding":"Case-control studies tied the 1989 US eosinophilia-myalgia syndrome epidemic to L-tryptophan supplements from one manufacturer (Showa Denko); cases fell abruptly after the products were recalled."}]},{"from":"aa_5htp","to":"m_reward","level":"established","effect":"helps","note":"5-HTP is turned directly into serotonin, by the same enzyme that turns levodopa into dopamine."},{"from":"aa_5htp","to":"depression","level":"mixed","effect":"helps","note":"In one small 4-week trial in Parkinson's, 5-HTP improved depression scores but not apathy; not yet repeated.","scope":["parkinsons"],"sources":[{"id":"pmid:32067288","citation":"Meloni M et al., Eur J Neurol","year":2020,"design":"RCT","finding":"In a 25-person randomised placebo-controlled crossover trial in Parkinson's, 4 weeks of 5-HTP improved clinician-rated depression scores but did not change apathy."}]},{"from":"aa_phenylalanine","to":"m_absorb","level":"established","effect":"harms","note":"Phenylalanine uses the same carrier as levodopa to get from the blood into the brain (in a direct test, a phenylalanine drink switched off the effect of a levodopa drip), so a large protein load close to a dose can blunt the dose in people with fluctuations; ordinary day-to-day swings matter less for most people.","scope":["parkinsons"],"dose":"timing","sources":[{"id":"pmid:6694694","citation":"Nutt JG et al., N Engl J Med","year":1984,"design":"small human experiment","finding":"In people with on-off Parkinson's on steady intravenous levodopa, high-protein meals or oral phenylalanine, leucine or isoleucine reversed the levodopa effect without lowering blood levodopa, pointing to competition at the brain's amino-acid carrier; glycine and lysine had no effect."},{"id":"pmid:3632370","citation":"Pincus JH & Barry KM, Arch Neurol","year":1987,"design":"small human experiment","finding":"In 7 people with severe fluctuations, regular and high-protein diets raised blood large neutral amino acids, and symptoms returned despite good blood levodopa; when these amino acids fell, symptoms eased."},{"id":"pmid:2795076","citation":"Frankel JP et al., J Neurol Neurosurg Psychiatry","year":1989,"design":"small human experiment","finding":"During steady levodopa infusion into the gut, oral protein loads worsened movement even though blood levodopa stayed steady, suggesting the competition matters most at the blood-brain barrier."},{"id":"pmid:2738591","citation":"Nutt JG et al., J Neurol Neurosurg Psychiatry","year":1989,"design":"small human experiment","finding":"On ordinary hospital meals, swings in blood large neutral amino acids were small next to swings in blood levodopa and were not an important cause of fluctuations in most of 11 patients."},{"id":"pmid:39240647","citation":"Pedrosa de Menezes AL et al., J Parkinsons Dis","year":2024,"design":"review","finding":"Review of the molecular steps of levodopa absorption, including its shared amino-acid transporters, and why absorption varies so much between and within people."}]},{"from":"aa_tyrosine","to":"m_absorb","level":"established","effect":"harms","note":"Tyrosine uses the same carrier as levodopa to get from the blood into the brain, so a large protein load close to a dose can blunt the dose in people with fluctuations; ordinary day-to-day swings matter less for most people.","scope":["parkinsons"],"dose":"timing","sources":[{"id":"pmid:6694694","citation":"Nutt JG et al., N Engl J Med","year":1984,"design":"small human experiment","finding":"In people with on-off Parkinson's on steady intravenous levodopa, high-protein meals or oral phenylalanine, leucine or isoleucine reversed the levodopa effect without lowering blood levodopa, pointing to competition at the brain's amino-acid carrier; glycine and lysine had no effect."},{"id":"pmid:3632370","citation":"Pincus JH & Barry KM, Arch Neurol","year":1987,"design":"small human experiment","finding":"In 7 people with severe fluctuations, regular and high-protein diets raised blood large neutral amino acids, and symptoms returned despite good blood levodopa; when these amino acids fell, symptoms eased."},{"id":"pmid:2795076","citation":"Frankel JP et al., J Neurol Neurosurg Psychiatry","year":1989,"design":"small human experiment","finding":"During steady levodopa infusion into the gut, oral protein loads worsened movement even though blood levodopa stayed steady, suggesting the competition matters most at the blood-brain barrier."},{"id":"pmid:2738591","citation":"Nutt JG et al., J Neurol Neurosurg Psychiatry","year":1989,"design":"small human experiment","finding":"On ordinary hospital meals, swings in blood large neutral amino acids were small next to swings in blood levodopa and were not an important cause of fluctuations in most of 11 patients."},{"id":"pmid:39240647","citation":"Pedrosa de Menezes AL et al., J Parkinsons Dis","year":2024,"design":"review","finding":"Review of the molecular steps of levodopa absorption, including its shared amino-acid transporters, and why absorption varies so much between and within people."}]},{"from":"aa_tryptophan","to":"m_absorb","level":"established","effect":"harms","note":"Tryptophan uses the same carrier as levodopa to get from the blood into the brain, so a large protein load close to a dose can blunt the dose in people with fluctuations; ordinary day-to-day swings matter less for most people.","scope":["parkinsons"],"dose":"timing","sources":[{"id":"pmid:6694694","citation":"Nutt JG et al., N Engl J Med","year":1984,"design":"small human experiment","finding":"In people with on-off Parkinson's on steady intravenous levodopa, high-protein meals or oral phenylalanine, leucine or isoleucine reversed the levodopa effect without lowering blood levodopa, pointing to competition at the brain's amino-acid carrier; glycine and lysine had no effect."},{"id":"pmid:3632370","citation":"Pincus JH & Barry KM, Arch Neurol","year":1987,"design":"small human experiment","finding":"In 7 people with severe fluctuations, regular and high-protein diets raised blood large neutral amino acids, and symptoms returned despite good blood levodopa; when these amino acids fell, symptoms eased."},{"id":"pmid:2795076","citation":"Frankel JP et al., J Neurol Neurosurg Psychiatry","year":1989,"design":"small human experiment","finding":"During steady levodopa infusion into the gut, oral protein loads worsened movement even though blood levodopa stayed steady, suggesting the competition matters most at the blood-brain barrier."},{"id":"pmid:2738591","citation":"Nutt JG et al., J Neurol Neurosurg Psychiatry","year":1989,"design":"small human experiment","finding":"On ordinary hospital meals, swings in blood large neutral amino acids were small next to swings in blood levodopa and were not an important cause of fluctuations in most of 11 patients."},{"id":"pmid:39240647","citation":"Pedrosa de Menezes AL et al., J Parkinsons Dis","year":2024,"design":"review","finding":"Review of the molecular steps of levodopa absorption, including its shared amino-acid transporters, and why absorption varies so much between and within people."}]},{"from":"protein","to":"aa_bcaa","level":"established","effect":"contains","note":"Protein is digested into its amino acids, including leucine, isoleucine and valine."},{"from":"protein","to":"aa_lysine","level":"established","effect":"contains","note":"Protein is digested into its amino acids, including lysine."},{"from":"protein","to":"aa_histidine","level":"established","effect":"contains","note":"Protein is digested into its amino acids, including histidine."},{"from":"protein","to":"aa_threonine","level":"established","effect":"contains","note":"Protein is digested into its amino acids, including threonine."},{"from":"dairy","to":"aa_bcaa","level":"established","effect":"contains","note":"Whey protein in milk is one of the richest sources of leucine."},{"from":"eggs","to":"aa_bcaa","level":"established","effect":"contains","note":"Egg protein supplies all three branched-chain amino acids."},{"from":"redmeat","to":"aa_bcaa","level":"established","effect":"contains","note":"Meat protein supplies all three branched-chain amino acids."},{"from":"legumes","to":"aa_lysine","level":"established","effect":"contains","note":"Beans and lentils are rich in lysine, the amino acid grains lack."},{"from":"soy","to":"aa_lysine","level":"established","effect":"contains","note":"Soy protein is rich in lysine."},{"from":"whitefish","to":"aa_histidine","level":"established","effect":"contains","note":"Fish and meat supply histidine."},{"from":"aa_bcaa","to":"s_muscle","level":"established","effect":"helps","note":"Muscle burns these amino acids, and leucine switches on muscle-protein building after a meal.","dose":"deficiency"},{"from":"aa_bcaa","to":"m_bone","level":"mixed","effect":"helps","note":"Leucine alone did not build muscle or strength in older adults; mixed with vitamin D and protein, small gains appeared on weak evidence.","sources":[{"id":"pmid:35845777","citation":"Guo Y et al., Front Nutr","year":2022,"design":"meta-analysis","finding":"Across 17 randomised trials in older adults, leucine on its own did not improve lean mass, grip or leg strength; leucine combined with vitamin D and other nutrients slightly improved grip strength and walking speed."},{"id":"pmid:40805998","citation":"Huang C & Hsieh MH, Nutrients","year":2025,"design":"meta-analysis","finding":"In older adults with sarcopenia, leucine supplements were linked with small gains in grip strength, muscle mass and walking speed, but the evidence was rated low quality."}]},{"from":"aa_threonine","to":"m_barrier","level":"established","effect":"helps","note":"The gut uses a lot of threonine to make the mucus that coats and protects its lining.","dose":"deficiency"},{"from":"aa_bcaa","to":"m_absorb","level":"established","effect":"harms","note":"Each of leucine, isoleucine and valine uses the same carrier as levodopa to get from the blood into the brain (leucine and isoleucine drinks switched off the effect of a levodopa drip in a direct test), so a large protein load close to a dose can blunt the dose in people with fluctuations; ordinary day-to-day swings matter less for most people.","scope":["parkinsons"],"dose":"timing","sources":[{"id":"pmid:6694694","citation":"Nutt JG et al., N Engl J Med","year":1984,"design":"small human experiment","finding":"In people with on-off Parkinson's on steady intravenous levodopa, high-protein meals or oral phenylalanine, leucine or isoleucine reversed the levodopa effect without lowering blood levodopa, pointing to competition at the brain's amino-acid carrier; glycine and lysine had no effect."},{"id":"pmid:3632370","citation":"Pincus JH & Barry KM, Arch Neurol","year":1987,"design":"small human experiment","finding":"In 7 people with severe fluctuations, regular and high-protein diets raised blood large neutral amino acids, and symptoms returned despite good blood levodopa; when these amino acids fell, symptoms eased."},{"id":"pmid:2795076","citation":"Frankel JP et al., J Neurol Neurosurg Psychiatry","year":1989,"design":"small human experiment","finding":"During steady levodopa infusion into the gut, oral protein loads worsened movement even though blood levodopa stayed steady, suggesting the competition matters most at the blood-brain barrier."},{"id":"pmid:2738591","citation":"Nutt JG et al., J Neurol Neurosurg Psychiatry","year":1989,"design":"small human experiment","finding":"On ordinary hospital meals, swings in blood large neutral amino acids were small next to swings in blood levodopa and were not an important cause of fluctuations in most of 11 patients."},{"id":"pmid:39240647","citation":"Pedrosa de Menezes AL et al., J Parkinsons Dis","year":2024,"design":"review","finding":"Review of the molecular steps of levodopa absorption, including its shared amino-acid transporters, and why absorption varies so much between and within people."}]},{"from":"aa_histidine","to":"m_absorb","level":"established","effect":"harms","note":"Histidine uses the same carrier as levodopa to get from the blood into the brain, so a large protein load close to a dose can blunt the dose in people with fluctuations; ordinary day-to-day swings matter less for most people.","scope":["parkinsons"],"dose":"timing","sources":[{"id":"pmid:6694694","citation":"Nutt JG et al., N Engl J Med","year":1984,"design":"small human experiment","finding":"In people with on-off Parkinson's on steady intravenous levodopa, high-protein meals or oral phenylalanine, leucine or isoleucine reversed the levodopa effect without lowering blood levodopa, pointing to competition at the brain's amino-acid carrier; glycine and lysine had no effect."},{"id":"pmid:3632370","citation":"Pincus JH & Barry KM, Arch Neurol","year":1987,"design":"small human experiment","finding":"In 7 people with severe fluctuations, regular and high-protein diets raised blood large neutral amino acids, and symptoms returned despite good blood levodopa; when these amino acids fell, symptoms eased."},{"id":"pmid:2795076","citation":"Frankel JP et al., J Neurol Neurosurg Psychiatry","year":1989,"design":"small human experiment","finding":"During steady levodopa infusion into the gut, oral protein loads worsened movement even though blood levodopa stayed steady, suggesting the competition matters most at the blood-brain barrier."},{"id":"pmid:2738591","citation":"Nutt JG et al., J Neurol Neurosurg Psychiatry","year":1989,"design":"small human experiment","finding":"On ordinary hospital meals, swings in blood large neutral amino acids were small next to swings in blood levodopa and were not an important cause of fluctuations in most of 11 patients."},{"id":"pmid:39240647","citation":"Pedrosa de Menezes AL et al., J Parkinsons Dis","year":2024,"design":"review","finding":"Review of the molecular steps of levodopa absorption, including its shared amino-acid transporters, and why absorption varies so much between and within people."}]},{"from":"aa_threonine","to":"m_absorb","level":"established","effect":"harms","note":"Threonine uses the same carrier as levodopa to get from the blood into the brain (more weakly than leucine), so a large protein load close to a dose can blunt the dose in people with fluctuations; ordinary day-to-day swings matter less for most people.","scope":["parkinsons"],"dose":"timing","sources":[{"id":"pmid:6694694","citation":"Nutt JG et al., N Engl J Med","year":1984,"design":"small human experiment","finding":"In people with on-off Parkinson's on steady intravenous levodopa, high-protein meals or oral phenylalanine, leucine or isoleucine reversed the levodopa effect without lowering blood levodopa, pointing to competition at the brain's amino-acid carrier; glycine and lysine had no effect."},{"id":"pmid:3632370","citation":"Pincus JH & Barry KM, Arch Neurol","year":1987,"design":"small human experiment","finding":"In 7 people with severe fluctuations, regular and high-protein diets raised blood large neutral amino acids, and symptoms returned despite good blood levodopa; when these amino acids fell, symptoms eased."},{"id":"pmid:2795076","citation":"Frankel JP et al., J Neurol Neurosurg Psychiatry","year":1989,"design":"small human experiment","finding":"During steady levodopa infusion into the gut, oral protein loads worsened movement even though blood levodopa stayed steady, suggesting the competition matters most at the blood-brain barrier."},{"id":"pmid:2738591","citation":"Nutt JG et al., J Neurol Neurosurg Psychiatry","year":1989,"design":"small human experiment","finding":"On ordinary hospital meals, swings in blood large neutral amino acids were small next to swings in blood levodopa and were not an important cause of fluctuations in most of 11 patients."},{"id":"pmid:39240647","citation":"Pedrosa de Menezes AL et al., J Parkinsons Dis","year":2024,"design":"review","finding":"Review of the molecular steps of levodopa absorption, including its shared amino-acid transporters, and why absorption varies so much between and within people."}]},{"from":"protein","to":"aa_glutamate","level":"established","effect":"contains","note":"Protein is digested into its amino acids, including glutamate."},{"from":"protein","to":"aa_glutamine","level":"established","effect":"contains","note":"Protein is digested into its amino acids, including glutamine."},{"from":"protein","to":"aa_glycine","level":"established","effect":"contains","note":"Protein is digested into its amino acids, including glycine."},{"from":"protein","to":"aa_serine","level":"established","effect":"contains","note":"Protein is digested into its amino acids, including serine."},{"from":"protein","to":"aa_aspartate","level":"established","effect":"contains","note":"Protein is digested into its amino acids, including aspartate."},{"from":"tomatoes","to":"aa_glutamate","level":"established","effect":"contains","note":"Ripe tomatoes are rich in free glutamate, the source of their savoury (umami) taste."},{"from":"mushrooms","to":"aa_glutamate","level":"established","effect":"contains","note":"Mushrooms are rich in free glutamate (umami)."},{"from":"dairy","to":"aa_glutamate","level":"established","effect":"contains","note":"Aged cheeses such as parmesan are rich in free glutamate."},{"from":"aa_glutamine","to":"aa_glutamate","level":"established","effect":"helps","note":"Nerve cells remake glutamate (and from it GABA) from glutamine supplied by support cells."},{"from":"aa_glutamate","to":"aa_gaba","level":"established","effect":"helps","note":"Nerve cells make GABA from glutamate with an enzyme that needs vitamin B6."},{"from":"aa_glutamate","to":"m_excit","level":"established","effect":"affects","note":"Glutamate is the brain's main 'go' signal; it must be balanced, as too much over-excites circuits (dietary glutamate barely reaches the brain)."},{"from":"aa_gaba","to":"m_excit","level":"established","effect":"affects","note":"GABA is the brain's main 'stop' signal; whether GABA swallowed as a supplement reaches the brain is unclear.","sources":[{"id":"pmid:26500584","citation":"Boonstra E et al., Front Psychol","year":2015,"design":"review","finding":"Whether swallowed GABA crosses the blood-brain barrier is unclear and contradictory; there is some evidence of a calming effect, but much of it comes from researchers with conflicts of interest."}]},{"from":"aa_glycine","to":"m_excit","level":"established","effect":"affects","note":"Glycine is a calming signal in the spinal cord and brainstem and a needed partner for NMDA glutamate receptors."},{"from":"aa_glycine","to":"insomnia","level":"mixed","effect":"helps","note":"Small trials in healthy people found glycine before bed improved sleep and next-day tiredness, with high risk of bias; not tested in Parkinson's.","sources":[{"id":"pmid:37851316","citation":"Soh J et al., Geroscience","year":2024,"design":"review","finding":"Systematic review of glycine given to adults: longer-term glycine improved sleep in healthy people, but those studies were small with a high risk of bias."},{"id":"pmid:22529837","citation":"Bannai M et al., Front Neurol","year":2012,"design":"placebo-controlled trial","finding":"In healthy volunteers with restricted sleep, glycine before bed reduced next-day fatigue and improved a vigilance test compared with placebo."}]},{"from":"aa_serine","to":"aa_glycine","level":"established","effect":"helps","note":"The body makes glycine from serine."},{"from":"aa_serine","to":"m_excit","level":"established","effect":"affects","note":"Its mirror-image form, D-serine, made in the brain, helps switch on NMDA glutamate receptors; a tiny Parkinson's pilot of D-serine was positive but not repeated.","sources":[{"id":"pmid:21733283","citation":"Gelfin E et al., Int J Neuropsychopharmacol","year":2012,"design":"RCT","finding":"In a 10-person double-blind placebo-controlled crossover pilot in Parkinson's, D-serine (the brain's own mirror-image form of serine, which helps switch on NMDA glutamate receptors) lowered movement and behaviour scores; larger studies were called for."}]},{"from":"aa_glutamine","to":"m_barrier","level":"established","effect":"helps","note":"Gut-lining cells burn glutamine as a main fuel.","dose":"deficiency"},{"from":"theanine","to":"m_excit","level":"lab","effect":"helps","note":"L-theanine, tea's own amino acid, resembles glutamate and in animal studies binds glutamate receptors and raises brain GABA.","sources":[{"id":"pmid:17182482","citation":"Nathan PJ et al., J Herb Pharmacother","year":2006,"design":"review","finding":"Animal studies suggest L-theanine binds glutamate receptors (AMPA, kainate, NMDA) with micromolar affinity and raises brain GABA, serotonin and dopamine."}]},{"from":"protein","to":"aa_methionine","level":"established","effect":"contains","note":"Protein is digested into its amino acids, including methionine."},{"from":"protein","to":"aa_cysteine","level":"established","effect":"contains","note":"Protein is digested into its amino acids, including cysteine."},{"from":"eggs","to":"aa_methionine","level":"established","effect":"contains","note":"Egg white is rich in methionine and cysteine."},{"from":"oilyfish","to":"aa_methionine","level":"established","effect":"contains","note":"Fish protein is rich in methionine."},{"from":"nuts","to":"aa_methionine","level":"established","effect":"contains","note":"Brazil nuts and sesame are unusually rich in methionine for plant foods."},{"from":"eggs","to":"aa_cysteine","level":"established","effect":"contains","note":"Egg white is rich in cysteine."},{"from":"shellfish","to":"aa_taurine","level":"established","effect":"contains","note":"Shellfish are among the richest taurine sources."},{"from":"redmeat","to":"aa_taurine","level":"established","effect":"contains","note":"Meat contains taurine; plant foods have almost none."},{"from":"oilyfish","to":"aa_taurine","level":"established","effect":"contains","note":"Fish contains taurine."},{"from":"aa_methionine","to":"m_methyl","level":"established","effect":"helps","note":"Methionine becomes SAM, the methyl donor; using it leaves homocysteine, and levodopa's breakdown uses up methyl groups and tends to raise homocysteine.","dose":"deficiency","sources":[{"id":"pmid:36922273","citation":"Ahlskog JE, Parkinsonism Relat Disord","year":2023,"design":"review","finding":"Levodopa tends to raise blood homocysteine because its breakdown by the enzyme COMT uses up methyl groups; B vitamins lower it, and whether everyone on levodopa needs them is still debated."}]},{"from":"aa_methionine","to":"aa_cysteine","level":"established","effect":"helps","note":"With vitamin B6, the body turns methionine (through homocysteine) into cysteine."},{"from":"aa_cysteine","to":"m_oxid","level":"established","effect":"helps","note":"Cysteine is the limiting building block of glutathione, the cell's main antioxidant; extra beyond a normal diet isn't shown to protect brain cells.","dose":"deficiency"},{"from":"nac","to":"aa_cysteine","level":"established","effect":"helps","note":"NAC is absorbed and turned into cysteine."},{"from":"aa_cysteine","to":"aa_taurine","level":"established","effect":"helps","note":"The body makes taurine from cysteine."},{"from":"aa_taurine","to":"s_liver","level":"established","effect":"helps","note":"The liver joins taurine to bile acids to make bile salts that digest fat."},{"from":"aa_methionine","to":"m_absorb","level":"established","effect":"harms","note":"Methionine uses the same carrier as levodopa to get from the blood into the brain, so a large protein load close to a dose can blunt the dose in people with fluctuations; ordinary day-to-day swings matter less for most people.","scope":["parkinsons"],"dose":"timing","sources":[{"id":"pmid:6694694","citation":"Nutt JG et al., N Engl J Med","year":1984,"design":"small human experiment","finding":"In people with on-off Parkinson's on steady intravenous levodopa, high-protein meals or oral phenylalanine, leucine or isoleucine reversed the levodopa effect without lowering blood levodopa, pointing to competition at the brain's amino-acid carrier; glycine and lysine had no effect."},{"id":"pmid:3632370","citation":"Pincus JH & Barry KM, Arch Neurol","year":1987,"design":"small human experiment","finding":"In 7 people with severe fluctuations, regular and high-protein diets raised blood large neutral amino acids, and symptoms returned despite good blood levodopa; when these amino acids fell, symptoms eased."},{"id":"pmid:2795076","citation":"Frankel JP et al., J Neurol Neurosurg Psychiatry","year":1989,"design":"small human experiment","finding":"During steady levodopa infusion into the gut, oral protein loads worsened movement even though blood levodopa stayed steady, suggesting the competition matters most at the blood-brain barrier."},{"id":"pmid:2738591","citation":"Nutt JG et al., J Neurol Neurosurg Psychiatry","year":1989,"design":"small human experiment","finding":"On ordinary hospital meals, swings in blood large neutral amino acids were small next to swings in blood levodopa and were not an important cause of fluctuations in most of 11 patients."},{"id":"pmid:39240647","citation":"Pedrosa de Menezes AL et al., J Parkinsons Dis","year":2024,"design":"review","finding":"Review of the molecular steps of levodopa absorption, including its shared amino-acid transporters, and why absorption varies so much between and within people."}]},{"from":"protein","to":"aa_arginine","level":"established","effect":"contains","note":"Protein is digested into its amino acids, including arginine."},{"from":"nuts","to":"aa_arginine","level":"established","effect":"contains","note":"Nuts and seeds are among the richest sources of arginine."},{"from":"peanuts","to":"aa_arginine","level":"established","effect":"contains","note":"Peanuts are rich in arginine."},{"from":"soy","to":"aa_arginine","level":"established","effect":"contains","note":"Soy protein is rich in arginine."},{"from":"redmeat","to":"aa_creatine","level":"established","effect":"contains","note":"Meat is the main dietary source of creatine; plants contain none."},{"from":"oilyfish","to":"aa_creatine","level":"established","effect":"contains","note":"Fish such as herring and salmon contain creatine."},{"from":"redmeat","to":"aa_carnitine","level":"established","effect":"contains","note":"Red meat is the richest food source of carnitine."},{"from":"aa_citrulline","to":"aa_arginine","level":"established","effect":"helps","note":"The kidneys turn citrulline into arginine."},{"from":"aa_arginine","to":"s_blood","level":"established","effect":"helps","note":"Vessel linings turn arginine into nitric oxide, which relaxes blood vessels; supplements lowered blood pressure slightly in small trials.","sources":[{"id":"pmid:42520885","citation":"Shi Y et al., Nitric Oxide","year":2026,"design":"meta-analysis","finding":"Five small randomised trials (202 people) found oral L-arginine lowered 24-hour systolic blood pressure by about 4 mmHg; more trials were called for."}]},{"from":"aa_arginine","to":"aa_creatine","level":"established","effect":"helps","note":"Creatine making starts from arginine (with glycine and methionine)."},{"from":"aa_creatine","to":"s_muscle","level":"established","effect":"helps","note":"Muscle stores creatine as phosphocreatine, a quick energy reserve for short bursts of effort."},{"from":"aa_creatine","to":"m_bone","level":"proven","effect":"helps","note":"Taken with resistance training, creatine gave a small extra gain in strength in older adults over training alone.","sources":[{"id":"pmid:42712402","citation":"Yao L et al., Front Nutr","year":2026,"design":"meta-analysis","finding":"In 11 randomised trials in adults over 60, creatine plus resistance training gave a small extra gain in strength over training alone (moderate certainty); gains in muscle mass and physical function were not significant."},{"id":"pmid:41388441","citation":"Liu S et al., Eur Rev Aging Phys Act","year":2025,"design":"meta-analysis","finding":"In 8 randomised trials (482 older adults), creatine with resistance training modestly improved leg strength and lean mass over training alone, but not upper-body strength."}]},{"from":"aa_creatine","to":"progression","level":"failed","effect":"helps","note":"Five or more years of creatine did not slow Parkinson's in a 1741-person trial (NET-PD LS-1), which was stopped early for futility.","scope":["parkinsons"],"sources":[{"id":"pmid:25668262","citation":"NINDS NET-PD Writing Group (Kieburtz K et al.), JAMA","year":2015,"design":"RCT","finding":"In 1741 people with early treated Parkinson's (NET-PD Long-term Study 1), creatine monohydrate for at least 5 years did not slow clinical decline versus placebo; the trial was stopped early for futility."},{"id":"pmid:24934384","citation":"Xiao Y et al., Cochrane Database Syst Rev","year":2014,"design":"meta-analysis","finding":"Two earlier randomised trials (194 people) showed no clear effect of creatine on movement, daily activities or quality of life in Parkinson's."}]},{"from":"aa_carnitine","to":"m_oxid","level":"established","effect":"helps","note":"Carnitine ferries fats into mitochondria to be burned for energy; extra beyond what the body makes isn't shown to do more.","dose":"deficiency"},{"from":"tx_tce","to":"parkinsons","level":"association","effect":"harms","note":"Exposure at work or through contaminated water is linked with higher Parkinson's risk.","sources":[{"id":"pmid:22083847","citation":"Goldman SM et al., Annals of Neurology","year":2012,"design":"case-control","finding":"In 99 twin pairs discordant for Parkinson's, trichloroethylene exposure was linked with about 6 times the odds; perchloroethylene showed a similar but not statistically certain trend."},{"id":"pmid:37184848","citation":"Goldman SM et al., JAMA Neurology","year":2023,"design":"cohort","finding":"Marines stationed at Camp Lejeune, whose water was heavily contaminated with trichloroethylene, had about 70% higher Parkinson's risk than those at an uncontaminated base."}]},{"from":"tx_tce","to":"s_kidneys","level":"established","effect":"harms","note":"Classed as a known cause of kidney cancer.","sources":[{"id":"pmid:23323277","citation":"Guha N et al. (IARC Monograph 106 working group), Lancet Oncology","year":2012,"design":"review","finding":"The WHO cancer agency classed trichloroethylene as a known cause of kidney cancer and perchloroethylene as a probable cause of bladder cancer."}]},{"from":"tx_perc","to":"s_bladder","level":"association","effect":"harms","note":"Classed as a probable cause of bladder cancer, based mainly on dry-cleaning workers.","sources":[{"id":"pmid:23323277","citation":"Guha N et al. (IARC Monograph 106 working group), Lancet Oncology","year":2012,"design":"review","finding":"The WHO cancer agency classed trichloroethylene as a known cause of kidney cancer and perchloroethylene as a probable cause of bladder cancer."}]},{"from":"tx_hexane","to":"neuropathy","level":"established","effect":"harms","note":"Heavy exposure damages long nerves, causing numbness and weakness that starts in the feet.","dose":"excess"},{"from":"tx_hexane","to":"s_peripheral","level":"established","effect":"harms","note":"Its breakdown product damages the inner scaffolding of long nerve fibres.","dose":"excess"},{"from":"tx_toluene","to":"s_cerebellum","level":"established","effect":"harms","note":"Years of heavy exposure or sniffing damage the cerebellum, causing unsteadiness and tremor.","dose":"excess"},{"from":"tx_toluene","to":"cognition","level":"established","effect":"harms","note":"Heavy long-term exposure damages brain white matter and slows thinking.","dose":"excess"},{"from":"wi_solvent_degreasing","to":"tx_tce","level":"established","effect":"harms","note":"Exposes to trichloroethylene: this job is a main way people breathe in or absorb it."},{"from":"wi_solvent_degreasing","to":"tx_perc","level":"established","effect":"harms","note":"Exposes to perchloroethylene: this job is a main way people breathe in or absorb it."},{"from":"tx_tobacco","to":"s_lungs","level":"proven","effect":"harms","note":"Smoking causes COPD and most lung cancers; in a randomised trial, quitting slowed lung function loss and lowered deaths.","sources":[{"id":"pmid:7966841","citation":"Anthonisen NR et al., JAMA","year":1994,"design":"RCT","finding":"In 5887 smokers with early lung obstruction, a randomised quit-smoking programme slowed the loss of lung function, mostly in those who stopped."},{"id":"pmid:15710956","citation":"Anthonisen NR et al., Ann Intern Med","year":2005,"design":"RCT","finding":"Over 14.5 years, people randomised to the quit-smoking programme had lower all-cause mortality than usual care; lung cancer was the leading cause of death."}]},{"from":"tx_tobacco","to":"bp_lungs","level":"established","effect":"harms","note":"Smoke damages the airways and air sacs of the lungs."},{"from":"tx_tobacco","to":"s_heart","level":"established","effect":"harms","note":"Smoking is a major cause of heart attacks."},{"from":"tx_tobacco","to":"s_blood","level":"established","effect":"harms","note":"Smoke damages blood-vessel linings and makes blood clot more easily, causing artery disease and stroke."},{"from":"tx_tobacco","to":"s_mouth","level":"established","effect":"harms","note":"Smoking causes gum disease and mouth cancers."},{"from":"tx_tobacco","to":"m_oxid","level":"established","effect":"harms","note":"Smoke carries oxidising chemicals that overwhelm the body's antioxidant defences."},{"from":"tx_tobacco","to":"m_inflam","level":"established","effect":"harms","note":"Smoking keeps the airways and blood vessels inflamed."},{"from":"tx_tobacco","to":"alzheimers","level":"association","effect":"harms","note":"Current smokers have higher rates of Alzheimer's and other dementia in long-term studies.","sources":[{"id":"pmid:25763939","citation":"Zhong G et al., PLoS One","year":2015,"design":"meta-analysis","finding":"In 37 prospective studies, current smokers had higher risk of all-cause dementia (RR 1.30) and Alzheimer's disease (RR 1.40) than never smokers."},{"id":"pmid:17573335","citation":"Anstey KJ et al., American Journal of Epidemiology","year":2007,"design":"meta-analysis","finding":"In 19 prospective studies, current smokers had higher risk of Alzheimer's disease (RR 1.79) and faster yearly decline on a memory-and-thinking test than never smokers."}]},{"from":"tx_tobacco","to":"cognition","level":"association","effect":"harms","note":"Current smokers' thinking scores decline faster with age than never smokers'.","sources":[{"id":"pmid:17573335","citation":"Anstey KJ et al., American Journal of Epidemiology","year":2007,"design":"meta-analysis","finding":"In 19 prospective studies, current smokers had higher risk of Alzheimer's disease (RR 1.79) and faster yearly decline on a memory-and-thinking test than never smokers."}]},{"from":"tx_tobacco","to":"ms","level":"association","effect":"harms","note":"Smokers have about 1.5 times the odds of multiple sclerosis, rising with how much they smoked.","sources":[{"id":"pmid:27160862","citation":"Poorolajal J et al., Journal of Public Health","year":2017,"design":"meta-analysis","finding":"In 34 studies, ever smokers had about 1.5 times the odds of multiple sclerosis, rising with pack-years."}]},{"from":"tx_tobacco","to":"parkinsons","level":"association","effect":"helps","note":"Smokers get Parkinson's less often, but easy quitting may be an early sign of the disease and nicotine patches did not slow it, so this is not a reason to smoke.","sources":[{"id":"pmid:12205639","citation":"Hernán MA et al., Annals of Neurology","year":2002,"design":"meta-analysis","finding":"Across 48 studies, ever smokers had about 40% lower Parkinson's risk than never smokers (RR 0.59), with a dose-response by pack-years."},{"id":"pmid:25217056","citation":"Ritz B et al., Neurology","year":2014,"design":"case-control","finding":"Among Danish former smokers, those who found quitting easy were more likely to develop Parkinson's, suggesting easier quitting is an early sign of the disease rather than tobacco protecting."},{"id":"pmid:38320207","citation":"Oertel WH et al. (NIC-PD), NEJM Evidence","year":2023,"design":"RCT","finding":"In 163 people with early Parkinson's, a year of nicotine patches did not slow progression; scores worsened slightly more on nicotine than placebo."}]},{"from":"tx_vaping","to":"s_lungs","level":"association","effect":"harms","note":"Vaping products, mostly illicit THC liquids with vitamin E acetate, caused a 2019 outbreak of serious lung injury; long-term lung effects of nicotine vaping are still unknown.","sources":[{"id":"pmid:31860793","citation":"Blount BC et al., New England Journal of Medicine","year":2020,"design":"case-control","finding":"Vitamin E acetate was found in lung fluid of 48 of 51 patients with vaping-associated lung injury (EVALI) and in none of the healthy comparison group."}]},{"from":"tx_bpa","to":"hm_oestrogen","level":"lab","effect":"affects","note":"BPA mimics oestrogen at its receptors in cells and animals, disrupting normal hormone signals; human effects are less certain.","sources":[{"id":"pmid:30473274","citation":"Sheng Z et al., Journal of Environmental Sciences","year":2019,"design":"lab","finding":"In cells, BPA acts through the membrane oestrogen receptor GPER and integrin signalling, explaining part of its oestrogen-like effects."},{"id":"pmid:23994667","citation":"Rochester JR, Reproductive Toxicology","year":2013,"design":"review","finding":"BPA is an endocrine disruptor that harms laboratory animals; 91 human studies link it to reproductive, developmental and metabolic outcomes, though causation is hard to establish."}]},{"from":"tx_phthalates","to":"hm_testosterone","level":"association","effect":"harms","note":"Higher phthalate levels are linked with lower testosterone in people of all ages.","sources":[{"id":"pmid:25121464","citation":"Meeker JD, Ferguson KK, Journal of Clinical Endocrinology & Metabolism","year":2014,"design":"cohort","finding":"In US NHANES 2011-2012 (cross-sectional), higher urinary phthalate metabolites went with lower testosterone in men, women and children."},{"id":"pmid:16079079","citation":"Swan SH et al., Environmental Health Perspectives","year":2005,"design":"cohort","finding":"Baby boys whose mothers had higher phthalate levels in pregnancy had shorter anogenital distance, a marker of lower testosterone action before birth."}]},{"from":"tx_phthalates","to":"s_reproductive","level":"association","effect":"harms","note":"Higher phthalates in pregnancy were linked with less-masculine genital measurements in baby boys.","sources":[{"id":"pmid:16079079","citation":"Swan SH et al., Environmental Health Perspectives","year":2005,"design":"cohort","finding":"Baby boys whose mothers had higher phthalate levels in pregnancy had shorter anogenital distance, a marker of lower testosterone action before birth."}]},{"from":"tx_pfas","to":"s_immune","level":"association","effect":"harms","note":"Children with more PFAS made fewer antibodies after routine vaccines.","sources":[{"id":"pmid:22274686","citation":"Grandjean P et al., JAMA","year":2012,"design":"cohort","finding":"In a Faroese birth cohort, children with higher PFAS levels had lower antibody levels after tetanus and diphtheria vaccination."}]},{"from":"tx_pfas","to":"s_kidneys","level":"association","effect":"harms","note":"Higher blood PFOA was linked with more kidney cancer years later.","sources":[{"id":"pmid:32944748","citation":"Shearer JJ et al., Journal of the National Cancer Institute","year":2021,"design":"case-control","finding":"In blood stored years before diagnosis, doubling PFOA was linked with about 1.7 times the odds of kidney cancer."}]},{"from":"tx_pbde","to":"cognition","level":"association","effect":"harms","note":"Higher flame-retardant levels at birth were linked with lower scores on children's mental and physical development tests.","sources":[{"id":"pmid:20056561","citation":"Herbstman JB et al., Environmental Health Perspectives","year":2010,"design":"cohort","finding":"Children with higher PBDE flame retardants in cord blood scored lower on mental and physical development tests up to age 6."}]},{"from":"tx_microplastics","to":"s_heart","level":"association","effect":"harms","note":"People with plastic particles in their artery plaque had more heart attacks, strokes and deaths; cause is not proven.","sources":[{"id":"pmid:38446676","citation":"Marfella R et al., New England Journal of Medicine","year":2024,"design":"cohort","finding":"People whose carotid artery plaque contained micro- and nanoplastics had more inflammation in the plaque and about 4.5 times the risk of heart attack, stroke or death over 34 months."}]},{"from":"tx_microplastics","to":"m_inflam","level":"association","effect":"harms","note":"Plaques containing microplastics showed more inflammation markers.","sources":[{"id":"pmid:38446676","citation":"Marfella R et al., New England Journal of Medicine","year":2024,"design":"cohort","finding":"People whose carotid artery plaque contained micro- and nanoplastics had more inflammation in the plaque and about 4.5 times the risk of heart attack, stroke or death over 34 months."}]},{"from":"tx_microplastics","to":"s_cortex","level":"association","effect":"harms","note":"Microplastics are found in human brain tissue, more in people who had dementia; whether they cause damage is unknown.","sources":[{"id":"pmid:39901044","citation":"Nihart AJ et al., Nature Medicine","year":2025,"design":"case-control","finding":"Microplastics, mostly polyethylene shards, were found in human brain, liver and kidney at autopsy, rising from 2016 to 2024 and higher in brains of people who had dementia."}]},{"from":"tx_paraquat","to":"parkinsons","level":"association","effect":"harms","note":"Farmers who used paraquat had higher odds of Parkinson's in several studies.","sources":[{"id":"pmid:21269927","citation":"Tanner CM et al., Environmental Health Perspectives","year":2011,"design":"case-control","finding":"In the Agricultural Health Study, Parkinson's was linked with use of rotenone (OR 2.5) and paraquat (OR 2.5)."},{"id":"pmid:30474499","citation":"Tangamornsuksan W et al., Archives of Environmental & Occupational Health","year":2019,"design":"meta-analysis","finding":"Pooling 13 case-control studies, paraquat exposure was linked with about 1.6 times the odds of Parkinson's."}]},{"from":"tx_paraquat","to":"m_oxid","level":"established","effect":"harms","note":"Paraquat makes reactive oxygen inside cells and overwhelms antioxidant defences."},{"from":"tx_paraquat","to":"s_lungs","level":"established","effect":"harms","note":"Swallowing paraquat scars the lungs and is often fatal.","dose":"excess"},{"from":"tx_rotenone","to":"parkinsons","level":"association","effect":"harms","note":"Farmers who used rotenone had about 2.5 times the odds of Parkinson's.","sources":[{"id":"pmid:21269927","citation":"Tanner CM et al., Environmental Health Perspectives","year":2011,"design":"case-control","finding":"In the Agricultural Health Study, Parkinson's was linked with use of rotenone (OR 2.5) and paraquat (OR 2.5)."}]},{"from":"tx_rotenone","to":"m_oxid","level":"established","effect":"harms","note":"Rotenone blocks the first step of energy-making in mitochondria."},{"from":"tx_organophosphates","to":"s_autonomic","level":"established","effect":"harms","note":"Blocking acetylcholine breakdown over-stimulates the automatic nerves: sweating, drooling, diarrhoea, slow pulse.","dose":"excess"},{"from":"tx_organophosphates","to":"s_muscle","level":"established","effect":"harms","note":"Over-stimulated muscles twitch, then weaken, including the breathing muscles.","dose":"excess"},{"from":"tx_organophosphates","to":"s_peripheral","level":"established","effect":"harms","note":"Some organophosphates cause a delayed nerve damage with weak, numb legs weeks after poisoning.","dose":"excess"},{"from":"tx_organochlorines","to":"parkinsons","level":"association","effect":"harms","note":"Higher dieldrin in blood taken decades before diagnosis was linked with Parkinson's in never smokers; evidence is limited.","sources":[{"id":"pmid:20350979","citation":"Weisskopf MG et al., Neurology","year":2010,"design":"case-control","finding":"In stored Finnish blood taken decades before diagnosis, higher dieldrin (an organochlorine pesticide) was linked with Parkinson's in never smokers; the overall trend was borderline."},{"id":"pmid:29729297","citation":"Yan D et al., Regulatory Toxicology and Pharmacology","year":2018,"design":"meta-analysis","finding":"Longer pesticide exposure was linked with modestly higher Parkinson's risk (OR 1.11 for 10 years); the authors call for better cohorts to test causation."}]},{"from":"wi_pesticide_application","to":"tx_paraquat","level":"established","effect":"harms","note":"Exposes to paraquat: this job is a main way people breathe in or absorb it."},{"from":"wi_pesticide_application","to":"tx_organophosphates","level":"established","effect":"harms","note":"Exposes to organophosphate insecticides: this job is a main way people breathe in or absorb it."},{"from":"tx_alcohol","to":"s_liver","level":"established","effect":"harms","note":"Heavy drinking causes fatty liver, alcoholic hepatitis and cirrhosis.","dose":"excess"},{"from":"tx_alcohol","to":"bp_internal_organs","level":"established","effect":"harms","note":"Heavy drinking damages the liver, pancreas and stomach lining.","dose":"excess"},{"from":"tx_alcohol","to":"thiamine","level":"established","effect":"harms","note":"Heavy drinking cuts thiamine intake, absorption and storage, so the body runs short.","dose":"excess"},{"from":"tx_alcohol","to":"memory","level":"established","effect":"harms","note":"Thiamine deficiency from heavy drinking causes Wernicke–Korsakoff syndrome: confusion, unsteady walking and lasting memory loss.","dose":"excess"},{"from":"tx_alcohol","to":"neuropathy","level":"established","effect":"harms","note":"Long-term heavy drinking damages the long nerves, causing numb, burning feet.","dose":"excess"},{"from":"tx_alcohol","to":"s_cerebellum","level":"established","effect":"harms","note":"Heavy drinking shrinks the cerebellum, causing a wide, unsteady walk.","dose":"excess"},{"from":"tx_alcohol","to":"s_heart","level":"proven","effect":"harms","note":"In regular drinkers with atrial fibrillation, stopping alcohol cut how often the irregular rhythm came back in a randomised trial.","sources":[{"id":"pmid:31893513","citation":"Voskoboinik A et al., N Engl J Med","year":2020,"design":"RCT","finding":"In regular drinkers with atrial fibrillation, randomly assigned abstinence cut recurrence over 6 months (53% vs 73%) and time spent in the rhythm."}]},{"from":"tx_alcohol","to":"s_cortex","level":"association","effect":"harms","note":"Lower grey-matter volume is seen even at moderate weekly drinking in large brain-scan studies.","sources":[{"id":"pmid:35653911","citation":"Topiwala A et al., NeuroImage: Clinical","year":2022,"design":"cohort","finding":"In 25,378 UK Biobank adults, lower total grey-matter volume was seen even at 7-14 UK units a week, with more drinking linked to more white-matter change."}]},{"from":"tx_alcohol","to":"alzheimers","level":"association","effect":"harms","note":"Genetic studies find dementia risk rising steadily with drinking; light drinking's apparent protection in older studies looks like bias.","sources":[{"id":"pmid:40987604","citation":"Topiwala A et al., BMJ Evidence-Based Medicine","year":2026,"design":"cohort","finding":"In 559,559 adults plus genetic (Mendelian randomisation) analyses, the apparent protection of light drinking disappeared: genetically predicted drinking raised dementia risk steadily with no safe low level."},{"id":"pmid:39290634","citation":"Zheng L et al., eClinicalMedicine","year":2024,"design":"cohort","finding":"In 313,958 UK Biobank drinkers, ordinary analysis showed a J-shape but genetic (Mendelian randomisation) analysis found dementia risk rising with alcohol intake."}]},{"from":"tx_pm25","to":"s_heart","level":"association","effect":"harms","note":"Long-term exposure is linked with more heart attacks and cardiovascular deaths.","sources":[{"id":"pmid:17267905","citation":"Miller KA et al., New England Journal of Medicine","year":2007,"design":"cohort","finding":"In 65,893 postmenopausal women, each 10 µg/m³ more long-term PM2.5 was linked with 24% more cardiovascular events."}]},{"from":"tx_pm25","to":"s_blood","level":"association","effect":"harms","note":"Days with more fine particle pollution are followed by more strokes.","sources":[{"id":"pmid:25810496","citation":"Shah AS et al., BMJ","year":2015,"design":"meta-analysis","finding":"Across 94 studies in 28 countries, days with higher PM2.5 and carbon monoxide were followed by more stroke admissions and deaths."}]},{"from":"tx_pm25","to":"alzheimers","level":"association","effect":"harms","note":"Long-term exposure is linked with more dementia; the size of the effect is still uncertain.","sources":[{"id":"pmid:37019461","citation":"Wilker EH et al., BMJ","year":2023,"design":"meta-analysis","finding":"Across 51 studies, PM2.5 was linked with more dementia; the pooled estimate was modest and uncertain overall (HR 1.04 per 2 µg/m³) but stronger in studies that actively diagnosed dementia (HR 1.42)."}]},{"from":"tx_pm25","to":"s_lungs","level":"established","effect":"harms","note":"Fine particles lodge deep in the lungs and inflame the airways, worsening asthma and COPD."},{"from":"tx_pm25","to":"m_inflam","level":"established","effect":"harms","note":"Particles trigger inflammation in the lungs that spills into the blood."},{"from":"tx_co","to":"s_blood","level":"established","effect":"harms","note":"Carbon monoxide grabs haemoglobin in place of oxygen, so the blood carries less oxygen.","dose":"excess"},{"from":"tx_co","to":"s_heart","level":"established","effect":"harms","note":"Oxygen starvation strains the heart and can trigger chest pain and rhythm problems.","dose":"excess"},{"from":"tx_co","to":"cognition","level":"established","effect":"harms","note":"After serious poisoning some survivors develop memory and thinking problems days to weeks later.","dose":"excess","sources":[{"id":"pmid:6860181","citation":"Choi IS, Archives of Neurology","year":1983,"design":"cohort","finding":"Of 2360 people with carbon monoxide poisoning, 65 developed delayed brain problems days to weeks later: mental decline, incontinence, a stiff short-stepped Parkinson-like gait; most recovered within a year."}]},{"from":"tx_co","to":"movement","level":"established","effect":"harms","note":"Delayed after-effects of poisoning can include Parkinson-like stiffness, masked face and short steps.","dose":"excess","sources":[{"id":"pmid:6860181","citation":"Choi IS, Archives of Neurology","year":1983,"design":"cohort","finding":"Of 2360 people with carbon monoxide poisoning, 65 developed delayed brain problems days to weeks later: mental decline, incontinence, a stiff short-stepped Parkinson-like gait; most recovered within a year."}]},{"from":"tx_co","to":"s_bg","level":"established","effect":"harms","note":"Oxygen starvation damages the globus pallidus, part of the basal ganglia.","dose":"excess"},{"from":"tx_diesel","to":"s_lungs","level":"association","effect":"harms","note":"Lung cancer deaths rose with diesel exhaust exposure in miners, after accounting for smoking.","sources":[{"id":"pmid:22393209","citation":"Silverman DT et al. (Diesel Exhaust in Miners Study), Journal of the National Cancer Institute","year":2012,"design":"case-control","finding":"In 12,315 miners, lung cancer deaths rose with estimated diesel exhaust exposure after adjusting for smoking."}]},{"from":"tx_diesel","to":"bp_lungs","level":"association","effect":"harms","note":"Diesel soot reaches deep lung tissue and is linked with lung cancer.","sources":[{"id":"pmid:22393209","citation":"Silverman DT et al. (Diesel Exhaust in Miners Study), Journal of the National Cancer Institute","year":2012,"design":"case-control","finding":"In 12,315 miners, lung cancer deaths rose with estimated diesel exhaust exposure after adjusting for smoking."}]},{"from":"tx_diesel","to":"tx_pm25","level":"established","effect":"contains","note":"Diesel soot is a major source of fine particle pollution."},{"from":"wi_carbon_monoxide","to":"tx_co","level":"established","effect":"harms","note":"Exposes to carbon monoxide: this job is a main way people breathe in or absorb it."},{"from":"tx_silica","to":"silicosis","level":"established","effect":"harms","note":"Breathing crystalline silica dust is the cause of silicosis."},{"from":"tx_silica","to":"s_lungs","level":"established","effect":"harms","note":"Silica scars the lungs and is linked with lung cancer.","sources":[{"id":"pmid:27814719","citation":"Poinen-Rughooputh S et al., BMC Public Health","year":2016,"design":"meta-analysis","finding":"Lung cancer risk was raised in workers exposed to silica dust, both with and without silicosis."}]},{"from":"tx_silica","to":"bp_lungs","level":"established","effect":"harms","note":"Silica dust lodges in the air sacs and forms scar nodules."},{"from":"tx_silica","to":"m_inflam","level":"established","effect":"harms","note":"Lung immune cells killed by silica release signals that keep inflammation and scarring going."},{"from":"tx_asbestos","to":"asbestos_disease","level":"established","effect":"harms","note":"Asbestos fibres cause asbestosis and mesothelioma."},{"from":"tx_asbestos","to":"s_lungs","level":"established","effect":"harms","note":"Asbestos causes lung scarring and lung cancer."},{"from":"tx_asbestos","to":"bp_lungs","level":"established","effect":"harms","note":"Fibres lodge in the lungs and the chest lining."},{"from":"wi_silica_dust","to":"tx_silica","level":"established","effect":"harms","note":"Exposes to crystalline silica: this job is a main way people breathe in or absorb it."},{"from":"wi_asbestos_work","to":"tx_asbestos","level":"established","effect":"harms","note":"Exposes to asbestos: this job is a main way people breathe in or absorb it."},{"from":"tx_lead","to":"cognition","level":"established","effect":"harms","note":"Lead lowers children's IQ and attention, with the steepest losses at the lowest levels; no safe level is known.","sources":[{"id":"pmid:16002379","citation":"Lanphear BP et al., Environmental Health Perspectives","year":2005,"design":"cohort","finding":"Pooling 7 birth cohorts (1333 children), higher blood lead went with lower IQ, with the steepest losses at the lowest levels."}]},{"from":"tx_lead","to":"s_blood","level":"association","effect":"harms","note":"Lead raises blood pressure, and higher blood lead is linked with more heart and stroke deaths.","sources":[{"id":"pmid:17431501","citation":"Navas-Acien A et al., Environ Health Perspect","year":2007,"design":"review","finding":"Systematic review concluding the evidence is sufficient to infer that lead exposure causes higher blood pressure; links with heart disease and stroke deaths were suggestive."},{"id":"pmid:29544878","citation":"Lanphear BP et al., Lancet Public Health","year":2018,"design":"cohort","finding":"In 14,289 US adults followed about 19 years, higher blood lead even at low levels was linked with more deaths from all causes and from cardiovascular disease."}]},{"from":"tx_lead","to":"s_kidneys","level":"established","effect":"harms","note":"Long-term lead exposure damages the kidneys.","dose":"excess"},{"from":"tx_lead","to":"s_peripheral","level":"established","effect":"harms","note":"High lead levels damage motor nerves, classically causing wrist drop.","dose":"excess"},{"from":"tx_mercury","to":"s_peripheral","level":"established","effect":"harms","note":"Mercury poisoning causes numbness and tingling in the hands, feet and around the mouth.","dose":"excess"},{"from":"tx_mercury","to":"s_cerebellum","level":"established","effect":"harms","note":"Methylmercury damages the cerebellum, causing clumsy, unsteady movement (as in Minamata disease).","dose":"excess"},{"from":"tx_mercury","to":"s_kidneys","level":"established","effect":"harms","note":"Inorganic mercury damages the kidney filters.","dose":"excess"},{"from":"tx_arsenic","to":"s_skin","level":"association","effect":"harms","note":"Arsenic in drinking water causes thickened, spotted skin, rising with dose; lesions improve when exposure falls.","sources":[{"id":"pmid:21576319","citation":"Argos M et al., American Journal of Epidemiology","year":2011,"design":"cohort","finding":"In a prospective Bangladesh cohort, arsenic in drinking water raised the incidence of skin lesions in a dose-dependent way, even below 100 µg/L."},{"id":"pmid:23060367","citation":"Seow WJ et al., Environmental Health Perspectives","year":2012,"design":"cohort","finding":"When well-water arsenic fell in a Bangladesh population, lower body arsenic was linked with more recovery from arsenic skin lesions."}]},{"from":"tx_arsenic","to":"bp_skin","level":"established","effect":"harms","note":"Arsenic produces thick, darkened patches on the palms, soles and trunk.","dose":"excess","sources":[{"id":"pmid:21750349","citation":"Hughes MF et al., Toxicological Sciences","year":2011,"design":"review","finding":"Chronic arsenic exposure, mainly from drinking water, affects several organ systems; the main concern is cancer of the skin, bladder and lung."}]},{"from":"tx_arsenic","to":"s_bladder","level":"established","effect":"harms","note":"Long-term arsenic exposure causes bladder cancer.","dose":"excess","sources":[{"id":"pmid:21750349","citation":"Hughes MF et al., Toxicological Sciences","year":2011,"design":"review","finding":"Chronic arsenic exposure, mainly from drinking water, affects several organ systems; the main concern is cancer of the skin, bladder and lung."}]},{"from":"tx_arsenic","to":"neuropathy","level":"established","effect":"harms","note":"Arsenic poisoning damages long nerves, causing numb, painful feet.","dose":"excess"},{"from":"tx_cadmium","to":"s_kidneys","level":"established","effect":"harms","note":"Cadmium collects in the kidneys for decades and damages the tubules.","sources":[{"id":"pmid:19409405","citation":"Järup L, Åkesson A, Toxicology and Applied Pharmacology","year":2009,"design":"review","finding":"Cadmium builds up in the kidney over decades (half-life 10-30 years), damaging the kidney tubules and bone; food and smoking are the main sources."}]},{"from":"tx_cadmium","to":"s_bones","level":"established","effect":"harms","note":"Cadmium weakens bone, directly and through kidney mineral loss.","dose":"excess","sources":[{"id":"pmid:19409405","citation":"Järup L, Åkesson A, Toxicology and Applied Pharmacology","year":2009,"design":"review","finding":"Cadmium builds up in the kidney over decades (half-life 10-30 years), damaging the kidney tubules and bone; food and smoking are the main sources."}]},{"from":"manganese","to":"manganism","level":"established","effect":"harms","note":"Heavy exposure (welding and mining fumes, contaminated water) builds up manganese in the brain and causes manganism.","dose":"excess"},{"from":"wi_lead_work","to":"tx_lead","level":"established","effect":"harms","note":"Exposes to lead: this job is a main way people breathe in or absorb it."},{"from":"br_scn","to":"m_clock","level":"established","effect":"helps","note":"The master clock in the brain that keeps the body's daily rhythm on time."},{"from":"br_scn","to":"hm_melatonin","level":"established","effect":"helps","note":"Sends the day-night signal that controls how much melatonin the pineal gland makes."},{"from":"iodine","to":"hm_thyroid","level":"established","effect":"helps","note":"Needed to build thyroid hormone. Too little or too much both disrupt it."},{"from":"selenium","to":"hm_thyroid","level":"established","effect":"helps","note":"Needed by the enzymes that turn the thyroid's inactive hormone into its active form."},{"from":"br_amygdala","to":"m_stress","level":"established","effect":"helps","note":"The fear centre that the stress and fear circuit runs through."},{"from":"br_accumbens","to":"m_reward","level":"established","effect":"helps","note":"A main hub of the reward circuit that drives mood and motivation."},{"from":"movement","to":"br_m1","level":"established","effect":"located","note":"The primary motor cortex sends the commands for voluntary movement, so slowness shows up here."},{"from":"br_cerebellum","to":"m_plastic","level":"established","effect":"helps","note":"Helps the body learn and fine-tune movements through practice."},{"from":"br_snc","to":"m_dopa","level":"established","effect":"helps","note":"The source of the dopamine neurons that feed the striatum."},{"from":"br_caudate","to":"m_cstc","level":"established","effect":"helps","note":"Part of the habit loop that lets the brain start and stop actions."},{"from":"br_dmnv","to":"m_motility","level":"established","effect":"helps","note":"The vagal centre in the brainstem that sends the signals moving food through the gut."},{"from":"hpylori","to":"s_stomach","level":"established","effect":"harms","note":"H. pylori lives in the stomach lining and causes gastritis and ulcers."},{"from":"sibo","to":"s_small_intestine","level":"established","effect":"harms","note":"Small-intestinal bacterial overgrowth is an excess of bacteria in the small intestine."},{"from":"cdiff","to":"s_colon","level":"established","effect":"harms","note":"C. difficile infection inflames the colon, usually after antibiotics."},{"from":"strep","to":"s_throat","level":"established","effect":"harms","note":"Group A strep causes strep throat."},{"from":"pging","to":"s_mouth","level":"established","effect":"harms","note":"P. gingivalis is a main bacterium in gum disease."},{"from":"fuso","to":"s_mouth","level":"established","effect":"harms","note":"Fusobacterium nucleatum is a common mouth bacterium that takes part in gum disease."},{"from":"mtb","to":"s_lungs","level":"established","effect":"harms","note":"Tuberculosis most often infects the lungs."},{"from":"chlamydia_pn","to":"s_lungs","level":"established","effect":"harms","note":"Chlamydia pneumoniae is a cause of pneumonia and bronchitis."},{"from":"klebsiella","to":"pneumonia","level":"established","effect":"harms","note":"Klebsiella is a recognised cause of pneumonia, especially in hospital patients."},{"from":"faecali","to":"m_inflam","level":"lab","effect":"helps","note":"In mice and cells this bacterium calmed gut inflammation, and it is low in people with Crohn disease.","sources":[{"id":"pmid:18936492","citation":"Sokol H et al., Proc Natl Acad Sci U S A","year":2008,"design":"cohort","finding":"F. prausnitzii was reduced in Crohn disease patients and lowered colitis severity and NF-kB activity in cell and mouse models."}]},{"from":"wi_struck_caught","to":"fracture","level":"established","effect":"harms","note":"Being struck by or caught in objects commonly breaks bones, especially in the hands and fingers."},{"from":"wi_struck_caught","to":"tbi","level":"established","effect":"harms","note":"Being struck on the head by a falling or moving object can cause a traumatic brain injury."},{"from":"wi_struck_caught","to":"bp_wrists_hands","level":"established","effect":"affects","note":"Crush and caught-in injuries often involve the hands and wrists as well as the fingers."},{"from":"wi_vehicle","to":"fracture","level":"established","effect":"harms","note":"Crash forces commonly break ribs, limbs and other bones."},{"from":"wi_vehicle","to":"tbi","level":"established","effect":"harms","note":"A crash can injure the brain through impact or sudden head movement."},{"from":"wi_vehicle","to":"bp_chest_ribs","level":"established","effect":"affects","note":"Seat-belt and steering-wheel forces in a crash often injure the chest and ribs."},{"from":"wi_head_impacts","to":"post_concussion","level":"established","effect":"harms","note":"Repeated or severe head blows can leave lingering concussion symptoms such as headache and poor concentration."},{"from":"wi_carbon_monoxide","to":"headache","level":"established","effect":"harms","note":"Headache is the most common early sign of carbon monoxide poisoning."},{"from":"wi_noise","to":"tinnitus","level":"established","effect":"harms","note":"Loud noise can damage the inner ear and cause ringing in the ears."},{"from":"wi_lead_work","to":"neuropathy","level":"established","effect":"harms","note":"Heavy lead exposure can damage peripheral nerves, classically causing weak wrists."},{"from":"wi_shift_work","to":"fatigue","level":"established","effect":"harms","note":"Working against the body clock disrupts sleep and leaves workers more tired."},{"from":"wi_silica_dust","to":"breathless","level":"established","effect":"harms","note":"Scarring of the lungs from silica dust makes breathing harder over time."},{"from":"wi_asbestos_work","to":"breathless","level":"established","effect":"harms","note":"Asbestos-related lung scarring and pleural disease cause shortness of breath."},{"from":"hbv","to":"s_liver","level":"established","effect":"harms","note":"Hepatitis B infects the liver and can cause chronic liver disease."},{"from":"hcv","to":"s_liver","level":"established","effect":"harms","note":"Hepatitis C infects the liver and can cause chronic liver disease."},{"from":"plasmodium","to":"s_blood","level":"established","effect":"harms","note":"Malaria parasites infect and destroy red blood cells."},{"from":"plasmodium","to":"s_liver","level":"established","effect":"harms","note":"Malaria parasites first multiply in the liver before entering the blood."},{"from":"giardia","to":"s_small_intestine","level":"established","effect":"harms","note":"Giardia lives in the small intestine and causes diarrhoea and poor absorption."},{"from":"hookworm","to":"s_small_intestine","level":"established","effect":"harms","note":"Hookworms attach to the wall of the small intestine and feed on blood."},{"from":"flu","to":"pneumonia","level":"established","effect":"harms","note":"Influenza can lead to pneumonia, the most serious common complication."},{"from":"hsv1","to":"s_mouth","level":"established","effect":"harms","note":"HSV-1 commonly causes cold sores around the mouth and then lies dormant in nerves."},{"from":"jc_virus","to":"s_cortex","level":"established","effect":"harms","note":"When immunity is weak, JC virus can infect the brain and cause progressive multifocal leukoencephalopathy."},{"from":"taenia","to":"s_cortex","level":"established","effect":"harms","note":"Pork tapeworm larvae can form cysts in the brain (neurocysticercosis)."},{"from":"light","to":"vitd","level":"established","effect":"helps","note":"Skin makes vitamin D when midday sun (UVB) falls on it; this is most people's main source, but indoor light lamps and winter sun far from the equator make little or none."},{"from":"fortified","to":"vitd","level":"established","effect":"contains","note":"Vitamin D is added to many milks, plant milks, spreads and breakfast cereals; amounts vary by country."},{"from":"b6","to":"m_dopa","level":"established","effect":"helps","note":"Vitamin B6 is needed by the enzyme that turns levodopa into dopamine; extra isn't shown to help, and high doses weaken plain levodopa taken without carbidopa.","dose":"deficiency"},{"from":"b6","to":"m_reward","level":"established","effect":"helps","note":"The same B6-dependent enzyme makes serotonin, a mood messenger; extra beyond a normal diet isn't shown to lift mood.","dose":"deficiency"},{"from":"vitc","to":"m_catechol","level":"established","effect":"helps","note":"The enzyme that turns dopamine into noradrenaline uses vitamin C as a helper, alongside copper; extra beyond normal isn't shown to do more.","dose":"deficiency"},{"from":"iron","to":"s_marrow","level":"established","effect":"helps","note":"The bone marrow needs iron to build haemoglobin, the oxygen carrier in red blood cells; lack causes anaemia."},{"from":"iron","to":"fatigue","level":"established","effect":"helps","note":"Iron-deficiency anaemia causes tiredness and breathlessness that lift when iron is restored; extra iron doesn't help tiredness when stores are normal, and too much is harmful.","dose":"deficiency"},{"from":"fortified","to":"iron","level":"established","effect":"contains","note":"Iron is added to many breakfast cereals and, in some countries, to flour."},{"from":"aa_lysine","to":"aa_carnitine","level":"established","effect":"helps","note":"The body builds carnitine from lysine (with methionine); a normal diet supplies enough."},{"from":"aa_methionine","to":"aa_carnitine","level":"established","effect":"helps","note":"Methionine supplies part of the carnitine molecule the body makes from lysine."},{"from":"aa_aspartate","to":"m_excit","level":"established","effect":"affects","note":"Aspartate acts as a 'go' signal on some nerve receptors (NMDA), like a weaker glutamate; eating it doesn't change brain levels much."},{"from":"protein","to":"s_muscle","level":"established","effect":"helps","note":"Muscle is built and repaired from the amino acids in protein; too little speeds muscle loss with age, while extra beyond needs isn't shown to build more without exercise.","dose":"deficiency"},{"from":"isoflavones","to":"equol_makers","level":"association","effect":"helps","note":"Soy isoflavones (daidzein) are what these gut bacteria turn into equol; people who eat more daidzein tend to carry more of them, though only some people make equol at all.","sources":[{"id":"pmid:30791484","citation":"Iino C et al., Nutrients","year":2019,"design":"cohort","finding":"In 1,044 adults, higher daidzein intake went with being an equol producer and with more Asaccharobacter celatus and Slackia isoflavoniconvertens in the gut (cross-sectional)."},{"id":"pmid:20519412","citation":"Setchell KD, Clerici C, J Nutr","year":2010,"design":"review","finding":"Equol is not made by the body itself but by certain gut bacteria from the soy isoflavone daidzein, and only some adults carry them."}]},{"from":"hm_cortisol","to":"br_hippocampus","level":"association","effect":"harms","note":"Months of very high cortisol (as in Cushing's disease) shrink the hippocampus, and it partly regrows once cortisol comes down.","dose":"excess","sources":[{"id":"pmid:10624540","citation":"Starkman MN et al., Biol Psychiatry","year":1999,"design":"cohort","finding":"In 22 people with Cushing's disease, hippocampal volume rose by up to 10% after surgery lowered cortisol, and the rise tracked how much cortisol fell."}]},{"from":"br_hippocampus","to":"hm_cortisol","level":"established","effect":"harms","note":"The hippocampus helps switch the stress response off, so it acts as a brake on cortisol release.","sources":[{"id":"pmid:27065163","citation":"Herman JP et al., Compr Physiol","year":2016,"design":"review","finding":"Cortisol switches off its own stress response partly through inhibition relayed by limbic structures such as the hippocampus."}]},{"from":"ptsd","to":"br_hippocampus","level":"association","effect":"affects","note":"Large pooled brain-scan studies find a slightly smaller hippocampus in people with PTSD; whether this is cause or result is not known.","sources":[{"id":"pmid:29217296","citation":"Logue MW et al., Biol Psychiatry","year":2018,"design":"case-control","finding":"Across 16 cohorts (1868 people), those with current PTSD had slightly smaller hippocampi than trauma-exposed people without PTSD (d = -0.17)."}]},{"from":"br_entorhinal","to":"s_limbic","level":"established","effect":"located","note":"Part of the limbic system, wired directly into the hippocampus."},{"from":"memory","to":"br_entorhinal","level":"established","effect":"located","note":"The entorhinal cortex feeds information into the hippocampus, so damage here blocks new memories from forming."},{"from":"alzheimers","to":"br_entorhinal","level":"established","effect":"affects","note":"Alzheimer's tau tangles appear here first, years before symptoms, and then spread into the hippocampus.","sources":[{"id":"pmid:1759558","citation":"Braak H & Braak E, Acta Neuropathol","year":1991,"design":"case-control","finding":"In 83 autopsy brains, tau tangles appeared first in the (trans)entorhinal region (stages I-II), then the entorhinal cortex and hippocampus (III-IV), then the wider cortex (V-VI)."}]},{"from":"parkinsons","to":"br_hippocampus","level":"association","effect":"affects","note":"Lewy changes reach a small part of the hippocampus (CA2) in Parkinson's, more in people with dementia, and the hippocampus shrinks faster in those with memory and thinking problems.","sources":[{"id":"pmid:31023342","citation":"Liu AKL et al., Acta Neuropathol Commun","year":2019,"design":"case-control","finding":"In 197 Parkinson's brains, Lewy pathology in the hippocampal CA2 region was significantly greater only in those with dementia, alongside loss of acetylcholine fibres."},{"id":"pmid:28468552","citation":"Schneider CB et al., Am J Alzheimers Dis Other Demen","year":2017,"design":"case-control","finding":"People with Parkinson's and mild cognitive impairment showed faster age-related hippocampal volume loss than cognitively healthy people with Parkinson's."}]},{"from":"lewy","to":"br_hippocampus","level":"established","effect":"affects","note":"Lewy changes in the CA2 part of the hippocampus are typical of this dementia, but the hippocampus shrinks far less than in Alzheimer's, which helps tell the two apart on scans.","sources":[{"id":"pmid:7912027","citation":"Dickson DW et al., Acta Neuropathol","year":1994,"design":"case-control (human autopsy)","finding":"Abnormal nerve fibres in the CA2/3 region of the hippocampus are characteristic of diffuse Lewy body disease and their extent tracks the number of cortical Lewy bodies."},{"id":"pmid:19022858","citation":"Burton EJ et al., Brain","year":2009,"design":"cohort","finding":"In autopsy-confirmed cases, medial temporal lobe shrinkage on MRI separated Alzheimer's from dementia with Lewy bodies with 91% sensitivity and 94% specificity; shrinkage tracked tangles, not Lewy bodies."}]},{"from":"m_plastic","to":"br_hippocampus","level":"established","effect":"located","note":"The strengthening of nerve connections that stores memories (long-term potentiation) was first discovered in the hippocampus.","sources":[{"id":"pmid:4727084","citation":"Bliss TV & Lomo T, J Physiol","year":1973,"design":"lab","finding":"Brief high-frequency stimulation of the pathway into the hippocampal dentate area produced a long-lasting strengthening of the connection (long-term potentiation)."}]},{"from":"exercise","to":"br_hippocampus","level":"mixed","effect":"helps","note":"One trial found a year of brisk walking enlarged the hippocampus in older adults, but pooled trials show only that exercise may slow its age-related shrinking.","sources":[{"id":"pmid:21282661","citation":"Erickson KI et al., PNAS","year":2011,"design":"RCT","finding":"In 120 older adults, a year of aerobic walking enlarged the front of the hippocampus by about 2% and improved spatial memory, while stretching controls lost volume."},{"id":"pmid:29113943","citation":"Firth J et al., NeuroImage","year":2018,"design":"meta-analysis","finding":"Across 14 controlled trials (737 people), aerobic exercise did not significantly change total hippocampal volume but preserved left hippocampal volume, mainly by preventing loss."}]},{"from":"hsv1","to":"br_hippocampus","level":"established","effect":"harms","note":"The rare brain infection herpes simplex encephalitis targets the inner temporal lobes, including the hippocampus, and often leaves lasting memory loss."},{"from":"wi_carbon_monoxide","to":"br_hippocampus","level":"association","effect":"harms","note":"After carbon monoxide poisoning, brain scans show a smaller hippocampus, and more shrinkage goes with later memory and thinking problems.","sources":[{"id":"pmid:40548357","citation":"Tang M et al., CNS Neurosci Ther","year":2025,"design":"case-control","finding":"Within 3 days of carbon monoxide poisoning, 47 patients had smaller hippocampi and subfields than controls, and smaller subfields went with later delayed brain injury."}]},{"from":"low_back_disc","to":"s_peripheral","level":"established","effect":"affects","note":"Sciatica is a pinched nerve root leaving the low spine."},{"from":"low_back_disc","to":"s_bones","level":"established","effect":"affects","note":"The disc and its joints are the injured structure."},{"from":"cervical_radiculopathy","to":"s_peripheral","level":"established","effect":"affects","note":"A pinched nerve root leaving the neck."},{"from":"knee_meniscus_oa","to":"s_bones","level":"established","effect":"affects","note":"Joint cartilage and the meniscus wear or tear."},{"from":"rotator_cuff","to":"s_muscle","level":"established","effect":"affects","note":"Tendons of the shoulder muscles fray or tear."},{"from":"epicondylitis","to":"s_muscle","level":"established","effect":"affects","note":"The forearm muscle tendons are strained where they attach at the elbow."},{"from":"inguinal_hernia","to":"s_muscle","level":"established","effect":"affects","note":"A gap in the belly-wall muscle lets gut push through."},{"from":"inguinal_hernia","to":"pain","level":"established","effect":"harms","note":"The bulge aches, especially on straining."},{"from":"tbi","to":"s_cortex","level":"established","effect":"affects","note":"The blow bruises and shears brain tissue."},{"from":"chronic_pain","to":"s_spinal","level":"established","effect":"affects","note":"Pain pathways in the spinal cord become over-sensitive."},{"from":"crps","to":"s_peripheral","level":"established","effect":"affects","note":"Starts after nerve or limb injury; the limb becomes exquisitely sensitive."},{"from":"crps","to":"s_autonomic","level":"established","effect":"affects","note":"Swelling, colour and sweating changes show the autonomic nerves are involved."},{"from":"nihl","to":"s_ears","level":"established","effect":"affects","note":"Noise destroys the hair cells of the inner ear."},{"from":"heat_illness","to":"s_kidneys","level":"established","effect":"affects","note":"Heat stroke and dehydration can injure the kidneys."},{"from":"msa","to":"bp_sexual_function","level":"established","effect":"affects","note":"Erectile dysfunction is an early sign of the autonomic failure in MSA."},{"from":"parkinsons","to":"bp_sexual_function","level":"established","effect":"affects","note":"Sexual dysfunction is a common non-motor symptom."},{"from":"ms","to":"bp_sexual_function","level":"established","effect":"affects","note":"Spinal cord damage disturbs the nerves to the pelvis."},{"from":"depression_c","to":"bp_sexual_function","level":"established","effect":"affects","note":"Loss of sexual interest is a core feature of depression."},{"from":"depression_c","to":"bp_psyche","level":"established","effect":"affects","note":"A psychiatric condition."},{"from":"adhd_c","to":"bp_psyche","level":"established","effect":"affects","note":"A mental-health condition of attention and impulse control."},{"from":"ocd_c","to":"bp_psyche","level":"established","effect":"affects","note":"A psychiatric condition."},{"from":"chronic_pain","to":"bp_sleep","level":"established","effect":"affects","note":"Pain that will not settle breaks sleep, and poor sleep feeds the pain."},{"from":"ptsd","to":"bp_sleep","level":"established","effect":"affects","note":"Nightmares and hyperarousal disturb sleep."},{"from":"post_concussion","to":"bp_sleep","level":"established","effect":"affects","note":"Poor sleep is part of the syndrome for months after a concussion."},{"from":"insomnia","to":"bp_sleep","level":"established","effect":"located","note":"A sleep problem."},{"from":"sleepy","to":"bp_sleep","level":"established","effect":"located","note":"A sleep problem: not enough restorative sleep at night."},{"from":"rbd","to":"bp_sleep","level":"established","effect":"located","note":"A sleep problem arising in dream (REM) sleep."},{"from":"occ_asthma","to":"bp_lungs","level":"established","effect":"affects","note":"A lung disease: the airways narrow and inflame."},{"from":"silicosis","to":"bp_lungs","level":"established","effect":"affects","note":"A lung disease: scarring from silica dust."},{"from":"asbestos_disease","to":"bp_lungs","level":"established","effect":"affects","note":"Lung scarring and cancer of the lung lining from asbestos fibres."},{"from":"heat_illness","to":"bp_internal_organs","level":"established","effect":"affects","note":"In heat stroke the kidneys and other organs can fail."},{"from":"wi_struck_caught","to":"bp_eyes","level":"established","effect":"affects","note":"Flying particles and metal fragments injure the eye surface."},{"from":"wi_assault","to":"bp_teeth","level":"established","effect":"affects","note":"Blows to the face break or knock out teeth."},{"from":"wi_slip_trip_fall","to":"bp_teeth","level":"established","effect":"affects","note":"A face-first fall breaks or knocks out teeth."},{"from":"wi_fall_height","to":"bp_thoracic_spine","level":"established","effect":"affects","note":"Compression fractures of the mid-back vertebrae."},{"from":"wi_lifting","to":"bp_thoracic_spine","level":"established","effect":"affects","note":"Mid-back muscle strains from heavy lifting."},{"from":"wi_fall_height","to":"bp_chest_ribs","level":"established","effect":"affects","note":"Rib fractures on landing."},{"from":"wi_struck_caught","to":"bp_chest_ribs","level":"established","effect":"affects","note":"Rib fractures and bruising from crush and blows."},{"from":"wi_fall_height","to":"bp_hips","level":"established","effect":"affects","note":"Hip and pelvic fractures on landing."},{"from":"parkinsons","to":"bp_head_brain","level":"established","effect":"affects","note":"A brain disease: dopamine cells in the midbrain are lost."},{"from":"lewy","to":"bp_head_brain","level":"established","effect":"affects","note":"A brain disease with Lewy bodies through the cortex and brainstem."},{"from":"msa","to":"bp_head_brain","level":"established","effect":"affects","note":"A brain disease affecting the basal ganglia, cerebellum and brainstem."},{"from":"alzheimers","to":"bp_head_brain","level":"established","effect":"affects","note":"A brain disease starting in the memory centres."},{"from":"huntingtons","to":"bp_head_brain","level":"established","effect":"affects","note":"An inherited brain disease wasting the striatum."},{"from":"ms","to":"bp_head_brain","level":"established","effect":"affects","note":"Scars (plaques) form in the brain as well as the spinal cord."},{"from":"epilepsy","to":"bp_head_brain","level":"established","effect":"affects","note":"Seizures arise from electrical storms in the brain."},{"from":"essential_tremor","to":"bp_head_brain","level":"established","effect":"affects","note":"A brain tremor disorder involving cerebellar loops."},{"from":"tourette","to":"bp_head_brain","level":"established","effect":"affects","note":"A brain condition of the habit circuits."},{"from":"manganism","to":"bp_head_brain","level":"established","effect":"affects","note":"Manganese builds up in the brain and damages movement circuits."},{"from":"post_concussion","to":"bp_head_brain","level":"established","effect":"affects","note":"Lingering effects of a brain injury."},{"from":"eo_lemon","to":"limonene","level":"established","effect":"contains","note":"Lemon peel oil is mostly limonene."},{"from":"eo_sweet_orange","to":"limonene","level":"established","effect":"contains","note":"Sweet orange oil is over 90% limonene."},{"from":"eo_bergamot","to":"limonene","level":"established","effect":"contains","note":"Limonene is the largest single compound in bergamot oil."},{"from":"eo_spearmint","to":"limonene","level":"established","effect":"contains","note":"Spearmint oil contains limonene alongside its main compound, carvone."},{"from":"eo_bergamot","to":"bergapten","level":"established","effect":"contains","note":"Ordinary bergamot oil contains bergapten unless labelled furocoumarin-free."},{"from":"bergapten","to":"s_skin","level":"established","effect":"harms","note":"Skin carrying bergapten burns and blisters when exposed to sunlight or tanning lamps, often leaving dark marks for months.","sources":[{"id":"pmid:871382","citation":"Zaynoun ST et al., Br J Dermatol","year":1977,"design":"lab","finding":"Bergapten was the only significant light-activated compound in bergamot oil and was about as phototoxic on human skin as the psoralen drug methoxsalen."},{"id":"pmid:11511848","citation":"Kaddu S et al., J Am Acad Dermatol","year":2001,"design":"review","finding":"Two people developed blistering burns after bergamot aromatherapy oil followed by UV light; bergamot's bergapten makes skin react to sunlight."}]},{"from":"limonene","to":"contact_dermatitis","level":"association","effect":"harms","note":"Air-oxidised limonene caused positive allergy patch tests in about 1 in 20 dermatitis patients tested.","sources":[{"id":"pmid:24702129","citation":"Audrain H et al., Br J Dermatol","year":2014,"design":"cohort","finding":"Among 4731 consecutive UK dermatitis patients, 5.0% reacted to oxidised limonene and 5.9% to oxidised linalool, while fresh (stabilised) forms rarely caused reactions."}]},{"from":"eo_sweet_orange","to":"anxiety","level":"mixed","effect":"helps","note":"Orange scent in a dental waiting room lowered anxiety in small studies, but people can't be blinded to a smell.","sources":[{"id":"pmid:16095639","citation":"Lehrner J et al., Physiol Behav","year":2005,"design":"RCT","finding":"Among 200 people waiting for dental treatment, ambient orange or lavender scent lowered anxiety and improved mood compared with no scent."},{"id":"pmid:32861206","citation":"Guo P et al., Int J Nurs Stud","year":2020,"design":"meta-analysis","finding":"Across 20 trials (1717 adults), aromatherapy, most often lavender, citrus or rose, lowered anxiety before surgery compared with control; blinding to a smell is hard."}]},{"from":"eo_peppermint","to":"menthol","level":"established","effect":"contains","note":"Menthol is the main compound in peppermint oil."},{"from":"eo_peppermint","to":"s_gut","level":"proven","effect":"helps","note":"Enteric-coated peppermint oil capsules eased overall symptoms and belly pain in irritable bowel syndrome (IBS) in pooled trials, though most trials were small and of low quality.","sources":[{"id":"pmid:24100754","citation":"Khanna R et al., J Clin Gastroenterol","year":2014,"design":"meta-analysis","finding":"Enteric-coated peppermint oil improved global IBS symptoms and belly pain versus placebo; side effects were mild, the commonest being heartburn."},{"id":"pmid:35942669","citation":"Ingrosso MR et al., Aliment Pharmacol Ther","year":2022,"design":"meta-analysis","finding":"Across 10 RCTs (1030 people) peppermint oil beat placebo for overall IBS symptoms and belly pain, but side effects were more common and evidence quality was very low."},{"id":"pmid:31470006","citation":"Weerts ZZRM et al., Gastroenterology","year":2020,"design":"RCT","finding":"In the largest trial (189 people) peppermint oil missed the regulator-recommended main pain endpoint, though small-intestine-release capsules improved pain and IBS severity as secondary outcomes; side effects were more common."}]},{"from":"eo_peppermint","to":"s_oesophagus","level":"proven","effect":"harms","note":"Heartburn was the most common side effect of peppermint oil capsules in trials, because it relaxes the valve at the top of the stomach.","sources":[{"id":"pmid:24100754","citation":"Khanna R et al., J Clin Gastroenterol","year":2014,"design":"meta-analysis","finding":"Enteric-coated peppermint oil improved global IBS symptoms and belly pain versus placebo; side effects were mild, the commonest being heartburn."},{"id":"pmid:35942669","citation":"Ingrosso MR et al., Aliment Pharmacol Ther","year":2022,"design":"meta-analysis","finding":"Across 10 RCTs (1030 people) peppermint oil beat placebo for overall IBS symptoms and belly pain, but side effects were more common and evidence quality was very low."}]},{"from":"eo_peppermint","to":"headache","level":"mixed","effect":"helps","note":"Peppermint oil rubbed on the forehead and temples eased tension-type headache about as well as paracetamol in one small double-blind trial.","sources":[{"id":"pmid:8805113","citation":"Göbel H et al., Nervenarzt","year":1996,"design":"RCT","finding":"In a double-blind crossover trial of 41 people with tension-type headache, peppermint oil in ethanol rubbed on forehead and temples reduced pain versus placebo, about as well as paracetamol."}]},{"from":"menthol","to":"m_painproc","level":"established","effect":"helps","note":"Menthol switches on the cold sensor TRPM8 in skin nerves, giving a cooling feeling that can compete with pain signals; how much this relieves real pain varies.","sources":[{"id":"pmid:17538622","citation":"Bautista DM et al., Nature","year":2007,"design":"lab","finding":"TRPM8, the receptor menthol switches on, is the main detector of cold in sensory nerves; mice lacking it barely sense cool temperatures."}]},{"from":"eo_lavender","to":"linalool","level":"established","effect":"contains","note":"Linalool and linalyl acetate together make up most of lavender oil."},{"from":"eo_clary_sage","to":"linalool","level":"established","effect":"contains","note":"Clary sage oil is mostly linalyl acetate and linalool."},{"from":"eo_ylang_ylang","to":"linalool","level":"established","effect":"contains","note":"Linalool is one of the main compounds in ylang-ylang oil."},{"from":"eo_lavender","to":"anxiety","level":"proven","effect":"helps","note":"Swallowed lavender-oil capsules (Silexan) eased anxiety more than placebo in pooled trials; just smelling lavender has weaker, mostly unblinded evidence.","sources":[{"id":"pmid:36717399","citation":"Dold M et al., Eur Arch Psychiatry Clin Neurosci","year":2023,"design":"meta-analysis","finding":"Across 5 placebo-controlled trials (1213 outpatients), swallowed lavender-oil capsules (Silexan) reduced anxiety scores more than placebo over ten weeks, with side effects similar to placebo; authors include the maker's staff."},{"id":"pmid:30439747","citation":"Greenberg MJ & Slyer JT, JBI Database Syst Rev","year":2018,"design":"review","finding":"A systematic search found no studies comparing swallowed lavender oil with inhaled lavender for sleep or anxiety."}]},{"from":"eo_lavender","to":"insomnia","level":"mixed","effect":"helps","note":"Smelling lavender improved self-rated sleep in small trials, mostly in older adults, but results varied hugely and people know when they smell lavender, so placebo effects can't be ruled out.","sources":[{"id":"pmid:41057090","citation":"Ostovar M et al., Exp Gerontol","year":2025,"design":"meta-analysis","finding":"In 10 trials in older adults, all using inhaled lavender, sleep-quality scores improved, but heterogeneity was very high and the authors call the evidence preliminary."},{"id":"pmid:30439747","citation":"Greenberg MJ & Slyer JT, JBI Database Syst Rev","year":2018,"design":"review","finding":"A systematic search found no studies comparing swallowed lavender oil with inhaled lavender for sleep or anxiety."}]},{"from":"eo_lavender","to":"m_excit","level":"lab","effect":"helps","note":"In lab studies lavender oil reduced calcium entry through nerve-cell calcium channels, a calming action partly like the drug pregabalin.","sources":[{"id":"pmid:23637742","citation":"Schuwald AM et al., PLoS One","year":2013,"design":"lab","finding":"At low concentrations lavender oil damped calcium entry through several types of nerve calcium channels in brain cells and in cell lines, partly resembling pregabalin."}]},{"from":"eo_lavender","to":"hm_oestrogen","level":"lab","effect":"affects","note":"Lavender oil weakly mimicked oestrogen and blocked testosterone in cells, and case reports link repeated skin use to breast growth in children that went away when stopped.","sources":[{"id":"pmid:17267908","citation":"Henley DV et al., N Engl J Med","year":2007,"design":"lab","finding":"Three boys developed breast growth while using lavender and tea tree oil products, which went away when they stopped; in human cell lines both oils had weak oestrogen-like and anti-testosterone activity."},{"id":"pmid:31393563","citation":"Ramsey JT et al., J Clin Endocrinol Metab","year":2019,"design":"lab","finding":"Four more children with breast growth linked to lavender fragrances improved when exposure stopped; some oil components acted like oestrogen in cells, but whether real-life levels are enough is unknown."}]},{"from":"linalool","to":"contact_dermatitis","level":"association","effect":"harms","note":"Once exposed to air, linalool forms compounds that are among the commonest causes of fragrance skin allergy on patch testing.","sources":[{"id":"pmid:22906042","citation":"Bråred Christensson J et al., Contact Dermatitis","year":2012,"design":"cohort","finding":"Air-oxidised linalool gave positive patch tests in 6.9% of 2900 consecutive dermatitis patients in six countries."},{"id":"pmid:24702129","citation":"Audrain H et al., Br J Dermatol","year":2014,"design":"cohort","finding":"Among 4731 consecutive UK dermatitis patients, 5.0% reacted to oxidised limonene and 5.9% to oxidised linalool, while fresh (stabilised) forms rarely caused reactions."}]},{"from":"eo_ylang_ylang","to":"contact_dermatitis","level":"association","effect":"harms","note":"Ylang-ylang was the essential oil that most often caused positive allergy patch tests in a large European clinic network.","sources":[{"id":"pmid:20946456","citation":"Uter W et al., Contact Dermatitis","year":2010,"design":"cohort","finding":"In German-speaking dermatology clinics, positive patch tests were most common to ylang-ylang oil (3.1%), lemongrass oil (1.8%), and sandalwood and clove oils (1.5% each)."},{"id":"pmid:27427818","citation":"de Groot AC & Schmidt E, Dermatitis","year":2016,"design":"review","finding":"Nearly 80 essential oils have caused contact allergy, mostly when used neat or concentrated; orange, tea tree, ylang-ylang, sandalwood and clove were among those with over 2% positive tests in tested patients."}]},{"from":"eo_wintergreen","to":"methyl_salicylate","level":"established","effect":"contains","note":"Wintergreen oil is about 98% methyl salicylate."},{"from":"methyl_salicylate","to":"seizures","level":"established","effect":"harms","note":"Salicylate poisoning from swallowed wintergreen oil, or heavy use on broken skin, can cause confusion, seizures and death; small children are most at risk.","dose":"excess","sources":[{"id":"pmid:17239735","citation":"Davis JE, J Emerg Med","year":2007,"design":"review","finding":"Oil of wintergreen is about 98% methyl salicylate; a teaspoon or less has caused well-documented deaths in children under six."},{"id":"pmid:41049912","citation":"Sidlak AM et al., Cureus","year":2025,"design":"review","finding":"Salicylate poisoning, including from skin products, causes vomiting, ringing in the ears, fast breathing, confusion, seizures and coma."}]},{"from":"methyl_salicylate","to":"tinnitus","level":"established","effect":"harms","note":"Ringing in the ears is an early sign of salicylate poisoning, including from methyl salicylate absorbed through the skin.","dose":"excess","sources":[{"id":"pmid:41049912","citation":"Sidlak AM et al., Cureus","year":2025,"design":"review","finding":"Salicylate poisoning, including from skin products, causes vomiting, ringing in the ears, fast breathing, confusion, seizures and coma."},{"id":"pmid:12147116","citation":"Bell AJ & Duggin G, Emerg Med","year":2002,"design":"review","finding":"A man developed salicylate poisoning with ringing in the ears and vomiting after a methyl salicylate cream was applied to broken skin under a dressing."}]},{"from":"methyl_salicylate","to":"s_blood","level":"established","effect":"harms","note":"Methyl salicylate rubbed on the skin is absorbed and can boost the blood thinner warfarin, raising the risk of dangerous bleeding.","sources":[{"id":"pmid:10860133","citation":"Joss JD & LeBlond RF, Ann Pharmacother","year":2000,"design":"review","finding":"A woman on stable warfarin developed a dangerously high clotting test (INR 12.2) after rubbing a methyl salicylate gel on her knees for eight days."},{"id":"pmid:7487701","citation":"Tam LS et al., Aust N Z J Med","year":1995,"design":"review","finding":"Case reports of warfarin's effect being boosted by Chinese medicines including methyl salicylate medicated oil."}]},{"from":"methyl_salicylate","to":"pain","level":"mixed","effect":"helps","note":"Better-quality trials found salicylate rubs no better than placebo for sprains and strains, with at most a small benefit in long-term pain.","sources":[{"id":"pmid:19588430","citation":"Matthews P et al., Cochrane Database Syst Rev","year":2009,"design":"meta-analysis","finding":"Better-quality trials showed no benefit of salicylate rubs over placebo for acute injuries; in chronic pain the benefit was small and poorer than anti-inflammatory gels."}]},{"from":"eo_smell_kit","to":"smell","level":"mixed","effect":"helps","note":"Sniffing four strong odours twice a day for months helped more people regain smell after viral infections in several studies, though trials can't be blinded and one large COVID-19 trial was inconclusive.","sources":[{"id":"pmid:32660334","citation":"Kattar N et al., Otolaryngol Head Neck Surg","year":2021,"design":"meta-analysis","finding":"In smell loss after viral infection, people who did smell training had 2.8 times the odds of a meaningful improvement compared with controls (4 studies pooled)."},{"id":"pmid:23929687","citation":"Damm M et al., Laryngoscope","year":2014,"design":"RCT","finding":"In 144 people with smell loss after infection, training with strong odours helped more than weak odours, especially if begun within a year (63% vs 19% improved)."},{"id":"pmid:36580304","citation":"Khan AM et al., JAMA Otolaryngol Head Neck Surg","year":2023,"design":"RCT","finding":"In 275 people with smell loss after COVID-19, essential-oil smell training variants did not differ on the main smell-test change, though more trained people than controls had a meaningful improvement."},{"id":"pmid:19235739","citation":"Hummel T et al., Laryngoscope","year":2009,"design":"cohort","finding":"Patients who sniffed rose, eucalyptus, lemon and clove twice daily for 12 weeks improved on smell tests, while untrained patients did not."},{"id":"pmid:23613901","citation":"Haehner A et al., PLoS One","year":2013,"design":"cohort","finding":"In 70 people with Parkinson's and smell loss, 12 weeks of the same four-odour training improved smell scores, while the untrained group was unchanged (not blinded)."}]},{"from":"eo_eucalyptus","to":"cineole","level":"established","effect":"contains","note":"Eucalyptus oil is mostly 1,8-cineole."},{"from":"eo_rosemary","to":"cineole","level":"established","effect":"contains","note":"1,8-Cineole is usually the largest compound in rosemary oil."},{"from":"eo_rosemary","to":"camphor","level":"established","effect":"contains","note":"Rosemary oil contains a substantial share of camphor."},{"from":"eo_camphor","to":"camphor","level":"established","effect":"contains","note":"Camphor oil contains camphor along with 1,8-cineole."},{"from":"camphor","to":"seizures","level":"established","effect":"harms","note":"Swallowing camphor, or rubbing it repeatedly on small children, can cause seizures; it is a well-known poison-centre problem.","dose":"excess","sources":[{"id":"pmid:19403490","citation":"Khine H et al., Pediatrics","year":2009,"design":"review","finding":"Three toddlers had seizures needing medicine to stop them after swallowing camphor or having it rubbed on the skin."},{"id":"pmid:16809137","citation":"Manoguerra AS et al., Clin Toxicol","year":2006,"design":"review","finding":"US poison centres record about 10,000 camphor ingestions a year; an expert guideline sets out when these need hospital care because camphor can cause seizures."},{"id":"pmid:31239862","citation":"Bahr TA et al., Evid Based Complement Alternat Med","year":2019,"design":"review","finding":"Oils such as sage, rosemary, camphor, eucalyptus and hyssop can trigger seizures because they contain thujone, 1,8-cineole or camphor; anti-seizure claims for other oils rest mostly on animal work."}]},{"from":"cineole","to":"seizures","level":"association","effect":"harms","note":"Seizures have followed heavy inhaling or swallowing of eucalyptus oil, including breakthrough seizures in people with epilepsy, though most children who swallow a little stay well.","dose":"excess","sources":[{"id":"pmid:29588965","citation":"Mathew T et al., Epilepsia Open","year":2017,"design":"review","finding":"Ten adults had seizures after inhaling eucalyptus oil, seen at three hospitals over two years."},{"id":"pmid:33813360","citation":"Mathew T et al., Epilepsy Res","year":2021,"design":"cohort","finding":"Over four years 55 people (8 months to 77 years) had seizures linked to eucalyptus- or camphor-containing oils, including first seizures and breakthrough seizures in people with epilepsy."},{"id":"pmid:31239862","citation":"Bahr TA et al., Evid Based Complement Alternat Med","year":2019,"design":"review","finding":"Oils such as sage, rosemary, camphor, eucalyptus and hyssop can trigger seizures because they contain thujone, 1,8-cineole or camphor; anti-seizure claims for other oils rest mostly on animal work."},{"id":"pmid:8240865","citation":"Webb NJ & Pitt WR, J Paediatr Child Health","year":1993,"design":"cohort","finding":"Of 41 children who swallowed eucalyptus oil, 80% had no symptoms and none needed life support, suggesting it is less toxic than once thought."}]},{"from":"cineole","to":"s_lungs","level":"mixed","effect":"helps","note":"Swallowed purified cineole capsules reduced COPD flare-ups and eased acute bronchitis in placebo-controlled trials, but both were funded by the maker and not independently repeated.","sources":[{"id":"pmid:19624838","citation":"Worth H et al., Respir Res","year":2009,"design":"RCT","finding":"In COPD, adding 1,8-cineole capsules to usual treatment for six months reduced flare-ups and breathlessness versus placebo; funded by the maker."},{"id":"pmid:24261680","citation":"Fischer J & Dethlefsen U, Cough","year":2013,"design":"RCT","finding":"In acute bronchitis, 1,8-cineole capsules improved symptom scores and cough frequency within four days versus placebo; maker-linked authors."}]},{"from":"eo_rosemary","to":"cognition","level":"mixed","effect":"helps","note":"In a room scented with rosemary, adults scored better on memory quality but were slower, in one small randomised experiment.","sources":[{"id":"pmid:12690999","citation":"Moss M et al., Int J Neurosci","year":2003,"design":"RCT","finding":"In 144 adults randomly assigned to a room scented with rosemary, lavender or nothing, rosemary improved memory quality but slowed memory speed, while lavender worsened working memory and reaction times."},{"id":"pmid:23983963","citation":"Moss M & Oliver L, Ther Adv Psychopharmacol","year":2012,"design":"lab","finding":"In 20 volunteers exposed to rosemary aroma, higher blood levels of 1,8-cineole correlated with better speed and accuracy on mental tasks (no control group)."}]},{"from":"eo_oregano","to":"carvacrol","level":"established","effect":"contains","note":"Carvacrol is the main compound in oregano oil."},{"from":"eo_oregano","to":"thymol","level":"established","effect":"contains","note":"Oregano oil also contains some thymol."},{"from":"eo_thyme","to":"thymol","level":"established","effect":"contains","note":"Thymol is the main compound in common thyme oil."},{"from":"eo_clove","to":"eugenol","level":"established","effect":"contains","note":"Clove oil is mostly eugenol."},{"from":"eo_cinnamon","to":"cinnamaldehyde","level":"established","effect":"contains","note":"Cinnamon bark oil is mostly cinnamaldehyde."},{"from":"thymol","to":"s_mouth","level":"proven","effect":"helps","note":"A mouthwash combining thymol with eucalyptol, menthol and methyl salicylate, used with brushing, reduced plaque and gum inflammation over six months in pooled trials.","sources":[{"id":"pmid:17608576","citation":"Stoeken JE et al., J Periodontol","year":2007,"design":"meta-analysis","finding":"In 11 six-month studies, an essential-oil mouthrinse added to brushing reduced plaque and gum inflammation versus control rinse."},{"id":"pmid:26227646","citation":"Araujo MWB et al., J Am Dent Assoc","year":2015,"design":"meta-analysis","finding":"Pooled six-month trials found more healthy gum sites and plaque-free sites with an essential-oil mouthrinse added to brushing and flossing; authors from the maker."}]},{"from":"eo_clove","to":"m_painproc","level":"mixed","effect":"helps","note":"A clove gel on the gum numbed needle pain about as well as benzocaine in one small trial.","sources":[{"id":"pmid:16530911","citation":"Alqareer A et al., J Dent","year":2006,"design":"RCT","finding":"In 73 volunteers, a homemade clove gel on the gum reduced needle-stick pain versus placebo about as much as benzocaine gel."}]},{"from":"eo_clove","to":"contact_dermatitis","level":"association","effect":"harms","note":"Clove oil is among the essential oils that most often cause positive allergy patch tests.","sources":[{"id":"pmid:20946456","citation":"Uter W et al., Contact Dermatitis","year":2010,"design":"cohort","finding":"In German-speaking dermatology clinics, positive patch tests were most common to ylang-ylang oil (3.1%), lemongrass oil (1.8%), and sandalwood and clove oils (1.5% each)."},{"id":"pmid:27427818","citation":"de Groot AC & Schmidt E, Dermatitis","year":2016,"design":"review","finding":"Nearly 80 essential oils have caused contact allergy, mostly when used neat or concentrated; orange, tea tree, ylang-ylang, sandalwood and clove were among those with over 2% positive tests in tested patients."}]},{"from":"eo_lemongrass","to":"contact_dermatitis","level":"association","effect":"harms","note":"Lemongrass oil was the second most common essential-oil allergen in a large European patch-test network.","sources":[{"id":"pmid:20946456","citation":"Uter W et al., Contact Dermatitis","year":2010,"design":"cohort","finding":"In German-speaking dermatology clinics, positive patch tests were most common to ylang-ylang oil (3.1%), lemongrass oil (1.8%), and sandalwood and clove oils (1.5% each)."}]},{"from":"cinnamaldehyde","to":"contact_dermatitis","level":"association","effect":"harms","note":"Cinnamon flavour (cinnamic aldehyde) in gum, toothpaste and oils is a recognised, often-missed cause of allergic rashes of the mouth and lips.","sources":[{"id":"pmid:25984687","citation":"Isaac-Renton M et al., Dermatitis","year":2015,"design":"review","finding":"Cinnamic aldehyde, the cinnamon flavour in gum, toothpaste, sweets and oils, causes allergic reactions inside the mouth that are often missed."}]},{"from":"eo_black_pepper","to":"swallow","level":"mixed","effect":"helps","note":"Sniffing black pepper oil before meals sped up the swallow reflex in one small trial in older people after stroke.","sources":[{"id":"pmid:16970649","citation":"Ebihara T et al., J Am Geriatr Soc","year":2006,"design":"RCT","finding":"In 105 nursing-home residents after stroke, sniffing black pepper oil before meals for a month shortened the delay before the swallow reflex compared with lavender oil or water."}]},{"from":"eo_tea_tree","to":"terpinen4ol","level":"established","effect":"contains","note":"Terpinen-4-ol is the main compound in tea tree oil."},{"from":"eo_frankincense","to":"alpha_pinene","level":"established","effect":"contains","note":"Alpha-pinene is usually the main compound in frankincense oil."},{"from":"eo_tea_tree","to":"s_skin","level":"mixed","effect":"helps","note":"Tea tree oil gel reduced acne spots and a solution cleared athlete's foot more than placebo, each in single small trials; evidence is low quality.","sources":[{"id":"pmid:25597924","citation":"Cao H et al., Cochrane Database Syst Rev","year":2015,"design":"meta-analysis","finding":"For acne, one small trial (60 people) showed tea tree oil gel reduced spots versus placebo; overall evidence for complementary therapies was low quality."},{"id":"pmid:17314442","citation":"Enshaieh S et al., Indian J Dermatol Venereol Leprol","year":2007,"design":"RCT","finding":"In 60 people with mild to moderate acne, tea tree oil gel reduced lesion counts and severity more than placebo gel over 45 days."},{"id":"pmid:12121393","citation":"Satchell AC et al., Australas J Dermatol","year":2002,"design":"RCT","finding":"In 158 people with athlete's foot, tea tree oil solution cleared the fungus in 64% versus 31% on placebo; about 4% developed dermatitis."},{"id":"pmid:8195735","citation":"Buck DS et al., J Fam Pract","year":1994,"design":"RCT","finding":"For toenail fungus, neat tea tree oil did about as well as clotrimazole solution over six months, but cure rates were low with both."}]},{"from":"eo_tea_tree","to":"contact_dermatitis","level":"association","effect":"harms","note":"Tea tree oil has caused more published allergic skin reactions than any other essential oil, especially when used neat or after it has oxidised.","sources":[{"id":"pmid:27173437","citation":"de Groot AC & Schmidt E, Contact Dermatitis","year":2016,"design":"review","finding":"Tea tree oil has caused the most published allergic reactions of any essential oil (0.1–3.5% of routinely tested patients); oxidised oil is a stronger allergen."},{"id":"pmid:12121393","citation":"Satchell AC et al., Australas J Dermatol","year":2002,"design":"RCT","finding":"In 158 people with athlete's foot, tea tree oil solution cleared the fungus in 64% versus 31% on placebo; about 4% developed dermatitis."}]},{"from":"eo_tea_tree","to":"hm_oestrogen","level":"lab","effect":"affects","note":"Tea tree oil weakly mimicked oestrogen in cells, and case reports link repeated skin use to breast growth in boys that went away when stopped.","sources":[{"id":"pmid:17267908","citation":"Henley DV et al., N Engl J Med","year":2007,"design":"lab","finding":"Three boys developed breast growth while using lavender and tea tree oil products, which went away when they stopped; in human cell lines both oils had weak oestrogen-like and anti-testosterone activity."}]},{"from":"boswellic_acids","to":"knee_meniscus_oa","level":"mixed","effect":"helps","note":"Swallowed Boswellia resin extracts eased knee osteoarthritis pain in several small trials, but a larger pooled analysis found no clear overall effect.","sources":[{"id":"pmid:32680575","citation":"Yu G et al., BMC Complement Med Ther","year":2020,"design":"meta-analysis","finding":"In 7 trials (545 people) Boswellia extracts reduced osteoarthritis pain and stiffness and improved function versus controls."},{"id":"pmid:39314013","citation":"Dalmonte T et al., Phytother Res","year":2024,"design":"meta-analysis","finding":"In 13 knee osteoarthritis trials the overall effect of Boswellia extracts was not significant because results varied widely, though placebo-controlled subgroups favoured Boswellia."}]},{"from":"eo_sandalwood","to":"contact_dermatitis","level":"association","effect":"harms","note":"Sandalwood oil is among the essential oils that most often cause positive allergy patch tests.","sources":[{"id":"pmid:20946456","citation":"Uter W et al., Contact Dermatitis","year":2010,"design":"cohort","finding":"In German-speaking dermatology clinics, positive patch tests were most common to ylang-ylang oil (3.1%), lemongrass oil (1.8%), and sandalwood and clove oils (1.5% each)."},{"id":"pmid:27427818","citation":"de Groot AC & Schmidt E, Dermatitis","year":2016,"design":"review","finding":"Nearly 80 essential oils have caused contact allergy, mostly when used neat or concentrated; orange, tea tree, ylang-ylang, sandalwood and clove were among those with over 2% positive tests in tested patients."}]},{"from":"m_allergy","to":"food_allergy","level":"established","effect":"helps","note":"When the allergy brake holds, foods are eaten without a reaction; food allergy is a failure of this tolerance."},{"from":"m_allergy","to":"anaphylaxis","level":"established","effect":"helps","note":"Anaphylaxis is the most severe result of mast cells releasing histamine all over the body."},{"from":"food_allergy","to":"hives","level":"established","effect":"harms","note":"Hives are the most common sign of a food allergic reaction."},{"from":"food_allergy","to":"angioedema","level":"established","effect":"harms","note":"Lips, eyes or tongue can swell soon after eating the food."},{"from":"food_allergy","to":"anaphylaxis","level":"established","effect":"harms","note":"Food is the most common cause of anaphylaxis in children."},{"from":"food_allergy","to":"s_immune","level":"established","effect":"affects","note":"An immune reaction against a harmless food protein."},{"from":"food_allergy","to":"s_gut","level":"established","effect":"affects","note":"Can cause mouth itching, vomiting, belly pain and diarrhoea."},{"from":"anaphylaxis","to":"angioedema","level":"established","effect":"harms","note":"Throat and tongue swelling can block breathing."},{"from":"anaphylaxis","to":"wheeze","level":"established","effect":"harms","note":"Airways tighten, causing wheeze and difficulty breathing."},{"from":"anaphylaxis","to":"hives","level":"established","effect":"harms","note":"Most, but not all, anaphylaxis comes with hives or flushing."},{"from":"anaphylaxis","to":"s_blood","level":"established","effect":"affects","note":"Blood vessels widen and leak, so blood pressure can fall and cause collapse."},{"from":"anaphylaxis","to":"s_lungs","level":"established","effect":"affects","note":"Narrowed airways make breathing hard."},{"from":"hives","to":"s_skin","level":"established","effect":"located","note":"Raised itchy wheals in the skin."},{"from":"angioedema","to":"s_skin","level":"established","effect":"located","note":"Swelling in the deeper layers of the skin, often lips and eyelids."},{"from":"angioedema","to":"s_throat","level":"established","effect":"located","note":"Swelling of the tongue and throat is the dangerous kind."},{"from":"itchy_nose_eyes","to":"s_eyes","level":"established","effect":"located","note":"Red, itchy, watery eyes (allergic conjunctivitis)."},{"from":"itchy_nose_eyes","to":"s_lungs","level":"established","effect":"located","note":"The nose is the entrance to the airways; it sneezes, runs and blocks."},{"from":"wheeze","to":"s_lungs","level":"established","effect":"located","note":"Comes from narrowed airways in the lungs."},{"from":"wheeze","to":"breathless","level":"established","effect":"harms","note":"Narrowed airways that wheeze also make it hard to get enough air."},{"from":"occ_asthma","to":"wheeze","level":"established","effect":"harms","note":"Wheeze is a core symptom of asthma caused by work exposures."},{"from":"oats","to":"coeliac_disease","level":"established","effect":"harms","note":"Gluten in wheat, barley and rye drives coeliac disease; pure oats are tolerated by most people with coeliac disease but are often contaminated with wheat."},{"from":"dairy","to":"lactose_intolerance","level":"established","effect":"harms","note":"Milk sugar causes bloating and loose stools when the lactase enzyme is low; hard cheese and yoghurt contain less lactose."},{"from":"dairy","to":"eoe","level":"established","effect":"harms","note":"Milk is the most common food trigger of eosinophilic oesophagitis."},{"from":"dairy","to":"fpies","level":"established","effect":"harms","note":"Cow's milk is one of the most common FPIES triggers in babies."},{"from":"soy","to":"fpies","level":"established","effect":"harms","note":"Soy is a common FPIES trigger, especially in babies who also react to milk."},{"from":"coeliac_disease","to":"m_barrier","level":"established","effect":"harms","note":"The immune attack flattens the small-intestine lining and makes it leaky until gluten is removed."},{"from":"coeliac_disease","to":"s_small_intestine","level":"established","effect":"affects","note":"Flattens the villi that absorb nutrients."},{"from":"coeliac_disease","to":"s_immune","level":"established","effect":"affects","note":"An autoimmune disease: the body's T cells attack its own gut lining when gluten is eaten."},{"from":"coeliac_disease","to":"nutrition","level":"established","effect":"harms","note":"Poor absorption can cause weight loss and low iron, folate, vitamin D and calcium."},{"from":"lactose_intolerance","to":"s_small_intestine","level":"established","effect":"affects","note":"The small-intestine lining makes too little lactase."},{"from":"lactose_intolerance","to":"s_colon","level":"established","effect":"affects","note":"Colon bacteria ferment the leftover lactose into gas and loose stools."},{"from":"eoe","to":"s_oesophagus","level":"established","effect":"affects","note":"Eosinophils inflame and stiffen the food pipe."},{"from":"eoe","to":"swallow","level":"established","effect":"harms","note":"Food sticks in the narrowed food pipe; it is a common cause of food getting stuck in young adults."},{"from":"fpies","to":"s_gut","level":"established","effect":"affects","note":"Inflammation of the gut causes repeated vomiting and sometimes diarrhoea."},{"from":"s_meningeal_lymph","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: drains brain fluid to the deep neck lymph nodes."},{"from":"s_glymphatic","to":"s_meningeal_lymph","level":"established","effect":"located","note":"Fluid from the brain's glymphatic flow drains out partly through the meningeal lymph vessels."},{"from":"s_glymphatic","to":"s_cortex","level":"established","effect":"located","note":"Runs through the whole brain along its blood vessels."},{"from":"insomnia","to":"s_glymphatic","level":"association","effect":"harms","note":"In small human studies a night without sleep slowed the brain's clearance of a test dye and raised amyloid levels, but mouse studies disagree on whether sleep speeds clearance.","sources":[{"id":"pmid:33829232","citation":"Eide PK et al., Brain","year":2021,"design":"case-control","finding":"In 7 people kept awake one night versus 17 who slept, an MRI tracer injected into spinal fluid cleared more slowly from most brain regions, and the next night's sleep did not make up for it."},{"id":"pmid:29632177","citation":"Shokri-Kojori E et al., PNAS","year":2018,"design":"cohort","finding":"In 20 healthy adults scanned with amyloid PET, one night without sleep raised β-amyloid signal in the right hippocampus and thalamus compared with a rested night."},{"id":"pmid:24136970","citation":"Xie L et al., Science","year":2013,"design":"lab","finding":"In live mice, natural sleep enlarged the space between brain cells by about 60% and sped up the clearance of β-amyloid by cerebrospinal fluid flow."},{"id":"pmid:38741022","citation":"Miao A et al., Nat Neurosci","year":2024,"design":"lab","finding":"In male mice, a different measuring method found brain clearance of tracer molecules was reduced, not increased, during sleep and anaesthesia."}]},{"from":"s_glymphatic","to":"alzheimers","level":"lab","effect":"helps","note":"In mice this fluid flow carries amyloid out of the brain; whether better clearance lowers Alzheimer's risk in people is unknown.","sources":[{"id":"pmid:22896675","citation":"Iliff JJ et al., Sci Transl Med","year":2012,"design":"lab","finding":"In mice, cerebrospinal fluid flows into the brain along the spaces around arteries and out along veins, carrying away dissolved waste including amyloid β; this flow depends on the water channel aquaporin-4."},{"id":"pmid:24136970","citation":"Xie L et al., Science","year":2013,"design":"lab","finding":"In live mice, natural sleep enlarged the space between brain cells by about 60% and sped up the clearance of β-amyloid by cerebrospinal fluid flow."}]},{"from":"s_meningeal_lymph","to":"alzheimers","level":"lab","effect":"helps","note":"In Alzheimer's model mice, damaging these drains let more amyloid build up; not tested in people.","sources":[{"id":"pmid:30046111","citation":"Da Mesquita S et al., Nature","year":2018,"design":"lab","finding":"In mice, meningeal lymph vessels drain brain fluid to neck lymph nodes; damaging them impaired memory and increased amyloid-β build-up in Alzheimer's model mice."}]},{"from":"s_meningeal_lymph","to":"parkinsons","level":"lab","effect":"helps","note":"In mice, blocking these drains let more α-synuclein build up; people with Parkinson's show slower drainage on MRI, but whether this matters is unknown.","sources":[{"id":"pmid:30867902","citation":"Zou W et al., Transl Neurodegener","year":2019,"design":"lab","finding":"In mice making a mutant human α-synuclein, tying off the deep neck lymph nodes (blocking meningeal lymph drainage) increased α-synuclein build-up, dopamine-cell loss and movement problems."},{"id":"pmid:33462448","citation":"Ding XB et al., Nat Med","year":2021,"design":"case-control","finding":"On contrast MRI, people with Parkinson's had slower flow in meningeal lymph vessels and delayed drainage to neck lymph nodes than people with atypical parkinsonism; in mice, blocking this flow increased α-synuclein pathology."}]},{"from":"s_lymph_neck","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: filters lymph from the head and neck."},{"from":"s_lymph_armpit","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: filters lymph from the arm and breast."},{"from":"s_lymph_groin","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: filters lymph from the leg."},{"from":"s_lymph_gut","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: the gut's own lymph nodes and patches."},{"from":"s_lymph_gut","to":"s_immune","level":"established","effect":"located","note":"Part of the immune system: the gut wall holds most of the body's immune cells."},{"from":"s_lymph_gut","to":"s_small_intestine","level":"established","effect":"located","note":"Peyer's patches sit in the wall of the small intestine."},{"from":"s_thoracic_duct","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: returns lymph to the blood."},{"from":"s_lymph_vessels","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: the vessels that carry lymph to the nodes."},{"from":"exercise","to":"s_lymph_vessels","level":"established","effect":"helps","note":"Working muscles squeeze lymph vessels and deeper breathing draws lymph up the thoracic duct, so moving keeps lymph flowing."},{"from":"inactivity","to":"s_lymph_vessels","level":"established","effect":"harms","note":"Without the muscle pump, lymph and fluid drain more slowly, so legs swell after long sitting or bed rest."},{"from":"s_muscle","to":"s_lymph_vessels","level":"established","effect":"helps","note":"Muscle contractions act as a pump that pushes lymph through its one-way valves."},{"from":"s_lungs","to":"s_thoracic_duct","level":"established","effect":"helps","note":"Each breath in lowers chest pressure, which helps pull lymph up the thoracic duct."},{"from":"lymphoedema","to":"s_lymph","level":"established","effect":"located","note":"Arises when lymph vessels or nodes can't drain fluid away, often after nodes are removed or irradiated in cancer treatment."},{"from":"lymphoedema","to":"s_skin","level":"established","effect":"located","note":"Fluid collects under the skin, which can thicken and get infected."},{"from":"exercise","to":"lymphoedema","level":"mixed","effect":"helps","note":"Exercise, even weight lifting, doesn't worsen lymphoedema and eases symptoms in trials; whether it prevents it is uncertain, as reviews disagree.","sources":[{"id":"pmid:19675330","citation":"Schmitz KH et al., N Engl J Med","year":2009,"design":"RCT","finding":"In 141 breast-cancer survivors with arm lymphoedema, a year of slowly progressive weight lifting (with a compression sleeve) did not increase swelling and improved symptoms and strength."},{"id":"pmid:35320145","citation":"Hayes SC et al., Med Sci Sports Exerc","year":2022,"design":"meta-analysis","finding":"Across 12 prevention and 36 treatment studies, exercise did not worsen cancer-related lymphoedema, did not clearly change its overall risk (RR 0.90, not significant; 0.49 when 5+ nodes removed), and improved pain, strength, fatigue and quality of life."},{"id":"pmid:41783998","citation":"Plinsinga ML et al., JNCI Cancer Spectr","year":2026,"design":"meta-analysis","finding":"Across 17 studies (2,739 people, mostly after breast cancer), exercise was linked with fewer people developing lymphoedema (RR 0.71), with low overall certainty."}]},{"from":"s_tonsils","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: lymph tissue guarding the throat."},{"from":"s_tonsils","to":"s_immune","level":"established","effect":"located","note":"Part of the immune system: first check of germs breathed in or swallowed."},{"from":"s_tonsils","to":"s_throat","level":"established","effect":"located","note":"Sits in the throat, at the back of the mouth and nose."},{"from":"s_thymus","to":"s_immune","level":"established","effect":"located","note":"Part of the immune system: where T cells mature."},{"from":"s_thymus","to":"s_lymph","level":"established","effect":"located","note":"A lymphoid organ of the lymphatic system."},{"from":"s_spleen","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: filters the blood rather than lymph."},{"from":"s_spleen","to":"s_immune","level":"established","effect":"located","note":"Part of the immune system: fights germs carried in the blood."},{"from":"swollen_nodes","to":"s_lymph","level":"established","effect":"located","note":"Arises in the lymph nodes."},{"from":"ebv","to":"swollen_nodes","level":"established","effect":"harms","note":"Glandular fever typically causes swollen, tender lymph nodes, especially in the neck."},{"from":"ebv","to":"s_tonsils","level":"established","effect":"harms","note":"The virus enters through the throat and infects immune cells in the tonsils, causing a very sore throat."},{"from":"ebv","to":"s_spleen","level":"established","effect":"harms","note":"Glandular fever often enlarges the spleen, which can rarely tear after a knock."},{"from":"nausea","to":"s_brainstem","level":"established","effect":"located","note":"The vomiting centre and its trigger zone sit in the brainstem."},{"from":"nausea","to":"s_stomach","level":"established","effect":"located","note":"Felt as sickness in the stomach, which empties backwards when vomiting."},{"from":"levodopa","to":"nausea","level":"established","effect":"harms","note":"Dopamine made from levodopa in the blood stimulates the brainstem trigger zone, so nausea is a common side effect, especially early on."},{"from":"stomach","to":"nausea","level":"established","effect":"harms","note":"A stomach that empties slowly leaves people feeling full and sick."},{"from":"gingerols","to":"nausea","level":"mixed","effect":"helps","note":"Ginger may ease pregnancy nausea, but Cochrane found the trial results limited and inconsistent.","sources":[{"id":"pmid:26348534","citation":"Matthews A et al., Cochrane Database Syst Rev","year":2015,"design":"meta-analysis","finding":"For nausea in early pregnancy, evidence for P6 acupressure, ear acupressure and P6 acustimulation was limited, and ginger's benefit was limited and inconsistent."}]},{"from":"pp_p6","to":"nausea","level":"proven","effect":"helps","note":"Pressing the inner-wrist point reduced nausea and vomiting after surgery versus sham in many trials (low certainty); evidence in pregnancy and chemotherapy is weaker.","sources":[{"id":"pmid:26522652","citation":"Lee A et al., Cochrane Database Syst Rev","year":2015,"design":"meta-analysis","finding":"In 59 trials (7667 people), wrist PC6 stimulation cut nausea after surgery versus sham (RR 0.68) and vomiting (RR 0.60), with low-quality evidence and no clear difference from anti-sickness drugs."},{"id":"pmid:40938065","citation":"Lee A et al., Cochrane Database Syst Rev","year":2025,"design":"meta-analysis","finding":"Network meta-analysis of 77 trials (9847 people): non-invasive PC6 stimulation such as wristbands may reduce postoperative nausea versus sham (RR 0.67, low confidence); side effects were minor."},{"id":"pmid:26348534","citation":"Matthews A et al., Cochrane Database Syst Rev","year":2015,"design":"meta-analysis","finding":"For nausea in early pregnancy, evidence for P6 acupressure, ear acupressure and P6 acustimulation was limited, and ginger's benefit was limited and inconsistent."},{"id":"pmid:16625560","citation":"Ezzo JM et al., Cochrane Database Syst Rev","year":2006,"design":"meta-analysis","finding":"In chemotherapy, acupressure slightly reduced acute nausea severity (SMD -0.19) but not vomiting or delayed symptoms, on top of standard anti-sickness drugs."}]},{"from":"h_acupressure","to":"anxiety","level":"mixed","effect":"helps","note":"Trials report less anxiety, especially before surgery, but studies vary hugely and most can't be fully blinded.","sources":[{"id":"pmid:35085025","citation":"Chen SR et al., J Integr Complement Med","year":2022,"design":"meta-analysis","finding":"27 trials found acupressure reduced anxiety, but heterogeneity was very high (I2 about 91%), so the authors urged caution."},{"id":"pmid:37321140","citation":"Xie W et al., Int J Nurs Stud","year":2023,"design":"meta-analysis","finding":"24 trials (2537 adults) found acupressure lowered anxiety before planned surgery versus usual care or placebo, with high heterogeneity (I2 86%)."},{"id":"pmid:26177378","citation":"Tan JY et al., PLoS One","year":2015,"design":"review","finding":"Across 66 sham-controlled acupressure trials, true pressure usually beat sham, but sham methods varied so much that no firm conclusion about which sham is adequate was possible."}]},{"from":"h_acupressure","to":"insomnia","level":"mixed","effect":"helps","note":"Hospital trials report better sleep, and a self-pressure course beat sleep-hygiene advice, but few trials compared it with sham pressure.","sources":[{"id":"pmid:40049603","citation":"Ling W et al., Nurs Health Sci","year":2025,"design":"meta-analysis","finding":"41 trials (3680 inpatients) found acupressure improved sleep quality versus control groups."},{"id":"pmid:35193046","citation":"Yeung WF et al., Phytomedicine","year":2022,"design":"RCT","finding":"In 200 people with insomnia disorder, self-acupressure taught in a short course improved insomnia severity more than sleep-hygiene education at week 4 (moderate effect, no sham arm)."}]},{"from":"h_acupressure","to":"fatigue","level":"mixed","effect":"helps","note":"Daily self-pressure reduced lasting fatigue in breast cancer survivors versus usual care, but there was no sham group.","sources":[{"id":"pmid:27388752","citation":"Zick SM et al., JAMA Oncol","year":2016,"design":"RCT","finding":"In 270 breast cancer survivors, two kinds of self-acupressure both reduced persistent fatigue versus usual care (no sham arm); only the relaxing set improved sleep."}]},{"from":"pp_gb20","to":"headache","level":"mixed","effect":"helps","note":"A small unblinded trial of pressure here helped chronic headache; for needles, sham needling did nearly as well as real.","sources":[{"id":"pmid:20128040","citation":"Hsieh LL et al., Am J Chin Med","year":2010,"design":"RCT","finding":"In 28 people with chronic headache, a month of acupressure (points including GB20) lowered pain more than a muscle relaxant, with no sham control."},{"id":"pmid:27092807","citation":"Linde K et al., Cochrane Database Syst Rev","year":2016,"design":"meta-analysis","finding":"For tension-type headache, needle acupuncture at least halved headache frequency in 51% of people versus 43% with sham needling (RR 1.3), a small edge over sham; trials versus usual care could not be blinded."}]},{"from":"pp_yintang","to":"anxiety","level":"mixed","effect":"helps","note":"Small trials before surgery found pressing between the eyebrows lowered anxiety, but they are few and small.","sources":[{"id":"pmid:29682147","citation":"Kwon CY & Lee B, Med Acupunct","year":2018,"design":"review","finding":"Five small randomised trials, mostly before surgery, found pressing or needling Yintang alone consistently lowered self-reported anxiety; the authors called for more rigorous trials."},{"id":"pmid:23270318","citation":"Acar HV et al., J Altern Complement Med","year":2013,"design":"RCT","finding":"In 52 surgical patients, a press needle at Yintang lowered state anxiety while a sham point did not."}]},{"from":"pp_ht7","to":"insomnia","level":"mixed","effect":"helps","note":"Pressing the wrist-crease point (with SP6) gave a small, not clearly significant sleep improvement versus sham.","sources":[{"id":"pmid:41709613","citation":"Cam Yanik T & Ugras GA, Florence Nightingale J Nurs","year":2025,"design":"RCT","finding":"In 60 surgical nurses, self-pressure on HT7 and SP6 for 4 weeks gave better sleep-quality scores than sham points, but the authors concluded the improvement was not significant overall."}]},{"from":"pp_ear_shenmen","to":"insomnia","level":"mixed","effect":"helps","note":"Ear-seed trials report better sleep, but they are biased and very inconsistent.","sources":[{"id":"pmid:41424527","citation":"Jun L et al., Front Sleep","year":2024,"design":"meta-analysis","finding":"23 trials (1689 people) found ear acupressure improved sleep-quality scores, with very high heterogeneity (I2 90%)."}]},{"from":"pp_ear_shenmen","to":"anxiety","level":"mixed","effect":"helps","note":"Ear pressure lowered anxiety in trials, but less so when compared with sham pressure.","sources":[{"id":"pmid:38417402","citation":"Hu N et al., Complement Med Res","year":2024,"design":"meta-analysis","finding":"25 trials found ear acupressure reduced anxiety, but 23 had some bias, and effects were larger in trials that avoided a sham control, hinting at a placebo effect of sham pressure."}]},{"from":"pp_li4","to":"pain","level":"mixed","effect":"helps","note":"Pressing the hand web lowered labour pain scores in small, poorly blinded trials; no good evidence for headache.","sources":[{"id":"pmid:42208134","citation":"Deniz D et al., Explore (NY)","year":2026,"design":"meta-analysis","finding":"Nine studies (including non-randomised ones) found LI4 acupressure reduced labour pain scores (mean difference about -2.2 points)."},{"id":"pmid:32811182","citation":"Chen Y et al., Acupunct Med","year":2021,"design":"meta-analysis","finding":"13 trials (1586 women) found acupressure added to standard care reduced labour pain compared with sham or standard care alone; the authors called the evidence moderate and asked for better trials."}]},{"from":"pp_st36","to":"m_inflam","level":"lab","effect":"helps","note":"In mice, electrical stimulation at this leg point triggered a nerve reflex that calmed body-wide inflammation; not shown for finger pressure in people.","sources":[{"id":"pmid:34646018","citation":"Liu S et al., Nature","year":2021,"design":"lab","finding":"In mice, low-intensity electrical stimulation at the ST36 site (but not an abdominal site) activated a vagus-to-adrenal reflex through specific deep sensory nerves and damped body-wide inflammation."},{"id":"pmid:39951921","citation":"Watanabe H et al., J Physiol Sci","year":2025,"design":"lab","finding":"In a 12-volunteer laboratory experiment, five minutes of pressure on ST36 did no better than sham pressure at changing heart rhythm or skin blood flow during a cold-water test."}]},{"from":"bp_shoulders","to":"s_peripheral","level":"established","effect":"located","note":"The nerves and vessels to the arm pass through the thoracic outlet above the shoulder, under the collarbone."},{"from":"bp_knees","to":"s_peripheral","level":"established","effect":"located","note":"The fibular (peroneal) nerve wraps around the bone just below the outer knee, close under the skin."},{"from":"bp_ankles_feet","to":"s_peripheral","level":"established","effect":"located","note":"The tibial nerve runs through the tarsal tunnel behind the inner ankle bone."},{"from":"dairy","to":"al_milk","level":"established","effect":"contains","note":"Milk, yoghurt and cheese contain the milk allergen proteins casein and whey."},{"from":"eggs","to":"al_egg","level":"established","effect":"contains","note":"Egg white holds most of the egg allergen proteins."},{"from":"oats","to":"al_wheat","level":"established","effect":"contains","note":"Whole-wheat foods in this group contain wheat proteins; oats themselves are not wheat."},{"from":"soy","to":"al_soy","level":"established","effect":"contains","note":"Tofu, tempeh, edamame and soy milk contain soy proteins."},{"from":"whitefish","to":"al_fish","level":"established","effect":"contains","note":"White fish contain parvalbumin, the main fish allergen."},{"from":"oilyfish","to":"al_fish","level":"established","effect":"contains","note":"Oily fish contain parvalbumin, the main fish allergen (often less than white fish)."},{"from":"shellfish","to":"al_shellfish","level":"established","effect":"contains","note":"Shrimp and other shellfish contain tropomyosin, the main shellfish allergen."},{"from":"al_milk","to":"food_allergy","level":"established","effect":"harms","note":"The most common food allergy in babies; usually outgrown."},{"from":"al_egg","to":"food_allergy","level":"established","effect":"harms","note":"A common food allergy in young children, especially with eczema; usually outgrown."},{"from":"al_wheat","to":"food_allergy","level":"established","effect":"harms","note":"Causes immediate allergic reactions; this is different from coeliac disease."},{"from":"al_soy","to":"food_allergy","level":"established","effect":"harms","note":"A usually mild childhood food allergy that is often outgrown."},{"from":"al_fish","to":"food_allergy","level":"established","effect":"harms","note":"A usually lifelong food allergy, often to several kinds of fish."},{"from":"al_shellfish","to":"food_allergy","level":"established","effect":"harms","note":"One of the most common food allergies in adults."},{"from":"eggs","to":"m_allergy","level":"mixed","effect":"helps","note":"Giving babies cooked egg from 4 to 6 months may lower egg allergy: pooled trials suggest so, but the largest trial missed its main goal.","scope":["food_allergy"],"sources":[{"id":"pmid:26943128","citation":"Perkin MR et al., N Engl J Med (EAT)","year":2016,"design":"RCT","finding":"Early introduction of six allergenic foods from 3 months did not significantly reduce food allergy by intention to treat (5.6% vs 7.1%), though egg allergy was lower among infants who followed the protocol."},{"id":"pmid:27654604","citation":"Ierodiakonou D et al., JAMA","year":2016,"design":"meta-analysis","finding":"Five trials gave moderate-certainty evidence that egg introduction at 4-6 months reduces egg allergy (RR 0.56)."}]},{"from":"m_allergy","to":"atopic_eczema","level":"established","effect":"helps","note":"Eczema is partly a weak skin barrier and partly an allergic-type immune reaction in the skin."},{"from":"m_allergy","to":"urticaria","level":"established","effect":"helps","note":"Hives come from skin mast cells releasing histamine, whether the trigger is an allergy or not."},{"from":"urticaria","to":"hives","level":"established","effect":"harms","note":"Hives are the defining sign."},{"from":"urticaria","to":"angioedema","level":"established","effect":"harms","note":"Deeper swelling occurs with hives in many people."},{"from":"urticaria","to":"s_skin","level":"established","effect":"affects","note":"Mast cells in the skin release histamine."},{"from":"atopic_eczema","to":"s_skin","level":"established","effect":"affects","note":"A leaky, inflamed skin barrier."},{"from":"atopic_eczema","to":"bp_skin","level":"established","effect":"affects","note":"A skin condition."},{"from":"atopic_eczema","to":"contact_dermatitis","level":"association","effect":"harms","note":"People with atopic eczema are about four times as likely to get hand eczema, including at work.","sources":[{"id":"pmid:29172235","citation":"Ruff SMD et al., Br J Dermatol","year":2018,"design":"meta-analysis","finding":"Atopic dermatitis was associated with higher point, 1-year and lifetime prevalence of hand eczema (ORs about 2.4 to 4.3), including occupational hand eczema."}]},{"from":"atopic_eczema","to":"food_allergy","level":"association","effect":"harms","note":"Babies with eczema, especially severe early eczema, are much more likely to develop food allergy, possibly because food proteins enter through broken skin.","sources":[{"id":"pmid:26897122","citation":"Tsakok T et al., J Allergy Clin Immunol","year":2016,"design":"review","finding":"Systematic review of 66 studies found a strong, dose-dependent association between atopic dermatitis and food allergy, with eczema usually preceding food sensitisation."}]},{"from":"probiotics","to":"atopic_eczema","level":"mixed","effect":"helps","note":"Probiotics taken by mothers in pregnancy or by babies were linked with less infant eczema in pooled trials, but strains and results vary and asthma was not prevented.","sources":[{"id":"pmid:34006167","citation":"Sun S et al., J Dermatolog Treat","year":2022,"design":"meta-analysis","finding":"In 21 studies probiotics lowered the risk of eczema in children, especially combinations and maternal intake, with no effect on asthma, rhinitis or wheeze."}]},{"from":"al_nickel","to":"contact_dermatitis","level":"established","effect":"harms","note":"The commonest cause of allergic contact dermatitis; a delayed T-cell reaction where metal touches skin."},{"from":"al_latex","to":"occ_asthma","level":"established","effect":"harms","note":"Breathing latex proteins from powdered gloves caused occupational asthma in health workers.","sources":[{"id":"pmid:16469822","citation":"LaMontagne AD et al., Occup Environ Med","year":2006,"design":"review","finding":"Substituting powdered latex gloves with low-protein powder-free or latex-free gloves greatly reduced latex aeroallergens, sensitisation and latex asthma in health workers."}]},{"from":"al_latex","to":"contact_dermatitis","level":"established","effect":"harms","note":"Chemicals added to rubber gloves are a common cause of allergic hand dermatitis."},{"from":"al_latex","to":"anaphylaxis","level":"established","effect":"harms","note":"Latex is a known cause of anaphylaxis, including during surgery."},{"from":"al_latex","to":"urticaria","level":"established","effect":"harms","note":"Touching latex can bring out hives at the contact site in allergic people."},{"from":"peanuts","to":"al_peanut","level":"established","effect":"contains","note":"Peanuts and peanut butter contain the peanut allergen proteins."},{"from":"nuts","to":"al_tree_nuts","level":"established","effect":"contains","note":"Walnuts and other tree nuts contain tree nut allergens; flax and pumpkin seeds in this group are not tree nuts."},{"from":"al_peanut","to":"food_allergy","level":"established","effect":"harms","note":"One of the most common and most dangerous food allergies; it usually lasts for life."},{"from":"al_tree_nuts","to":"food_allergy","level":"established","effect":"harms","note":"A common lifelong food allergy that can cause anaphylaxis."},{"from":"al_sesame","to":"food_allergy","level":"established","effect":"harms","note":"A major food allergy, often hidden in hummus, tahini and baked goods."},{"from":"peanuts","to":"m_allergy","level":"proven","effect":"helps","note":"Babies at high risk who ate peanut foods regularly from 4 to 11 months old were far less likely to be peanut-allergic at age 5 than those who avoided peanut; whole nuts are a choking risk for young children.","scope":["food_allergy"],"sources":[{"id":"pmid:25705822","citation":"Du Toit G et al., N Engl J Med","year":2015,"design":"RCT","finding":"In 640 high-risk infants, peanut allergy at 60 months was 1.9% with early consumption vs 13.7% with avoidance in skin-test-negative infants."},{"id":"pmid:27654604","citation":"Ierodiakonou D et al., JAMA","year":2016,"design":"meta-analysis","finding":"Moderate-certainty evidence that peanut introduction at 4-11 months and egg introduction at 4-6 months reduce peanut and egg allergy."}]},{"from":"al_pollen","to":"allergic_rhinitis","level":"established","effect":"harms","note":"Pollen is the cause of seasonal hay fever."},{"from":"al_pollen","to":"food_allergy","level":"established","effect":"harms","note":"Pollen allergy can cause an itchy mouth from raw apple, cherry, kiwi, carrot, celery or hazelnut (pollen-food syndrome); cooked versions are usually fine.","sources":[{"id":"pmid:39278756","citation":"Kato Y et al., Allergol Int","year":2025,"design":"review","finding":"Pollen-food allergy syndrome arises when IgE to pollen cross-reacts with similar proteins in foods, usually giving mouth symptoms and occasionally anaphylaxis."}]},{"from":"al_dust_mite","to":"allergic_rhinitis","level":"established","effect":"harms","note":"The most common cause of year-round allergic rhinitis."},{"from":"al_dust_mite","to":"allergic_asthma","level":"established","effect":"harms","note":"A leading trigger of allergic asthma worldwide."},{"from":"al_pet_dander","to":"allergic_rhinitis","level":"established","effect":"harms","note":"Causes sneezing and itchy eyes around animals, and in homes where they have been."},{"from":"al_mould","to":"allergic_asthma","level":"established","effect":"harms","note":"Mould allergy, especially to Alternaria, is linked with severe asthma attacks."},{"from":"al_cockroach","to":"allergic_asthma","level":"established","effect":"harms","note":"A major asthma trigger in children living in crowded city housing."},{"from":"m_allergy","to":"allergic_rhinitis","level":"established","effect":"helps","note":"Hay fever is the allergy brake failing for breathed-in proteins in the nose."},{"from":"m_allergy","to":"allergic_asthma","level":"established","effect":"helps","note":"Allergic asthma is the allergy brake failing for breathed-in proteins in the airways."},{"from":"allergic_rhinitis","to":"itchy_nose_eyes","level":"established","effect":"harms","note":"Sneezing, runny nose and itchy eyes are the core symptoms."},{"from":"allergic_rhinitis","to":"s_lungs","level":"established","effect":"affects","note":"Inflames the lining of the nose, the start of the airway."},{"from":"allergic_rhinitis","to":"allergic_asthma","level":"association","effect":"harms","note":"Adults with allergic hay fever were more likely to develop asthma over the next nine years.","sources":[{"id":"pmid:18805333","citation":"Shaaban R et al., Lancet","year":2008,"design":"cohort","finding":"In 6461 adults followed for 8.8 years, allergic and non-allergic rhinitis both raised the risk of new asthma, independent of atopy."}]},{"from":"allergic_asthma","to":"wheeze","level":"established","effect":"harms","note":"Narrowed airways cause wheeze."},{"from":"allergic_asthma","to":"breathless","level":"established","effect":"harms","note":"Airway narrowing during attacks makes it hard to breathe."},{"from":"allergic_asthma","to":"s_lungs","level":"established","effect":"affects","note":"Inflamed, twitchy airways that narrow with triggers."},{"from":"allergic_asthma","to":"bp_lungs","level":"established","effect":"affects","note":"A lung disease of the airways."},{"from":"al_venom","to":"anaphylaxis","level":"established","effect":"harms","note":"Insect stings are a leading cause of anaphylaxis in adults."},{"from":"al_penicillin","to":"anaphylaxis","level":"established","effect":"harms","note":"Penicillins are among the medicines that can, rarely, cause anaphylaxis.","sources":[{"id":"pmid:30644987","citation":"Shenoy ES et al., JAMA","year":2019,"design":"review","finding":"About 10% of the US population report penicillin allergy, but clinically significant IgE- or T-cell-mediated penicillin hypersensitivity is uncommon."}]},{"from":"al_other_drugs","to":"anaphylaxis","level":"established","effect":"harms","note":"Medicines are a leading cause of anaphylaxis in adults and during surgery."},{"from":"redmeat","to":"al_alpha_gal","level":"established","effect":"contains","note":"Beef, lamb and pork contain the alpha-gal sugar; chicken, turkey and fish do not."},{"from":"al_alpha_gal","to":"food_allergy","level":"established","effect":"harms","note":"A red-meat allergy that usually starts in adults who have had tick bites.","sources":[{"id":"pmid:21453959","citation":"Commins SP et al., J Allergy Clin Immunol","year":2011,"design":"cohort","finding":"IgE antibodies to alpha-gal rose 20-fold or more after tick bites and correlated strongly with tick-bite history."}]},{"from":"al_alpha_gal","to":"anaphylaxis","level":"association","effect":"harms","note":"Can cause anaphylaxis 3 to 6 hours after eating red meat, which makes the cause easy to miss.","sources":[{"id":"pmid:19070355","citation":"Commins SP et al., J Allergy Clin Immunol","year":2009,"design":"cohort","finding":"24 patients with IgE to alpha-gal reported anaphylaxis or hives 3-6 hours after eating beef, pork or lamb, with fewer episodes on avoidance."}]},{"from":"al_other_drugs","to":"urticaria","level":"established","effect":"harms","note":"Aspirin and anti-inflammatory painkillers can bring on or worsen hives without being a true allergy."},{"from":"atopic_eczema","to":"allergic_asthma","level":"association","effect":"harms","note":"Children with eczema, especially severe or long-lasting eczema, are about twice as likely to develop asthma later (the 'atopic march').","sources":[{"id":"pmid:34384834","citation":"Li H et al., J Am Acad Dermatol","year":2022,"design":"meta-analysis","finding":"Across 39 studies, atopic dermatitis carried a pooled RR of 2.16 for later asthma, higher for persistent (3.36) and severe disease."},{"id":"pmid:25335105","citation":"Belgrave DC et al., PLoS Med","year":2014,"design":"cohort","finding":"Eczema, wheeze and rhinitis develop in several different patterns; only a small minority of children follow the classic eczema-then-asthma-then-rhinitis sequence."}]},{"from":"vitd","to":"food_allergy","level":"association","effect":"helps","note":"Babies with low vitamin D were more likely to have peanut or egg allergy in one large Australian study; supplements have not been shown to prevent it.","sources":[{"id":"pmid:23453797","citation":"Allen KJ et al., J Allergy Clin Immunol","year":2013,"design":"cohort","finding":"Among infants of Australian-born parents, vitamin D insufficiency was associated with challenge-proven peanut and egg allergy."}]},{"from":"m_micro","to":"m_allergy","level":"lab","effect":"helps","note":"Gut bacteria from healthy babies, including a butyrate maker, protected mice from milk allergy; this has not been shown in people.","sources":[{"id":"pmid:30643289","citation":"Feehley T et al., Nat Med","year":2019,"design":"lab","finding":"Germ-free mice colonised with faeces from healthy but not cow's-milk-allergic infants were protected from anaphylaxis to milk; Anaerostipes caccae was protective."}]},{"from":"hookworm","to":"allergic_asthma","level":"failed","effect":"helps","note":"People with natural hookworm infection have less asthma in population studies, but deliberate hookworm infection did not improve asthma in a small placebo-controlled trial.","sources":[{"id":"pmid:20030661","citation":"Feary JR et al., Clin Exp Allergy","year":2010,"design":"RCT","finding":"Ten hookworm larvae vs placebo in 32 people with allergic asthma gave no significant improvement in airway responsiveness, asthma control or skin sensitisation."},{"id":"pmid:16778161","citation":"Leonardi-Bee et al., Am J Respir Crit Care Med","year":2006,"design":"meta-analysis","finding":"Across 9 studies, current hookworm infection was linked with roughly half the odds of asthma, more so with heavier infection; parasites in general were not protective."}]},{"from":"curcumin","to":"movement","level":"failed","effect":"helps","note":"In a small 9-month trial in people with Parkinson's, curcumin added to usual medicines did not improve movement scores or quality of life compared with placebo.","scope":["parkinsons"],"sources":[{"id":"pmid:35636380","citation":"Ghodsi H et al., Clinical Neurology and Neurosurgery","year":2022,"design":"RCT","finding":"In 60 people with Parkinson's, nanomicelle curcumin for 9 months did not differ from placebo on MDS-UPDRS or PDQ-39 at any time point; the authors judged the trial unsuccessful."}]},{"from":"black_seed","to":"m_micro","level":"lab","effect":"helps","note":"In human stool samples grown in the lab, black-seed extract raised the bacteria's output of butyrate and other short-chain fatty acids, while turmeric did little; not yet tested by eating it.","sources":[{"id":"pmid:41343511","citation":"Mahalak KK et al., PLoS One","year":2025,"design":"lab","finding":"In ex vivo human gut microbiota cultures, black cumin seed extract raised acetate, propionate and butyrate, while turmeric and cinnamon extracts had little overall effect."}]},{"from":"turmeric","to":"s_liver","level":"association","effect":"harms","note":"Rarely, turmeric supplements have caused serious liver inflammation, usually after 1 to 4 months and mostly in people with one inherited immune type; some products also contained black pepper extract, and the spice in food has not been implicated.","dose":"excess","sources":[{"id":"pmid:36252717","citation":"Halegoua-DeMarzio D et al., American Journal of Medicine","year":2023,"design":"review","finding":"Ten turmeric-associated liver injury cases in the US Drug-Induced Liver Injury Network: mostly hepatocellular, latency 1-4 months, one death, 7 of 10 carried HLA-B*35:01, and 3 of 7 tested products also contained piperine."},{"id":"pmid:42364655","citation":"Akhtar N et al., Pharmaceutical Biology","year":2026,"design":"review","finding":"A USP expert review found liver injury with turmeric/curcuminoid supplements is very rare, often involves other products, usually resolves on stopping, and recommended a cautionary label."},{"id":"pmid:39995754","citation":"Shrestha A et al., Case Reports in Gastroenterology","year":2025,"design":"review","finding":"Case report and review of significant drug-induced liver injury after turmeric and black pepper 'wellness shots', discussing formulations with enhanced absorption."}]},{"from":"black_seed","to":"contact_dermatitis","level":"association","effect":"harms","note":"Black-seed oil rubbed on the skin has caused severe allergic rashes in a published series of patients.","sources":[{"id":"pmid:39759250","citation":"Zhivov E et al., Journal of Clinical and Aesthetic Dermatology","year":2024,"design":"review","finding":"A case series of eight patients with severe skin reactions after applying Nigella sativa oil to the skin, stressing patch testing and asking about herbal use."}]},{"from":"black_seed","to":"s_blood","level":"proven","effect":"helps","note":"Black-seed capsules or oil lowered blood pressure a little and improved cholesterol in pooled trials; taking turmeric with it has not clearly done more than black seed alone, and in people who get dizzy on standing extra lowering is untested.","sources":[{"id":"pmid:35975622","citation":"Golpour-Hamedani S et al., Critical Reviews in Food Science and Nutrition","year":2024,"design":"meta-analysis","finding":"Across 17 randomised trials (1048 people), nigella supplementation lowered systolic blood pressure by about 4.6 mmHg and diastolic by about 3.1 mmHg."},{"id":"pmid:38777430","citation":"Rounagh M et al., Clinical Nutrition ESPEN","year":2024,"design":"meta-analysis","finding":"Across 34 randomised trials (2278 adults), Nigella sativa lowered total cholesterol, LDL cholesterol and triglycerides and raised HDL cholesterol."},{"id":"pmid:25847554","citation":"Amin F et al., Complementary Therapies in Medicine","year":2015,"design":"RCT","finding":"In 250 men with metabolic syndrome over 8 weeks, black seed alone lowered lipids and fasting sugar and turmeric alone lowered LDL and CRP versus placebo; the pair at about 60% of each dose improved more measures (body fat, sugar, lipids, CRP) versus placebo."},{"id":"pmid:38020740","citation":"Sadeghzadeh Z et al., Journal of Caring Sciences","year":2023,"design":"RCT","finding":"In a 4-arm trial of 120 postmenopausal women over 6 months (black seed, nanomicelle curcumin, both, or placebo), each improved some lipid and blood-sugar measures, but the combination was not better than either alone."}]},{"from":"black_seed","to":"m_inflam","level":"proven","effect":"helps","note":"Black-seed powder or oil lowered blood markers of inflammation (CRP, IL-6) in a meta-analysis of many small trials; which compound does it, and any effect on brain inflammation, are untested.","sources":[{"id":"pmid:40714301","citation":"Jafari A et al., Pharmacological Research","year":2025,"design":"meta-analysis","finding":"Across 82 randomised trials (5026 people), Nigella sativa seed or oil lowered blood CRP, IL-6 and TNF-alpha along with blood pressure, sugar and cholesterol."}]},{"from":"toxocara","to":"cognition","level":"association","effect":"harms","note":"Some large population studies link past Toxocara infection with slightly worse scores on certain thinking tests, but not all studies agree.","sources":[{"id":"pmid:26374832","citation":"Erickson et al., Folia Parasitol","year":2015,"design":"cohort","finding":"In over 4,000 US adults aged 21 to 59 (NHANES), Toxocara antibodies predicted worse symbol-digit substitution scores after adjusting for education, poverty and blood lead, but not other tests."},{"id":"pmid:36849240","citation":"Kruszon-Moran et al., J Epidemiol Community Health","year":2023,"design":"cohort","finding":"In US adults over 60 (NHANES 2011-2014), Toxocara seropositivity was linked with lower processing-speed scores, mainly in certain subgroups, after adjustment."},{"id":"pmid:42734739","citation":"Rostami et al., Infection","year":2026,"design":"cohort","finding":"In about 1,450 older adults in northern Iran, Toxocara seropositivity was not significantly associated with cognitive impairment on the MMSE."}]},{"from":"toxocara","to":"allergic_asthma","level":"association","effect":"harms","note":"Children with asthma more often carry antibodies to Toxocara, whose larvae pass through the lungs; whether it causes asthma is not proven.","sources":[{"id":"pmid:42175712","citation":"Singh et al., Trans R Soc Trop Med Hyg","year":2026,"design":"meta-analysis","finding":"Across 23 case-control studies, asthmatic children had higher odds of Toxocara seropositivity (pooled OR about 2.6), with marked heterogeneity and possible test cross-reactivity."}]},{"from":"toxocara","to":"s_eyes","level":"established","effect":"harms","note":"A single larva reaching the eye can inflame the retina and damage sight, usually in one eye of a child (ocular toxocariasis).","sources":[{"id":"pmid:40621999","citation":"Lopez-Alamillo et al., Clin Microbiol Rev","year":2025,"design":"review","finding":"Toxocara larvae do not mature in humans but migrate to the lungs, liver, muscles, eyes and central nervous system, causing visceral, ocular and neurological disease."}]},{"from":"toxocara","to":"s_liver","level":"established","effect":"harms","note":"Wandering larvae inflame the liver and raise allergy-type white cells in the blood (visceral larva migrans).","sources":[{"id":"pmid:40621999","citation":"Lopez-Alamillo et al., Clin Microbiol Rev","year":2025,"design":"review","finding":"Toxocara larvae do not mature in humans but migrate to the lungs, liver, muscles, eyes and central nervous system, causing visceral, ocular and neurological disease."}]},{"from":"toxocara","to":"s_lungs","level":"established","effect":"harms","note":"Larvae passing through the lungs can cause cough and wheeze.","sources":[{"id":"pmid:40621999","citation":"Lopez-Alamillo et al., Clin Microbiol Rev","year":2025,"design":"review","finding":"Toxocara larvae do not mature in humans but migrate to the lungs, liver, muscles, eyes and central nervous system, causing visceral, ocular and neurological disease."}]},{"from":"hookworm","to":"coeliac_disease","level":"failed","effect":"helps","note":"In a small placebo-controlled trial, deliberate hookworm infection did not protect the gut of people with coeliac disease from a wheat challenge.","sources":[{"id":"pmid:21408161","citation":"Daveson et al., PLoS One","year":2011,"design":"RCT","finding":"In 20 adults with coeliac disease, hookworm infection did not prevent the worsening of gut biopsy and gluten-specific immune measures after a wheat challenge, compared with placebo."}]},{"from":"hookworm","to":"iron","level":"established","effect":"harms","note":"Hookworms feed on blood in the gut, a leading cause of iron-deficiency anaemia where they are common."},{"from":"ascaris","to":"s_small_intestine","level":"established","effect":"harms","note":"Adult worms live in the small intestine; a heavy tangle can block the gut, especially in children."},{"from":"ascaris","to":"s_lungs","level":"established","effect":"harms","note":"Larvae pass through the lungs on their way to the gut and can cause a short spell of cough, wheeze and fever."},{"from":"ascaris","to":"allergic_asthma","level":"association","effect":"harms","note":"People currently infected with Ascaris have somewhat more asthma in pooled population studies, the opposite of what is seen with hookworm.","sources":[{"id":"pmid:16778161","citation":"Leonardi-Bee et al., Am J Respir Crit Care Med","year":2006,"design":"meta-analysis","finding":"Across 20 studies, current Ascaris lumbricoides infection was linked with higher odds of asthma (OR about 1.34), while hookworm was linked with lower odds."}]},{"from":"deworming","to":"ascaris","level":"proven","effect":"helps","note":"Common deworming medicines cured most roundworm infections in randomised trials.","sources":[{"id":"pmid:32289194","citation":"Conterno et al., Cochrane Database Syst Rev","year":2020,"design":"meta-analysis","finding":"Across 30 trials, single-dose albendazole, mebendazole or ivermectin each cured about nine in ten Ascaris infections versus about one in six on placebo."}]},{"from":"deworming","to":"cognition","level":"failed","effect":"helps","note":"Regularly deworming all schoolchildren in areas with worms did not improve thinking-test scores or school performance in large pooled trials.","sources":[{"id":"pmid:31508807","citation":"Taylor-Robinson et al., Cochrane Database Syst Rev","year":2019,"design":"meta-analysis","finding":"Public health deworming programmes probably had little or no effect on haemoglobin, formal cognition tests or school performance (moderate-certainty evidence)."},{"id":"pmid:37131850","citation":"Welch et al., Campbell Syst Rev","year":2019,"design":"meta-analysis","finding":"Individual-participant data from 19 trials (about 32,000 children) showed little effect of mass deworming on nutrition or cognition, with no subgroup benefiting significantly."}]},{"from":"s_nose","to":"s_lungs","level":"established","effect":"located","note":"The nose is the entrance to the airways."},{"from":"s_nose","to":"s_smell","level":"established","effect":"located","note":"Smell-sensing nerve cells sit in a small patch of lining in the roof of the nose."},{"from":"itchy_nose_eyes","to":"s_nose","level":"established","effect":"located","note":"Sneezing, a runny nose and a blocked nose come from the nasal lining."},{"from":"allergic_rhinitis","to":"s_nose","level":"established","effect":"affects","note":"Hay fever inflames and swells the lining of the nose."},{"from":"chronic_rhinosinusitis","to":"s_nose","level":"established","effect":"affects","note":"Inflames the lining of the nose and sinuses."},{"from":"chronic_rhinosinusitis","to":"smell","level":"established","effect":"harms","note":"Swelling and polyps stop odours reaching the smell receptors, so smell is often reduced; it is one of the main symptoms."},{"from":"tx_tobacco","to":"chronic_rhinosinusitis","level":"association","effect":"harms","note":"Current and past smokers are more likely to have chronic sinusitis.","sources":[{"id":"pmid:38112394","citation":"Tan CJ et al., Laryngoscope","year":2024,"design":"meta-analysis","finding":"Current and past smokers had higher odds of chronic rhinosinusitis than never-smokers."}]},{"from":"h_saline_irrigation","to":"chronic_rhinosinusitis","level":"proven","effect":"helps","note":"Rinsing the nose with salty water improved sinus symptoms in small trials, though the evidence is low certainty.","sources":[{"id":"pmid:27115216","citation":"Chong LY et al., Cochrane Database Syst Rev","year":2016,"design":"meta-analysis","finding":"In a small randomised trial, large-volume salty-water nasal irrigation improved sinus-specific quality of life over usual care at three and six months; evidence low to very low certainty."}]},{"from":"s_middle_ear","to":"s_ears","level":"established","effect":"located","note":"The sound-carrying part of the ear."},{"from":"otitis_media","to":"s_middle_ear","level":"established","effect":"affects","note":"Infection and fluid fill the middle ear behind the eardrum."},{"from":"otitis_media","to":"bp_ears","level":"established","effect":"affects","note":"Earache and temporary muffled hearing."},{"from":"tx_tobacco","to":"otitis_media","level":"association","effect":"harms","note":"Children whose parents smoke have more repeated ear infections and glue ear.","sources":[{"id":"pmid:9577522","citation":"Strachan DP, Cook DG, Thorax","year":1998,"design":"meta-analysis","finding":"Children whose parents smoked had higher odds of recurrent middle-ear infection and middle-ear fluid (glue ear); the authors judged the link likely causal."}]},{"from":"s_vestibular","to":"s_ears","level":"established","effect":"located","note":"The balance part of the inner ear, joined to the cochlea."},{"from":"falls","to":"s_vestibular","level":"established","effect":"located","note":"When the inner-ear balance organs fail, the body loses one of its main senses of position and falls become more likely."},{"from":"vertigo","to":"s_vestibular","level":"established","effect":"located","note":"Arises when signals from the balance organs are wrong or unequal between the two ears."},{"from":"vertigo","to":"nausea","level":"established","effect":"harms","note":"Mismatched balance signals commonly cause nausea and vomiting."},{"from":"bppv","to":"vertigo","level":"established","effect":"harms","note":"Brief spinning attacks set off by head position are the defining symptom."},{"from":"bppv","to":"s_vestibular","level":"established","effect":"affects","note":"Loose crystals sit in a semicircular canal."},{"from":"bppv","to":"bp_ears","level":"established","effect":"affects","note":"An inner-ear balance disorder."},{"from":"bppv","to":"falls","level":"association","effect":"harms","note":"People with BPPV walk more unsteadily and fall more often than people without it.","sources":[{"id":"pmid:36897200","citation":"Pauwels S et al., J Neurol Phys Ther","year":2023,"design":"meta-analysis","finding":"People with BPPV walked more slowly and fell more often than controls; after repositioning manoeuvres, falls and fear of falling decreased."}]},{"from":"menieres","to":"vertigo","level":"established","effect":"harms","note":"Repeated attacks of spinning vertigo are the main symptom."},{"from":"menieres","to":"tinnitus","level":"established","effect":"harms","note":"Ringing or roaring in the affected ear is part of the attacks."},{"from":"menieres","to":"s_vestibular","level":"established","effect":"affects","note":"Fluid pressure disturbs the balance organs."},{"from":"menieres","to":"s_ears","level":"established","effect":"affects","note":"Affects both hearing and balance parts of one inner ear."},{"from":"menieres","to":"bp_ears","level":"established","effect":"affects","note":"Hearing loss and balance attacks in the affected ear."},{"from":"h_epley","to":"bppv","level":"proven","effect":"helps","note":"Repositioning moves the loose crystals and stopped vertigo in far more people than a sham manoeuvre.","sources":[{"id":"pmid:25485940","citation":"Hilton MP, Pinder DK, Cochrane Database Syst Rev","year":2014,"design":"meta-analysis","finding":"In 11 randomised trials, the Epley manoeuvre resolved posterior-canal BPPV vertigo far more often than a sham or no treatment (56% vs 21%), with no serious harms."}]},{"from":"h_vestibular_rehab","to":"vertigo","level":"proven","effect":"helps","note":"Balance and gaze exercises reduced dizziness after inner-ear balance loss in randomised trials.","sources":[{"id":"pmid:27406654","citation":"Hillier S, McDonnell M, Eur J Phys Rehabil Med (abridged Cochrane review)","year":2016,"design":"meta-analysis","finding":"In 39 studies of one-sided inner-ear balance loss, vestibular rehabilitation reduced dizziness more than control or no treatment, with no reported harms."}]},{"from":"h_vestibular_rehab","to":"m_plastic","level":"established","effect":"helps","note":"Works by training the brain to recalibrate to altered balance signals (central compensation)."},{"from":"s_cochlea","to":"s_ears","level":"established","effect":"located","note":"The hearing part of the inner ear."},{"from":"nihl","to":"s_cochlea","level":"established","effect":"affects","note":"Loud noise wears out the hair cells of the cochlea, high pitches first."},{"from":"tinnitus","to":"s_cochlea","level":"established","effect":"located","note":"Ringing often starts after cochlear hair cells are damaged, as the brain's hearing pathways turn up their own activity."},{"from":"presbycusis","to":"s_cochlea","level":"established","effect":"affects","note":"Hair cells and nerve fibres in the cochlea wear out with age."},{"from":"presbycusis","to":"bp_ears","level":"established","effect":"affects","note":"Gradual hearing loss in both ears."},{"from":"presbycusis","to":"tinnitus","level":"established","effect":"harms","note":"Ringing in the ears often accompanies age-related hearing loss."},{"from":"presbycusis","to":"cognition","level":"association","effect":"harms","note":"People with hearing loss are more likely to develop thinking problems and dementia over time; whether hearing loss causes this is not settled.","sources":[{"id":"pmid:29222544","citation":"Loughrey DG et al., JAMA Otolaryngol Head Neck Surg","year":2018,"design":"meta-analysis","finding":"Across 36 studies, age-related hearing loss measured by audiometry was associated with poorer cognition and, in prospective cohorts, with higher odds of cognitive impairment and dementia."}]},{"from":"presbycusis","to":"falls","level":"association","effect":"harms","note":"Hearing loss goes with a higher risk of falls, even after allowing for other risk factors.","sources":[{"id":"pmid:40111358","citation":"Yeo BSY et al., JAMA Otolaryngol Head Neck Surg","year":2025,"design":"meta-analysis","finding":"In 27 studies with over five million people, hearing loss was linked to higher odds and higher later risk of falls after adjusting for other factors."}]},{"from":"h_hearing_aids","to":"presbycusis","level":"proven","effect":"helps","note":"Hearing aids improve everyday hearing and hearing-related quality of life; they do not reverse the loss.","sources":[{"id":"pmid:42644645","citation":"Ferguson MA et al., Cochrane Database Syst Rev","year":2026,"design":"meta-analysis","finding":"In 16 randomised trials of adults with mild to moderate hearing loss, hearing aids likely produce a large improvement in hearing-related quality of life (moderate certainty)."}]},{"from":"h_hearing_aids","to":"nihl","level":"proven","effect":"helps","note":"Hearing aids improve everyday hearing in mild to moderate hearing loss of any cause; they do not reverse the damage.","sources":[{"id":"pmid:42644645","citation":"Ferguson MA et al., Cochrane Database Syst Rev","year":2026,"design":"meta-analysis","finding":"In 16 randomised trials of adults with mild to moderate hearing loss, hearing aids likely produce a large improvement in hearing-related quality of life (moderate certainty)."}]},{"from":"h_hearing_aids","to":"cognition","level":"mixed","effect":"helps","note":"In the largest trial, hearing aids did not slow thinking decline overall, only possibly in higher-risk people, though long-term observational studies look favourable.","sources":[{"id":"pmid:37478886","citation":"Lin FR et al., Lancet (ACHIEVE)","year":2023,"design":"RCT","finding":"In 977 adults aged 70-84 with hearing loss, a hearing intervention did not slow 3-year cognitive decline overall, though a prespecified analysis suggested benefit in the higher-risk subgroup."},{"id":"pmid:36469314","citation":"Yeo BSY et al., JAMA Neurol","year":2023,"design":"meta-analysis","finding":"Across mostly observational studies, use of hearing aids or cochlear implants was associated with lower long-term risk of cognitive decline."}]},{"from":"s_larynx","to":"s_throat","level":"established","effect":"located","note":"Sits in the front of the throat, below the tongue base."},{"from":"s_larynx","to":"s_lungs","level":"established","effect":"located","note":"The top of the windpipe; it guards the entrance to the lungs."},{"from":"speech","to":"s_larynx","level":"established","effect":"located","note":"A soft, breathy voice comes partly from vocal folds that close less fully and with less effort.","sources":[{"id":"pmid:40435744","citation":"Castro ACAF et al., Braz J Otorhinolaryngol","year":2025,"design":"cohort","finding":"In 18 people with Parkinson's examined by videolaryngostroboscopy, 94% had visible laryngeal changes and most reported a hoarse or weak voice."}]},{"from":"swallow","to":"s_larynx","level":"established","effect":"located","note":"The voice box must lift and close quickly during each swallow; when it is slow, food or saliva can slip into the airway."},{"from":"pneumonia","to":"s_larynx","level":"established","effect":"located","note":"Aspiration happens when the larynx fails to seal the airway in time."},{"from":"parkinsons","to":"s_larynx","level":"established","effect":"affects","note":"Most people with Parkinson's show changes in how the vocal folds move and close.","sources":[{"id":"pmid:40435744","citation":"Castro ACAF et al., Braz J Otorhinolaryngol","year":2025,"design":"cohort","finding":"In 18 people with Parkinson's examined by videolaryngostroboscopy, 94% had visible laryngeal changes and most reported a hoarse or weak voice."}]},{"from":"osa","to":"s_throat","level":"established","effect":"affects","note":"The throat repeatedly narrows or closes during sleep."},{"from":"osa","to":"sleepy","level":"established","effect":"harms","note":"Repeated night-time awakenings cause daytime sleepiness."},{"from":"osa","to":"insomnia","level":"established","effect":"harms","note":"Breathing pauses repeatedly break up sleep."},{"from":"osa","to":"headache","level":"established","effect":"harms","note":"Morning headaches are a common feature."},{"from":"osa","to":"bp_sleep","level":"established","effect":"affects","note":"A sleep-breathing disorder."},{"from":"h_cpap","to":"osa","level":"proven","effect":"helps","note":"Air pressure keeps the throat open and stops the pauses in breathing.","sources":[{"id":"pmid:16855960","citation":"Giles TL et al., Cochrane Database Syst Rev","year":2006,"design":"meta-analysis","finding":"In 36 randomised trials, CPAP reduced daytime sleepiness and improved quality of life in moderate to severe obstructive sleep apnoea compared with control."},{"id":"pmid:24470706","citation":"Neikrug AB et al., Sleep","year":2014,"design":"RCT","finding":"In people with Parkinson's and sleep apnoea, therapeutic versus placebo CPAP reduced apnoea events, improved oxygen levels and deepened sleep."}]},{"from":"h_cpap","to":"sleepy","level":"proven","effect":"helps","note":"CPAP reduced daytime sleepiness in sleep apnoea in randomised trials.","scope":["osa"],"sources":[{"id":"pmid:16855960","citation":"Giles TL et al., Cochrane Database Syst Rev","year":2006,"design":"meta-analysis","finding":"In 36 randomised trials, CPAP reduced daytime sleepiness and improved quality of life in moderate to severe obstructive sleep apnoea compared with control."},{"id":"pmid:24470706","citation":"Neikrug AB et al., Sleep","year":2014,"design":"RCT","finding":"In people with Parkinson's and sleep apnoea, CPAP reduced objectively measured daytime sleepiness."}]},{"from":"head_neck_cancer","to":"s_throat","level":"established","effect":"affects","note":"Grows in the lining of the throat and voice box."},{"from":"head_neck_cancer","to":"s_mouth","level":"established","effect":"affects","note":"Mouth cancers arise on the tongue, gums, cheek and floor of the mouth."},{"from":"head_neck_cancer","to":"s_lymph_neck","level":"established","effect":"affects","note":"Often spreads first to the lymph nodes of the neck."},{"from":"head_neck_cancer","to":"swollen_nodes","level":"established","effect":"harms","note":"A painless lump in the neck can be the first sign."},{"from":"head_neck_cancer","to":"swallow","level":"established","effect":"harms","note":"Tumours and their treatment commonly make swallowing difficult."},{"from":"tx_tobacco","to":"head_neck_cancer","level":"established","effect":"harms","note":"Smoking is a main cause, and together with alcohol accounts for most cases.","sources":[{"id":"pmid:19190158","citation":"Hashibe M et al., Cancer Epidemiol Biomarkers Prev","year":2009,"design":"case-control","finding":"Pooling 17 case-control studies, tobacco and alcohol together accounted for about 72% of head and neck cancers, and their combined effect was greater than multiplying the two risks."}]},{"from":"tx_alcohol","to":"head_neck_cancer","level":"established","effect":"harms","note":"Alcohol is a cause, and with tobacco the risk rises more than the two added together.","sources":[{"id":"pmid:19190158","citation":"Hashibe M et al., Cancer Epidemiol Biomarkers Prev","year":2009,"design":"case-control","finding":"Pooling 17 case-control studies, tobacco and alcohol together accounted for about 72% of head and neck cancers, and their combined effect was greater than multiplying the two risks."}]},{"from":"hpv","to":"head_neck_cancer","level":"established","effect":"harms","note":"High-risk HPV types cause most throat (oropharyngeal) cancers in many countries."},{"from":"h_hpv_vaccine","to":"hpv","level":"proven","effect":"helps","note":"Vaccination prevented infection with the targeted HPV types, including in the mouth, in a randomised trial.","sources":[{"id":"pmid:23873171","citation":"Herrero R et al., PLoS One","year":2013,"design":"RCT","finding":"Four years after randomisation, women given the HPV16/18 vaccine had about 93% fewer oral HPV16/18 infections than women given a control vaccine."},{"id":"pmid:41992160","citation":"Douyat LM, Spencer A, BMC Cancer","year":2026,"design":"review","finding":"Across studies, vaccinated people had much lower rates of oral vaccine-type HPV infection; effects on cancer itself are not yet measured."}]},{"from":"s_retina","to":"s_eyes","level":"established","effect":"located","note":"Part of the eye: the light-sensing lining at the back."},{"from":"s_photoreceptors","to":"s_retina","level":"established","effect":"located","note":"The light-catching layer of the retina."},{"from":"s_retinal_ganglion","to":"s_retina","level":"established","effect":"located","note":"The innermost, output layer of the retina."},{"from":"s_rpe","to":"s_retina","level":"established","effect":"located","note":"The outermost layer of the retina, behind the rods and cones."},{"from":"s_macula","to":"s_retina","level":"established","effect":"located","note":"The centre of the retina, used for sharp vision."},{"from":"s_choroid","to":"s_eyes","level":"established","effect":"located","note":"Part of the eye wall: the blood layer between retina and sclera."},{"from":"s_choroid","to":"s_rpe","level":"established","effect":"helps","note":"Its blood supplies oxygen and nutrients to the pigment layer and the rods and cones."},{"from":"s_rpe","to":"s_photoreceptors","level":"established","effect":"helps","note":"Recycles the rods' and cones' vitamin A pigment and clears their worn-out tips every day."},{"from":"s_photoreceptors","to":"s_retinal_ganglion","level":"established","effect":"helps","note":"Rod and cone signals pass through the middle retina to the ganglion cells, which send them to the brain."},{"from":"vita","to":"s_photoreceptors","level":"established","effect":"helps","note":"Forms the light-catching pigment in rods and cones; lack causes night blindness, while extra beyond normal needs does not improve sight.","dose":"deficiency"},{"from":"lutein","to":"s_macula","level":"established","effect":"affects","note":"Lutein collects in the macula as the yellow pigment that filters blue light; supplements raise this pigment, but in trials they did not slow macular degeneration."},{"from":"eggs","to":"lutein","level":"established","effect":"contains","note":"Egg yolk contains lutein and zeaxanthin in an easily absorbed fatty form."},{"from":"s_retinal_ganglion","to":"br_scn","level":"established","effect":"helps","note":"Special light-sensing ganglion cells send brightness signals straight to the body clock."},{"from":"s_cornea","to":"s_eyes","level":"established","effect":"located","note":"Part of the eye: its clear front window."},{"from":"s_iris","to":"s_eyes","level":"established","effect":"located","note":"Part of the eye: the coloured ring that sizes the pupil."},{"from":"s_lens","to":"s_eyes","level":"established","effect":"located","note":"Part of the eye: the clear lens behind the pupil."},{"from":"s_ciliary_body","to":"s_eyes","level":"established","effect":"located","note":"Part of the eye: the ring around the lens that focuses it and makes the eye's fluid."},{"from":"s_ciliary_body","to":"s_lens","level":"established","effect":"helps","note":"Its muscle changes the lens shape so we can focus up close."},{"from":"s_sclera","to":"s_eyes","level":"established","effect":"located","note":"Part of the eye: its tough white outer wall."},{"from":"s_vitreous","to":"s_eyes","level":"established","effect":"located","note":"Part of the eye: the clear gel that fills it."},{"from":"s_autonomic","to":"s_iris","level":"established","effect":"helps","note":"Autonomic nerves widen and narrow the pupil to match the light."},{"from":"s_enamel","to":"s_mouth","level":"established","effect":"located","note":"Enamel covers the crown of every tooth in the mouth."},{"from":"s_dentine","to":"s_mouth","level":"established","effect":"located","note":"Dentine lies under the enamel and forms the bulk of each tooth."},{"from":"s_dental_pulp","to":"s_mouth","level":"established","effect":"located","note":"The pulp is the living core inside each tooth."},{"from":"s_tooth_roots","to":"s_bones","level":"established","effect":"located","note":"Tooth roots sit in sockets in the jaw bones, held by a ligament."},{"from":"calcium","to":"s_enamel","level":"established","effect":"helps","note":"Enamel and dentine are built from calcium phosphate crystals; extra calcium beyond a normal diet isn't shown to strengthen adult teeth.","dose":"deficiency"},{"from":"phosphorus","to":"s_enamel","level":"established","effect":"helps","note":"Phosphate is the other half of the mineral that makes enamel and dentine."},{"from":"caries","to":"s_enamel","level":"established","effect":"affects","note":"Acid from plaque bacteria dissolves the enamel first."},{"from":"caries","to":"s_dental_pulp","level":"established","effect":"affects","note":"Untreated decay reaches the pulp, which becomes inflamed or infected."},{"from":"caries","to":"bp_teeth","level":"established","effect":"affects","note":"Decay destroys tooth structure and is a leading reason teeth are lost."},{"from":"caries","to":"pain","level":"established","effect":"harms","note":"Decay that reaches the pulp causes toothache."},{"from":"sugar","to":"caries","level":"association","effect":"harms","note":"People who eat more free sugars, and more often, have more tooth decay in population studies.","sources":[{"id":"pmid:24323509","citation":"Moynihan PJ & Kelly SA, J Dent Res","year":2014,"design":"review","finding":"Systematic review informing the WHO sugars guideline: consistent evidence of a relationship between amount of sugars eaten and caries, with lower caries when free sugars were below 10% of energy."},{"id":"pmid:35302414","citation":"Moores CJ et al., J Dent Res","year":2022,"design":"review","finding":"Ten-year update: most cohort, cross-sectional and ecological studies in children and adults found more caries with higher sugars intake."}]},{"from":"h_fluoride_toothpaste","to":"caries","level":"proven","effect":"helps","note":"Trials show brushing with fluoride toothpaste prevents tooth decay compared with non-fluoride toothpaste.","sources":[{"id":"pmid:12535435","citation":"Marinho VC et al., Cochrane Database Syst Rev","year":2003,"design":"meta-analysis","finding":"70 trials with 42,300 children: fluoride toothpaste reduced decayed, missing and filled tooth surfaces by about a quarter versus placebo paste."},{"id":"pmid:30829399","citation":"Walsh T et al., Cochrane Database Syst Rev","year":2019,"design":"meta-analysis","finding":"96 studies support fluoride toothpaste over non-fluoride toothpaste for preventing caries, with a dose-response effect in children and adolescents."}]},{"from":"h_fluoride_varnish","to":"caries","level":"proven","effect":"helps","note":"Trials in children found fluoride varnish prevents tooth decay, with moderate-certainty evidence.","sources":[{"id":"pmid:23846772","citation":"Marinho VC et al., Cochrane Database Syst Rev","year":2013,"design":"meta-analysis","finding":"22 trials: fluoride varnish reduced decayed surfaces by about 43% in permanent teeth and 37% in baby teeth; evidence moderate quality with high heterogeneity."}]},{"from":"h_water_fluoridation","to":"caries","level":"association","effect":"helps","note":"Fluoridated water was linked with less tooth decay in children, but the extra benefit is small in recent studies where fluoride toothpaste is common.","sources":[{"id":"pmid:39362658","citation":"Iheozor-Ejiofor Z et al., Cochrane Database Syst Rev","year":2024,"design":"meta-analysis","finding":"Contemporary non-randomised studies suggest starting water fluoridation may slightly reduce decay in children, with smaller effects than pre-1975 studies; no adult caries data and insufficient evidence on stopping it."}]},{"from":"s_lacrimal","to":"s_eyes","level":"established","effect":"located","note":"Part of the eye's protective system, in the upper outer eye socket."},{"from":"s_lacrimal","to":"s_cornea","level":"established","effect":"helps","note":"The tear film feeds and protects the cornea."},{"from":"s_eyelids","to":"s_eyes","level":"established","effect":"located","note":"Part of the eye's protective system."},{"from":"s_eyelids","to":"s_cornea","level":"established","effect":"helps","note":"Each blink spreads fresh tears over the cornea."},{"from":"s_eye_muscles","to":"s_eyes","level":"established","effect":"located","note":"Attached to each eyeball to turn it."},{"from":"s_brainstem","to":"s_eye_muscles","level":"established","effect":"helps","note":"Three cranial nerves from the brainstem steer the eye muscles."},{"from":"s_autonomic","to":"s_lacrimal","level":"established","effect":"helps","note":"Autonomic nerves switch on tear production."},{"from":"amd","to":"s_macula","level":"established","effect":"affects","note":"Damages the macula, the part of the retina used for sharp central vision."},{"from":"amd","to":"s_rpe","level":"established","effect":"affects","note":"The pigment support layer under the macula wears out."},{"from":"amd","to":"bp_eyes","level":"established","effect":"affects","note":"Affects the eyes."},{"from":"tx_tobacco","to":"amd","level":"association","effect":"harms","note":"Smokers, especially current smokers, more often develop macular degeneration.","sources":[{"id":"pmid:18652983","citation":"Cong R et al., Ann Epidemiol","year":2008,"design":"meta-analysis","finding":"Across 13 studies, ever smoking was linked to higher risk of age-related macular degeneration, with current smokers at higher risk than past smokers."}]},{"from":"h_areds","to":"amd","level":"proven","effect":"helps","note":"In people who already have intermediate AMD, the AREDS formula modestly slows progression to late AMD; it does not prevent AMD in people without it.","sources":[{"id":"pmid:11594942","citation":"AREDS Research Group, Arch Ophthalmol","year":2001,"design":"RCT","finding":"In 3,640 people, antioxidants plus zinc lowered the odds of progression to advanced AMD, mainly in those who already had intermediate AMD or advanced AMD in one eye."},{"id":"pmid:37702300","citation":"Evans JR, Lawrenson JG, Cochrane Database Syst Rev","year":2023,"design":"meta-analysis","finding":"In people with AMD, antioxidant vitamin and mineral supplements (mostly AREDS) probably slow progression to late AMD; the benefit is meaningful mainly for intermediate AMD and small for early AMD."},{"id":"pmid:28756617","citation":"Evans JR, Lawrenson JG, Cochrane Database Syst Rev","year":2017,"design":"meta-analysis","finding":"In people without AMD, vitamin E or beta-carotene supplements do not prevent or delay AMD; there is no evidence for lutein/zeaxanthin in prevention."}]},{"from":"lutein","to":"amd","level":"failed","effect":"helps","note":"Adding lutein/zeaxanthin to the AREDS formula did not further slow AMD in the main analysis; it is used in place of beta-carotene for safety.","sources":[{"id":"pmid:23644932","citation":"AREDS2 Research Group, JAMA","year":2013,"design":"RCT","finding":"Adding lutein/zeaxanthin or omega-3 (DHA/EPA) to the AREDS formula did not further reduce progression to advanced AMD; lutein/zeaxanthin was suggested as a substitute for beta-carotene, which raised lung cancers in former smokers."},{"id":"pmid:37702300","citation":"Evans JR, Lawrenson JG, Cochrane Database Syst Rev","year":2023,"design":"meta-analysis","finding":"In people with AMD, antioxidant vitamin and mineral supplements (mostly AREDS) probably slow progression to late AMD; the benefit is meaningful mainly for intermediate AMD and small for early AMD."}]},{"from":"omega3","to":"amd","level":"failed","effect":"helps","note":"Adding fish-oil omega-3 to the AREDS formula did not slow AMD in a large trial.","sources":[{"id":"pmid:23644932","citation":"AREDS2 Research Group, JAMA","year":2013,"design":"RCT","finding":"Adding lutein/zeaxanthin or omega-3 (DHA/EPA) to the AREDS formula did not further reduce progression to advanced AMD; lutein/zeaxanthin was suggested as a substitute for beta-carotene, which raised lung cancers in former smokers."}]},{"from":"diabetic_retinopathy","to":"s_retina","level":"established","effect":"affects","note":"Damages the small blood vessels of the retina."},{"from":"diabetic_retinopathy","to":"bp_eyes","level":"established","effect":"affects","note":"Affects the eyes."},{"from":"s_retinal_ganglion","to":"s_optic_nerve","level":"established","effect":"helps","note":"The ganglion cells' fibres bundle together to form the optic nerve."},{"from":"s_optic_nerve","to":"s_eyes","level":"established","effect":"located","note":"Leaves the back of the eye at the optic disc."},{"from":"s_optic_nerve","to":"s_optic_chiasm","level":"established","effect":"helps","note":"Each optic nerve carries its eye's signals to the chiasm."},{"from":"s_optic_chiasm","to":"s_pituitary","level":"established","effect":"located","note":"Lies just above the pituitary gland, which is why pituitary tumours can affect sight."},{"from":"s_optic_chiasm","to":"s_lgn","level":"established","effect":"helps","note":"After crossing, the fibres run on as the optic tracts to the thalamus relay."},{"from":"s_lgn","to":"br_thalamus","level":"established","effect":"located","note":"Part of the thalamus, at its back."},{"from":"s_lgn","to":"br_visual","level":"established","effect":"helps","note":"Relays the eyes' signals to the visual cortex."},{"from":"parkinsons","to":"vision_pd","level":"association","effect":"harms","note":"Many people with Parkinson's see contrast and colour less well even with normal eyesight on the letter chart.","sources":[{"id":"pmid:27412389","citation":"Weil RS et al., Brain","year":2016,"design":"review","finding":"People with Parkinson's have specific changes in colour vision and contrast sensitivity starting in the retina, plus problems with complex visual tasks; visual deficits relate to hallucinations."},{"id":"pmid:36806480","citation":"Alves JN et al., J Neurol Neurosurg Psychiatry","year":2023,"design":"review","finding":"Retinal electrical responses are delayed and weaker in Parkinson's and retinal dopamine neurons are lost; functional retinal measures are more consistent than OCT thickness measures."},{"id":"pmid:32161030","citation":"Borm CDJM et al., Neurology","year":2020,"design":"case-control","finding":"In 848 people with Parkinson's and 250 controls, 82% vs 48% reported eye symptoms, across the eye surface, inside the eye, eye movements and optic nerve, and they often disrupted daily life."}]},{"from":"vision_pd","to":"s_retina","level":"established","effect":"located","note":"Starts partly in the retina, where contrast is first processed."},{"from":"vision_pd","to":"br_visual","level":"established","effect":"located","note":"Also involves the visual cortex and its nearby areas."},{"from":"parkinsons","to":"s_retina","level":"association","effect":"affects","note":"Eye scans (OCT) find the inner retinal layers slightly thinner on average in Parkinson's, sometimes years before diagnosis, but the overlap with healthy people is large.","sources":[{"id":"pmid:24465663","citation":"Yu JG et al., PLoS One","year":2014,"design":"meta-analysis","finding":"Across 13 case-control studies, people with Parkinson's had a thinner retinal nerve fibre layer on OCT than healthy controls."},{"id":"pmid:37800768","citation":"Lee YW et al., Medicine (Baltimore)","year":2023,"design":"meta-analysis","finding":"Across 32 studies, the ganglion-cell layers and the macula were thinner on OCT in Parkinson's than in controls, with wide variation between studies."},{"id":"pmid:37604659","citation":"Wagner SK et al., Neurology","year":2023,"design":"cohort","finding":"In large UK eye-clinic and UK Biobank data, a thinner ganglion-cell layer and inner nuclear layer went with having Parkinson's and with being diagnosed with it years later."},{"id":"pmid:36806480","citation":"Alves JN et al., J Neurol Neurosurg Psychiatry","year":2023,"design":"review","finding":"Retinal electrical responses are delayed and weaker in Parkinson's and retinal dopamine neurons are lost; functional retinal measures are more consistent than OCT thickness measures."}]},{"from":"vision_pd","to":"hallucinations","level":"association","effect":"harms","note":"Ongoing visual problems were linked to minor hallucinations, such as a sense of something passing at the edge of sight.","sources":[{"id":"pmid:24405755","citation":"Urwyler P et al., Parkinsonism Relat Disord","year":2014,"design":"case-control","finding":"Double vision was reported by 18% of 88 Parkinson's patients vs 1% of controls; recurrent visual complaints predicted minor hallucinations but not complex ones."},{"id":"pmid:27412389","citation":"Weil RS et al., Brain","year":2016,"design":"review","finding":"People with Parkinson's have specific changes in colour vision and contrast sensitivity starting in the retina, plus problems with complex visual tasks; visual deficits relate to hallucinations."}]},{"from":"s_uterus","to":"s_reproductive","level":"established","effect":"located","note":"Part of the female reproductive organs."},{"from":"s_cervix","to":"s_uterus","level":"established","effect":"located","note":"The cervix is the lower end of the womb."},{"from":"s_fallopian_tubes","to":"s_reproductive","level":"established","effect":"located","note":"Part of the female reproductive organs: they carry the egg from the ovary to the womb."},{"from":"hm_oestrogen","to":"s_uterus","level":"established","effect":"helps","note":"Oestrogen thickens the womb lining in the first half of each cycle."},{"from":"hm_progesterone","to":"s_uterus","level":"established","effect":"helps","note":"After an egg is released, progesterone readies and holds the womb lining; when it falls, the lining is shed as a period."},{"from":"hm_oxytocin","to":"s_uterus","level":"established","effect":"helps","note":"Oxytocin makes the womb muscle contract in labour and helps it clamp down after birth."},{"from":"hpv","to":"s_cervix","level":"established","effect":"harms","note":"Long-lasting infection with high-risk HPV types causes nearly all cervical cancers.","sources":[{"id":"pmid:10451482","citation":"Walboomers JM et al., J Pathol","year":1999,"design":"case-control","finding":"High-risk HPV DNA was found in 99.7% of invasive cervical cancers worldwide, supporting HPV as a necessary cause."}]},{"from":"period_pain","to":"s_uterus","level":"established","effect":"located","note":"Comes from the womb muscle contracting as its lining is shed."},{"from":"heavy_periods","to":"s_uterus","level":"established","effect":"located","note":"The bleeding comes from the shedding womb lining."},{"from":"heavy_periods","to":"iron","level":"established","effect":"harms","note":"The blood lost each month drains iron stores; heavy periods are a leading cause of iron deficiency and anaemia in women.","sources":[{"id":"pmid:36706856","citation":"Munro MG et al., Am J Obstet Gynecol","year":2023,"design":"review","finding":"Heavy menstrual bleeding is a major, under-recognised cause of iron deficiency and iron-deficiency anaemia in reproductive-aged women."}]},{"from":"pp_sp6","to":"period_pain","level":"mixed","effect":"helps","note":"Pressing the inner-shin point eased period pain more than sham pressure in small, low-quality trials.","sources":[{"id":"pmid:27863617","citation":"Abaraogu UO et al., Complement Ther Clin Pract","year":2016,"design":"meta-analysis","finding":"Six small trials (461 women) suggested SP6 acupressure eased period pain for up to 3 hours, but studies were generally low quality with high risk of bias."},{"id":"pmid:41138782","citation":"Yu X et al., Complement Ther Med","year":2025,"design":"meta-analysis","finding":"23 trials found acupressure reduced period pain more than placebo acupressure (about 1.6 points on a 10-point scale), but the evidence was rated low quality."}]},{"from":"exercise","to":"period_pain","level":"proven","effect":"helps","note":"In a review of small, low-quality trials, regular exercise through the month eased period pain by a meaningful amount.","sources":[{"id":"pmid:31538328","citation":"Armour M et al., Cochrane Database Syst Rev","year":2019,"design":"meta-analysis","finding":"Regular exercise reduced menstrual pain intensity by about 25 mm on a 100 mm scale versus no exercise, on low-quality evidence."}]},{"from":"s_gums","to":"s_mouth","level":"established","effect":"located","note":"The gums line the jaws and seal around every tooth."},{"from":"vitc","to":"s_gums","level":"established","effect":"helps","note":"Needed to make the collagen that holds gums together; severe lack (scurvy) makes gums swell and bleed, but extra beyond a normal diet isn't shown to treat gum disease.","dose":"deficiency"},{"from":"gingivitis","to":"s_gums","level":"established","effect":"affects","note":"Plaque along the gum line makes the gums red, swollen and bleed easily."},{"from":"gingivitis","to":"periodontitis","level":"established","effect":"harms","note":"Gingivitis comes first; in some people, especially smokers, it progresses to destructive gum disease, though most gingivitis never does."},{"from":"periodontitis","to":"s_gums","level":"established","effect":"affects","note":"Destroys the ligament and bone that hold teeth; gums recede and pockets form."},{"from":"periodontitis","to":"bp_teeth","level":"established","effect":"affects","note":"Teeth loosen and can be lost as their supporting bone is destroyed."},{"from":"pging","to":"periodontitis","level":"established","effect":"harms","note":"P. gingivalis is a key bacterium in the plaque of destructive gum disease."},{"from":"fuso","to":"periodontitis","level":"established","effect":"harms","note":"Fusobacterium nucleatum helps build the plaque community found in gum disease."},{"from":"tx_tobacco","to":"periodontitis","level":"association","effect":"harms","note":"Smokers develop and lose bone to gum disease more often in long-term studies.","sources":[{"id":"pmid:29656920","citation":"Leite FRM et al., Am J Prev Med","year":2018,"design":"meta-analysis","finding":"Pooled prospective studies: smoking increased the risk of periodontitis incidence or progression by 85% (risk ratio 1.85)."}]},{"from":"periodontitis","to":"alzheimers","level":"association","effect":"harms","note":"People with gum disease or many missing teeth are a little more likely to develop dementia, but the link is weaker in better studies and is not shown to be causal.","sources":[{"id":"pmid:42747062","citation":"Demmer RT et al., J Periodontal Res","year":2026,"design":"meta-analysis","finding":"28 cohort studies: severe periodontitis (HR 1.16), edentulism and low tooth count were associated with higher dementia/MCI risk; estimates were weaker in lower risk-of-bias studies."},{"id":"pmid:34202071","citation":"Guo H et al., Int J Environ Res Public Health","year":2021,"design":"meta-analysis","finding":"Periodontitis was associated with higher risk of dementia and cognitive impairment."}]},{"from":"periodontitis","to":"s_heart","level":"association","effect":"harms","note":"Gum disease is linked with heart attack and stroke independent of smoking, but treating gums has not been shown to prevent them.","sources":[{"id":"pmid:32011025","citation":"Sanz M et al., J Clin Periodontol","year":2020,"design":"review","finding":"EFP and World Heart Federation consensus: significant epidemiological associations between periodontitis and cardiovascular disease."},{"id":"pmid:22514251","citation":"Lockhart PB et al., Circulation","year":2012,"design":"review","finding":"AHA statement: observational studies support an association independent of known confounders but do not support causation; no evidence periodontal treatment prevents atherosclerotic disease."}]},{"from":"periodontitis","to":"m_inflam","level":"association","effect":"harms","note":"Gum disease goes with higher inflammation markers in the blood, which fall in the short term after gum treatment.","sources":[{"id":"pmid:22514251","citation":"Lockhart PB et al., Circulation","year":2012,"design":"review","finding":"Periodontal interventions reduced systemic inflammation and endothelial dysfunction in short-term studies."}]},{"from":"h_interdental","to":"gingivitis","level":"mixed","effect":"helps","note":"Cleaning between teeth on top of brushing may reduce gum inflammation a little, but the trial evidence is low certainty.","sources":[{"id":"pmid:30968949","citation":"Worthington HV et al., Cochrane Database Syst Rev","year":2019,"design":"meta-analysis","finding":"Floss or interdental brushes plus toothbrushing may reduce gingivitis or plaque more than toothbrushing alone; evidence low to very low certainty and effects possibly not clinically important."}]},{"from":"h_mouthwash","to":"gingivitis","level":"proven","effect":"helps","note":"Chlorhexidine rinse used with brushing cuts plaque a lot in trials, but improves mild gum inflammation only slightly.","sources":[{"id":"pmid:28362061","citation":"James P et al., Cochrane Database Syst Rev","year":2017,"design":"meta-analysis","finding":"High-quality evidence of a large plaque reduction and a gingivitis reduction not considered clinically relevant in people with mild gingivitis, with chlorhexidine rinse as an adjunct to brushing."}]},{"from":"h_mouthwash","to":"oral_nitrate","level":"association","effect":"harms","note":"Antiseptic mouthwash also kills the helpful bacteria that turn nitrate into nitrite, seen in small human studies.","sources":[{"id":"pmid:23183324","citation":"Kapil V et al., Free Radic Biol Med","year":2013,"design":"lab","finding":"In healthy volunteers, a week of antiseptic mouthwash reduced oral and plasma nitrite and slightly raised blood pressure."},{"id":"pmid:32210245","citation":"Bescos R et al., Sci Rep","year":2020,"design":"lab","finding":"Non-randomised placebo-controlled crossover in 36 people: 7 days of chlorhexidine shifted the salivary microbiome, made saliva more acidic and lowered saliva and plasma nitrite."}]},{"from":"br_red_nucleus","to":"s_brainstem","level":"established","effect":"located","note":"The red nucleus is part of the midbrain, the top of the brainstem."},{"from":"br_pag","to":"s_brainstem","level":"established","effect":"located","note":"The periaqueductal grey is part of the midbrain, the top of the brainstem."},{"from":"m_absorb","to":"s_small_intestine","level":"established","effect":"located","note":"Levodopa is absorbed in the upper small intestine."},{"from":"m_absorb","to":"s_stomach","level":"established","effect":"located","note":"How fast the stomach empties sets how soon levodopa reaches the place it is absorbed."},{"from":"m_barrier","to":"s_gut","level":"established","effect":"located","note":"The gut barrier is the lining of the intestines."},{"from":"m_motility","to":"s_gut","level":"established","effect":"located","note":"Gut motility is the movement of the gut wall that pushes food along."},{"from":"m_micro","to":"s_colon","level":"established","effect":"located","note":"Gut bacteria make butyrate mostly in the large intestine, from fibre."},{"from":"m_bp","to":"s_blood","level":"established","effect":"located","note":"Blood pressure depends on blood volume and how tight the vessels are."},{"from":"m_bp","to":"s_heart","level":"established","effect":"located","note":"The heart's pumping is one half of blood pressure."},{"from":"m_bp","to":"s_kidneys","level":"established","effect":"located","note":"The kidneys set blood volume by how much salt and water they keep."},{"from":"m_bone","to":"s_bones","level":"established","effect":"located","note":"Bone strength is about the skeleton."},{"from":"m_bone","to":"s_muscle","level":"established","effect":"located","note":"Muscle strength is the other half of this mechanism."},{"from":"m_bladderctl","to":"s_bladder","level":"established","effect":"located","note":"Bladder control is about when the bladder muscle squeezes and relaxes."},{"from":"m_bladderctl","to":"s_brainstem","level":"established","effect":"located","note":"A centre in the pons, part of the brainstem, coordinates emptying the bladder."},{"from":"m_inflam","to":"s_immune","level":"established","effect":"located","note":"Inflammation is run by the immune system."},{"from":"m_allergy","to":"s_immune","level":"established","effect":"located","note":"Tolerance to foods and pollen is learned by the immune system."},{"from":"m_methyl","to":"s_liver","level":"established","effect":"located","note":"The liver does most of the body's methylation and clears homocysteine."},{"from":"s_ureters","to":"s_kidneys","level":"established","effect":"located","note":"The ureters start at the kidneys and drain their urine."},{"from":"s_ureters","to":"s_bladder","level":"established","effect":"located","note":"The ureters end in the bladder wall."},{"from":"tx_rotenone","to":"br_snc","level":"lab","effect":"harms","note":"In rats, rotenone selectively killed the dopamine cells of the substantia nigra.","sources":[{"id":"pmid:12504863","citation":"Sherer TB et al., Exp Neurol","year":2003,"design":"lab","finding":"Chronic rotenone in rats caused highly selective nigrostriatal dopamine cell loss while sparing nearby nuclei."}]},{"from":"tx_organochlorines","to":"br_snc","level":"association","effect":"harms","note":"Post-mortem studies found more organochlorine pesticide residues in the brains of people with Parkinson's.","sources":[{"id":"pmid:10706031","citation":"Corrigan FM et al., J Toxicol Environ Health A","year":2000,"design":"case-control","finding":"Lindane and dieldrin levels were higher in the substantia nigra of Parkinson's brains than in control brains."},{"id":"pmid:7517654","citation":"Fleming L et al., Ann Neurol","year":1994,"design":"case-control","finding":"Dieldrin was found in 6 of 20 Parkinson's brains and none of 14 control brains at post-mortem."}]},{"from":"tx_pbde","to":"s_thyroid","level":"association","effect":"harms","note":"Higher flame-retardant levels have been linked with thyroid disease, though studies of thyroid hormone levels disagree.","sources":[{"id":"pmid:27215290","citation":"Allen JG et al., Environ Health","year":2016,"design":"cohort","finding":"US women with the highest blood PBDE levels had higher odds of current thyroid disease, more so after menopause."},{"id":"pmid:25992849","citation":"Zhao X et al., PLoS One","year":2015,"design":"meta-analysis","finding":"Across studies, PBDE levels did not consistently correlate with thyroid hormones; the relationship may depend on exposure level."}]},{"from":"tx_bpa","to":"s_testes","level":"association","effect":"harms","note":"Higher BPA in urine has been linked with lower sperm counts and altered sex hormones in men.","sources":[{"id":"pmid:38668517","citation":"Lu L et al., Toxics","year":2024,"design":"meta-analysis","finding":"Urinary BPA was negatively associated with sperm concentration and total sperm count, and linked with changes in reproductive hormones."}]},{"from":"m_dopa","to":"s_bg","level":"established","effect":"located","note":"Dopamine for movement is made in the substantia nigra and released in the striatum, both in the basal ganglia."},{"from":"m_nurr1","to":"br_snc","level":"established","effect":"located","note":"Nurr1 is a gene switch that dopamine cells of the substantia nigra need to develop and stay healthy."},{"from":"m_iron","to":"br_snc","level":"established","effect":"located","note":"The substantia nigra is one of the most iron-rich parts of the brain, and iron is needed to make dopamine."},{"from":"m_aden","to":"s_bg","level":"established","effect":"located","note":"The adenosine receptor that caffeine blocks in movement control is concentrated in the striatum."},{"from":"m_reward","to":"s_limbic","level":"established","effect":"located","note":"Mood and reward run through the limbic system and the nucleus accumbens."},{"from":"m_cstc","to":"s_bg","level":"established","effect":"located","note":"Habit loops run from the cortex through the basal ganglia and thalamus and back."},{"from":"m_cstc","to":"s_prefrontal","level":"established","effect":"located","note":"The prefrontal cortex is the braking part of the habit loop."},{"from":"m_catechol","to":"s_prefrontal","level":"established","effect":"located","note":"This mechanism is about dopamine and noradrenaline in the prefrontal cortex."},{"from":"m_stress","to":"s_limbic","level":"established","effect":"located","note":"Fear and stress responses start in the amygdala, part of the limbic system."},{"from":"m_stress","to":"s_hypo","level":"established","effect":"located","note":"The hypothalamus turns stress into hormone signals through the pituitary and adrenal glands."},{"from":"m_clock","to":"br_scn","level":"established","effect":"located","note":"The body's master 24-hour clock is the suprachiasmatic nucleus in the hypothalamus."},{"from":"m_painproc","to":"s_spinal","level":"established","effect":"located","note":"Pain signals are first processed and turned up or down in the spinal cord."},{"from":"m_painproc","to":"br_thalamus","level":"established","effect":"located","note":"The thalamus relays pain signals up to the cortex."},{"from":"hm_calcitriol","to":"s_kidneys","level":"established","effect":"located","note":"The kidneys do the last step that turns vitamin D into active calcitriol."},{"from":"isolation","to":"bp_psyche","level":"established","effect":"located","note":"Social withdrawal is a change in mood and behaviour, part of mental health."},{"from":"wi_bloodborne","to":"s_blood","level":"established","effect":"affects","note":"Needlestick and splash exposures carry viruses directly into the blood."},{"from":"wi_bloodborne","to":"s_liver","level":"established","effect":"affects","note":"Hepatitis B and C caught this way infect the liver."},{"from":"s_breasts","to":"s_reproductive","level":"established","effect":"located","note":"Counted with the reproductive organs: they make milk to feed a baby."},{"from":"hm_oestrogen","to":"s_breasts","level":"established","effect":"helps","note":"Oestrogen grows the breast ducts at puberty and through each cycle."},{"from":"hm_progesterone","to":"s_breasts","level":"established","effect":"helps","note":"Progesterone develops the milk lobules and causes the swelling and tenderness some women feel before a period."},{"from":"hm_prolactin","to":"s_breasts","level":"established","effect":"helps","note":"Prolactin makes the breasts produce milk after birth."},{"from":"hm_oxytocin","to":"s_breasts","level":"established","effect":"helps","note":"Oxytocin squeezes milk out to the nipple when the baby feeds (the let-down reflex)."},{"from":"breast_cancer","to":"s_breasts","level":"established","effect":"affects","note":"Starts in the breast's ducts or lobules."},{"from":"breast_cancer","to":"s_lymph_armpit","level":"established","effect":"affects","note":"Breast cancer usually spreads first to the armpit lymph nodes, which are checked when it is treated."},{"from":"hm_oestrogen","to":"breast_cancer","level":"established","effect":"harms","note":"Most breast cancers carry oestrogen receptors and grow when oestrogen stimulates them, which is why some treatments block oestrogen."},{"from":"tx_alcohol","to":"breast_cancer","level":"association","effect":"harms","note":"Breast cancer risk rises steadily with how much alcohol women drink, in pooled data from 53 studies.","sources":[{"id":"pmid:12439712","citation":"Hamajima N et al. (Collaborative Group on Hormonal Factors in Breast Cancer), Br J Cancer","year":2002,"design":"meta-analysis","finding":"Pooled individual data from 53 studies (58,515 women with breast cancer) showed risk rising steadily with alcohol intake, not explained by smoking."}]},{"from":"h_mammography","to":"breast_cancer","level":"proven","effect":"helps","note":"In randomised trials, mammography screening lowered breast-cancer deaths by a modest amount, at the cost of some overdiagnosis and many false alarms.","sources":[{"id":"pmid:23117178","citation":"Independent UK Panel on Breast Cancer Screening (Marmot MG et al.), Lancet","year":2012,"design":"meta-analysis","finding":"Trials showed a relative reduction of about 20% in breast-cancer deaths among women invited to screening, with roughly one death prevented for every three overdiagnosed cases."},{"id":"pmid:23737396","citation":"Gotzsche PC, Jorgensen KJ, Cochrane Database Syst Rev","year":2013,"design":"meta-analysis","finding":"Assuming a 15% cut in breast-cancer deaths and 30% overdiagnosis, for 2000 women invited over 10 years one avoids dying of breast cancer and ten are treated unnecessarily; the adequately randomised trials showed less effect."}]},{"from":"s_salivary_glands","to":"s_mouth","level":"established","effect":"located","note":"Their ducts open into the mouth inside the cheeks and under the tongue."},{"from":"dry_mouth","to":"s_salivary_glands","level":"established","effect":"located","note":"Arises when the salivary glands make too little saliva."},{"from":"dry_mouth","to":"s_mouth","level":"established","effect":"located","note":"Felt as a dry, sticky or sore mouth."},{"from":"dry_mouth","to":"swallow","level":"established","effect":"harms","note":"Without enough saliva, food is hard to chew into a soft lump and swallow."},{"from":"parkinsons","to":"dry_mouth","level":"association","effect":"harms","note":"People with Parkinson's make less resting saliva and often have a dry mouth, sometimes at the same time as drooling.","sources":[{"id":"pmid:42769625","citation":"Baram S et al., J Oral Microbiol","year":2026,"design":"case-control","finding":"Patients with Parkinson's had significantly lower unstimulated whole saliva flow and more xerostomia and drooling than matched controls."},{"id":"pmid:41546443","citation":"van Dijk BDM et al., Gerodontology","year":2026,"design":"cohort","finding":"Survey of 111 people with Parkinson's: xerostomia in 64.9%, drooling in 27.0%, both together in 18.0%."}]},{"from":"h_botox_saliva","to":"swallow","level":"proven","effect":"helps","note":"For drooling in Parkinson's, salivary-gland injections reduced drooling in placebo-controlled trials; it does not improve swallowing itself.","scope":["parkinsons"],"sources":[{"id":"pmid:37828600","citation":"Yang CL et al., BMC Pharmacol Toxicol","year":2023,"design":"meta-analysis","finding":"8 RCTs, 259 patients with Parkinson's: botulinum toxin reduced Drooling Severity Frequency Scale scores versus placebo (high certainty) with more adverse events (low certainty)."}]},{"from":"s_tongue","to":"s_mouth","level":"established","effect":"located","note":"Fills the floor of the mouth."},{"from":"s_tongue","to":"s_throat","level":"established","effect":"located","note":"Its back part forms the front wall of the throat and starts each swallow."},{"from":"s_jaw_tmj","to":"s_bones","level":"established","effect":"located","note":"The mandible is a bone and the TMJ is a joint of the skull."},{"from":"s_jaw_tmj","to":"s_mouth","level":"established","effect":"located","note":"The jaws carry the teeth and open and close the mouth."},{"from":"bp_face_jaw","to":"s_jaw_tmj","level":"established","effect":"located","note":"The claimed body part 'face and jaw' includes the jaw bone and joint."},{"from":"bruxism","to":"bp_teeth","level":"established","effect":"affects","note":"Grinding wears down, chips and cracks teeth."},{"from":"bruxism","to":"s_jaw_tmj","level":"established","effect":"affects","note":"Clenching overloads the chewing muscles and jaw joints."},{"from":"anxiety","to":"bruxism","level":"association","effect":"harms","note":"Stress and anxiety go with more clenching and grinding in observational studies.","sources":[{"id":"pmid:40127752","citation":"Belenda González I et al., J Dent","year":2025,"design":"review","finding":"Systematic review of 10 observational studies: there seems to be an association between bruxism, temporomandibular disorders and stress, anxiety and depression."}]},{"from":"tmd","to":"s_jaw_tmj","level":"established","effect":"affects","note":"Pain and stiffness in the jaw joints and chewing muscles."},{"from":"tmd","to":"bp_face_jaw","level":"established","effect":"affects","note":"Jaw-joint pain is claimed under face and jaw."},{"from":"tmd","to":"pain","level":"established","effect":"harms","note":"Causes ongoing pain in the jaw, face and around the ear."},{"from":"bruxism","to":"tmd","level":"association","effect":"harms","note":"People who grind or clench have about twice the odds of a jaw-joint disorder in observational studies.","sources":[{"id":"pmid:37474733","citation":"Mortazavi N et al., Evid Based Dent","year":2023,"design":"meta-analysis","finding":"20 observational studies: bruxism increased the odds of TMD (OR 2.25), awake bruxism OR 2.51, sleep bruxism OR 2.06."}]},{"from":"uti","to":"s_bladder","level":"established","effect":"affects","note":"Most urinary infections are bladder infections (cystitis)."},{"from":"uti","to":"s_urethra","level":"established","effect":"affects","note":"Bacteria reach the bladder by climbing the urethra."},{"from":"uti","to":"s_kidneys","level":"established","effect":"affects","note":"An infection that climbs to the kidneys causes fever and back pain and needs prompt treatment."},{"from":"uti","to":"bladder","level":"established","effect":"harms","note":"An infected bladder causes urgency, frequency and getting up at night."},{"from":"uti","to":"pain","level":"established","effect":"harms","note":"Infection causes burning on passing urine and lower-belly or back pain."},{"from":"proanthocyanidins","to":"uti","level":"proven","effect":"helps","note":"Cranberry products cut repeat urinary infections by about a third in women with recurrent infections, children and after procedures, but not in care-home residents or people whose bladders do not empty because of nerve problems.","sources":[{"id":"pmid:37068952","citation":"Williams G et al., Cochrane Database of Systematic Reviews","year":2023,"design":"meta-analysis","finding":"Across 50 trials (8857 people), cranberry products cut repeat urinary infections by about 30% in women with recurrent infections, children and people after procedures, but showed little or no benefit in older people in care homes or in people whose bladders do not empty properly because of nerve problems."}]},{"from":"fluids","to":"uti","level":"proven","effect":"helps","note":"In women with repeat bladder infections who drank little, drinking more water nearly halved infections in a year-long trial.","sources":[{"id":"pmid:30285042","citation":"Hooton TM et al., JAMA Internal Medicine","year":2018,"design":"RCT","finding":"In 140 premenopausal women with recurrent cystitis who drank little, adding water daily for a year nearly halved bladder infections (1.7 vs 3.2 episodes) compared with no extra fluid."}]},{"from":"parkinsons","to":"uti","level":"association","effect":"harms","note":"Urinary infections are common in people with Parkinson's in hospital, more so with catheters and dementia.","sources":[{"id":"pmid:41693549","citation":"Kamo H et al., Movement Disorders Clinical Practice","year":2026,"design":"cohort","finding":"In over 321,000 hospital stays of people with Parkinson's, 18.9% involved a urinary infection; catheters, dementia and emergency admission raised the risk, and infection was linked with delirium and longer stays."}]},{"from":"uti","to":"cognition","level":"association","effect":"harms","note":"In people with Parkinson's in hospital, urinary infection was linked with delirium (sudden confusion) and longer stays.","sources":[{"id":"pmid:41693549","citation":"Kamo H et al., Movement Disorders Clinical Practice","year":2026,"design":"cohort","finding":"In over 321,000 hospital stays of people with Parkinson's, 18.9% involved a urinary infection; catheters, dementia and emergency admission raised the risk, and infection was linked with delirium and longer stays."}]},{"from":"hm_testosterone","to":"s_prostate","level":"established","effect":"helps","note":"The prostate needs testosterone, turned into the stronger DHT inside the gland, to grow and work."},{"from":"hm_testosterone","to":"bph","level":"established","effect":"harms","note":"An enlarged prostate only develops when male hormones are present; medicines that block DHT shrink the gland."},{"from":"bph","to":"s_prostate","level":"established","effect":"affects","note":"The inner part of the prostate grows and squeezes the urethra it surrounds."},{"from":"bph","to":"s_bladder","level":"established","effect":"affects","note":"Pushing urine past a narrowed outlet makes the bladder muscle work harder; over years it can thicken and stop emptying fully."},{"from":"bph","to":"bladder","level":"established","effect":"harms","note":"An enlarged prostate often causes urgency, frequent urination and getting up at night."},{"from":"bph","to":"d_weak_stream","level":"established","effect":"harms","note":"A narrowed outlet gives a weak, hesitant stream and a feeling of not emptying."},{"from":"d_weak_stream","to":"s_prostate","level":"established","effect":"located","note":"In men the commonest cause is the prostate narrowing the urethra."},{"from":"d_weak_stream","to":"s_bladder","level":"established","effect":"located","note":"A weak bladder muscle can also leave urine behind."},{"from":"prostate_cancer","to":"s_prostate","level":"established","effect":"affects","note":"The cancer starts in the gland cells of the prostate, usually in its outer part."},{"from":"prostate_cancer","to":"s_bones","level":"established","effect":"affects","note":"When prostate cancer spreads, it most often goes to the bones, especially the spine and pelvis."},{"from":"h_psa_screening","to":"prostate_cancer","level":"proven","effect":"helps","note":"PSA screening slightly lowers deaths from prostate cancer, but also finds many harmless cancers that then get treated.","sources":[{"id":"pmid:42134821","citation":"Franco JV et al., Cochrane Database of Systematic Reviews","year":2026,"design":"meta-analysis","finding":"Across six trials (about 789,000 men), PSA screening likely cuts prostate cancer deaths slightly (about 2 fewer per 1000 men, moderate certainty, mainly from the European ERSPC trial), may make little or no difference to deaths from any cause, and raises diagnoses of early cancers by about half."},{"id":"pmid:38581198","citation":"Martin RM et al., JAMA","year":2024,"design":"RCT","finding":"In the UK CAP trial of about 415,000 men, a single invitation to a PSA test reduced prostate cancer deaths at 15 years (0.69% vs 0.78%), a small absolute benefit, while increasing detection of low-grade cancers."}]},{"from":"ed","to":"s_penis","level":"established","effect":"located","note":"An erection is the penis filling with blood under nerve control."},{"from":"ed","to":"bp_sexual_function","level":"established","effect":"located","note":"Erectile problems are the most common way sexual function is affected in men."},{"from":"ed","to":"s_blood","level":"established","effect":"located","note":"Most erectile dysfunction is a blood-flow problem in the small penile arteries."},{"from":"ed","to":"s_autonomic","level":"established","effect":"located","note":"The nerve signal that starts an erection is carried by autonomic (automatic) nerves from the low spine."},{"from":"ed","to":"s_heart","level":"association","effect":"located","note":"Erectile dysfunction is an early warning sign: men who have it go on to have more heart attacks and strokes, because the same artery disease affects both.","sources":[{"id":"pmid:21920268","citation":"Dong JY et al., Journal of the American College of Cardiology","year":2011,"design":"meta-analysis","finding":"In 12 prospective cohorts (36,744 men), men with erectile dysfunction had about 48% more cardiovascular disease, 46% more coronary heart disease and 35% more stroke, even after accounting for usual risk factors."}]},{"from":"parkinsons","to":"ed","level":"established","effect":"harms","note":"Parkinson's damages the brain and autonomic nerves that control erections, and erection problems are common in men with it."},{"from":"msa","to":"ed","level":"established","effect":"harms","note":"Erectile failure is often one of the earliest signs of multiple system atrophy in men, sometimes years before other symptoms."},{"from":"tx_tobacco","to":"ed","level":"association","effect":"harms","note":"Smokers have about one and a half times the risk of erectile dysfunction; former smokers have less excess risk.","sources":[{"id":"pmid:23573257","citation":"Cao S et al., PLoS One","year":2013,"design":"meta-analysis","finding":"In prospective cohort studies, current smokers had about 1.5 times the odds of erectile dysfunction, and former smokers about 1.3 times, compared with never smokers."}]},{"from":"exercise","to":"ed","level":"proven","effect":"helps","note":"In trials, regular aerobic exercise improved erectile function in men with erection problems.","sources":[{"id":"pmid:27707739","citation":"Silva AB et al., British Journal of Sports Medicine","year":2017,"design":"meta-analysis","finding":"Across 7 randomised trials of men with erectile dysfunction, aerobic, pelvic-floor or combined exercise improved erectile function scores compared with control."},{"id":"pmid:37814532","citation":"Khera M et al., Journal of Sexual Medicine","year":2023,"design":"meta-analysis","finding":"Across 11 randomised trials, aerobic exercise improved erectile function scores compared with no exercise, with larger gains in men with worse function at the start."}]},{"from":"hm_testosterone","to":"ed","level":"proven","effect":"helps","note":"In men with clearly low testosterone, treatment modestly improved erections and more clearly improved desire; it was not tested here for men with normal levels.","sources":[{"id":"pmid:28434676","citation":"Corona G et al., European Urology","year":2017,"design":"meta-analysis","finding":"Across 14 placebo-controlled trials (2298 men), testosterone treatment modestly improved erectile function scores in men with low testosterone."},{"id":"pmid:27355400","citation":"Cunningham GR et al., Journal of Clinical Endocrinology and Metabolism","year":2016,"design":"RCT","finding":"In 470 men aged 65 or older with low testosterone and low libido, a year of testosterone gel improved sexual activity and desire compared with placebo."}]},{"from":"male_hypogonadism","to":"hm_testosterone","level":"established","effect":"harms","note":"By definition, the testes make too little testosterone."},{"from":"male_hypogonadism","to":"s_testes","level":"established","effect":"affects","note":"Either the testes themselves fail, or they get no signal to work."},{"from":"male_hypogonadism","to":"s_pituitary","level":"established","effect":"affects","note":"When the cause is in the pituitary, it fails to send the hormone (LH) that tells the testes to make testosterone."},{"from":"male_hypogonadism","to":"bp_sexual_function","level":"established","effect":"affects","note":"Low testosterone reduces sex drive and can contribute to erection problems."},{"from":"male_hypogonadism","to":"m_bone","level":"established","effect":"harms","note":"Without enough sex hormone, bone thins over years."},{"from":"hm_prolactin","to":"hm_testosterone","level":"established","effect":"harms","note":"Too much prolactin switches off the brain signals that drive the testes, lowering testosterone."},{"from":"hm_testosterone","to":"s_sperm_ducts","level":"established","effect":"helps","note":"High testosterone inside the testes and epididymis is needed for sperm to form and mature."},{"from":"d_incontinence","to":"s_bladder","level":"established","effect":"located","note":"Leakage comes from the bladder squeezing at the wrong time, or its outlet failing to stay shut."},{"from":"bladder","to":"d_incontinence","level":"established","effect":"harms","note":"When urgency cannot be held long enough to reach the toilet, it becomes urge leakage."},{"from":"parkinsons","to":"d_incontinence","level":"established","effect":"harms","note":"An overactive bladder plus slow movement makes urge leakage common in Parkinson's."},{"from":"msa","to":"d_incontinence","level":"established","effect":"harms","note":"Leakage and poor emptying are early, prominent features of multiple system atrophy."},{"from":"ms","to":"d_incontinence","level":"established","effect":"harms","note":"Spinal cord damage in MS disrupts bladder control, causing urgency and leakage."},{"from":"pelvic","to":"d_incontinence","level":"mixed","effect":"helps","note":"Pelvic-floor training is proven to help women with stress leakage, but formal therapy sessions did not reduce leakage in men after prostate surgery.","sources":[{"id":"pmid:30288727","citation":"Dumoulin C et al., Cochrane Database Syst Rev","year":2018,"design":"meta-analysis","finding":"Across 31 trials (1817 women), pelvic-floor muscle training made women with stress incontinence about eight times more likely to report cure than no treatment (high-quality evidence)."},{"id":"pmid:21741700","citation":"Glazener C et al., Lancet","year":2011,"design":"RCT","finding":"In two trials of men still leaking 6 weeks after prostate surgery, four one-to-one pelvic-floor therapy sessions did not reduce incontinence at 12 months compared with standard care and advice."}]},{"from":"d_incontinence","to":"falls","level":"association","effect":"harms","note":"People with urine leakage fall more often, partly from rushing to the toilet, especially at night.","sources":[{"id":"pmid:34010311","citation":"Moon S et al., PLoS One","year":2021,"design":"meta-analysis","finding":"Across 38 studies (230,129 people), urinary incontinence was linked with about 1.6 times the odds of falling, in both men and women and for both urge and stress leakage."}]},{"from":"tx_tobacco","to":"s_bladder","level":"association","effect":"harms","note":"Cancer-causing chemicals from smoke are filtered into urine and sit against the bladder lining; smokers get bladder cancer about four times as often.","sources":[{"id":"pmid:21846855","citation":"Freedman ND et al., JAMA","year":2011,"design":"cohort","finding":"In about 468,000 men and women, current smokers had about four times, and former smokers about twice, the risk of bladder cancer of never smokers."},{"id":"pmid:35332429","citation":"Zhao X et al., International Urology and Nephrology","year":2022,"design":"meta-analysis","finding":"A dose-response meta-analysis confirmed that bladder cancer risk rises with the amount smoked."}]},{"from":"oral_cancer","to":"s_mouth","level":"established","effect":"affects","note":"Starts in the lining of the tongue, gums, cheeks, lips or floor of the mouth."},{"from":"oral_cancer","to":"s_lymph_neck","level":"established","effect":"affects","note":"Spreads first to the lymph nodes of the neck."},{"from":"tx_tobacco","to":"oral_cancer","level":"established","effect":"harms","note":"Smoking and chewing tobacco are leading causes of mouth cancer.","sources":[{"id":"pmid:19190158","citation":"Hashibe M et al., Cancer Epidemiol Biomarkers Prev","year":2009,"design":"case-control","finding":"Pooled 17 case-control studies (11,221 cases): tobacco and alcohol had a greater-than-multiplicative joint effect on head and neck cancer; together they explained 64% of oral cavity cancer."}]},{"from":"tx_alcohol","to":"oral_cancer","level":"established","effect":"harms","note":"Alcohol causes mouth cancer, and with smoking the risk multiplies.","sources":[{"id":"pmid:19190158","citation":"Hashibe M et al., Cancer Epidemiol Biomarkers Prev","year":2009,"design":"case-control","finding":"Joint tobacco and alcohol use carried far more risk of head and neck cancer than either alone (interaction 2.15)."}]},{"from":"s_vagina","to":"s_reproductive","level":"established","effect":"located","note":"Part of the female reproductive organs."},{"from":"hm_oestrogen","to":"s_vagina","level":"established","effect":"helps","note":"Oestrogen keeps the vaginal lining thick and moist; after menopause it thins and dries."},{"from":"menopause","to":"hm_oestrogen","level":"established","effect":"harms","note":"At menopause the ovaries stop making most of their oestrogen."},{"from":"menopause","to":"s_ovaries","level":"established","effect":"affects","note":"The ovaries run out of eggs and stop their monthly cycle."},{"from":"menopause","to":"m_bone","level":"established","effect":"harms","note":"Bone loss speeds up for several years after menopause as oestrogen falls, raising the risk of osteoporosis."},{"from":"menopause","to":"s_vagina","level":"established","effect":"affects","note":"With less oestrogen the vaginal and urinary lining thins and dries, which can cause soreness, painful sex and urinary symptoms."},{"from":"menopause","to":"depression","level":"association","effect":"harms","note":"In women with no history of depression, depressed mood was about four times more likely during the menopause transition than before it.","sources":[{"id":"pmid:16585466","citation":"Freeman EW et al., Arch Gen Psychiatry","year":2006,"design":"cohort","finding":"In an 8-year population cohort, high depression scores were more than four times as likely during the menopausal transition as before it."}]},{"from":"menopause","to":"s_heart","level":"association","effect":"harms","note":"Women whose menopause came before 45 had more heart disease than those with later menopause.","sources":[{"id":"pmid:27627190","citation":"Muka T et al., JAMA Cardiol","year":2016,"design":"meta-analysis","finding":"Across 32 studies (310,329 women), menopause before 45 was linked with a 50% higher risk of coronary heart disease and higher cardiovascular death."}]},{"from":"menopause","to":"hot_flushes","level":"established","effect":"harms","note":"Most women have hot flushes or night sweats around menopause."},{"from":"hot_flushes","to":"s_hypo","level":"established","effect":"located","note":"They start in the hypothalamus's temperature-control centre when oestrogen falls.","sources":[{"id":"pmid:30572747","citation":"Anderson RA et al., Climacteric","year":2019,"design":"review","finding":"Neurokinin B signalling in hypothalamic neurons links falling oestrogen to hot flushes, and blocking it relieves them quickly."}]},{"from":"hot_flushes","to":"insomnia","level":"association","effect":"harms","note":"Sleep trouble is most common in late perimenopause, and hot flushes are one of the factors linked with it.","sources":[{"id":"pmid:12544673","citation":"Kravitz HM et al., Menopause (SWAN)","year":2003,"design":"cohort","finding":"In 12,603 women aged 40 to 55, difficulty sleeping peaked in late perimenopause and was linked with menopausal stage and with hot flushes."}]},{"from":"h_hrt","to":"hm_oestrogen","level":"established","effect":"helps","note":"Replaces the oestrogen the ovaries no longer make."},{"from":"h_hrt","to":"hot_flushes","level":"proven","effect":"helps","note":"Hormone therapy was highly effective against hot flushes and night sweats in placebo-controlled trials.","sources":[{"id":"pmid:15495039","citation":"MacLennan AH et al., Cochrane Database Syst Rev","year":2004,"design":"meta-analysis","finding":"Oral oestrogen with or without progestogen reduced hot-flush frequency far more than placebo (about 75% fewer), with a large placebo effect too."}]},{"from":"h_hrt","to":"fracture","level":"proven","effect":"helps","note":"In the Women's Health Initiative trial, oestrogen plus progestin cut fractures, including hip fractures, while it was taken.","sources":[{"id":"pmid:14519707","citation":"Cauley JA et al., JAMA (WHI)","year":2003,"design":"RCT","finding":"Oestrogen plus progestin reduced total fractures by about a quarter (HR 0.76) and raised hip bone density in healthy postmenopausal women."},{"id":"pmid:24084921","citation":"Manson JE et al., JAMA (WHI)","year":2013,"design":"RCT","finding":"Benefits of both WHI hormone regimens included fewer hip fractures; most benefits and risks faded after stopping."}]},{"from":"h_hrt","to":"s_heart","level":"mixed","effect":"harms","note":"In the WHI trials, oestrogen plus progestin started at an average age of 63 slightly raised heart attacks while oestrogen alone did not, and results were more favourable in women in their 50s, so the effect depends on age and type.","sources":[{"id":"pmid:12117397","citation":"Rossouw JE et al., JAMA (WHI)","year":2002,"design":"RCT","finding":"The oestrogen-plus-progestin trial was stopped early because risks (breast cancer, heart disease, stroke, blood clots) exceeded benefits (fewer fractures and colorectal cancers)."},{"id":"pmid:24084921","citation":"Manson JE et al., JAMA (WHI)","year":2013,"design":"RCT","finding":"Coronary heart disease HR 1.18 with oestrogen plus progestin and 0.94 with oestrogen alone; younger women on oestrogen alone had more favourable results; therapy not supported for chronic disease prevention."}]},{"from":"hm_insulin","to":"pcos","level":"established","effect":"harms","note":"High insulin from insulin resistance pushes the ovaries to make more testosterone, worsening PCOS.","sources":[{"id":"pmid:23065822","citation":"Diamanti-Kandarakis E, Dunaif A, Endocr Rev","year":2012,"design":"review","finding":"Insulin resistance is common in PCOS, and insulin acts as a co-gonadotropin on the ovary to raise androgen production."}]},{"from":"pcos","to":"hm_testosterone","level":"established","effect":"affects","note":"In PCOS the ovaries make more testosterone and related androgens than usual."},{"from":"pcos","to":"s_ovaries","level":"established","effect":"affects","note":"Eggs are released irregularly or not at all, and many small follicles collect in the ovaries."},{"from":"pcos","to":"s_skin","level":"established","effect":"affects","note":"Extra androgens cause acne, extra facial and body hair, and sometimes thinning scalp hair."},{"from":"exercise","to":"pcos","level":"proven","effect":"helps","note":"Diet and exercise programmes lowered androgen levels and weight a little in small, low-quality trials; effects on periods and fertility were not tested.","sources":[{"id":"pmid:30921477","citation":"Lim SS et al., Cochrane Database Syst Rev","year":2019,"design":"meta-analysis","finding":"Lifestyle intervention may improve free androgen index, weight and BMI in women with PCOS (low-quality evidence); no trials reported live birth or menstrual regularity."},{"id":"pmid:37580861","citation":"Teede HJ et al., Eur J Endocrinol","year":2023,"design":"review","finding":"The 2023 international evidence-based PCOS guideline sets diagnostic criteria and management recommendations, noting the evidence is generally low quality."}]},{"from":"pregnancy","to":"folate","level":"established","effect":"harms","note":"Pregnancy greatly raises the need for folate, which the fast-growing baby uses to copy DNA."},{"from":"pregnancy","to":"iron","level":"established","effect":"harms","note":"Pregnancy greatly raises iron needs (more blood, the baby and the placenta), so iron stores often run low; supplements reduced anaemia in mothers in trials.","sources":[{"id":"pmid:39145520","citation":"Finkelstein JL et al., Cochrane Database Syst Rev","year":2024,"design":"meta-analysis","finding":"Daily oral iron in pregnancy probably reduces maternal iron-deficiency anaemia at term; for most other outcomes there was little difference or the evidence was uncertain."}]},{"from":"pregnancy","to":"hm_progesterone","level":"established","effect":"affects","note":"The placenta makes large amounts of progesterone, which keeps the womb quiet and the pregnancy going."},{"from":"pregnancy","to":"constipation","level":"established","effect":"harms","note":"Constipation is common in pregnancy as progesterone slows the gut and the growing womb presses on it."},{"from":"pregnancy","to":"pre_eclampsia","level":"established","effect":"harms","note":"Pre-eclampsia only happens in pregnancy, usually after 20 weeks, or just after birth."},{"from":"pre_eclampsia","to":"s_blood","level":"established","effect":"affects","note":"Factors from the placenta damage the lining of blood vessels and raise blood pressure.","sources":[{"id":"pmid:34051884","citation":"Chappell LC et al., Lancet","year":2021,"design":"review","finding":"Placental malperfusion releases soluble factors that injure maternal vessel lining, causing hypertension and multi-organ injury; delivery is the only cure."}]},{"from":"pre_eclampsia","to":"s_kidneys","level":"established","effect":"affects","note":"Damaged kidney filters leak protein into the urine."},{"from":"pre_eclampsia","to":"s_liver","level":"established","effect":"affects","note":"Severe pre-eclampsia can injure the liver, causing pain under the right ribs."},{"from":"pre_eclampsia","to":"seizures","level":"established","effect":"harms","note":"Seizures in pre-eclampsia are called eclampsia and are an emergency."},{"from":"pre_eclampsia","to":"s_heart","level":"association","effect":"harms","note":"Women who had pre-eclampsia have about twice the risk of heart disease and more high blood pressure and stroke in later life.","sources":[{"id":"pmid:17975258","citation":"Bellamy L et al., BMJ","year":2007,"design":"meta-analysis","finding":"After pre-eclampsia, relative risks were 3.7 for hypertension, 2.16 for ischaemic heart disease and 1.81 for stroke over 10 to 14 years; no rise in cancer."}]},{"from":"calcium","to":"pre_eclampsia","level":"mixed","effect":"helps","note":"An earlier review found calcium supplements cut pre-eclampsia, mostly in small trials, but the latest review of trustworthy trials found little or no difference.","sources":[{"id":"pmid:30277579","citation":"Hofmeyr GJ et al., Cochrane Database Syst Rev","year":2018,"design":"meta-analysis","finding":"High-dose calcium may reduce pre-eclampsia, especially with low-calcium diets (low-quality evidence), and the effect may be overestimated by small-study effects."},{"id":"pmid:41330480","citation":"Cluver CA et al., Cochrane Database Syst Rev","year":2025,"design":"meta-analysis","finding":"Calcium versus placebo may make little to no difference to pre-eclampsia; high-certainty evidence from the large trials showed little to no difference."}]},{"from":"stress_incontinence","to":"s_bladder","level":"established","effect":"located","note":"Urine escapes from the bladder when the outlet's supports are weak."},{"from":"pregnancy","to":"stress_incontinence","level":"association","effect":"harms","note":"Women who have given birth leak urine more often, especially after vaginal birth; caesarean birth carries a smaller extra risk.","sources":[{"id":"pmid:12621134","citation":"Rortveit G et al., N Engl J Med","year":2003,"design":"cohort","finding":"Compared with caesarean birth, vaginal delivery was linked with more incontinence (odds ratio 1.7), mainly stress incontinence; caesarean was still linked with more than no births."}]},{"from":"pelvic","to":"stress_incontinence","level":"proven","effect":"helps","note":"Pelvic-floor muscle training cured or improved leaking on effort in women in many trials, and structured training early in pregnancy helped prevent leaking late in pregnancy and after birth.","sources":[{"id":"pmid:30288727","citation":"Dumoulin C et al., Cochrane Database Syst Rev","year":2018,"design":"meta-analysis","finding":"Pelvic-floor muscle training cured or improved stress and all other types of urinary incontinence in women compared with no treatment."},{"id":"pmid:32378735","citation":"Woodley SJ et al., Cochrane Database Syst Rev","year":2020,"design":"meta-analysis","finding":"Early structured pelvic-floor training in pregnancy for continent women may prevent incontinence in late pregnancy and after birth; its effect as treatment after birth is uncertain."}]},{"from":"cataract","to":"s_lens","level":"established","effect":"affects","note":"The lens turns cloudy."},{"from":"cataract","to":"bp_eyes","level":"established","effect":"affects","note":"Affects the eyes."},{"from":"tx_tobacco","to":"cataract","level":"association","effect":"harms","note":"Smokers, especially current smokers, more often develop cataract.","sources":[{"id":"pmid:22599585","citation":"Ye J et al., Invest Ophthalmol Vis Sci","year":2012,"design":"meta-analysis","finding":"Across 21 studies, ever smoking was linked to higher risk of age-related cataract, especially the nuclear type; current smokers had higher risk than past smokers."}]},{"from":"lutein","to":"cataract","level":"failed","effect":"helps","note":"In a large trial, lutein/zeaxanthin supplements did not reduce the need for cataract surgery overall.","sources":[{"id":"pmid:23645227","citation":"AREDS2 Research Group, JAMA Ophthalmol","year":2013,"design":"RCT","finding":"Lutein/zeaxanthin supplements had no overall effect on the need for cataract surgery or vision loss over about five years."}]},{"from":"glaucoma","to":"s_optic_nerve","level":"established","effect":"affects","note":"The optic nerve's fibres are lost; the disc looks cupped."},{"from":"glaucoma","to":"s_retinal_ganglion","level":"established","effect":"affects","note":"The retinal ganglion cells die."},{"from":"glaucoma","to":"bp_eyes","level":"established","effect":"affects","note":"Affects the eyes."},{"from":"h_eye_pressure","to":"glaucoma","level":"proven","effect":"helps","note":"Lowering eye pressure slows glaucoma and delays it in people with raised pressure, though lost vision does not come back.","sources":[{"id":"pmid:12365904","citation":"Heijl A et al., Arch Ophthalmol","year":2002,"design":"RCT","finding":"In early open-angle glaucoma, lowering eye pressure made worsening less frequent (45% vs 62%) and later over about six years."},{"id":"pmid:12049574","citation":"Kass MA et al., Arch Ophthalmol","year":2002,"design":"RCT","finding":"In people with raised eye pressure, pressure-lowering eye drops delayed or prevented the onset of open-angle glaucoma."}]},{"from":"parkinsons","to":"dry_eye","level":"association","effect":"harms","note":"Fewer blinks and a less sensitive cornea make dry eye more common in Parkinson's.","sources":[{"id":"pmid:14745050","citation":"Biousse V et al., Neurology","year":2004,"design":"case-control","finding":"Early untreated Parkinson's patients had more eye-surface irritation, altered tear film, reduced blinking and weaker eye convergence than controls."},{"id":"pmid:22832867","citation":"Reddy VC et al., Cornea","year":2013,"design":"case-control","finding":"People with Parkinson's or PSP blinked less, had less sensitive corneas and more eye-surface damage than controls, which may keep dry eye from being noticed."},{"id":"pmid:32161030","citation":"Borm CDJM et al., Neurology","year":2020,"design":"case-control","finding":"In 848 people with Parkinson's and 250 controls, 82% vs 48% reported eye symptoms, across the eye surface, inside the eye, eye movements and optic nerve, and they often disrupted daily life."}]},{"from":"dry_eye","to":"s_cornea","level":"established","effect":"located","note":"The surface of the cornea dries and gets irritated."},{"from":"dry_eye","to":"s_lacrimal","level":"established","effect":"located","note":"Arises when the tear film is too thin or evaporates too fast."},{"from":"omega3","to":"dry_eye","level":"failed","effect":"helps","note":"A large year-long trial found fish-oil omega-3 supplements did no better than placebo for dry eye.","sources":[{"id":"pmid:29652551","citation":"DREAM Study Research Group, N Engl J Med","year":2018,"design":"RCT","finding":"In 535 people with moderate-to-severe dry eye, a year of fish-oil omega-3 supplements did no better than olive-oil placebo on symptoms or eye-surface signs."}]},{"from":"parkinsons","to":"diplopia","level":"association","effect":"harms","note":"Double vision is reported by roughly one in ten to one in three people with Parkinson's, often from weak eye convergence.","sources":[{"id":"pmid:24405755","citation":"Urwyler P et al., Parkinsonism Relat Disord","year":2014,"design":"case-control","finding":"Double vision was reported by 18% of 88 Parkinson's patients vs 1% of controls; recurrent visual complaints predicted minor hallucinations but not complex ones."},{"id":"pmid:38541012","citation":"Ungureanu L et al., J Pers Med","year":2024,"design":"review","finding":"Across 43 studies, 10-38% of people with Parkinson's had double vision, linked to convergence problems, motor fluctuations, visual hallucinations and cognitive decline."},{"id":"pmid:32161030","citation":"Borm CDJM et al., Neurology","year":2020,"design":"case-control","finding":"In 848 people with Parkinson's and 250 controls, 82% vs 48% reported eye symptoms, across the eye surface, inside the eye, eye movements and optic nerve, and they often disrupted daily life."}]},{"from":"diplopia","to":"s_eye_muscles","level":"established","effect":"located","note":"The two eyes' muscles fail to keep them aligned."},{"from":"diplopia","to":"hallucinations","level":"association","effect":"harms","note":"People with Parkinson's who have double vision more often also have visual hallucinations.","sources":[{"id":"pmid:38541012","citation":"Ungureanu L et al., J Pers Med","year":2024,"design":"review","finding":"Across 43 studies, 10-38% of people with Parkinson's had double vision, linked to convergence problems, motor fluctuations, visual hallucinations and cognitive decline."}]},{"from":"fibroids","to":"s_uterus","level":"established","effect":"affects","note":"Fibroids grow in or on the muscle wall of the womb.","sources":[{"id":"pmid:27335259","citation":"Stewart EA et al., Nat Rev Dis Primers","year":2016,"design":"review","finding":"Fibroids are common benign clonal tumours of uterine muscle, earlier and more severe in Black women, accounting for a third to half of hysterectomies."}]},{"from":"fibroids","to":"heavy_periods","level":"established","effect":"harms","note":"Fibroids, especially those bulging into the womb cavity, are a common cause of heavy periods."},{"from":"fibroids","to":"bladder","level":"established","effect":"harms","note":"Large fibroids can press on the bladder, so people need to pass urine more often."},{"from":"hm_oestrogen","to":"fibroids","level":"established","effect":"harms","note":"Fibroids grow under oestrogen, which is why they shrink after menopause."},{"from":"hm_progesterone","to":"fibroids","level":"established","effect":"harms","note":"Progesterone also drives fibroid growth; medicines that block its receptor shrink them."},{"from":"hm_oestrogen","to":"endometriosis","level":"established","effect":"harms","note":"Endometriosis is fed by oestrogen, which is why hormone treatments that lower it ease symptoms.","sources":[{"id":"pmid:30026507","citation":"Zondervan KT et al., Nat Rev Dis Primers","year":2018,"design":"review","finding":"Endometriosis is a common inflammatory disease affecting about 5 to 10% of reproductive-age women, linked to pelvic pain and infertility, with a favourable hormonal environment among its drivers."}]},{"from":"endometriosis","to":"period_pain","level":"established","effect":"harms","note":"Severe, worsening period pain is the commonest symptom of endometriosis."},{"from":"endometriosis","to":"pain","level":"established","effect":"harms","note":"It also causes long-lasting pelvic pain between periods and pain during sex or bowel movements."},{"from":"endometriosis","to":"s_ovaries","level":"established","effect":"affects","note":"Endometriosis on the ovary can form blood-filled cysts (endometriomas)."},{"from":"endometriosis","to":"s_fallopian_tubes","level":"established","effect":"affects","note":"Scarring and adhesions can distort or block the tubes, one reason it makes pregnancy harder."},{"from":"endometriosis","to":"s_colon","level":"established","effect":"affects","note":"Deep endometriosis can grow into the bowel wall, causing painful bowel movements."},{"from":"endometriosis","to":"bp_sexual_function","level":"established","effect":"affects","note":"Deep pelvic deposits make sex painful for many women with endometriosis."},{"from":"h_hrt","to":"breast_cancer","level":"proven","effect":"harms","note":"Oestrogen plus progestin raised breast cancer in the WHI trial and risk grows with years of use; oestrogen alone, in women without a womb, did not raise it in that trial.","sources":[{"id":"pmid:12117397","citation":"Rossouw JE et al., JAMA (WHI)","year":2002,"design":"RCT","finding":"Oestrogen plus progestin increased invasive breast cancer in healthy postmenopausal women, and the trial was stopped early."},{"id":"pmid:24084921","citation":"Manson JE et al., JAMA (WHI)","year":2013,"design":"RCT","finding":"Invasive breast cancer HR 1.24 with oestrogen plus progestin (1.28 cumulatively), but 0.79 with oestrogen alone."},{"id":"pmid:31474332","citation":"Collaborative Group on Hormonal Factors in Breast Cancer, Lancet","year":2019,"design":"meta-analysis","finding":"Pooled worldwide data show breast-cancer risk rises with duration of hormone therapy, more with oestrogen plus progestagen than oestrogen alone."}]},{"from":"s_spleen_white_pulp","to":"s_spleen","level":"established","effect":"located","note":"Part of the spleen: its immune islands."},{"from":"s_spleen_red_pulp","to":"s_spleen","level":"established","effect":"located","note":"Part of the spleen: its blood-filtering bulk."},{"from":"s_marrow","to":"s_lymph","level":"established","effect":"located","note":"A primary lymphoid organ: where B cells are made and trained."},{"from":"s_marrow","to":"s_thymus","level":"established","effect":"helps","note":"The marrow sends the young T-cell precursors that the thymus trains."},{"from":"plasmodium","to":"s_spleen_red_pulp","level":"established","effect":"harms","note":"Malaria-infected red cells are trapped and destroyed in the red pulp, which enlarges the spleen."},{"from":"s_lymph_supraclavicular","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: a group of lymph nodes."},{"from":"s_lymph_mediastinal","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: a group of lymph nodes."},{"from":"s_lymph_mesenteric","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: a group of lymph nodes."},{"from":"s_lymph_para_aortic","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: a group of lymph nodes."},{"from":"s_lymph_iliac","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: a group of lymph nodes."},{"from":"s_lymph_popliteal","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: a group of lymph nodes."},{"from":"s_lymph_mediastinal","to":"s_lungs","level":"established","effect":"located","note":"Sit around the windpipe and at the roots of the lungs, filtering their lymph."},{"from":"s_lymph_mesenteric","to":"s_lymph_gut","level":"established","effect":"located","note":"Part of the gut's immune tissue: the nodes in its mesentery."},{"from":"mtb","to":"s_lymph_mediastinal","level":"established","effect":"harms","note":"Tuberculosis often swells the lymph nodes at the root of the lung, especially in children."},{"from":"ebv","to":"mononucleosis","level":"established","effect":"harms","note":"EBV is the usual cause of glandular fever when first caught in the teens or later."},{"from":"mononucleosis","to":"s_spleen","level":"established","effect":"affects","note":"The spleen often swells and can, rarely, tear, mostly in the first three weeks.","sources":[{"id":"pmid:20505178","citation":"Luzuriaga K & Sullivan JL, N Engl J Med","year":2010,"design":"review","finding":"Review of glandular fever: caused by a first EBV infection; sore throat, fever, swollen lymph nodes and an enlarged spleen are typical."},{"id":"pmid:37245117","citation":"Toti JMA et al., Swiss Med Wkly","year":2023,"design":"review","finding":"Across published cases, spleen rupture in glandular fever mostly happened within three weeks of symptoms starting and was occasionally fatal."}]},{"from":"mononucleosis","to":"s_tonsils","level":"established","effect":"affects","note":"The tonsils swell and are often coated white."},{"from":"mononucleosis","to":"swollen_nodes","level":"established","effect":"harms","note":"Swollen, tender neck lymph nodes are a typical sign."},{"from":"lymphoma","to":"s_lymph","level":"established","effect":"affects","note":"Most lymphomas start in lymph nodes."},{"from":"lymphoma","to":"swollen_nodes","level":"established","effect":"harms","note":"Painless lymph nodes that keep growing are the commonest first sign."},{"from":"lymphoma","to":"s_spleen","level":"established","effect":"affects","note":"Lymphoma often enlarges the spleen."},{"from":"ebv","to":"lymphoma","level":"association","effect":"harms","note":"EBV is found in the cancer cells of some lymphomas, such as endemic Burkitt lymphoma and part of Hodgkin lymphoma, and helps cause them.","sources":[{"id":"pmid:31186275","citation":"Murray PG & Young LS, Blood","year":2019,"design":"review","finding":"EBV is an accepted cause of tumours that always carry it (such as endemic Burkitt lymphoma) and plays a causal part in the share of Hodgkin lymphomas that carry the virus."}]},{"from":"hiv","to":"lymphoma","level":"established","effect":"harms","note":"A weakened immune system from untreated HIV raises the risk of lymphoma."},{"from":"filaria","to":"s_lymph_vessels","level":"established","effect":"harms","note":"Adult worms live in the lymph vessels and damage and widen them."},{"from":"filaria","to":"lymphoedema","level":"established","effect":"harms","note":"The main cause of lymphoedema worldwide, leading in advanced cases to elephantiasis."},{"from":"sx_axillary_nodes","to":"s_lymph_armpit","level":"established","effect":"harms","note":"Removes some or most of the armpit lymph nodes."},{"from":"sx_axillary_nodes","to":"lymphoedema","level":"association","effect":"harms","note":"About one in five women get arm lymphoedema after breast cancer, much more often after full armpit node removal than after sentinel node biopsy.","sources":[{"id":"pmid:23540561","citation":"DiSipio T et al., Lancet Oncol","year":2013,"design":"meta-analysis","finding":"About one in five women developed arm lymphoedema after breast cancer, rising for up to two years after surgery; the risk was higher after full armpit node removal."},{"id":"pmid:18838709","citation":"McLaughlin SA et al., J Clin Oncol","year":2008,"design":"cohort","finding":"Five years after surgery, lymphoedema was much less common after sentinel node biopsy alone than after full armpit node dissection, but not absent."}]},{"from":"s_lymph_gut","to":"s_malt","level":"established","effect":"located","note":"The gut's part of the mucosa-associated lymph tissue."},{"from":"s_tonsils","to":"s_malt","level":"established","effect":"located","note":"The throat's part of the mucosa-associated lymph tissue."},{"from":"s_malt","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: immune tissue in the body's linings."},{"from":"s_palatine_tonsils","to":"s_tonsils","level":"established","effect":"located","note":"Part of Waldeyer's ring."},{"from":"s_adenoids","to":"s_tonsils","level":"established","effect":"located","note":"Part of Waldeyer's ring."},{"from":"s_lingual_tonsil","to":"s_tonsils","level":"established","effect":"located","note":"Part of Waldeyer's ring."},{"from":"s_peyers_patches","to":"s_lymph_gut","level":"established","effect":"located","note":"Part of the gut's lymph tissue."},{"from":"s_peyers_patches","to":"s_small_intestine","level":"established","effect":"located","note":"Sit in the wall of the small intestine, mostly the ileum."},{"from":"s_appendix","to":"s_lymph_gut","level":"established","effect":"located","note":"Its wall is rich in gut lymph follicles."},{"from":"s_appendix","to":"s_colon","level":"established","effect":"located","note":"Hangs from the caecum, the start of the large intestine."},{"from":"s_lymph_node","to":"s_lymph","level":"established","effect":"located","note":"Lymph nodes are the filters of the lymphatic system."},{"from":"s_lymph_node_capsule","to":"s_lymph_node","level":"established","effect":"located","note":"Part of every lymph node."},{"from":"s_lymph_follicles","to":"s_lymph_node","level":"established","effect":"located","note":"Part of every lymph node."},{"from":"s_lymph_paracortex","to":"s_lymph_node","level":"established","effect":"located","note":"Part of every lymph node."},{"from":"s_lymph_medulla","to":"s_lymph_node","level":"established","effect":"located","note":"Part of every lymph node."},{"from":"s_high_endothelial_venules","to":"s_lymph_paracortex","level":"established","effect":"located","note":"Sit in the T-cell zone of the node."},{"from":"s_lymph_neck","to":"s_lymph_node","level":"established","effect":"located","note":"Made of individual lymph nodes."},{"from":"s_lymph_armpit","to":"s_lymph_node","level":"established","effect":"located","note":"Made of individual lymph nodes."},{"from":"s_lymph_groin","to":"s_lymph_node","level":"established","effect":"located","note":"Made of individual lymph nodes."},{"from":"swollen_nodes","to":"s_lymph_follicles","level":"established","effect":"located","note":"Nodes swell mostly because B cells in the follicles multiply into germinal centres (and T cells in the paracortex multiply too)."},{"from":"hiv","to":"s_lymph_paracortex","level":"established","effect":"harms","note":"HIV infects and depletes helper T cells in the lymph nodes, wearing down their T-cell zones."},{"from":"s_lymph_capillaries","to":"s_lymph_vessels","level":"established","effect":"located","note":"Part of the lymph vessel network: its starting point, where fluid enters."},{"from":"s_lymphangion","to":"s_lymph_vessels","level":"established","effect":"located","note":"Part of the collecting lymph vessels: the valved segment that pumps."},{"from":"s_lacteals","to":"s_lymph_vessels","level":"established","effect":"located","note":"Part of the lymph vessel network: its fat-absorbing capillaries in the gut."},{"from":"s_lacteals","to":"s_small_intestine","level":"established","effect":"located","note":"Sits in the centre of each villus of the small intestine."},{"from":"s_lymph_capillaries","to":"s_skin","level":"established","effect":"located","note":"Lymph capillaries form a dense mesh in the skin."},{"from":"s_muscle","to":"s_lymphangion","level":"established","effect":"helps","note":"Working muscles squeeze the collecting vessels from outside, adding to each segment's own pumping."},{"from":"exercise","to":"s_lymphangion","level":"established","effect":"helps","note":"Moving muscles squeeze the collecting vessels, and lymph flow rises several-fold during exercise."},{"from":"s_cisterna_chyli","to":"s_thoracic_duct","level":"established","effect":"located","note":"The sac where the thoracic duct begins."},{"from":"s_right_lymph_duct","to":"s_lymph","level":"established","effect":"located","note":"Part of the lymphatic system: returns lymph from the upper right body to the blood."},{"from":"s_lacteals","to":"s_cisterna_chyli","level":"established","effect":"located","note":"Chyle from the lacteals reaches the blood through the cisterna chyli and the thoracic duct."},{"from":"s_lungs","to":"s_cisterna_chyli","level":"established","effect":"helps","note":"Breathing moves the diaphragm and shifts belly and chest pressure, which pushes lymph from the cisterna chyli up the thoracic duct."},{"from":"h_mld","to":"lymphoedema","level":"mixed","effect":"helps","note":"Trials disagree: some found less new swelling or pain, most found little extra drop in limb volume when added to compression.","sources":[{"id":"pmid:25994425","citation":"Ezzo J et al., Cochrane Database Syst Rev","year":2015,"design":"meta-analysis","finding":"Across randomised trials, adding manual lymphatic drainage to compression gave inconsistent extra reduction in arm swelling; pain and heaviness improved in most people whichever treatment they had."},{"id":"pmid:35370085","citation":"Lin Y et al., Clin Breast Cancer","year":2022,"design":"meta-analysis","finding":"Manual lymphatic drainage lowered the rate of new lymphoedema and eased pain after breast cancer surgery, but did not reduce arm volume in established lymphoedema."},{"id":"pmid:33285693","citation":"Liang M et al., Medicine (Baltimore)","year":2020,"design":"meta-analysis","finding":"Pooled trials found no significant reduction in lymphoedema from manual lymphatic drainage after breast cancer surgery."}]},{"from":"h_compression","to":"lymphoedema","level":"proven","effect":"helps","note":"Wearing compression sleeves after breast cancer surgery made arm swelling less likely and later in a randomised trial and a meta-analysis.","sources":[{"id":"pmid:35108031","citation":"Paramanandam VS et al., J Clin Oncol","year":2022,"design":"RCT","finding":"Women at high risk who wore compression sleeves after breast cancer surgery developed arm swelling less often and later over the first year than those without sleeves."},{"id":"pmid:41389304","citation":"Cheng H et al., Breast Cancer Res Treat","year":2025,"design":"meta-analysis","finding":"Across 1532 patients, compression sleeves reduced how often lymphoedema developed after breast cancer surgery and reduced arm volume or circumference."}]},{"from":"h_mld","to":"s_lymph_vessels","level":"association","effect":"helps","note":"In a small imaging study, lymph moved about a quarter faster and the vessels pumped more often right after one drainage session; how long this lasts is not known.","sources":[{"id":"pmid:21530723","citation":"Tan IC et al., Arch Phys Med Rehabil","year":2011,"design":"cohort","finding":"In 10 people with lymphoedema and 12 healthy controls, near-infrared fluorescence imaging showed apparent lymph velocity rose by about 23-28% and the time between lymph pumping events shortened immediately after a manual lymphatic drainage session."}]},{"from":"h_compression","to":"s_lymph_vessels","level":"established","effect":"helps","note":"Pressure from outside reduces fluid leaking into the tissue and makes muscle movement pump lymph harder."},{"from":"bp_sleep","to":"s_glymphatic","level":"association","effect":"helps","note":"In a small human study one night without sleep slowed the brain's clearance of a tracer; in mice, studies disagree on whether sleep speeds clearance.","sources":[{"id":"pmid:33829232","citation":"Eide PK et al., Brain","year":2021,"design":"case-control","finding":"In people given a tracer into the spinal fluid, one night without sleep slowed its clearance from most brain regions compared with people who slept, and a night of recovery sleep did not make up for it."},{"id":"pmid:24136970","citation":"Xie L et al., Science","year":2013,"design":"lab","finding":"In mice, sleep widened the spaces between brain cells by about 60% and sped up clearance of amyloid."},{"id":"pmid:38741022","citation":"Miao A et al., Nat Neurosci","year":2024,"design":"lab","finding":"In mice, brain clearance of injected dyes was reduced, not increased, during sleep and anaesthesia, challenging the sleep-clearance idea."}]},{"from":"s_glymphatic","to":"parkinsons","level":"association","effect":"helps","note":"An indirect MRI marker of brain fluid flow is lower in Parkinson's; whether poor clearance helps cause the disease, or follows from it, is unknown.","sources":[{"id":"pmid:34271425","citation":"McKnight CD et al., Parkinsonism Relat Disord","year":2021,"design":"case-control","finding":"An MRI marker of fluid movement along brain vessels (ALPS index) was lower in people with Parkinson's than in people with essential tremor, and fell with age."}]},{"from":"gallstones","to":"s_gallbladder","level":"established","effect":"affects","note":"Gallstones form in the gallbladder and can block its outlet."},{"from":"sx_cholecystectomy","to":"s_gallbladder","level":"established","effect":"affects","note":"The whole gallbladder is removed; bile then flows straight from the liver into the gut."},{"from":"sx_cholecystectomy","to":"gallstones","level":"mixed","effect":"helps","note":"Removing the gallbladder stops gallstone attacks returning, but for uncomplicated gallstones a large trial found similar quality of life with watchful waiting.","sources":[{"id":"pmid:38084426","citation":"Ahmed I et al. (C-GALL), BMJ","year":2023,"design":"RCT","finding":"In 434 adults with uncomplicated symptomatic gallstones, pain-related quality of life at 18 months was similar with watchful (conservative) management or keyhole gallbladder removal; 25% of the conservative group had surgery anyway."}]},{"from":"sx_cholecystectomy","to":"s_colon","level":"association","effect":"harms","note":"About 1 in 6 people get new loose or urgent stools after gallbladder removal, often from extra bile reaching the large bowel.","sources":[{"id":"pmid:18522570","citation":"Fisher M et al., ANZ J Surg","year":2008,"design":"cohort","finding":"About 17% of people reported troublesome new diarrhoea 6-12 months after keyhole gallbladder removal, more often if younger than 50."}]},{"from":"sx_cholecystectomy","to":"bp_internal_organs","level":"established","effect":"affects","note":"An internal organ in the belly is removed."},{"from":"appendicitis","to":"s_colon","level":"established","effect":"affects","note":"The appendix hangs off the first part of the large bowel; when inflamed it can burst into the belly."},{"from":"sx_appendectomy","to":"appendicitis","level":"established","effect":"helps","note":"Removing the inflamed appendix cures appendicitis; antibiotics alone work for many, but about 3 in 10 still needed surgery within 3 months in a large trial.","sources":[{"id":"pmid:33017106","citation":"CODA Collaborative, N Engl J Med","year":2020,"design":"RCT","finding":"In 1552 adults, antibiotics were not worse than appendectomy for 30-day health status, but 29% of the antibiotics group had their appendix removed within 90 days (41% if an appendix stone was present)."}]},{"from":"sx_appendectomy","to":"s_colon","level":"established","effect":"affects","note":"The appendix is removed from where it joins the large bowel."},{"from":"sx_colectomy","to":"s_colon","level":"established","effect":"affects","note":"Part of the large bowel is removed and the ends rejoined, so stool may be looser or more frequent afterwards.","sources":[{"id":"pmid:29936195","citation":"Croese AD et al., Int J Surg","year":2018,"design":"meta-analysis","finding":"About 41% of people had major low anterior resection syndrome (urgency, frequency, clustering, leakage) after rectal cancer surgery that keeps the anus."}]},{"from":"sx_colectomy","to":"bp_internal_organs","level":"established","effect":"affects","note":"An internal organ in the belly is partly removed."},{"from":"sx_ostomy","to":"s_colon","level":"established","effect":"affects","note":"Stool leaves through an opening in the belly wall instead of the anus."},{"from":"sx_ostomy","to":"s_kidneys","level":"association","effect":"harms","note":"An ileostomy can lose a lot of water and salt; dehydration, which strains the kidneys, is the commonest reason for going back to hospital.","sources":[{"id":"pmid:22228161","citation":"Messaris E et al., Dis Colon Rectum","year":2012,"design":"cohort","finding":"Of 603 people given a loop ileostomy, 17% were readmitted within 60 days, and dehydration was the commonest reason (43% of readmissions)."}]},{"from":"sx_ostomy","to":"bp_abdomen","level":"association","effect":"harms","note":"About 1 in 3 people with a stoma develop a hernia bulge in the belly wall beside it.","sources":[{"id":"pmid:20010354","citation":"Pilgrim CH et al., Dis Colon Rectum","year":2010,"design":"cohort","finding":"In a prospective audit, 33% of people with a stoma developed a parastomal hernia (46% after sigmoid colostomy, 22% after ileostomy)."}]},{"from":"sx_gastrectomy","to":"s_stomach","level":"established","effect":"affects","note":"Part or all of the stomach is removed, so meals must be smaller and more frequent."},{"from":"sx_gastrectomy","to":"b12","level":"established","effect":"harms","note":"Without the stomach's intrinsic factor, vitamin B12 cannot be absorbed from food; about half of people become deficient.","sources":[{"id":"pmid:37669168","citation":"Bahardoust M et al., Eur J Cancer Prev","year":2024,"design":"meta-analysis","finding":"Pooled across 14 studies, about 49% of people had vitamin B12 deficiency after gastrectomy for stomach cancer."}]},{"from":"sx_gastrectomy","to":"iron","level":"established","effect":"harms","note":"Less stomach acid and bypassed upper gut mean iron from food is absorbed poorly."},{"from":"sx_splenectomy","to":"s_spleen","level":"established","effect":"affects","note":"The spleen is removed entirely."},{"from":"sx_splenectomy","to":"s_immune","level":"established","effect":"harms","note":"Without the spleen, the blood is cleared of some bacteria more slowly, so serious infections stay more likely for life.","sources":[{"id":"pmid:19841456","citation":"Thomsen RW et al., Ann Intern Med","year":2009,"design":"cohort","finding":"In 3812 Danes after splenectomy, the risk of hospital contact for infection was 4.6 times the general population at 3-12 months and still 2.5 times after the first year."}]},{"from":"sx_splenectomy","to":"opsi","level":"established","effect":"harms","note":"Removing the spleen is what creates the risk of overwhelming blood infection.","sources":[{"id":"pmid:19841456","citation":"Thomsen RW et al., Ann Intern Med","year":2009,"design":"cohort","finding":"In 3812 Danes after splenectomy, the risk of hospital contact for infection was 4.6 times the general population at 3-12 months and still 2.5 times after the first year."}]},{"from":"sx_splenectomy","to":"bp_internal_organs","level":"established","effect":"affects","note":"An internal organ is removed, often after a ruptured spleen from a work or vehicle injury."},{"from":"opsi","to":"s_blood","level":"established","effect":"affects","note":"Bacteria multiply in the bloodstream and can cause sepsis within hours."},{"from":"h_asplenia_vaccines","to":"opsi","level":"established","effect":"helps","note":"Guidelines recommend these vaccines for everyone without a working spleen to lower the chance of overwhelming infection.","sources":[{"id":"pmid:12448592","citation":"Davies JM et al. (British Committee for Standards in Haematology), Clin Med","year":2002,"design":"review","finding":"Guideline for people with no working spleen: vaccination (pneumococcal, meningococcal, Hib, flu), antibiotic cover and prompt treatment of fever."}]},{"from":"sx_kidney_transplant","to":"s_kidneys","level":"established","effect":"helps","note":"A working donor kidney takes over cleaning the blood, and long-term survival is better than staying on dialysis.","sources":[{"id":"pmid:10580071","citation":"Wolfe RA et al., N Engl J Med","year":1999,"design":"cohort","finding":"After a short early rise, long-term death rates for kidney transplant recipients were 48-82% lower than for similar people who stayed on dialysis on the waiting list."}]},{"from":"sx_kidney_transplant","to":"s_immune","level":"established","effect":"harms","note":"Lifelong anti-rejection drugs dampen the immune system, so infections are more common and can be unusual.","sources":[{"id":"pmid:18094380","citation":"Fishman JA, N Engl J Med","year":2007,"design":"review","finding":"Anti-rejection drugs leave transplant recipients open to common and unusual infections, with a predictable timeline after surgery."}]},{"from":"sx_kidney_transplant","to":"s_skin","level":"association","effect":"harms","note":"Skin cancers are far more common after a kidney transplant because the immune system is held down.","sources":[{"id":"pmid:22886725","citation":"Krynitz B et al., Int J Cancer","year":2013,"design":"cohort","finding":"In 10,476 Swedish transplant recipients, squamous-cell skin cancer was 121 times (kidney) and 32 times (liver) the general-population rate, and other cancers about 2.3 times."}]},{"from":"sx_kidney_transplant","to":"bp_internal_organs","level":"established","effect":"affects","note":"An internal organ is added low in the belly."},{"from":"sx_liver_transplant","to":"s_liver","level":"established","effect":"helps","note":"A donor liver takes over the work of a liver that has failed."},{"from":"sx_liver_transplant","to":"s_immune","level":"established","effect":"harms","note":"Lifelong anti-rejection drugs dampen the immune system, so infections are more common.","sources":[{"id":"pmid:18094380","citation":"Fishman JA, N Engl J Med","year":2007,"design":"review","finding":"Anti-rejection drugs leave transplant recipients open to common and unusual infections, with a predictable timeline after surgery."}]},{"from":"sx_liver_transplant","to":"s_skin","level":"association","effect":"harms","note":"Skin cancers are much more common after a liver transplant because the immune system is held down.","sources":[{"id":"pmid:22886725","citation":"Krynitz B et al., Int J Cancer","year":2013,"design":"cohort","finding":"In 10,476 Swedish transplant recipients, squamous-cell skin cancer was 121 times (kidney) and 32 times (liver) the general-population rate, and other cancers about 2.3 times."}]},{"from":"sx_liver_transplant","to":"bp_internal_organs","level":"established","effect":"affects","note":"An internal organ is replaced."},{"from":"sx_pancreatectomy","to":"s_pancreas","level":"established","effect":"affects","note":"Part or all of the pancreas is removed, taking insulin-making and enzyme-making tissue with it."},{"from":"sx_pancreatectomy","to":"hm_insulin","level":"established","effect":"harms","note":"Removing pancreas tissue removes insulin-making islets: diabetes follows about 1 in 6 Whipple operations and every total removal.","sources":[{"id":"pmid:29779868","citation":"Scholten L et al., Surgery","year":2018,"design":"meta-analysis","finding":"About 16% of people developed new diabetes after a Whipple operation (6% needing insulin)."},{"id":"pmid:31502658","citation":"Scholten L et al., Br J Surg","year":2019,"design":"review","finding":"After total pancreatectomy everyone has diabetes; 44% reported symptoms of enzyme shortage and overall quality of life was moderately lower than the general population."}]},{"from":"sx_pancreatectomy","to":"pancreatic_insufficiency","level":"established","effect":"harms","note":"Removing pancreas tissue lowers digestive enzymes; about 4 in 10 people have enzyme shortage after a Whipple.","sources":[{"id":"pmid:33483914","citation":"Moore JV et al., J Gastrointest Surg","year":2021,"design":"review","finding":"Across 30 studies, poor digestive-enzyme output followed about 43% of Whipple operations and 12% of tail (distal) pancreatectomies."}]},{"from":"pancreatic_insufficiency","to":"s_pancreas","level":"established","effect":"affects","note":"The enzyme-making part of the pancreas does not deliver enough enzymes."},{"from":"obesity","to":"s_fat","level":"established","effect":"affects","note":"Obesity is an excess of stored body fat."},{"from":"type2_diabetes","to":"hm_insulin","level":"established","effect":"affects","note":"The body responds poorly to insulin and cannot make enough extra to keep blood sugar normal."},{"from":"sx_gastric_bypass","to":"s_stomach","level":"established","effect":"affects","note":"Most of the stomach and the first part of the small intestine are bypassed by a small stomach pouch."},{"from":"sx_gastric_bypass","to":"obesity","level":"proven","effect":"helps","note":"In randomised trials, gastric bypass gave large weight loss that lasted at least 10 years.","sources":[{"id":"pmid:35731535","citation":"Salminen P et al. (SLEEVEPASS), JAMA Surg","year":2022,"design":"RCT","finding":"At 10 years both operations gave lasting weight loss (somewhat more with bypass); oesophagitis was more common after sleeve (31% vs 7%)."},{"id":"pmid:28199805","citation":"Schauer PR et al. (STAMPEDE), N Engl J Med","year":2017,"design":"RCT","finding":"At 5 years, more people with type 2 diabetes reached good blood-sugar control after gastric bypass (29%) or sleeve (23%) than with medical therapy alone (5%), and they lost more weight."}]},{"from":"sx_gastric_bypass","to":"type2_diabetes","level":"proven","effect":"helps","note":"In a randomised trial, far more people reached good blood-sugar control after bypass than with medicines alone.","sources":[{"id":"pmid:28199805","citation":"Schauer PR et al. (STAMPEDE), N Engl J Med","year":2017,"design":"RCT","finding":"At 5 years, more people with type 2 diabetes reached good blood-sugar control after gastric bypass (29%) or sleeve (23%) than with medical therapy alone (5%), and they lost more weight."}]},{"from":"sx_gastric_bypass","to":"b12","level":"established","effect":"harms","note":"Bypassing the stomach removes most intrinsic factor and acid, so vitamin B12 runs low without lifelong supplements.","sources":[{"id":"pmid:28392254","citation":"Parrott J et al. (ASMBS guideline), Surg Obes Relat Dis","year":2017,"design":"review","finding":"Guideline: vitamin and mineral deficiencies (B12, iron, calcium, vitamin D and others) are common after weight-loss surgery and need lifelong supplements and monitoring."}]},{"from":"sx_gastric_bypass","to":"iron","level":"established","effect":"harms","note":"Iron is mainly absorbed in the bypassed first part of the small intestine, so iron deficiency is common.","sources":[{"id":"pmid:28392254","citation":"Parrott J et al. (ASMBS guideline), Surg Obes Relat Dis","year":2017,"design":"review","finding":"Guideline: vitamin and mineral deficiencies (B12, iron, calcium, vitamin D and others) are common after weight-loss surgery and need lifelong supplements and monitoring."}]},{"from":"sx_gastric_bypass","to":"calcium","level":"established","effect":"harms","note":"Calcium is mainly absorbed in the bypassed upper small intestine, so bones can thin without supplements.","sources":[{"id":"pmid:28392254","citation":"Parrott J et al. (ASMBS guideline), Surg Obes Relat Dis","year":2017,"design":"review","finding":"Guideline: vitamin and mineral deficiencies (B12, iron, calcium, vitamin D and others) are common after weight-loss surgery and need lifelong supplements and monitoring."}]},{"from":"sx_gastric_bypass","to":"vitd","level":"established","effect":"harms","note":"Fat-soluble vitamin D is absorbed less after bypass, adding to the calcium shortfall.","sources":[{"id":"pmid:28392254","citation":"Parrott J et al. (ASMBS guideline), Surg Obes Relat Dis","year":2017,"design":"review","finding":"Guideline: vitamin and mineral deficiencies (B12, iron, calcium, vitamin D and others) are common after weight-loss surgery and need lifelong supplements and monitoring."}]},{"from":"sx_gastric_bypass","to":"tx_alcohol","level":"association","effect":"harms","note":"After bypass, a modest drink can push blood alcohol over the driving limit within minutes, and alcohol problems become more common from the second year.","sources":[{"id":"pmid:23507629","citation":"Steffen KJ et al., Surg Obes Relat Dis","year":2013,"design":"cohort","finding":"After gastric bypass, a modest drink pushed blood alcohol above the US driving limit within about 10 minutes in all participants."},{"id":"pmid:22710289","citation":"King WC et al., JAMA","year":2012,"design":"cohort","finding":"Alcohol use disorder symptoms rose from 7.6% before to 9.6% in the second year after bariatric surgery, mainly after gastric bypass."}]},{"from":"sx_sleeve_gastrectomy","to":"s_stomach","level":"established","effect":"affects","note":"Most of the stomach is removed, leaving a narrow tube."},{"from":"sx_sleeve_gastrectomy","to":"obesity","level":"proven","effect":"helps","note":"In randomised trials, sleeve gastrectomy gave large weight loss that lasted at least 10 years.","sources":[{"id":"pmid:35731535","citation":"Salminen P et al. (SLEEVEPASS), JAMA Surg","year":2022,"design":"RCT","finding":"At 10 years both operations gave lasting weight loss (somewhat more with bypass); oesophagitis was more common after sleeve (31% vs 7%)."},{"id":"pmid:28199805","citation":"Schauer PR et al. (STAMPEDE), N Engl J Med","year":2017,"design":"RCT","finding":"At 5 years, more people with type 2 diabetes reached good blood-sugar control after gastric bypass (29%) or sleeve (23%) than with medical therapy alone (5%), and they lost more weight."}]},{"from":"sx_sleeve_gastrectomy","to":"type2_diabetes","level":"proven","effect":"helps","note":"In a randomised trial, more people reached good blood-sugar control after a sleeve than with medicines alone.","sources":[{"id":"pmid:28199805","citation":"Schauer PR et al. (STAMPEDE), N Engl J Med","year":2017,"design":"RCT","finding":"At 5 years, more people with type 2 diabetes reached good blood-sugar control after gastric bypass (29%) or sleeve (23%) than with medical therapy alone (5%), and they lost more weight."}]},{"from":"sx_sleeve_gastrectomy","to":"s_oesophagus","level":"proven","effect":"harms","note":"In a randomised trial, inflammation of the gullet from acid reflux was about four times more common after a sleeve than after a bypass.","sources":[{"id":"pmid:35731535","citation":"Salminen P et al. (SLEEVEPASS), JAMA Surg","year":2022,"design":"RCT","finding":"At 10 years both operations gave lasting weight loss (somewhat more with bypass); oesophagitis was more common after sleeve (31% vs 7%)."}]},{"from":"sx_thyroidectomy","to":"s_thyroid","level":"established","effect":"affects","note":"All or part of the thyroid gland is removed."},{"from":"sx_thyroidectomy","to":"hm_thyroid","level":"established","effect":"harms","note":"With the whole thyroid gone the body makes no thyroid hormone, so replacement is needed for life."},{"from":"sx_thyroidectomy","to":"calcium","level":"association","effect":"harms","note":"Bruising or removal of the parathyroid glands lowers blood calcium; common for a few weeks, permanent in a small minority.","sources":[{"id":"pmid:39824725","citation":"Niu A et al., Am J Surg","year":2025,"design":"cohort","finding":"In 1182 total thyroidectomies, 17% had temporary low parathyroid function and 0.5% permanent, in a high-volume centre."}]},{"from":"sx_thyroidectomy","to":"s_larynx","level":"association","effect":"harms","note":"The nerve to the vocal cords runs behind the thyroid; about 3-4% get a weak or hoarse voice, usually temporary.","sources":[{"id":"pmid:21520117","citation":"Higgins TS et al., Laryngoscope","year":2011,"design":"meta-analysis","finding":"Across 64,699 nerves at risk, vocal-cord paralysis after thyroidectomy occurred in about 3.5-3.7% (most temporary), with or without nerve monitoring."}]},{"from":"sx_adrenalectomy","to":"s_adrenal","level":"established","effect":"affects","note":"One or both adrenal glands are removed."},{"from":"sx_adrenalectomy","to":"hm_cortisol","level":"established","effect":"harms","note":"Removing both adrenals stops cortisol production, so replacement is needed for life; after one side the other usually copes."},{"from":"sx_nephrectomy","to":"s_kidneys","level":"established","effect":"affects","note":"One kidney is removed and the other takes over its work; later kidney failure is slightly more likely but still rare.","sources":[{"id":"pmid:24519297","citation":"Muzaale AD et al., JAMA","year":2014,"design":"cohort","finding":"Kidney failure 15 years after donating a kidney was 30.8 per 10,000 donors versus 3.9 per 10,000 matched healthy non-donors: higher, but still small."}]},{"from":"sx_nephrectomy","to":"bp_internal_organs","level":"established","effect":"affects","note":"An internal organ is removed, sometimes after an injury."},{"from":"sx_tonsillectomy","to":"s_tonsils","level":"established","effect":"affects","note":"The tonsils (and often adenoids) are removed."},{"from":"sx_tonsillectomy","to":"osa","level":"proven","effect":"helps","note":"In children with sleep apnoea, removing tonsils and adenoids normalised sleep studies more often than waiting and improved behaviour.","sources":[{"id":"pmid:23692173","citation":"Marcus CL et al. (CHAT), N Engl J Med","year":2013,"design":"RCT","finding":"In children with sleep apnoea, early adenotonsillectomy normalised sleep studies more often than watchful waiting (79% vs 46%) and improved behaviour and quality of life, but not attention test scores."}]},{"from":"sx_tonsillectomy","to":"s_throat","level":"association","effect":"harms","note":"Bleeding from the throat after tonsil removal affects a few in every hundred, sometimes needing a return to theatre.","sources":[{"id":"pmid:25515059","citation":"Söderman AC et al., Clin Otolaryngol","year":2015,"design":"cohort","finding":"In 15,734 Swedish tonsillectomies, bleeding occurred early in 3.2% and late in 9.4%, and 2.7% returned to theatre."}]},{"from":"sx_lobectomy","to":"s_lungs","level":"established","effect":"affects","note":"A lobe of lung is removed, so less lung is left to move air."},{"from":"sx_lobectomy","to":"breathless","level":"association","effect":"harms","note":"Losing a lobe lowers breathing capacity; exercise capacity mostly recovers within a year, and removing less lung keeps more.","sources":[{"id":"pmid:35461558","citation":"Saji H et al. (JCOG0802), Lancet","year":2022,"design":"RCT","finding":"In small lung cancers, removing a whole lobe lowered breathing capacity (FEV1) at 1 year more than removing a segment (difference 3.5%), and segmentectomy gave better 5-year survival."},{"id":"pmid:17976462","citation":"Nagamatsu Y et al., J Thorac Cardiovasc Surg","year":2007,"design":"cohort","finding":"After lobectomy, exercise capacity dropped to about 80% at 2 weeks and recovered to about 95% of baseline by 1 year."}]},{"from":"sx_lobectomy","to":"bp_lungs","level":"established","effect":"affects","note":"Part of a lung is removed."},{"from":"sx_peg","to":"s_stomach","level":"established","effect":"affects","note":"A tube passes through the belly wall into the stomach so food can bypass the mouth and throat."},{"from":"sx_peg","to":"nutrition","level":"association","effect":"helps","note":"A stomach tube keeps food and fluids going in when swallowing fails and fails less often than a nose tube; in advanced dementia no benefit is shown.","sources":[{"id":"pmid:25997528","citation":"Gomes CA et al., Cochrane Database Syst Rev","year":2015,"design":"meta-analysis","finding":"In 11 trials, gastrostomy (PEG) tubes failed less often than nose tubes, with no clear difference in deaths or aspiration pneumonia."},{"id":"pmid:19370678","citation":"Sampson EL et al., Cochrane Database Syst Rev","year":2009,"design":"review","finding":"In advanced dementia, no evidence that tube feeding prolongs life, improves nutrition or prevents pressure sores."}]},{"from":"sx_peg","to":"pneumonia","level":"failed","effect":"helps","note":"A feeding tube does not stop saliva going down the wrong way, and trials did not show fewer aspiration pneumonias.","sources":[{"id":"pmid:25997528","citation":"Gomes CA et al., Cochrane Database Syst Rev","year":2015,"design":"meta-analysis","finding":"In 11 trials, gastrostomy (PEG) tubes failed less often than nose tubes, with no clear difference in deaths or aspiration pneumonia."}]},{"from":"sx_hysterectomy","to":"s_reproductive","level":"established","effect":"affects","note":"The womb is removed, so periods stop and pregnancy is no longer possible."},{"from":"sx_oophorectomy","to":"s_ovaries","level":"established","effect":"affects","note":"Both ovaries are removed."},{"from":"sx_oophorectomy","to":"hm_oestrogen","level":"established","effect":"harms","note":"Removing both ovaries before menopause stops most oestrogen production at once: an immediate surgical menopause."},{"from":"sx_oophorectomy","to":"hm_progesterone","level":"established","effect":"harms","note":"Without ovaries there is no ovulation and progesterone production stops."},{"from":"sx_oophorectomy","to":"s_heart","level":"association","effect":"harms","note":"Removing both ovaries at hysterectomy, especially before 50 without hormone therapy, is linked with more coronary heart disease and death.","sources":[{"id":"pmid:19384117","citation":"Parker WH et al. (Nurses' Health Study), Obstet Gynecol","year":2009,"design":"cohort","finding":"Removing both ovaries at hysterectomy for benign disease was linked with higher all-cause death (HR 1.12) and coronary disease (HR 1.17), and less breast and ovarian cancer."}]},{"from":"sx_oophorectomy","to":"parkinsons","level":"association","effect":"harms","note":"Women who had both ovaries removed before menopause later had more parkinsonism, most clearly when surgery was before age 43.","sources":[{"id":"pmid:36287560","citation":"Rocca WA et al., JAMA Netw Open","year":2022,"design":"cohort","finding":"Removing both ovaries before menopause was linked with more parkinsonism (HR 1.59), most strongly when done before age 43."},{"id":"pmid:17761549","citation":"Rocca WA et al., Neurology","year":2008,"design":"cohort","finding":"Women who had one or both ovaries removed before menopause had a higher later risk of parkinsonism, increasing with younger age at surgery."}]},{"from":"sx_prostatectomy","to":"s_reproductive","level":"established","effect":"affects","note":"The prostate and seminal vesicles are removed, so no semen is produced at orgasm."},{"from":"sx_prostatectomy","to":"s_bladder","level":"proven","effect":"harms","note":"In a randomised trial, prostate removal caused more urine leakage than monitoring or radiotherapy, improving over time but not fully.","sources":[{"id":"pmid:27626365","citation":"Donovan JL et al. (ProtecT), N Engl J Med","year":2016,"design":"RCT","finding":"Of active monitoring, surgery and radiotherapy for prostate cancer, prostatectomy had the largest and most lasting harm to erections and urinary control."}]},{"from":"sx_prostatectomy","to":"bp_sexual_function","level":"proven","effect":"harms","note":"In a randomised trial, prostate removal had the largest and most lasting harm to erections of the treatments compared.","sources":[{"id":"pmid:27626365","citation":"Donovan JL et al. (ProtecT), N Engl J Med","year":2016,"design":"RCT","finding":"Of active monitoring, surgery and radiotherapy for prostate cancer, prostatectomy had the largest and most lasting harm to erections and urinary control."}]},{"from":"sx_mastectomy","to":"bp_chest_ribs","level":"established","effect":"affects","note":"Breast tissue is removed from the chest wall, leaving a scar across the chest."},{"from":"sx_mastectomy","to":"s_lymph_armpit","level":"established","effect":"affects","note":"Armpit lymph nodes are often removed to check or treat cancer spread."},{"from":"sx_mastectomy","to":"lymphoedema","level":"association","effect":"harms","note":"About 1 in 5 women develop arm swelling after breast cancer treatment, more often when many armpit lymph nodes are removed.","sources":[{"id":"pmid:23540561","citation":"DiSipio T et al., Lancet Oncol","year":2013,"design":"meta-analysis","finding":"About 1 in 6 women overall, and more than 1 in 5 in prospective studies, develop arm lymphoedema after breast cancer, rising for up to 2 years."}]},{"from":"sx_amputation","to":"bp_ankles_feet","level":"established","effect":"affects","note":"Leg and foot amputations remove the foot and ankle and sometimes the lower leg."},{"from":"sx_amputation","to":"bp_wrists_hands","level":"established","effect":"affects","note":"Arm amputations, often after crush injuries, remove the hand or wrist."},{"from":"sx_amputation","to":"bp_fingers","level":"established","effect":"affects","note":"Finger and thumb amputations are among the commonest work-related amputations."},{"from":"sx_amputation","to":"chronic_pain","level":"association","effect":"harms","note":"About 6 in 10 people feel lasting pain in the missing limb (phantom limb pain).","sources":[{"id":"pmid:33052924","citation":"Limakatso K et al., PLoS One","year":2020,"design":"meta-analysis","finding":"About 64% of people with an amputation report phantom limb pain."}]},{"from":"sx_valve_replacement","to":"s_heart","level":"proven","effect":"helps","note":"In people with a severely narrowed aortic valve, a new valve improved symptoms and cut deaths in a randomised trial.","sources":[{"id":"pmid:20961243","citation":"Leon MB et al. (PARTNER), N Engl J Med","year":2010,"design":"RCT","finding":"In severe aortic stenosis unfit for open surgery, a catheter-placed valve cut 1-year deaths from 50.7% to 30.7%."}]},{"from":"sx_valve_replacement","to":"bp_heart_circulation","level":"established","effect":"affects","note":"A heart valve is replaced."},{"from":"sx_stents","to":"s_heart","level":"proven","effect":"helps","note":"Stents save lives in a heart attack and can ease angina, but in stable disease they did not prevent heart attacks or deaths compared with medicines.","sources":[{"id":"pmid:12517460","citation":"Keeley EC et al., Lancet","year":2003,"design":"meta-analysis","finding":"In 23 trials of major heart attack, opening the artery with angioplasty lowered short-term death (7% vs 9%) and reinfarction compared with clot-busting drugs."},{"id":"pmid:38015442","citation":"Rajkumar CA et al. (ORBITA-2), N Engl J Med","year":2023,"design":"RCT","finding":"In stable angina with little or no anti-angina medication, stenting reduced angina more than a placebo procedure."},{"id":"pmid:29103656","citation":"Al-Lamee R et al. (ORBITA), Lancet","year":2018,"design":"RCT","finding":"In stable angina on full medication, stenting did not improve exercise time more than a placebo procedure."},{"id":"pmid:32227755","citation":"Maron DJ et al. (ISCHEMIA), N Engl J Med","year":2020,"design":"RCT","finding":"In stable coronary disease, an early invasive strategy (stents or bypass) did not reduce heart attacks or deaths over 3.2 years compared with medicines first."}]},{"from":"sx_stents","to":"bp_heart_circulation","level":"established","effect":"affects","note":"Metal stents are left inside the heart arteries."},{"from":"sx_cabg","to":"s_heart","level":"proven","effect":"helps","note":"In people with coronary disease and a weak heart, bypass surgery lowered heart deaths over 10 years in a randomised trial.","sources":[{"id":"pmid:27040723","citation":"Velazquez EJ et al. (STICH), N Engl J Med","year":2016,"design":"RCT","finding":"In coronary disease with a weak heart, bypass surgery plus medicines lowered death from heart causes over 10 years (40.5% vs 49.3%)."}]},{"from":"sx_cabg","to":"bp_chest_ribs","level":"established","effect":"affects","note":"The breastbone is split and wired together again."},{"from":"sx_hip_replacement","to":"bp_hips","level":"proven","effect":"helps","note":"In a randomised trial, hip replacement improved pain and function in severe hip arthritis much more than exercise training.","sources":[{"id":"pmid:39476341","citation":"Frydendal T et al., N Engl J Med","year":2024,"design":"RCT","finding":"In severe hip osteoarthritis, hip replacement improved hip pain and function scores much more than resistance training at 6 months."}]},{"from":"sx_hip_replacement","to":"s_bones","level":"established","effect":"affects","note":"The hip joint surfaces are replaced with an artificial joint fixed into the bone."},{"from":"sx_knee_replacement","to":"knee_meniscus_oa","level":"proven","effect":"helps","note":"In a randomised trial, knee replacement plus rehab eased arthritis pain and improved function more than rehab alone, with more complications.","sources":[{"id":"pmid:26488691","citation":"Skou ST et al., N Engl J Med","year":2015,"design":"RCT","finding":"Knee replacement plus rehabilitation improved pain and function more than rehabilitation alone at 12 months, with more serious adverse events (24 vs 6)."}]},{"from":"sx_knee_replacement","to":"bp_knees","level":"established","effect":"affects","note":"The knee joint surfaces are replaced."},{"from":"sx_spinal_fusion","to":"bp_lumbar_spine","level":"established","effect":"affects","note":"Vertebrae in the low back are joined into one solid bone."},{"from":"sx_spinal_fusion","to":"low_back_disc","level":"mixed","effect":"helps","note":"For chronic low back pain, fusion did better than usual care but no better than intensive rehabilitation in the long run.","sources":[{"id":"pmid:11725230","citation":"Fritzell P et al., Spine","year":2001,"design":"RCT","finding":"Lumbar fusion reduced back pain and disability more than usual non-surgical care at 2 years."},{"id":"pmid:24200413","citation":"Mannion AF et al., Spine J","year":2013,"design":"RCT","finding":"About 11 years after three trials of chronic low back pain, people given spinal fusion did no better on disability than those given intensive exercise and cognitive rehabilitation."}]},{"from":"sx_cataract_surgery","to":"s_lens","level":"established","effect":"affects","note":"The clouded natural lens is replaced with a clear artificial lens.","sources":[{"id":"pmid:35673348","citation":"Horn JD et al., Clin Ophthalmol","year":2022,"design":"cohort","finding":"In 89,947 eyes, 28% had clouding behind the new lens (posterior capsule opacification) diagnosed within a year and 10% needed a laser clear-out."}]},{"from":"sx_cataract_surgery","to":"bp_eyes","level":"established","effect":"affects","note":"The lens inside the eye is replaced."},{"from":"sx_cataract_surgery","to":"falls","level":"proven","effect":"helps","note":"In a randomised trial, first-eye cataract surgery cut falls by about a third in older women; for the second eye it is less certain.","sources":[{"id":"pmid:15615747","citation":"Harwood RH et al., Br J Ophthalmol","year":2005,"design":"RCT","finding":"In older women, first-eye cataract surgery cut the rate of falls by 34% and fractures over 12 months."},{"id":"pmid:16364936","citation":"Foss AJ et al., Age Ageing","year":2006,"design":"RCT","finding":"Second-eye cataract surgery improved vision and confidence; the 32% lower fall rate was not statistically certain."}]},{"from":"sx_pacemaker","to":"s_heart","level":"established","effect":"helps","note":"A pacemaker keeps the heart beating at a safe rate when its own electrical system is too slow or blocked."},{"from":"sx_pacemaker","to":"bp_heart_circulation","level":"established","effect":"affects","note":"A device sits under the collarbone with wires into the heart."},{"from":"sx_icd","to":"s_heart","level":"proven","effect":"helps","note":"In randomised trials, an implanted defibrillator lowered deaths in people with a weak heart by about a quarter to a third.","sources":[{"id":"pmid:11907286","citation":"Moss AJ et al. (MADIT-II), N Engl J Med","year":2002,"design":"RCT","finding":"After a heart attack with a weak heart, an implanted defibrillator cut deaths by 31% over about 20 months."},{"id":"pmid:15659722","citation":"Bardy GH et al. (SCD-HeFT), N Engl J Med","year":2005,"design":"RCT","finding":"In heart failure with a weak heart, an implanted defibrillator lowered deaths by 23% over about 4 years; amiodarone did not."}]},{"from":"sx_icd","to":"bp_heart_circulation","level":"established","effect":"affects","note":"A device sits under the collarbone with a wire into the heart."},{"from":"sx_dbs","to":"br_stn","level":"established","effect":"affects","note":"In Parkinson's the electrodes usually sit in the subthalamic nucleus, whose overactivity they calm."},{"from":"sx_dbs","to":"bp_head_brain","level":"established","effect":"affects","note":"Electrodes are placed through the skull into deep brain centres."},{"from":"sx_dbs","to":"movement","level":"proven","effect":"helps","note":"In randomised trials, DBS improved slowness and stiffness more than best medication.","scope":["parkinsons"],"sources":[{"id":"pmid:16943402","citation":"Deuschl G et al., N Engl J Med","year":2006,"design":"RCT","finding":"In advanced Parkinson's, subthalamic stimulation improved quality of life and motor scores more than medication alone at 6 months."},{"id":"pmid:23406026","citation":"Schuepbach WM et al. (EARLYSTIM), N Engl J Med","year":2013,"design":"RCT","finding":"With early motor complications, stimulation beat medical therapy on quality of life, motor disability and fluctuations at 2 years; 17.7% had serious surgery- or device-related events."}]},{"from":"sx_dbs","to":"off","level":"proven","effect":"helps","note":"In randomised trials, DBS added about 4-5 hours a day of good ON time and reduced fluctuations compared with medication alone.","scope":["parkinsons"],"sources":[{"id":"pmid:19126811","citation":"Weaver FM et al., JAMA","year":2009,"design":"RCT","finding":"DBS added about 4.6 hours a day of good ON time without troublesome dyskinesia versus best medical therapy, with small drops in some thinking-speed tests."},{"id":"pmid:23406026","citation":"Schuepbach WM et al. (EARLYSTIM), N Engl J Med","year":2013,"design":"RCT","finding":"With early motor complications, stimulation beat medical therapy on quality of life, motor disability and fluctuations at 2 years; 17.7% had serious surgery- or device-related events."}]},{"from":"sx_dbs","to":"speech","level":"association","effect":"harms","note":"Speech often becomes less clear after subthalamic DBS, by about 15% on average, though some people improve.","scope":["parkinsons"],"sources":[{"id":"pmid:21068426","citation":"Tripoliti E et al., Neurology","year":2011,"design":"cohort","finding":"One year after subthalamic DBS, speech intelligibility fell by about 14-17% on average (versus about 4% on medication alone), though some people improved."}]},{"from":"sx_dbs","to":"depression","level":"association","effect":"harms","note":"Mood can drop after DBS and suicide is more common in the first year, so mood is checked before and after surgery.","scope":["parkinsons"],"sources":[{"id":"pmid:18941146","citation":"Voon V et al., Brain","year":2008,"design":"cohort","finding":"Across 5311 people with subthalamic DBS, 0.45% died by suicide and 0.90% attempted it, with first-year rates above the general population; depression after surgery was the main risk factor."}]},{"from":"sx_dbs","to":"essential_tremor","level":"association","effect":"helps","note":"Thalamic stimulation suppressed severe tremor in almost everyone treated and improved daily function more than a destructive lesion did.","sources":[{"id":"pmid:10675426","citation":"Schuurman PR et al., N Engl J Med","year":2000,"design":"RCT","finding":"In severe tremor, thalamic stimulation suppressed tremor in 30 of 33 people and improved daily function more than thalamotomy, with fewer side effects."}]},{"from":"dystonia","to":"s_bg","level":"established","effect":"affects","note":"Dystonia arises from faulty movement control in the basal ganglia circuits."},{"from":"sx_dbs","to":"dystonia","level":"proven","effect":"helps","note":"In a sham-controlled trial, pallidal stimulation greatly reduced dystonia movements, with benefit lasting.","sources":[{"id":"pmid:17093249","citation":"Kupsch A et al., N Engl J Med","year":2006,"design":"RCT","finding":"In generalised or segmental dystonia, pallidal stimulation reduced movement scores far more than sham stimulation at 3 months, and benefit held at 6 months."}]},{"from":"sx_cochlear_implant","to":"s_cochlea","level":"established","effect":"affects","note":"An electrode lies inside the cochlea and stimulates the hearing nerve directly."},{"from":"sx_cochlear_implant","to":"bp_ears","level":"established","effect":"affects","note":"An implant sits behind and inside the ear."},{"from":"sx_cochlear_implant","to":"presbycusis","level":"association","effect":"helps","note":"People with severe hearing loss understand words and sentences much better after a cochlear implant.","sources":[{"id":"pmid:34106734","citation":"Schafer EC et al., Am J Audiol","year":2021,"design":"meta-analysis","finding":"Adults of all ages gained large improvements in word and sentence recognition after cochlear implantation."}]},{"from":"sx_cochlear_implant","to":"cognition","level":"association","effect":"helps","note":"Thinking-test scores improved slightly after cochlear implantation in adults.","sources":[{"id":"pmid:42886997","citation":"Joyce CA et al., Otol Neurotol","year":2026,"design":"meta-analysis","finding":"Across 20 studies (798 recipients), thinking-test scores improved slightly after cochlear implantation."}]},{"from":"sx_hysterectomy","to":"s_uterus","level":"established","effect":"affects","note":"Removes the womb"},{"from":"sx_prostatectomy","to":"s_prostate","level":"established","effect":"affects","note":"Removes the prostate"},{"from":"sx_mastectomy","to":"s_breasts","level":"established","effect":"affects","note":"Removes breast tissue"},{"from":"sx_appendectomy","to":"s_appendix","level":"established","effect":"affects","note":"Removes the appendix"},{"from":"sx_oophorectomy","to":"menopause","level":"established","effect":"affects","note":"Removing both ovaries before natural menopause brings menopause on at once"},{"from":"sx_prostatectomy","to":"d_incontinence","level":"established","effect":"harms","note":"Leaking urine is common after prostate removal; it often improves over the first year"},{"from":"s_renal_cortex","to":"s_kidneys","level":"established","effect":"located","note":"The cortex is the outer layer of the kidney, where the filters sit."},{"from":"s_renal_pyramids","to":"s_kidneys","level":"established","effect":"located","note":"The pyramids form the inner part of the kidney (the medulla)."},{"from":"s_renal_papillae","to":"s_renal_pyramids","level":"established","effect":"located","note":"Each papilla is the inner tip of a pyramid, where urine leaves the kidney tissue."},{"from":"s_renal_papillae","to":"s_renal_calyces","level":"established","effect":"located","note":"Urine drips from each papilla into the cup-shaped calyx around it."},{"from":"s_renal_calyces","to":"s_renal_pelvis","level":"established","effect":"located","note":"The calyces join to empty into the renal pelvis."},{"from":"s_renal_pelvis","to":"s_kidneys","level":"established","effect":"located","note":"The renal pelvis is the collecting funnel in the middle of the kidney."},{"from":"s_renal_pelvis","to":"s_ureters","level":"established","effect":"located","note":"The renal pelvis narrows into the ureter at the kidney's inner notch."},{"from":"s_renal_arteries","to":"s_kidneys","level":"established","effect":"located","note":"Each kidney gets its blood from a renal artery off the aorta."},{"from":"s_renal_arteries","to":"m_bp","level":"established","effect":"located","note":"The kidneys sense pressure in their arteries and release renin when it drops, which raises blood pressure."},{"from":"s_renal_veins","to":"s_kidneys","level":"established","effect":"located","note":"Each kidney drains through a renal vein to the large vein beside the spine."},{"from":"s_renal_interlobar_vessels","to":"s_renal_arteries","level":"established","effect":"located","note":"Interlobar vessels are branches of the renal artery and vein running between the pyramids."},{"from":"s_renal_arcuate_vessels","to":"s_renal_interlobar_vessels","level":"established","effect":"located","note":"Arcuate vessels arch over the base of each pyramid where the interlobar vessels reach it."},{"from":"s_renal_arcuate_vessels","to":"s_renal_cortex","level":"established","effect":"located","note":"Arcuate vessels run along the edge of the cortex and send small branches up into it."},{"from":"uti","to":"s_renal_pelvis","level":"established","effect":"affects","note":"A kidney infection (pyelonephritis) inflames the renal pelvis and the kidney tissue around it."},{"from":"ckd","to":"s_kidneys","level":"established","effect":"affects","note":"Chronic kidney disease is a slow, lasting loss of the kidneys' filtering units."},{"from":"ckd","to":"hm_calcitriol","level":"established","effect":"harms","note":"Failing kidneys make less active vitamin D (calcitriol), so less calcium is absorbed."},{"from":"ckd","to":"m_bone","level":"established","effect":"harms","note":"Low calcitriol, phosphate build-up and overactive parathyroid glands weaken bone in advanced kidney disease."},{"from":"ckd","to":"m_bp","level":"established","effect":"affects","note":"Damaged kidneys hold on to salt and water, which raises blood pressure, and high pressure in turn damages the kidneys further."},{"from":"ckd","to":"s_heart","level":"association","effect":"harms","note":"The lower kidney filtering falls, the more heart attacks, strokes and heart failure occur, even after other risks are counted.","sources":[{"id":"pmid:15385656","citation":"Go AS et al., N Engl J Med","year":2004,"design":"cohort","finding":"In over a million adults, lower estimated GFR was independently linked with a graded rise in cardiovascular events, hospitalisation and death."}]},{"from":"ckd","to":"parkinsons","level":"association","effect":"harms","note":"In millions of older Koreans, weaker kidney function and protein in the urine were linked with a higher chance of later developing Parkinson's; this does not show that one causes the other.","sources":[{"id":"pmid:31021467","citation":"Nam GE et al., Mov Disord","year":2019,"design":"cohort","finding":"Among 3.58 million adults aged 65 or over, lower eGFR and dipstick proteinuria were independently associated with higher incidence of Parkinson's disease over about 5 years."}]},{"from":"parkinsons","to":"ckd","level":"association","effect":"harms","note":"People with Parkinson's were more likely to have their kidney function fall over the next few years, so kidney checks matter.","sources":[{"id":"pmid:41983553","citation":"Mitsuno R et al., Nephrol Dial Transplant","year":2026,"design":"cohort","finding":"In a nationwide cohort of 1.66 million adults, Parkinson's disease was independently associated with a composite of end-stage kidney disease, starting kidney replacement therapy or a 30% or greater eGFR decline."}]},{"from":"s_airways","to":"s_lungs","level":"established","effect":"located","note":"The windpipe and bronchi are the air tubes of the lungs."},{"from":"s_alveoli","to":"s_lungs","level":"established","effect":"located","note":"The air sacs at the end of the airways make up most of the lung."},{"from":"s_pleura","to":"s_lungs","level":"established","effect":"located","note":"The pleura is the thin double lining wrapped around each lung."},{"from":"s_diaphragm","to":"s_lungs","level":"established","effect":"helps","note":"The diaphragm is the main muscle that pulls air into the lungs."},{"from":"s_spinal","to":"s_diaphragm","level":"established","effect":"helps","note":"The phrenic nerves that drive the diaphragm leave the spinal cord in the neck."},{"from":"s_pulmonary_arteries","to":"s_lungs","level":"established","effect":"located","note":"The pulmonary arteries carry blood from the heart through the lungs to pick up oxygen."},{"from":"s_heart","to":"s_pulmonary_arteries","level":"established","effect":"helps","note":"The right side of the heart pumps blood into the lung arteries."},{"from":"s_airways","to":"s_larynx","level":"established","effect":"located","note":"The windpipe starts just below the voice box."},{"from":"allergic_asthma","to":"s_airways","level":"established","effect":"affects","note":"Asthma tightens, swells and clogs the bronchi with mucus."},{"from":"occ_asthma","to":"s_airways","level":"established","effect":"affects","note":"Work-caused asthma narrows the bronchi just like other asthma."},{"from":"wheeze","to":"s_airways","level":"established","effect":"located","note":"Wheeze is the sound of air squeezing through narrowed bronchi."},{"from":"pneumonia","to":"s_alveoli","level":"established","effect":"located","note":"In pneumonia the air sacs fill with fluid and pus, so less oxygen gets in."},{"from":"silicosis","to":"s_alveoli","level":"established","effect":"affects","note":"Silica dust lodges in the deepest air sacs, where it triggers scarring."},{"from":"tx_pm25","to":"s_alveoli","level":"established","effect":"harms","note":"Fine particles are small enough to reach and inflame the air sacs."},{"from":"asbestos_disease","to":"s_pleura","level":"established","effect":"affects","note":"Asbestos fibres work their way to the lung lining, causing plaques, thickening and mesothelioma."},{"from":"tx_asbestos","to":"s_pleura","level":"established","effect":"harms","note":"Breathed-in asbestos fibres migrate to the pleura and can cause mesothelioma decades later."},{"from":"hm_vasopressin","to":"hyponatraemia","level":"established","effect":"harms","note":"Too much vasopressin makes the kidneys keep water, which dilutes the salt in the blood.","dose":"excess"},{"from":"hyponatraemia","to":"s_kidneys","level":"established","effect":"located","note":"Blood sodium is set by how much water the kidneys keep or let go."},{"from":"hyponatraemia","to":"falls","level":"association","effect":"harms","note":"People with low blood sodium had about twice the odds of falling, even when the drop was mild.","sources":[{"id":"pmid:29920727","citation":"Corona G et al., Clin Endocrinol (Oxf)","year":2018,"design":"meta-analysis","finding":"Across 15 studies (about 52,000 patients), hyponatraemia was associated with higher odds of falls (OR about 2.1), already raised at mildly low sodium."},{"id":"pmid:16431193","citation":"Renneboog B et al., Am J Med","year":2006,"design":"case-control","finding":"Patients with mild chronic hyponatraemia were admitted for falls far more often than matched controls and showed gait and attention deficits that improved when sodium was corrected."}]},{"from":"hyponatraemia","to":"fracture","level":"association","effect":"harms","note":"Low blood sodium was linked with more fractures, especially hip fractures.","sources":[{"id":"pmid:29920727","citation":"Corona G et al., Clin Endocrinol (Oxf)","year":2018,"design":"meta-analysis","finding":"Hyponatraemia was associated with higher odds of bone fractures, particularly hip fractures (OR about 2.0)."}]},{"from":"hyponatraemia","to":"cognition","level":"association","effect":"harms","note":"Even mildly low blood sodium slowed attention on tests, and this improved once sodium was brought back to normal.","sources":[{"id":"pmid:16431193","citation":"Renneboog B et al., Am J Med","year":2006,"design":"case-control","finding":"In a small prospective test group, attention and tandem-gait performance were worse during mild hyponatraemia than after correction."}]},{"from":"copd","to":"s_lungs","level":"established","effect":"affects","note":"COPD narrows the small airways and destroys air-sac walls, trapping air in the lungs."},{"from":"copd","to":"bp_lungs","level":"established","effect":"affects","note":"COPD is a long-term lung condition and can be work-related when dusts or fumes contributed."},{"from":"copd","to":"breathless","level":"established","effect":"harms","note":"Breathlessness on effort is the main symptom of COPD and worsens as it progresses."},{"from":"copd","to":"wheeze","level":"established","effect":"harms","note":"Narrowed airways in COPD often wheeze, especially during flare-ups."},{"from":"copd","to":"d_cough","level":"established","effect":"harms","note":"A daily cough with phlegm is typical of COPD, often for years before diagnosis."},{"from":"copd","to":"fatigue","level":"established","effect":"harms","note":"The extra work of breathing and low activity in COPD leave people tired."},{"from":"d_cough","to":"s_lungs","level":"established","effect":"located","note":"Cough clears the airways of the lungs."},{"from":"allergic_asthma","to":"d_cough","level":"established","effect":"harms","note":"Asthma commonly causes cough, often worse at night or with exercise."},{"from":"occ_asthma","to":"d_cough","level":"established","effect":"harms","note":"Work-caused asthma brings cough that is often better on days off."},{"from":"tx_tobacco","to":"copd","level":"established","effect":"harms","note":"Smoking is the main cause of COPD; stopping slows further lung damage.","sources":[{"id":"pmid:871704","citation":"Fletcher C, Peto R, Br Med J","year":1977,"design":"cohort","finding":"In susceptible smokers, smoking caused irreversible airflow obstruction; after stopping, the rate of further lung-function loss returned to normal."}]},{"from":"tx_pm25","to":"copd","level":"association","effect":"harms","note":"Days with more fine-particle pollution are linked to more COPD hospital admissions and deaths.","sources":[{"id":"pmid:26111257","citation":"Li MH et al., Chest","year":2016,"design":"meta-analysis","finding":"Short-term rises in PM2.5 were associated with small increases in COPD hospitalisations and mortality across 18 studies."}]},{"from":"pulmonary_embolism","to":"s_lungs","level":"established","effect":"affects","note":"A clot blocks blood flow to part of the lung, so less oxygen reaches the blood."},{"from":"pulmonary_embolism","to":"s_heart","level":"established","effect":"affects","note":"A large clot makes the right side of the heart pump against a blockage and can make it fail."},{"from":"pulmonary_embolism","to":"s_blood","level":"established","effect":"affects","note":"PE is a clot that formed in the veins and travelled with the blood to the lungs."},{"from":"pulmonary_embolism","to":"bp_lungs","level":"established","effect":"affects","note":"A clot in the lung can follow a work injury, surgery or long immobility."},{"from":"pulmonary_embolism","to":"breathless","level":"established","effect":"harms","note":"Sudden breathlessness is the most common sign of a clot in the lung."},{"from":"inactivity","to":"pulmonary_embolism","level":"association","effect":"harms","note":"Being confined to bed, hospital or a care home makes clots in the legs and lungs much more likely.","sources":[{"id":"pmid:10737280","citation":"Heit JA et al., Arch Intern Med","year":2000,"design":"case-control","finding":"Hospital or nursing-home confinement, surgery, trauma, cancer and neurological disease with limb weakness were independent risk factors for deep-vein thrombosis and pulmonary embolism."}]},{"from":"pregnancy","to":"pulmonary_embolism","level":"association","effect":"harms","note":"Clots are about four times more likely in pregnancy and the weeks after birth, highest after birth.","sources":[{"id":"pmid:16287790","citation":"Heit JA et al., Ann Intern Med","year":2005,"design":"cohort","finding":"Venous thromboembolism was about 4.3 times more common in pregnant or postpartum women, and pulmonary embolism risk was highest postpartum."}]},{"from":"tx_tobacco","to":"pulmonary_embolism","level":"association","effect":"harms","note":"Smoking slightly raises the risk of blood clots in the veins and lungs.","sources":[{"id":"pmid:24068896","citation":"Cheng YJ et al., PLoS Med","year":2013,"design":"meta-analysis","finding":"Across 32 observational studies, current smokers had about a 23% higher risk of venous thromboembolism than never smokers, rising with amount smoked."}]},{"from":"osa","to":"s_blood","level":"association","effect":"harms","note":"The more breathing pauses at night, the more likely high blood pressure develops in later years.","sources":[{"id":"pmid:10805822","citation":"Peppard PE et al., N Engl J Med","year":2000,"design":"cohort","finding":"Baseline sleep-disordered breathing predicted hypertension four years later in a dose-response manner, independent of weight, age, sex, alcohol and smoking."}]},{"from":"osa","to":"parkinsons","level":"association","effect":"harms","note":"In a very large veterans' study, people with sleep apnoea were slightly more likely to develop Parkinson's, and fewer did if they started CPAP early; it is not shown to be a cause.","sources":[{"id":"pmid:41284280","citation":"Neilson LE et al., JAMA Neurol","year":2025,"design":"cohort","finding":"Among 11.3 million US veterans, OSA was associated with about 1.6 extra Parkinson's cases per 1000 people at 6 years, and early CPAP use was associated with fewer cases."}]},{"from":"exercise","to":"osa","level":"proven","effect":"helps","note":"Regular aerobic and strength exercise reduces breathing pauses and daytime sleepiness in sleep apnoea, even without much weight loss.","sources":[{"id":"pmid:39150699","citation":"Lin CF et al., J Clin Sleep Med","year":2024,"design":"meta-analysis","finding":"Across 12 randomised trials, exercise training reduced the apnoea-hypopnoea index and daytime sleepiness compared with control."}]},{"from":"h_emst","to":"swallow","level":"proven","effect":"helps","note":"In a sham-controlled trial, breathing-out muscle training made swallowing safer in people with Parkinson's; its effect on pneumonia is untested.","scope":["parkinsons"],"sources":[{"id":"pmid:21098406","citation":"Troche MS et al., Neurology","year":2010,"design":"RCT","finding":"In 60 people with Parkinson's, four weeks of active versus sham EMST improved swallow safety (penetration-aspiration scores) and hyolaryngeal movement."}]},{"from":"h_emst","to":"s_larynx","level":"proven","effect":"helps","note":"Training the breathing-out muscles strengthened airway protection during swallowing in one sham-controlled trial in Parkinson's (Troche 2010)","sources":[{"id":"pmid:21098406","citation":"Troche MS et al., Neurology","year":2010,"design":"RCT","finding":"In 60 people with Parkinson's, four weeks of active versus sham EMST improved swallow safety (penetration-aspiration scores) and hyolaryngeal movement."}]},{"from":"s_heart_ra","to":"s_heart","level":"established","effect":"located","note":"One of the heart's four chambers."},{"from":"s_heart_rv","to":"s_heart","level":"established","effect":"located","note":"One of the heart's four chambers."},{"from":"s_heart_la","to":"s_heart","level":"established","effect":"located","note":"One of the heart's four chambers."},{"from":"s_heart_lv","to":"s_heart","level":"established","effect":"located","note":"One of the heart's four chambers, the main pump."},{"from":"s_valve_mitral","to":"s_heart","level":"established","effect":"located","note":"One of the heart's four valves."},{"from":"s_valve_tricuspid","to":"s_heart","level":"established","effect":"located","note":"One of the heart's four valves."},{"from":"s_valve_aortic","to":"s_heart","level":"established","effect":"located","note":"One of the heart's four valves."},{"from":"s_valve_pulmonary","to":"s_heart","level":"established","effect":"located","note":"One of the heart's four valves."},{"from":"s_coronary_arteries","to":"s_heart","level":"established","effect":"located","note":"They run on the heart's surface and feed its muscle."},{"from":"s_conduction_system","to":"s_heart","level":"established","effect":"located","note":"Specialised muscle inside the heart walls that sets and spreads each beat."},{"from":"s_aorta","to":"s_blood","level":"established","effect":"located","note":"The main trunk of the arteries."},{"from":"s_veins","to":"s_blood","level":"established","effect":"located","note":"Veins carry blood back to the heart."},{"from":"lung_cancer","to":"s_lungs","level":"established","effect":"affects","note":"Lung cancer grows from the lining of the airways or air sacs."},{"from":"lung_cancer","to":"bp_lungs","level":"established","effect":"affects","note":"Lung cancer can be work-related after asbestos, silica, diesel or other carcinogen exposure."},{"from":"lung_cancer","to":"breathless","level":"established","effect":"harms","note":"A growing tumour or fluid around the lung causes breathlessness."},{"from":"lung_cancer","to":"s_lymph","level":"established","effect":"affects","note":"Lung cancer usually spreads first to the lymph nodes in the middle of the chest."},{"from":"tx_tobacco","to":"lung_cancer","level":"established","effect":"harms","note":"Smoking causes most lung cancers; the risk falls over the years after stopping.","sources":[{"id":"pmid:26274395","citation":"Ngamwong Y et al., PLoS One","year":2015,"design":"meta-analysis","finding":"Smoking without asbestos exposure was associated with about 5.7 times the odds of lung cancer, and smoking plus asbestos with about 8.7 times."}]},{"from":"tx_asbestos","to":"lung_cancer","level":"established","effect":"harms","note":"Asbestos causes lung cancer, and the risk is much higher in people who also smoke.","sources":[{"id":"pmid:26274395","citation":"Ngamwong Y et al., PLoS One","year":2015,"design":"meta-analysis","finding":"Asbestos exposure in non-smokers was associated with about 1.7 times the odds of lung cancer, with an additive interaction with smoking."}]},{"from":"tx_silica","to":"lung_cancer","level":"association","effect":"harms","note":"Workers exposed to silica dust have higher lung-cancer rates, even without silicosis.","sources":[{"id":"pmid:27814719","citation":"Poinen-Rughooputh S et al., BMC Public Health","year":2016,"design":"meta-analysis","finding":"Lung-cancer mortality and incidence were raised in silica-exposed workers, in both those with and without silicosis, with an exposure-response trend."}]},{"from":"tx_pm25","to":"lung_cancer","level":"association","effect":"harms","note":"Long-term outdoor fine-particle pollution is linked to a modestly higher lung-cancer risk, including in never-smokers.","sources":[{"id":"pmid:24911630","citation":"Hamra GB et al., Environ Health Perspect","year":2014,"design":"meta-analysis","finding":"Across 18 studies, each increase in long-term PM2.5 exposure was associated with about a 9% higher lung-cancer risk."}]},{"from":"h_lung_ct_screening","to":"lung_cancer","level":"proven","effect":"helps","note":"In people with heavy smoking histories, regular low-dose CT scans lowered lung-cancer deaths, at the cost of many false alarms.","sources":[{"id":"pmid:21714641","citation":"National Lung Screening Trial Research Team, N Engl J Med","year":2011,"design":"RCT","finding":"Among 53,454 high-risk people, low-dose CT screening reduced lung-cancer mortality compared with chest X-ray; over 95% of positive results were false positives."},{"id":"pmid:31995683","citation":"de Koning HJ et al., N Engl J Med","year":2020,"design":"RCT","finding":"In the NELSON trial, volume CT screening of current and former smokers lowered lung-cancer deaths at 10 years compared with no screening."}]},{"from":"d_chest_pain","to":"s_heart","level":"established","effect":"located","note":"Angina is the heart muscle signalling that it is short of oxygen."},{"from":"d_palpitations","to":"s_heart","level":"established","effect":"located","note":"The sensation of the heart's own rhythm."},{"from":"d_leg_swelling","to":"s_blood","level":"established","effect":"located","note":"Fluid seeps out of the small vessels into the tissues of the legs."},{"from":"h_bp_medicines","to":"oh","level":"established","effect":"harms","note":"Lowering blood pressure can deepen the drop on standing, so these medicines are reviewed when someone with Parkinson's gets dizzy on standing."},{"from":"h_statins","to":"s_blood","level":"proven","effect":"helps","note":"In randomised trials, lowering LDL cholesterol with statins reduced artery blockages causing heart attacks and strokes.","sources":[{"id":"pmid:21067804","citation":"Cholesterol Treatment Trialists' Collaboration, Lancet","year":2010,"design":"meta-analysis","finding":"In 26 randomised statin trials (about 170,000 people), lowering LDL cholesterol reduced heart attacks, artery-opening procedures and ischaemic strokes, in proportion to how far LDL fell."}]},{"from":"h_cardiac_rehab","to":"s_heart","level":"proven","effect":"helps","note":"In randomised trials in people with coronary heart disease, exercise-based rehabilitation reduced heart attacks and hospital stays.","sources":[{"id":"pmid:34741536","citation":"Dibben G et al., Cochrane Database Syst Rev","year":2021,"design":"meta-analysis","finding":"85 trials in people with coronary heart disease: exercise-based cardiac rehabilitation cut heart attacks (high certainty) and all hospital admissions over 6-12 months, with little effect on cardiovascular death in that time."}]},{"from":"h_anticoagulants","to":"s_blood","level":"established","effect":"helps","note":"Slows blood clotting; the trade-off is more bleeding."},{"from":"parkinsons","to":"s_heart","level":"association","effect":"affects","note":"The heart's own sympathetic nerves die back early in Parkinson's, from their endings inward, which shows on a heart scan (MIBG) and contributes to dizziness on standing.","sources":[{"id":"pmid:18079166","citation":"Orimo S et al., Brain","year":2008,"design":"case-control","finding":"Post-mortem study: the heart's sympathetic nerves degenerate in Parkinson's and dementia with Lewy bodies, early and from the nerve endings inward, with alpha-synuclein clumps in them first, which explains low cardiac MIBG uptake; multiple system atrophy hearts were largely spared."}]},{"from":"lewy","to":"s_heart","level":"association","effect":"affects","note":"The heart's sympathetic nerves are lost in dementia with Lewy bodies too, and a heart nerve scan (MIBG) is one of the tests used to support the diagnosis.","sources":[{"id":"pmid:18079166","citation":"Orimo S et al., Brain","year":2008,"design":"case-control","finding":"Post-mortem study: the heart's sympathetic nerves degenerate in Parkinson's and dementia with Lewy bodies, early and from the nerve endings inward, with alpha-synuclein clumps in them first, which explains low cardiac MIBG uptake; multiple system atrophy hearts were largely spared."},{"id":"pmid:28592453","citation":"McKeith IG et al., Neurology (DLB Consortium)","year":2017,"design":"review","finding":"Consensus diagnostic criteria list low uptake on MIBG heart scans (loss of the heart's sympathetic nerves) as an indicative biomarker of dementia with Lewy bodies."}]},{"from":"s_les","to":"s_oesophagus","level":"established","effect":"located","note":"The valve is the lowest few centimetres of the gullet."},{"from":"s_les","to":"s_stomach","level":"established","effect":"located","note":"It guards the stomach's upper opening."},{"from":"s_duodenum","to":"s_small_intestine","level":"established","effect":"located","note":"The duodenum is the first part of the small intestine."},{"from":"s_ileum","to":"s_small_intestine","level":"established","effect":"located","note":"The ileum is the last part of the small intestine."},{"from":"s_rectum_anus","to":"s_colon","level":"established","effect":"located","note":"The rectum is the final part of the large intestine."},{"from":"s_bile_ducts","to":"s_liver","level":"established","effect":"located","note":"Bile ducts begin inside the liver and carry its bile out."},{"from":"s_bile_ducts","to":"s_gallbladder","level":"established","effect":"located","note":"The gallbladder fills and empties through its duct into the common bile duct."},{"from":"s_bile_ducts","to":"s_duodenum","level":"established","effect":"located","note":"The common bile duct opens into the duodenum."},{"from":"s_bile_ducts","to":"s_pancreas","level":"established","effect":"located","note":"The lower bile duct runs through the head of the pancreas and shares an opening with the pancreatic duct."},{"from":"s_portal_vein","to":"s_liver","level":"established","effect":"located","note":"The portal vein delivers blood from the gut into the liver."},{"from":"s_portal_vein","to":"s_blood","level":"established","effect":"located","note":"It is part of the venous system."},{"from":"hpylori","to":"s_duodenum","level":"established","effect":"harms","note":"H. pylori in the stomach drives the acid and inflammation behind most duodenal ulcers."},{"from":"gallstones","to":"s_bile_ducts","level":"established","effect":"affects","note":"A gallstone that slips into the common bile duct can block it, causing jaundice, infection or pancreatitis."},{"from":"constipation","to":"s_rectum_anus","level":"established","effect":"located","note":"Part of Parkinson's constipation is trouble emptying the rectum because the pelvic floor does not relax."},{"from":"s_nephron","to":"s_kidneys","level":"established","effect":"located","note":"Each kidney is made of about a million nephrons."},{"from":"s_glomeruli","to":"s_nephron","level":"established","effect":"located","note":"The glomerulus is the filter at the start of each nephron."},{"from":"s_glomeruli","to":"s_renal_cortex","level":"established","effect":"located","note":"All the glomeruli sit in the outer layer of the kidney."},{"from":"s_renal_arcuate_vessels","to":"s_glomeruli","level":"established","effect":"located","note":"Small branches of the arcuate arteries carry blood up to the glomeruli."},{"from":"s_renal_tubules","to":"s_nephron","level":"established","effect":"located","note":"The proximal and distal tubules are the coiled parts of each nephron."},{"from":"s_renal_tubules","to":"s_renal_cortex","level":"established","effect":"located","note":"The coiled tubules lie in the cortex around the glomeruli."},{"from":"s_loop_of_henle","to":"s_nephron","level":"established","effect":"located","note":"The loop of Henle is the hairpin in the middle of each nephron."},{"from":"s_loop_of_henle","to":"s_renal_pyramids","level":"established","effect":"located","note":"The loops dip down into the pyramids, giving them their stripes."},{"from":"s_collecting_ducts","to":"s_renal_pyramids","level":"established","effect":"located","note":"Collecting ducts run down through the pyramids."},{"from":"s_collecting_ducts","to":"s_renal_papillae","level":"established","effect":"located","note":"Collecting ducts open on the tip of each pyramid, the papilla."},{"from":"hm_vasopressin","to":"s_collecting_ducts","level":"established","effect":"located","note":"Vasopressin opens water channels in the collecting ducts so less water is lost in urine."},{"from":"hm_calcitriol","to":"s_renal_tubules","level":"established","effect":"located","note":"The last step in making active vitamin D happens in the proximal tubule cells."},{"from":"tx_cadmium","to":"s_renal_tubules","level":"established","effect":"harms","note":"Cadmium builds up in the proximal tubule cells over decades and damages them."},{"from":"tx_mercury","to":"s_renal_tubules","level":"established","effect":"harms","note":"Inorganic mercury is taken up and injures the proximal tubules."},{"from":"pre_eclampsia","to":"s_glomeruli","level":"established","effect":"affects","note":"Pre-eclampsia swells the lining of the glomerular capillaries, so protein leaks into the urine."},{"from":"aki","to":"s_kidneys","level":"established","effect":"affects","note":"Acute kidney injury is a sudden drop in the kidneys' filtering."},{"from":"dehydration","to":"aki","level":"established","effect":"harms","note":"Too little fluid lowers blood flow to the kidneys and can tip them into acute injury, especially in older people."},{"from":"heat_illness","to":"aki","level":"established","effect":"harms","note":"Heat stroke causes acute kidney injury through fluid loss and muscle breakdown."},{"from":"aki","to":"ckd","level":"association","effect":"harms","note":"People who had acute kidney injury were much more likely to develop lasting kidney disease later.","sources":[{"id":"pmid:22113526","citation":"Coca SG et al., Kidney Int","year":2012,"design":"meta-analysis","finding":"Across 13 cohort studies, AKI was independently associated with higher risk of later CKD (pooled adjusted HR 8.8), end-stage kidney disease and death, graded by AKI severity."}]},{"from":"aki","to":"parkinsons","level":"association","effect":"harms","note":"In one large Taiwanese study, people who had acute kidney injury were later diagnosed with Parkinson's more often; this does not show cause.","sources":[{"id":"pmid:27707607","citation":"Lin SY et al., Eur J Intern Med","year":2016,"design":"cohort","finding":"9,380 AKI patients had a higher incidence of Parkinson's disease than 37,484 matched controls over about 7 years (adjusted HR 1.47)."}]},{"from":"aki","to":"hyperkalaemia","level":"established","effect":"harms","note":"When the kidneys suddenly stop working, potassium builds up quickly."},{"from":"ckd","to":"hyperkalaemia","level":"established","effect":"harms","note":"Advanced kidney disease lowers the kidneys' ability to get rid of potassium."},{"from":"hyperkalaemia","to":"s_heart","level":"established","effect":"harms","note":"High potassium disturbs the heart's electrical signals and can stop the heart."},{"from":"potassium","to":"hyperkalaemia","level":"established","effect":"harms","note":"Healthy kidneys clear dietary potassium easily; in advanced kidney disease a high intake can push blood levels too high.","scope":["ckd"],"dose":"excess"},{"from":"ibs","to":"s_gut","level":"established","effect":"affects","note":"IBS changes how the gut's nerves sense and how its muscles move, without visible damage."},{"from":"ibs","to":"s_colon","level":"established","effect":"affects","note":"Bowel habit changes in IBS come mostly from the large intestine."},{"from":"ibs","to":"bp_internal_organs","level":"established","effect":"affects","note":"IBS is a disorder of the gut, an internal organ."},{"from":"ibs","to":"d_abdominal_pain","level":"established","effect":"harms","note":"Repeated belly pain linked to opening the bowels is the defining symptom of IBS."},{"from":"ibs","to":"d_bloating","level":"established","effect":"harms","note":"Most people with IBS have bloating."},{"from":"ibs","to":"d_diarrhoea","level":"established","effect":"harms","note":"Diarrhoea is the main bowel pattern in one type of IBS."},{"from":"ibs","to":"constipation","level":"established","effect":"harms","note":"Constipation is the main bowel pattern in another type of IBS."},{"from":"d_abdominal_pain","to":"s_gut","level":"established","effect":"located","note":"Felt in the belly, from the gut or other belly organs."},{"from":"d_bloating","to":"s_colon","level":"established","effect":"located","note":"Most gut gas is made by bacteria in the large intestine."},{"from":"d_diarrhoea","to":"s_colon","level":"established","effect":"located","note":"The large intestine normally takes back water from stool; diarrhoea happens when that fails or is overwhelmed."},{"from":"d_diarrhoea","to":"dehydration","level":"established","effect":"harms","note":"Diarrhoea loses water and salts, which can dehydrate, especially the very young and old."},{"from":"eo_peppermint","to":"ibs","level":"proven","effect":"helps","note":"Peppermint oil capsules eased overall IBS symptoms and belly pain more than placebo in pooled trials, though the trials were of low quality and side effects such as heartburn were more common.","sources":[{"id":"pmid:35942669","citation":"Ingrosso MR et al., Aliment Pharmacol Ther","year":2022,"design":"meta-analysis","finding":"In 10 RCTs (1030 patients) peppermint oil beat placebo for global IBS symptoms and belly pain, with more adverse events; evidence quality very low."}]},{"from":"h_low_fodmap","to":"ibs","level":"proven","effect":"helps","note":"A low-FODMAP diet improved overall IBS symptoms, belly pain and bloating more than usual diet and other diets in a pooled analysis of trials.","sources":[{"id":"pmid:34376515","citation":"Black CJ et al., Gut","year":2022,"design":"meta-analysis","finding":"Network meta-analysis of 13 RCTs (944 patients): low-FODMAP diet ranked first for global symptoms, pain and bloating, superior to habitual diet."}]},{"from":"h_low_fodmap","to":"d_bloating","level":"proven","effect":"helps","note":"In trials in IBS, a low-FODMAP diet reduced bloating more than standard dietary advice.","sources":[{"id":"pmid:34376515","citation":"Black CJ et al., Gut","year":2022,"design":"meta-analysis","finding":"Low-FODMAP diet was superior to standard BDA/NICE dietary advice for abdominal bloating or distension."}]},{"from":"cbt","to":"ibs","level":"proven","effect":"helps","note":"Cognitive behavioural therapy and gut-directed hypnotherapy left fewer people with IBS symptoms than control treatments in many trials, though most trials had a high risk of bias.","sources":[{"id":"pmid:32276950","citation":"Black CJ et al., Gut","year":2020,"design":"meta-analysis","finding":"Network meta-analysis of 41 RCTs (4072 people): self-help and face-to-face CBT and gut-directed hypnotherapy were efficacious for IBS; risk of bias high."}]},{"from":"campylobacter","to":"ibs","level":"association","effect":"harms","note":"About one in ten people develop IBS after a bout of bacterial gut infection, roughly six times the usual odds.","sources":[{"id":"pmid:17661757","citation":"Thabane M et al., Aliment Pharmacol Ther","year":2007,"design":"meta-analysis","finding":"Across 18 studies, acute gut infection raised the odds of later IBS about sixfold; pooled incidence about 10%."}]},{"from":"salmonella","to":"ibs","level":"association","effect":"harms","note":"IBS can follow food poisoning, including Salmonella, in about one in ten people.","sources":[{"id":"pmid:17661757","citation":"Thabane M et al., Aliment Pharmacol Ther","year":2007,"design":"meta-analysis","finding":"Across 18 studies, acute gut infection raised the odds of later IBS about sixfold; pooled incidence about 10%."}]},{"from":"cdiff","to":"d_diarrhoea","level":"established","effect":"harms","note":"C. difficile toxins inflame the colon and cause watery diarrhoea, usually after antibiotics."},{"from":"campylobacter","to":"d_diarrhoea","level":"established","effect":"harms","note":"The commonest bacterial cause of food-poisoning diarrhoea, often bloody."},{"from":"giardia","to":"d_diarrhoea","level":"established","effect":"harms","note":"Giardia coats the small intestine and causes greasy, long-lasting diarrhoea and bloating."},{"from":"lactose_intolerance","to":"d_bloating","level":"established","effect":"harms","note":"Unabsorbed milk sugar is fermented in the colon into gas."},{"from":"coeliac_disease","to":"d_diarrhoea","level":"established","effect":"harms","note":"Flattened villi absorb poorly, causing diarrhoea, though many adults have no gut symptoms."},{"from":"hypertension","to":"s_blood","level":"established","effect":"affects","note":"Persistently high pressure stiffens and damages artery walls."},{"from":"hypertension","to":"s_heart_lv","level":"established","effect":"affects","note":"Pumping against high pressure thickens and stiffens the left ventricle."},{"from":"hypertension","to":"s_kidneys","level":"established","effect":"affects","note":"High pressure damages the kidneys' tiny filtering vessels."},{"from":"hypertension","to":"bp_heart_circulation","level":"established","effect":"affects","note":"A disease of the heart and blood vessels."},{"from":"sodium","to":"hypertension","level":"proven","effect":"harms","note":"In randomised trials, eating less salt for at least a month lowered blood pressure, most in people whose pressure was high.","dose":"excess","sources":[{"id":"pmid:23558162","citation":"He FJ, Li J, MacGregor GA, BMJ (Cochrane review)","year":2013,"design":"meta-analysis","finding":"34 randomised trials: modestly cutting salt for at least four weeks lowered blood pressure, more so in people with high blood pressure."}]},{"from":"tx_alcohol","to":"hypertension","level":"proven","effect":"harms","note":"In trials, people who drank heavily and cut down lowered their blood pressure; in light drinkers cutting down made little difference.","dose":"excess","sources":[{"id":"pmid:29253389","citation":"Roerecke M et al., Lancet Public Health","year":2017,"design":"meta-analysis","finding":"36 trials: in people who drank more than about two drinks a day, cutting down lowered blood pressure; in lighter drinkers it made no significant difference."}]},{"from":"exercise","to":"hypertension","level":"proven","effect":"helps","note":"In randomised trials, regular endurance or strength training lowered resting blood pressure.","sources":[{"id":"pmid:23525435","citation":"Cornelissen VA, Smart NA, J Am Heart Assoc","year":2013,"design":"meta-analysis","finding":"93 randomised trials: endurance, resistance and isometric training each lowered resting blood pressure in adults."}]},{"from":"osa","to":"hypertension","level":"association","effect":"harms","note":"People with more breathing pauses in sleep were more likely to develop high blood pressure over the following years.","sources":[{"id":"pmid:10805822","citation":"Peppard PE et al., N Engl J Med","year":2000,"design":"cohort","finding":"Wisconsin Sleep Cohort: the more breathing pauses in sleep at the start, the more likely people had high blood pressure four years later, after adjusting for weight and other factors."}]},{"from":"stroke","to":"s_cortex","level":"established","effect":"affects","note":"Most strokes damage the brain's outer layer and the wiring beneath it."},{"from":"stroke","to":"s_blood","level":"established","effect":"affects","note":"A stroke starts in a blood vessel: a blockage or a bleed."},{"from":"stroke","to":"bp_head_brain","level":"established","effect":"affects","note":"Stroke injures the brain."},{"from":"stroke","to":"speech","level":"established","effect":"harms","note":"Damage to the language areas or the nerves for speech muscles causes lost or slurred speech."},{"from":"stroke","to":"swallow","level":"association","effect":"harms","note":"About half of people after a stroke have swallowing problems, which raise the risk of pneumonia.","sources":[{"id":"pmid:16269630","citation":"Martino R et al., Stroke","year":2005,"design":"meta-analysis","finding":"Swallowing problems were found in about half or more of stroke patients depending on the test, and they raised the risk of pneumonia about threefold."}]},{"from":"stroke","to":"depression","level":"association","effect":"harms","note":"About a third of stroke survivors have depression at some stage.","sources":[{"id":"pmid:15879342","citation":"Hackett ML et al., Stroke","year":2005,"design":"meta-analysis","finding":"51 observational studies: about a third of stroke survivors had depression at some stage."}]},{"from":"tx_tobacco","to":"stroke","level":"association","effect":"harms","note":"Smokers have more strokes, and even a few cigarettes a day carry a sizeable share of the risk.","sources":[{"id":"pmid:29367388","citation":"Hackshaw A et al., BMJ","year":2018,"design":"meta-analysis","finding":"141 cohort studies: smoking even one cigarette a day carried about half the excess risk of coronary heart disease and a third of the excess stroke risk of smoking twenty."},{"id":"pmid:27431356","citation":"O'Donnell MJ et al. (INTERSTROKE), Lancet","year":2016,"design":"case-control","finding":"In 32 countries, ten modifiable factors (led by high blood pressure, then lack of regular exercise, blood fats, diet, waist, stress, smoking, heart causes, heavy alcohol and diabetes) accounted for about 90% of stroke risk."}]},{"from":"exercise","to":"stroke","level":"association","effect":"helps","note":"People who exercised regularly had fewer strokes across 32 countries.","sources":[{"id":"pmid:27431356","citation":"O'Donnell MJ et al. (INTERSTROKE), Lancet","year":2016,"design":"case-control","finding":"In 32 countries, ten modifiable factors (led by high blood pressure, then lack of regular exercise, blood fats, diet, waist, stress, smoking, heart causes, heavy alcohol and diabetes) accounted for about 90% of stroke risk."}]},{"from":"type2_diabetes","to":"stroke","level":"association","effect":"harms","note":"Diabetes roughly doubles the risk of a stroke from a blocked artery.","sources":[{"id":"pmid:20609967","citation":"Emerging Risk Factors Collaboration (Sarwar N et al.), Lancet","year":2010,"design":"meta-analysis","finding":"102 cohort studies (about 700,000 people): diabetes roughly doubled the risk of coronary heart disease and ischaemic stroke, independent of other risk factors."}]},{"from":"tx_alcohol","to":"stroke","level":"association","effect":"harms","note":"Heavy or binge drinking was linked to more strokes, including bleeding strokes.","dose":"excess","sources":[{"id":"pmid:27431356","citation":"O'Donnell MJ et al. (INTERSTROKE), Lancet","year":2016,"design":"case-control","finding":"In 32 countries, ten modifiable factors (led by high blood pressure, then lack of regular exercise, blood fats, diet, waist, stress, smoking, heart causes, heavy alcohol and diabetes) accounted for about 90% of stroke risk."}]},{"from":"pneumothorax","to":"s_pleura","level":"established","effect":"affects","note":"In a pneumothorax air gets between the two layers of the pleura."},{"from":"pneumothorax","to":"s_lungs","level":"established","effect":"affects","note":"Air around the lung lets it partly collapse."},{"from":"pneumothorax","to":"bp_lungs","level":"established","effect":"affects","note":"A collapsed lung can follow a chest injury at work, such as a fall or rib fracture."},{"from":"pneumothorax","to":"breathless","level":"established","effect":"harms","note":"Sudden breathlessness with one-sided chest pain is the typical start of a collapsed lung."},{"from":"tx_tobacco","to":"pneumothorax","level":"association","effect":"harms","note":"Smokers are many times more likely to have a spontaneous collapsed lung, more so the more they smoke.","sources":[{"id":"pmid:3677805","citation":"Bense L et al., Chest","year":1987,"design":"case-control","finding":"Smoking raised the relative risk of a first spontaneous pneumothorax about ninefold in women and 22-fold in men, with a dose-response relationship."}]},{"from":"copd","to":"pneumothorax","level":"established","effect":"harms","note":"Damaged, blistered lung in emphysema can burst and leak air."},{"from":"pulmonary_embolism","to":"s_pulmonary_arteries","level":"established","effect":"affects","note":"The travelling clot lodges in the lung arteries and blocks blood flow."},{"from":"lung_cancer","to":"d_cough","level":"established","effect":"harms","note":"A new cough that won't go away, or coughing blood, is a common sign of lung cancer."},{"from":"lung_cancer","to":"s_airways","level":"established","effect":"affects","note":"Many lung cancers start in the lining of the bronchi."},{"from":"h_pulmonary_rehab","to":"copd","level":"proven","effect":"helps","note":"Supervised exercise and education reduce breathlessness and fatigue and improve quality of life in COPD.","sources":[{"id":"pmid:25705944","citation":"McCarthy B et al., Cochrane Database Syst Rev","year":2015,"design":"meta-analysis","finding":"Across 65 randomised trials in COPD, pulmonary rehabilitation improved breathlessness, fatigue, emotional function, sense of control and exercise capacity versus usual care."}]},{"from":"h_pulmonary_rehab","to":"breathless","level":"proven","effect":"helps","note":"Pulmonary rehab makes everyday activity less breathless for people with COPD.","scope":["copd"],"sources":[{"id":"pmid:25705944","citation":"McCarthy B et al., Cochrane Database Syst Rev","year":2015,"design":"meta-analysis","finding":"Pulmonary rehabilitation improved the dyspnoea domain of the Chronic Respiratory Questionnaire beyond the clinically important difference."}]},{"from":"h_smoking_cessation","to":"copd","level":"proven","effect":"helps","note":"Stopping smoking slows the loss of lung function in early COPD and lowers death rates over the long term.","sources":[{"id":"pmid:7966841","citation":"Anthonisen NR et al., JAMA","year":1994,"design":"RCT","finding":"In 5887 smokers with early airflow obstruction, a smoking intervention programme slowed the decline of FEV1, most in those who quit."},{"id":"pmid:15710956","citation":"Anthonisen NR et al., Ann Intern Med","year":2005,"design":"RCT","finding":"At 14.5 years, all-cause mortality was lower in the group randomised to the smoking cessation intervention."}]},{"from":"h_inhaled_steroids","to":"allergic_asthma","level":"proven","effect":"helps","note":"Regular inhaled steroid preventers improve lung function and symptoms in asthma and are linked to fewer asthma deaths.","sources":[{"id":"pmid:18843640","citation":"Adams NP et al., Cochrane Database Syst Rev","year":2008,"design":"meta-analysis","finding":"In 86 placebo-controlled trials in chronic asthma, inhaled fluticasone improved FEV1, peak flow and symptoms and reduced reliever use, with more hoarseness and oral thrush."},{"id":"pmid:10922423","citation":"Suissa S et al., N Engl J Med","year":2000,"design":"case-control","finding":"In a population cohort, regular use of low-dose inhaled corticosteroids was associated with a lower rate of death from asthma."}]},{"from":"h_inhaled_steroids","to":"s_airways","level":"established","effect":"helps","note":"Inhaled steroids act directly on the airway lining, calming inflammation."},{"from":"h_flu_vaccine","to":"copd","level":"proven","effect":"helps","note":"Flu vaccination reduced COPD flare-ups in trials, though the trials were few and small.","sources":[{"id":"pmid:29943802","citation":"Kopsaftis Z et al., Cochrane Database Syst Rev","year":2018,"design":"meta-analysis","finding":"Inactivated influenza vaccine reduced the total number of exacerbations per person with COPD versus placebo (two RCTs, low-quality evidence); mortality effects could not be assessed."}]},{"from":"copd","to":"s_airways","level":"established","effect":"affects","note":"COPD inflames and narrows the bronchi and fills them with mucus (chronic bronchitis)."},{"from":"copd","to":"s_alveoli","level":"established","effect":"affects","note":"Emphysema destroys the walls between air sacs, leaving fewer, larger, floppy spaces."},{"from":"d_cough","to":"s_airways","level":"established","effect":"located","note":"Cough is triggered by irritation of the airway lining."},{"from":"obesity","to":"osa","level":"established","effect":"harms","note":"Extra weight around the neck and belly narrows the airway in sleep; the main risk factor for sleep apnoea"},{"from":"sx_hip_replacement","to":"pulmonary_embolism","level":"established","effect":"harms","note":"Clots in the leg veins after hip or knee replacement can travel to the lungs; that's why blood-thinners and early walking are standard afterwards"},{"from":"sx_knee_replacement","to":"pulmonary_embolism","level":"established","effect":"harms","note":"Clots in the leg veins after knee replacement can travel to the lungs; prevention is standard care"},{"from":"sx_lobectomy","to":"lung_cancer","level":"established","effect":"helps","note":"Removing the lobe holding an early lung cancer is the standard curative treatment"},{"from":"h_sglt2_inhibitors","to":"ckd","level":"proven","effect":"helps","note":"In large trials these tablets slowed kidney disease and lowered heart deaths, with or without diabetes.","sources":[{"id":"pmid:32970396","citation":"Heerspink HJL et al., N Engl J Med","year":2020,"design":"RCT","finding":"In 4,304 people with CKD (with or without type 2 diabetes), dapagliflozin lowered the composite of large eGFR decline, end-stage kidney disease or renal/cardiovascular death vs placebo (HR 0.61)."},{"id":"pmid:36331190","citation":"EMPA-KIDNEY Collaborative Group, N Engl J Med","year":2023,"design":"RCT","finding":"In 6,609 people with CKD at risk of progression, empagliflozin lowered progression of kidney disease or cardiovascular death vs placebo (HR 0.72)."}]},{"from":"h_sglt2_inhibitors","to":"s_renal_tubules","level":"established","effect":"located","note":"They act on a sugar-and-salt pump in the proximal tubule."},{"from":"h_ras_blockers","to":"ckd","level":"proven","effect":"helps","note":"In people with diabetic kidney disease, these medicines slowed the path to kidney failure more than their effect on blood pressure alone would explain.","sources":[{"id":"pmid:11565518","citation":"Brenner BM et al., N Engl J Med","year":2001,"design":"RCT","finding":"In type 2 diabetic nephropathy (RENAAL), losartan reduced doubling of creatinine and end-stage renal disease vs placebo, beyond blood-pressure effects, and lowered proteinuria."},{"id":"pmid:11565517","citation":"Lewis EJ et al., N Engl J Med","year":2001,"design":"RCT","finding":"In type 2 diabetic nephropathy (IDNT), irbesartan reduced the composite of doubling of creatinine, end-stage renal disease or death vs placebo and vs amlodipine, independent of blood pressure."}]},{"from":"h_ras_blockers","to":"hyperkalaemia","level":"established","effect":"harms","note":"These medicines make the kidney keep potassium, so blood levels are checked."},{"from":"h_ras_blockers","to":"s_glomeruli","level":"established","effect":"located","note":"They lower the pressure inside the glomeruli by relaxing their outflow vessel."},{"from":"sodium","to":"ckd","level":"proven","effect":"harms","note":"In trials of people with kidney disease, eating less salt lowered blood pressure and protein in the urine; whether it slows kidney failure long-term is not yet shown.","sources":[{"id":"pmid:34164803","citation":"McMahon EJ et al., Cochrane Database Syst Rev","year":2021,"design":"meta-analysis","finding":"High-certainty evidence that salt reduction lowered blood pressure in CKD and albuminuria in earlier-stage CKD in the short term; long-term effects on CKD progression were not studied."}]},{"from":"h_dialysis","to":"ckd","level":"established","effect":"helps","note":"In kidney failure, dialysis takes over cleaning the blood and keeps people alive."},{"from":"h_dialysis","to":"hyperkalaemia","level":"established","effect":"helps","note":"Dialysis removes extra potassium from the blood."},{"from":"aki","to":"s_renal_tubules","level":"established","effect":"affects","note":"The commonest kind inside the kidney is injury to the tubule cells from low blood flow or toxins."},{"from":"hyperkalaemia","to":"s_collecting_ducts","level":"established","effect":"located","note":"The collecting ducts are where the kidney decides how much potassium to let out."},{"from":"type2_diabetes","to":"ckd","level":"established","effect":"harms","note":"Diabetes is the commonest cause of kidney failure: years of high blood sugar damage the glomeruli."},{"from":"atrial_fibrillation","to":"s_heart_la","level":"established","effect":"affects","note":"The rhythm usually starts in and stretches the left atrium, where clots can form."},{"from":"atrial_fibrillation","to":"s_conduction_system","level":"established","effect":"affects","note":"Chaotic atrial signals replace the sinus node's orderly beat."},{"from":"atrial_fibrillation","to":"d_palpitations","level":"established","effect":"harms","note":"An irregular, often fast heartbeat that can be felt."},{"from":"atrial_fibrillation","to":"breathless","level":"established","effect":"harms","note":"A fast, irregular beat pumps less efficiently, so effort brings on breathlessness."},{"from":"tx_alcohol","to":"atrial_fibrillation","level":"proven","effect":"harms","note":"In a randomised trial, regular drinkers with AF who stopped drinking had fewer recurrences.","dose":"excess","sources":[{"id":"pmid:31893513","citation":"Voskoboinik A et al., N Engl J Med","year":2020,"design":"RCT","finding":"In regular drinkers with atrial fibrillation, randomly assigned abstinence cut recurrence over 6 months and time spent in the rhythm."}]},{"from":"osa","to":"atrial_fibrillation","level":"association","effect":"harms","note":"Sleep apnoea, and how far oxygen drops at night, predicted new AF in people under 65.","sources":[{"id":"pmid:17276180","citation":"Gami AS et al., J Am Coll Cardiol","year":2007,"design":"cohort","finding":"3,542 adults who had a sleep study: obstructive sleep apnoea and the depth of night-time oxygen drops predicted new atrial fibrillation in people under 65."}]},{"from":"heart_failure","to":"s_heart_lv","level":"established","effect":"affects","note":"The left ventricle squeezes weakly or fills poorly."},{"from":"heart_failure","to":"bp_heart_circulation","level":"established","effect":"affects","note":"A disease of the heart's pumping."},{"from":"heart_failure","to":"breathless","level":"established","effect":"harms","note":"Blood backs up into the lungs, worst on effort or lying flat."},{"from":"heart_failure","to":"fatigue","level":"established","effect":"harms","note":"Too little blood reaches working muscles."},{"from":"heart_failure","to":"d_leg_swelling","level":"established","effect":"harms","note":"The body holds salt and water, which pools in the legs."},{"from":"h_cardiac_rehab","to":"heart_failure","level":"proven","effect":"helps","note":"In randomised trials, exercise-based rehabilitation reduced hospital admissions and improved quality of life in heart failure.","sources":[{"id":"pmid:30695817","citation":"Long L et al., Cochrane Database Syst Rev","year":2019,"design":"meta-analysis","finding":"44 trials in heart failure: exercise-based cardiac rehabilitation probably reduced hospital admissions and improved quality of life; effect on deaths was uncertain in the short term."}]},{"from":"sx_icd","to":"heart_failure","level":"proven","effect":"helps","note":"In heart failure with a weak heart, an implanted defibrillator lowered deaths in a randomised trial.","sources":[{"id":"pmid:15659722","citation":"Bardy GH et al. (SCD-HeFT), N Engl J Med","year":2005,"design":"RCT","finding":"In heart failure with a weak heart, an implanted defibrillator lowered deaths over about 4 years; amiodarone did not."}]},{"from":"sodium","to":"heart_failure","level":"failed","effect":"harms","note":"Cutting salt further did not reduce deaths, hospital stays or emergency visits in a randomised trial in heart failure.","dose":"excess","sources":[{"id":"pmid:35381194","citation":"Ezekowitz JA et al. (SODIUM-HF), Lancet","year":2022,"design":"RCT","finding":"806 people with heart failure: a low-salt diet did not reduce deaths, hospital stays or emergency visits over a year compared with usual care."}]},{"from":"aortic_stenosis","to":"s_valve_aortic","level":"established","effect":"affects","note":"The aortic valve stiffens with calcium and narrows."},{"from":"aortic_stenosis","to":"s_heart_lv","level":"established","effect":"affects","note":"Pushing through a narrow valve thickens the left ventricle."},{"from":"aortic_stenosis","to":"breathless","level":"established","effect":"harms","note":"Breathlessness on effort is a main warning sign."},{"from":"aortic_stenosis","to":"d_chest_pain","level":"established","effect":"harms","note":"The thickened muscle can run short of oxygen on effort."},{"from":"aortic_stenosis","to":"heart_failure","level":"established","effect":"harms","note":"Left untreated, severe narrowing wears the ventricle out."},{"from":"sx_valve_replacement","to":"aortic_stenosis","level":"proven","effect":"helps","note":"In severe aortic stenosis, a new valve cut deaths in a randomised trial.","sources":[{"id":"pmid:20961243","citation":"Leon MB et al. (PARTNER), N Engl J Med","year":2010,"design":"RCT","finding":"In severe aortic stenosis in people who could not have open surgery, a catheter-placed valve cut deaths at one year compared with standard care."}]},{"from":"coronary_artery_disease","to":"s_coronary_arteries","level":"established","effect":"affects","note":"Plaque narrows the heart's own arteries."},{"from":"coronary_artery_disease","to":"bp_heart_circulation","level":"established","effect":"affects","note":"A disease of the heart's arteries."},{"from":"coronary_artery_disease","to":"d_chest_pain","level":"established","effect":"harms","note":"A narrowed artery starves the muscle during effort, felt as angina."},{"from":"coronary_artery_disease","to":"heart_attack","level":"established","effect":"harms","note":"A plaque that cracks can set off a clot that blocks the artery."},{"from":"heart_attack","to":"s_coronary_arteries","level":"established","effect":"affects","note":"A clot suddenly blocks a coronary artery."},{"from":"heart_attack","to":"s_heart_lv","level":"established","effect":"affects","note":"The heart muscle beyond the blockage dies and scars, usually in the left ventricle."},{"from":"heart_attack","to":"d_chest_pain","level":"established","effect":"harms","note":"The classic sign is crushing chest pain, though some people, especially older people and those with diabetes, feel little."},{"from":"tx_tobacco","to":"coronary_artery_disease","level":"association","effect":"harms","note":"Smokers get more coronary heart disease, and even one cigarette a day carries about half the excess risk of twenty.","sources":[{"id":"pmid:29367388","citation":"Hackshaw A et al., BMJ","year":2018,"design":"meta-analysis","finding":"141 cohort studies: smoking even one cigarette a day carried about half the excess risk of coronary heart disease and a third of the excess stroke risk of smoking twenty."}]},{"from":"type2_diabetes","to":"coronary_artery_disease","level":"association","effect":"harms","note":"Diabetes roughly doubles the risk of coronary heart disease.","sources":[{"id":"pmid:20609967","citation":"Emerging Risk Factors Collaboration (Sarwar N et al.), Lancet","year":2010,"design":"meta-analysis","finding":"102 cohort studies (about 700,000 people): diabetes roughly doubled the risk of coronary heart disease and ischaemic stroke, independent of other risk factors."}]},{"from":"exercise","to":"coronary_artery_disease","level":"association","effect":"helps","note":"More leisure-time activity goes with less coronary heart disease, with the biggest gain from none to some.","sources":[{"id":"pmid:21810663","citation":"Sattelmair J et al., Circulation","year":2011,"design":"meta-analysis","finding":"33 cohort studies: more leisure-time physical activity was linked to lower coronary heart disease risk, with the biggest gain going from none to some."}]},{"from":"h_statins","to":"heart_attack","level":"proven","effect":"helps","note":"In randomised trials, lowering LDL cholesterol with statins reduced heart attacks.","sources":[{"id":"pmid:21067804","citation":"Cholesterol Treatment Trialists' Collaboration, Lancet","year":2010,"design":"meta-analysis","finding":"In 26 randomised statin trials (about 170,000 people), lowering LDL cholesterol reduced heart attacks, artery-opening procedures and ischaemic strokes, in proportion to how far LDL fell."}]},{"from":"h_cardiac_rehab","to":"heart_attack","level":"proven","effect":"helps","note":"In randomised trials in people with coronary heart disease, exercise-based rehabilitation reduced further heart attacks.","sources":[{"id":"pmid:34741536","citation":"Dibben G et al., Cochrane Database Syst Rev","year":2021,"design":"meta-analysis","finding":"85 trials in coronary heart disease: exercise-based cardiac rehabilitation cut heart attacks (high certainty) and all hospital admissions over 6-12 months."}]},{"from":"sx_stents","to":"heart_attack","level":"proven","effect":"helps","note":"During a major heart attack, opening the artery with a balloon and stent lowered deaths and repeat attacks compared with clot-busting drugs.","sources":[{"id":"pmid:12517460","citation":"Keeley EC et al., Lancet","year":2003,"design":"meta-analysis","finding":"23 randomised trials in major heart attack: opening the artery with angioplasty lowered short-term deaths and repeat heart attacks compared with clot-busting drugs."}]},{"from":"sx_stents","to":"d_chest_pain","level":"proven","effect":"helps","note":"In stable angina, stents eased chest pain more than a placebo procedure, although in stable disease they did not prevent heart attacks or deaths.","sources":[{"id":"pmid:38015442","citation":"Rajkumar CA et al. (ORBITA-2), N Engl J Med","year":2023,"design":"RCT","finding":"In stable angina with little or no anti-angina medication, stenting reduced angina more than a placebo procedure."},{"id":"pmid:32227755","citation":"Maron DJ et al. (ISCHEMIA), N Engl J Med","year":2020,"design":"RCT","finding":"In stable coronary disease, an early invasive strategy (stents or bypass) did not reduce heart attacks or deaths compared with medicines first."}]},{"from":"sx_cabg","to":"coronary_artery_disease","level":"proven","effect":"helps","note":"In coronary disease with a weak heart, bypass surgery lowered heart deaths over ten years in a randomised trial.","sources":[{"id":"pmid:27040723","citation":"Velazquez EJ et al. (STICH), N Engl J Med","year":2016,"design":"RCT","finding":"In coronary disease with a weak heart, bypass surgery plus medicines lowered death from heart causes over 10 years compared with medicines alone."}]},{"from":"dvt","to":"s_veins","level":"established","effect":"affects","note":"A clot forms in a deep vein, usually in the leg."},{"from":"dvt","to":"s_blood","level":"established","effect":"affects","note":"Blood clots where it should stay liquid."},{"from":"dvt","to":"d_leg_swelling","level":"established","effect":"harms","note":"A clot blocking a deep vein makes that leg swell and ache."},{"from":"h_hrt","to":"dvt","level":"proven","effect":"harms","note":"In the WHI randomised trial, oestrogen plus progestin doubled the rate of deep vein clots and lung clots.","sources":[{"id":"pmid:15467059","citation":"Cushman M et al., JAMA (WHI)","year":2004,"design":"RCT","finding":"In 16,608 postmenopausal women, oestrogen plus progestin doubled venous clots (deep vein thrombosis and pulmonary embolism) compared with placebo, more so with age and obesity."}]},{"from":"pregnancy","to":"dvt","level":"association","effect":"harms","note":"Vein clots are about four times more common in pregnancy and the weeks after birth, highest after delivery.","sources":[{"id":"pmid:16287790","citation":"Heit JA et al., Ann Intern Med","year":2005,"design":"cohort","finding":"Population study over 30 years: venous clots were about four times more common during pregnancy and the weeks after birth, highest after delivery."}]},{"from":"inactivity","to":"dvt","level":"association","effect":"harms","note":"Sitting still for long periods slows blood in the leg veins; long journeys roughly double the clot risk.","sources":[{"id":"pmid:19581633","citation":"Chandra D, Parisini E, Mozaffarian D, Ann Intern Med","year":2009,"design":"meta-analysis","finding":"14 studies: travellers had about twice the risk of venous clots, rising with longer journeys."}]},{"from":"crohns","to":"s_ileum","level":"established","effect":"affects","note":"The end of the small intestine is the commonest place for Crohn's."},{"from":"crohns","to":"s_colon","level":"established","effect":"affects","note":"Crohn's often inflames patches of the large intestine."},{"from":"crohns","to":"s_immune","level":"established","effect":"affects","note":"The gut's immune system over-reacts to normal gut bacteria."},{"from":"crohns","to":"bp_internal_organs","level":"established","effect":"affects","note":"Crohn's affects the bowel."},{"from":"crohns","to":"d_abdominal_pain","level":"established","effect":"harms","note":"Cramping pain, often low on the right, is common."},{"from":"crohns","to":"d_diarrhoea","level":"established","effect":"harms","note":"Inflamed bowel absorbs poorly and leaks fluid."},{"from":"crohns","to":"nutrition","level":"established","effect":"harms","note":"Inflammation and poor absorption cause weight loss and shortages such as B12 and iron."},{"from":"crohns","to":"m_barrier","level":"established","effect":"harms","note":"The inflamed gut lining is leakier."},{"from":"ulcerative_colitis","to":"s_colon","level":"established","effect":"affects","note":"Inflames the lining of the large intestine continuously."},{"from":"ulcerative_colitis","to":"s_rectum_anus","level":"established","effect":"affects","note":"Ulcerative colitis always involves the rectum."},{"from":"ulcerative_colitis","to":"s_immune","level":"established","effect":"affects","note":"An immune attack on the colon's lining."},{"from":"ulcerative_colitis","to":"bp_internal_organs","level":"established","effect":"affects","note":"Ulcerative colitis affects the bowel."},{"from":"ulcerative_colitis","to":"d_diarrhoea","level":"established","effect":"harms","note":"Bloody diarrhoea with urgency is the typical symptom."},{"from":"ulcerative_colitis","to":"m_barrier","level":"established","effect":"harms","note":"The ulcerated lining no longer seals the gut."},{"from":"tx_tobacco","to":"crohns","level":"association","effect":"harms","note":"Smokers get Crohn's disease more often.","sources":[{"id":"pmid:17120402","citation":"Mahid SS et al., Mayo Clin Proc","year":2006,"design":"meta-analysis","finding":"Current smoking was associated with Crohn's disease (OR 1.76)."}]},{"from":"tx_tobacco","to":"ulcerative_colitis","level":"association","effect":"helps","note":"Current smokers get ulcerative colitis less often, but ex-smokers get it more often and smoking's harms far outweigh this, so it is not a reason to smoke.","sources":[{"id":"pmid:17120402","citation":"Mahid SS et al., Mayo Clin Proc","year":2006,"design":"meta-analysis","finding":"Current smoking was associated with lower odds of ulcerative colitis (OR 0.58) and former smoking with higher odds (OR 1.79)."}]},{"from":"crohns","to":"parkinsons","level":"association","effect":"harms","note":"People with inflammatory bowel disease were diagnosed with Parkinson's more often, and less often if treated with anti-TNF drugs, in a large health-records study.","sources":[{"id":"pmid:29710331","citation":"Peter I et al., JAMA Neurol","year":2018,"design":"cohort","finding":"Among 144,018 people with IBD, Parkinson's incidence was 28% higher than matched controls; anti-TNF exposure was associated with 78% lower incidence."}]},{"from":"ulcerative_colitis","to":"parkinsons","level":"association","effect":"harms","note":"People with inflammatory bowel disease were diagnosed with Parkinson's more often, and less often if treated with anti-TNF drugs, in a large health-records study.","sources":[{"id":"pmid:29710331","citation":"Peter I et al., JAMA Neurol","year":2018,"design":"cohort","finding":"Among 144,018 people with IBD, Parkinson's incidence was 28% higher than matched controls; anti-TNF exposure was associated with 78% lower incidence."}]},{"from":"sx_colectomy","to":"ulcerative_colitis","level":"established","effect":"helps","note":"Removing the whole colon and rectum ends ulcerative colitis in the bowel, usually with a stoma or an internal pouch made from small intestine."},{"from":"sx_colectomy","to":"crohns","level":"established","effect":"helps","note":"Removing a narrowed or damaged section treats complications, but Crohn's often comes back elsewhere."},{"from":"sx_ostomy","to":"ulcerative_colitis","level":"established","effect":"helps","note":"An ileostomy is often made after the colon is removed for severe colitis."},{"from":"masld","to":"s_liver","level":"established","effect":"affects","note":"Fat builds up inside liver cells."},{"from":"masld","to":"bp_internal_organs","level":"established","effect":"affects","note":"Fatty liver affects the liver."},{"from":"obesity","to":"masld","level":"established","effect":"harms","note":"Excess body fat, especially round the belly, is the main driver of fatty liver."},{"from":"type2_diabetes","to":"masld","level":"established","effect":"harms","note":"Most people with type 2 diabetes have fatty liver, and they are more likely to progress to scarring."},{"from":"exercise","to":"masld","level":"proven","effect":"helps","note":"In trials, exercise training reduced liver fat meaningfully more often than no exercise, even without much weight loss.","sources":[{"id":"pmid:36705333","citation":"Stine JG et al., Am J Gastroenterol","year":2023,"design":"meta-analysis","finding":"In 14 RCTs (551 people with fatty liver), exercise training tripled the odds of a 30% or greater fall in MRI liver fat, independent of clinically significant weight loss."}]},{"from":"masld","to":"cirrhosis","level":"established","effect":"harms","note":"In a minority, fatty liver inflammation scars the liver over years, ending in cirrhosis."},{"from":"tx_alcohol","to":"cirrhosis","level":"established","effect":"harms","note":"Years of heavy drinking are a leading cause of cirrhosis."},{"from":"hbv","to":"cirrhosis","level":"established","effect":"harms","note":"Chronic hepatitis B can scar the liver into cirrhosis."},{"from":"hcv","to":"cirrhosis","level":"established","effect":"harms","note":"Chronic hepatitis C is a leading cause of cirrhosis; modern treatment cures the infection."},{"from":"coffee","to":"cirrhosis","level":"association","effect":"helps","note":"Coffee drinkers get cirrhosis less often in population studies, with lower risk at higher intakes; trials have not tested this.","sources":[{"id":"pmid:26806124","citation":"Kennedy OJ et al., Aliment Pharmacol Ther","year":2016,"design":"meta-analysis","finding":"In 9 cohort and case-control studies (432,133 people), higher coffee intake was associated with substantially lower cirrhosis risk, including alcoholic cirrhosis."}]},{"from":"cirrhosis","to":"s_liver","level":"established","effect":"affects","note":"Scar tissue replaces healthy liver."},{"from":"cirrhosis","to":"s_portal_vein","level":"established","effect":"affects","note":"Scarring dams the blood flow through the liver, raising portal vein pressure."},{"from":"cirrhosis","to":"bp_internal_organs","level":"established","effect":"affects","note":"Cirrhosis affects the liver."},{"from":"cirrhosis","to":"d_jaundice","level":"established","effect":"harms","note":"A failing liver cannot clear bilirubin."},{"from":"cirrhosis","to":"cognition","level":"established","effect":"harms","note":"Toxins such as ammonia that the liver should clear reach the brain, causing confusion and slowed thinking (hepatic encephalopathy)."},{"from":"cirrhosis","to":"movement","level":"association","effect":"harms","note":"A few people with cirrhosis develop Parkinson-like slowness and stiffness, linked to manganese the liver fails to clear building up in the basal ganglia.","sources":[{"id":"pmid:23220368","citation":"Tryc AB et al., J Hepatol","year":2013,"design":"cohort","finding":"Cirrhosis-related parkinsonism was found in 4.2% of 214 cirrhosis patients, with reduced striatal dopamine receptor or transporter imaging; levodopa helped only briefly."}]},{"from":"cirrhosis","to":"liver_cancer","level":"established","effect":"harms","note":"Most liver cancers arise in a cirrhotic liver."},{"from":"hbv","to":"liver_cancer","level":"established","effect":"harms","note":"Chronic hepatitis B causes liver cancer, sometimes even without cirrhosis."},{"from":"liver_cancer","to":"s_liver","level":"established","effect":"affects","note":"The cancer grows from liver cells."},{"from":"d_jaundice","to":"s_liver","level":"established","effect":"located","note":"Jaundice reflects bilirubin the liver and bile ducts have not cleared."},{"from":"sx_liver_transplant","to":"cirrhosis","level":"established","effect":"helps","note":"A transplant replaces a liver that has failed from cirrhosis."},{"from":"gerd","to":"s_les","level":"established","effect":"affects","note":"Reflux happens when the valve at the bottom of the gullet opens too often or is weak."},{"from":"gerd","to":"s_oesophagus","level":"established","effect":"affects","note":"Refluxed acid inflames the lining of the gullet."},{"from":"gerd","to":"bp_internal_organs","level":"established","effect":"affects","note":"Reflux disease affects the gullet and stomach."},{"from":"gerd","to":"heartburn","level":"established","effect":"harms","note":"Heartburn and regurgitation are the typical symptoms of reflux."},{"from":"gerd","to":"barretts","level":"established","effect":"harms","note":"Years of acid reflux can change the gullet's lining into Barrett's oesophagus."},{"from":"heartburn","to":"s_oesophagus","level":"established","effect":"located","note":"Felt where acid touches the lower gullet, behind the breastbone."},{"from":"barretts","to":"s_oesophagus","level":"established","effect":"affects","note":"The lining of the lower gullet changes type."},{"from":"h_ppi","to":"heartburn","level":"proven","effect":"helps","note":"In placebo-controlled trials, proton pump inhibitors made heartburn go away in many more people than placebo.","sources":[{"id":"pmid:23728637","citation":"Sigterman KE et al., Cochrane Database Syst Rev","year":2013,"design":"meta-analysis","finding":"In 34 RCTs of reflux-type symptoms, PPIs markedly reduced the risk of heartburn persisting versus placebo (RR 0.37 in empirical treatment) and outperformed H2 blockers and prokinetics."}]},{"from":"h_ppi","to":"gerd","level":"proven","effect":"helps","note":"Acid suppression relieves reflux symptoms in trials; it treats the acid, not the leaky valve, so symptoms often return when stopped.","sources":[{"id":"pmid:23728637","citation":"Sigterman KE et al., Cochrane Database Syst Rev","year":2013,"design":"meta-analysis","finding":"PPIs were more effective than placebo, H2 blockers and prokinetics for heartburn remission in reflux disease."}]},{"from":"obesity","to":"gerd","level":"association","effect":"harms","note":"People who are overweight or obese have reflux more often, in pooled population studies.","sources":[{"id":"pmid:16952280","citation":"Corley DA, Kubo A, Am J Gastroenterol","year":2006,"design":"meta-analysis","finding":"In 20 studies, higher BMI was associated with GERD (US studies: OR about 1.6 overweight, 2.2 obese); European results were inconsistent."}]},{"from":"tx_tobacco","to":"gerd","level":"association","effect":"harms","note":"Smoking is linked with more reflux, and people who quit had better reflux symptoms in a large population study.","sources":[{"id":"pmid:24322837","citation":"Ness-Jensen E et al., Am J Gastroenterol","year":2014,"design":"cohort","finding":"In the HUNT cohort (29,610 people), stopping daily smoking was associated with improvement of severe reflux symptoms among those on reflux medicine, mainly in people of normal weight."}]},{"from":"sx_sleeve_gastrectomy","to":"gerd","level":"proven","effect":"harms","note":"After a sleeve, new or worse reflux is much more common than after gastric bypass in randomised trials.","sources":[{"id":"pmid:39384655","citation":"Memon MA et al., Surg Endosc","year":2024,"design":"meta-analysis","finding":"In 5 RCTs with 5-year follow-up, sleeve gastrectomy led to more medical and surgical treatment for worsening or new GERD than Roux-en-Y bypass."}]},{"from":"pregnancy","to":"heartburn","level":"established","effect":"harms","note":"Pregnancy hormones relax the valve at the bottom of the gullet and the growing womb pushes up on the stomach."},{"from":"s_vagus","to":"s_autonomic","level":"established","effect":"located","note":"The vagus is the main nerve of the 'rest and digest' half of the automatic nervous system."},{"from":"br_dmnv","to":"s_vagus","level":"established","effect":"helps","note":"This brainstem nucleus sends the signals that travel down the vagus to keep the stomach and gut moving."},{"from":"s_vagus","to":"s_heart","level":"established","effect":"helps","note":"Vagus signals slow the heartbeat at rest; this is why the pulse speeds up and slows down slightly with each breath."},{"from":"s_vagus","to":"s_stomach","level":"established","effect":"helps","note":"The vagus switches on stomach acid and the stomach's squeezing, which empties it into the gut."},{"from":"s_vagus","to":"m_motility","level":"established","effect":"helps","note":"Together with the gut's own nerves, vagus signals drive the muscle waves that move food along."},{"from":"s_vagus","to":"s_gut","level":"established","effect":"helps","note":"The main nerve link between gut and brain; most of its fibres carry messages from the gut up to the brain."},{"from":"s_vagus","to":"s_throat","level":"established","effect":"helps","note":"Branches of the vagus work the throat muscles used in swallowing."},{"from":"s_vagus","to":"s_larynx","level":"established","effect":"helps","note":"A branch of the vagus works the vocal cords; damage to it makes the voice hoarse."},{"from":"nausea","to":"s_vagus","level":"established","effect":"located","note":"Signals from an irritated or overstretched gut travel up the vagus to the brainstem's vomiting centre."},{"from":"s_vagus","to":"m_inflam","level":"lab","effect":"helps","note":"In rats, stimulating the vagus damped the body-wide inflammatory response to bacterial toxins (the 'inflammatory reflex').","sources":[{"id":"pmid:10839541","citation":"Borovikova et al., Nature","year":2000,"design":"lab","finding":"Electrical stimulation of the vagus nerve in rats with endotoxin shock lowered TNF and prevented shock, and acetylcholine reduced cytokine release from human immune cells in culture."}]},{"from":"parkinsons","to":"s_vagus","level":"association","effect":"affects","note":"On ultrasound the vagus nerve is slightly thinner in Parkinson's, and weak vagus control of the heartbeat has been found years before diagnosis.","sources":[{"id":"pmid:39140586","citation":"Radziwon & Sławek, Neurol Neurochir Pol","year":2024,"design":"meta-analysis","finding":"Across 12 case-control ultrasound studies the vagus nerve was modestly smaller in Parkinson's, and smaller size went with weaker heart parasympathetic function and worse motor scores."},{"id":"pmid:25707861","citation":"Alonso et al., Ann Neurol","year":2015,"design":"cohort","finding":"Among 12,162 adults followed about 18 years, those with the lowest heart-rate variability had about two to three times the risk of later Parkinson's."}]},{"from":"sx_vagotomy","to":"s_vagus","level":"established","effect":"affects","note":"Cuts the vagus branches that supply the stomach and, in the full (truncal) operation, most of the gut."},{"from":"sx_vagotomy","to":"s_stomach","level":"established","effect":"affects","note":"Lowers stomach acid, which was the reason for the operation."},{"from":"sx_vagotomy","to":"stomach","level":"established","effect":"harms","note":"Without the vagus the stomach empties slowly, which is why surgeons usually widened its outlet at the same time."},{"from":"sx_vagotomy","to":"d_diarrhoea","level":"established","effect":"harms","note":"Some people have lasting diarrhoea after a full (truncal) vagotomy."},{"from":"sx_vagotomy","to":"parkinsons","level":"association","effect":"helps","note":"People whose main vagus trunks had been cut had somewhat fewer Parkinson's diagnoses decades later in Danish and Swedish records, but the overall results were not clear-cut and only some analyses showed it.","sources":[{"id":"pmid:26031848","citation":"Svensson et al., Ann Neurol","year":2015,"design":"cohort","finding":"In Denmark, truncal vagotomy was linked to lower Parkinson's risk after more than 20 years of follow-up (HR 0.53), though the overall estimate was not significant; superselective vagotomy showed no link."},{"id":"pmid:28446653","citation":"Liu et al., Neurology","year":2017,"design":"cohort","finding":"In Sweden, vagotomy overall was not linked to Parkinson's risk (HR 0.96), with a suggestion of lower risk after truncal vagotomy at least 5 years before diagnosis (HR 0.59)."}]},{"from":"sx_vagotomy","to":"m_inflam","level":"association","effect":"harms","note":"People who had a full vagotomy developed rheumatoid arthritis more often later, fitting the idea that the vagus helps hold inflammation back.","sources":[{"id":"pmid:40380285","citation":"Baker et al., Arthritis Res Ther","year":2025,"design":"cohort","finding":"In Danish registries, truncal vagotomy was linked to 2.6 times the rate of later rheumatoid arthritis, while superselective vagotomy and osteoarthritis showed no link."}]},{"from":"h_vns","to":"epilepsy","level":"proven","effect":"helps","note":"In people whose seizures resist medicines, stronger stimulation halved seizures in more people than weak stimulation in controlled trials.","sources":[{"id":"pmid:35833911","citation":"Panebianco et al., Cochrane Database Syst Rev","year":2022,"design":"meta-analysis","finding":"In 5 randomised trials (439 people) with drug-resistant focal seizures, high-level VNS gave a 50% or greater seizure reduction more often than low-level VNS (RR 1.73); hoarseness was more common (RR 2.17)."}]},{"from":"h_vns","to":"depression_c","level":"mixed","effect":"helps","note":"In a large sham-controlled trial in very hard-to-treat depression, the main measure did not differ, but several other symptom and quality-of-life measures favoured real stimulation.","sources":[{"id":"pmid:42642808","citation":"Conway et al., Am J Psychiatry","year":2026,"design":"review","finding":"The RECOVER trial (493 people) missed its prespecified primary outcome, while secondary measures of symptoms, function and quality of life significantly favoured active over sham VNS."}]},{"from":"h_vns","to":"m_inflam","level":"proven","effect":"helps","note":"In one large sham-controlled trial, vagus stimulation eased rheumatoid arthritis in people whom standard drugs had not helped; earlier it lowered an inflammation signal (TNF) in the blood.","sources":[{"id":"pmid:41429981","citation":"Tesser et al., Nat Med","year":2026,"design":"RCT","finding":"In 242 people with drug-resistant rheumatoid arthritis, active vagus stimulation gave more 20% improvements at 3 months than sham (35% vs 24%)."},{"id":"pmid:27382171","citation":"Koopman et al., PNAS","year":2016,"design":"cohort","finding":"An implanted vagus stimulator reduced blood TNF, IL-1 and IL-6 production in epilepsy patients and reduced TNF production and disease activity in an open study of rheumatoid arthritis."}]},{"from":"h_vns","to":"s_larynx","level":"proven","effect":"harms","note":"A hoarse voice while the device fires is the commonest side effect, because the vagus also works the vocal cords.","sources":[{"id":"pmid:35833911","citation":"Panebianco et al., Cochrane Database Syst Rev","year":2022,"design":"meta-analysis","finding":"Hoarseness was about twice as common with high-level as with low-level stimulation (RR 2.17)."}]},{"from":"h_tvns","to":"movement","level":"mixed","effect":"helps","note":"Small trials in Parkinson's disagree: pooled results showed less freezing when walking but no change in standard movement scores.","scope":["parkinsons"],"sources":[{"id":"pmid:39733649","citation":"Abouelmagd et al., J Clin Neurosci","year":2025,"design":"meta-analysis","finding":"Across 8 small RCTs and 2 other studies (217 people), non-invasive vagus stimulation reduced freezing of gait but did not change UPDRS movement scores, walking speed or Timed Up and Go."},{"id":"pmid:41068419","citation":"Sigurdsson et al., J Neurol","year":2025,"design":"RCT","finding":"In 33 people with Parkinson's, 12 weeks of home neck stimulation versus sham was feasible and safe but had minimal effects on gait and thinking."},{"id":"pmid:41549029","citation":"Wang et al., Neurotherapeutics","year":2026,"design":"RCT","finding":"In a single-blind sham-controlled trial, three weeks of home ear stimulation lowered movement scores and improved sleep and quality of life in Parkinson's."}]},{"from":"h_tvns","to":"m_inflam","level":"failed","effect":"helps","note":"Ear stimulation did no better than sham at easing rheumatoid arthritis in a controlled trial, unlike the implanted device.","sources":[{"id":"pmid:37390360","citation":"Baker et al., Arthritis Rheumatol","year":2023,"design":"RCT","finding":"In 113 people with active rheumatoid arthritis, auricular vagus stimulation did not beat sham at 12 weeks (ACR20 25.0% vs 26.9%)."}]},{"from":"h_slow_breathing","to":"s_heart","level":"proven","effect":"helps","note":"Slow breathing raises the beat-to-beat variation in heart rate that reflects vagus control, both during practice and after weeks of practice.","sources":[{"id":"pmid:35623448","citation":"Laborde et al., Neurosci Biobehav Rev","year":2022,"design":"meta-analysis","finding":"Across 223 studies, voluntary slow breathing increased vagally mediated heart-rate variability during the session, immediately after one session, and after multi-session interventions."}]},{"from":"pancreatitis","to":"s_pancreas","level":"established","effect":"affects","note":"The pancreas becomes inflamed by its own enzymes."},{"from":"pancreatitis","to":"bp_internal_organs","level":"established","effect":"affects","note":"Pancreatitis affects the pancreas."},{"from":"pancreatitis","to":"d_abdominal_pain","level":"established","effect":"harms","note":"Severe upper belly pain going through to the back is the main symptom."},{"from":"pancreatitis","to":"pancreatic_insufficiency","level":"established","effect":"harms","note":"Chronic pancreatitis destroys enzyme-making tissue, so fat is poorly digested."},{"from":"pancreatitis","to":"hm_insulin","level":"established","effect":"harms","note":"Chronic pancreatitis also destroys insulin-making islets, causing a form of diabetes."},{"from":"gallstones","to":"pancreatitis","level":"established","effect":"harms","note":"A gallstone stuck at the shared bile and pancreatic duct opening is a leading cause of acute pancreatitis."},{"from":"tx_alcohol","to":"pancreatitis","level":"established","effect":"harms","note":"Heavy drinking is a leading cause of both acute and chronic pancreatitis."},{"from":"tx_tobacco","to":"pancreatitis","level":"association","effect":"harms","note":"Smokers get acute and chronic pancreatitis more often, with risk rising with how much they smoke.","sources":[{"id":"pmid:31668562","citation":"Aune D et al., Pancreatology","year":2019,"design":"meta-analysis","finding":"In 10 prospective studies, current smokers had higher risk of acute pancreatitis (RR 1.49) and similarly of chronic pancreatitis, with a dose-response."}]},{"from":"sx_cholecystectomy","to":"pancreatitis","level":"established","effect":"helps","note":"Removing the gallbladder after gallstone pancreatitis prevents further gallstone attacks."},{"from":"pancreatic_cancer","to":"s_pancreas","level":"established","effect":"affects","note":"The cancer grows from the lining of the pancreatic ducts."},{"from":"pancreatic_cancer","to":"bp_internal_organs","level":"established","effect":"affects","note":"Pancreatic cancer affects the pancreas."},{"from":"pancreatic_cancer","to":"d_jaundice","level":"established","effect":"harms","note":"A tumour in the head of the pancreas squeezes the bile duct, often causing painless jaundice."},{"from":"tx_tobacco","to":"pancreatic_cancer","level":"established","effect":"harms","note":"Smoking is an established cause of pancreatic cancer."},{"from":"pancreatitis","to":"pancreatic_cancer","level":"established","effect":"harms","note":"Long-standing chronic pancreatitis raises pancreatic cancer risk."},{"from":"sx_pancreatectomy","to":"pancreatic_cancer","level":"established","effect":"helps","note":"Removing the tumour with part of the pancreas (often a Whipple operation) is the only potentially curative treatment."},{"from":"gallstones","to":"d_abdominal_pain","level":"established","effect":"harms","note":"A stone blocking the gallbladder outlet causes attacks of pain under the right ribs, often after a fatty meal."},{"from":"gallstones","to":"d_jaundice","level":"established","effect":"harms","note":"A stone blocking the common bile duct backs bile up into the blood."},{"from":"colorectal_cancer","to":"s_colon","level":"established","effect":"affects","note":"Most bowel cancers start in the lining of the colon."},{"from":"colorectal_cancer","to":"s_rectum_anus","level":"established","effect":"affects","note":"About a third start in the rectum."},{"from":"colorectal_cancer","to":"bp_internal_organs","level":"established","effect":"affects","note":"Bowel cancer affects the large intestine."},{"from":"fibre","to":"colorectal_cancer","level":"association","effect":"helps","note":"People who eat more fibre, especially cereal fibre and whole grains, get bowel cancer less often in long-term studies.","sources":[{"id":"pmid:22074852","citation":"Aune D et al., BMJ","year":2011,"design":"meta-analysis","finding":"In 25 prospective studies, higher total fibre, cereal fibre and whole-grain intake were each associated with lower colorectal cancer risk."}]},{"from":"redmeat","to":"colorectal_cancer","level":"association","effect":"harms","note":"Processed meat is classed as a cause of bowel cancer and red meat as a probable cause, based on population studies.","sources":[{"id":"pmid:26514947","citation":"Bouvard V et al. (IARC Working Group), Lancet Oncol","year":2015,"design":"review","finding":"IARC classified processed meat as carcinogenic (Group 1) and red meat as probably carcinogenic (Group 2A), mainly for colorectal cancer."}]},{"from":"tx_alcohol","to":"colorectal_cancer","level":"established","effect":"harms","note":"Alcohol is an established cause of bowel cancer, and risk rises with the amount drunk."},{"from":"h_bowel_screening","to":"colorectal_cancer","level":"proven","effect":"helps","note":"In randomised trials, stool blood-test screening reduced bowel cancer deaths, and camera screening reduced both new cancers and deaths.","sources":[{"id":"pmid:9721111","citation":"Towler B et al., BMJ","year":1998,"design":"meta-analysis","finding":"In 4 RCTs (about 330,000 people), faecal occult blood test screening reduced colorectal cancer mortality by 16%."},{"id":"pmid:38333601","citation":"Wang D et al., Prev Med Rep","year":2024,"design":"meta-analysis","finding":"In 5 RCTs of sigmoidoscopy or colonoscopy screening, colorectal cancer incidence (RR 0.78) and mortality (RR 0.75) were lower in the screened group."}]},{"from":"ulcerative_colitis","to":"colorectal_cancer","level":"association","effect":"harms","note":"People with ulcerative colitis get bowel cancer more often than others, though the extra risk has fallen over the decades.","sources":[{"id":"pmid:31929014","citation":"Olén O et al., Lancet","year":2020,"design":"cohort","finding":"In Scandinavian national cohorts, ulcerative colitis was associated with higher colorectal cancer incidence (HR 1.66) and death, with excess risk declining over time."}]},{"from":"sx_colectomy","to":"colorectal_cancer","level":"established","effect":"helps","note":"Removing the section of bowel with the cancer and its lymph nodes is the main curative treatment."},{"from":"diverticular_disease","to":"s_colon","level":"established","effect":"affects","note":"Pouches form in the colon wall, mostly the sigmoid colon."},{"from":"diverticular_disease","to":"bp_internal_organs","level":"established","effect":"affects","note":"Diverticular disease affects the large intestine."},{"from":"diverticular_disease","to":"d_abdominal_pain","level":"established","effect":"harms","note":"Diverticulitis typically causes pain low on the left of the belly."},{"from":"fibre","to":"diverticular_disease","level":"association","effect":"helps","note":"People eating the most fibre were about 40% less likely to be admitted to hospital or die with diverticular disease in a large British study.","sources":[{"id":"pmid:21771850","citation":"Crowe FL et al., BMJ","year":2011,"design":"cohort","finding":"In EPIC-Oxford, vegetarians had 31% lower risk of diverticular disease and the highest fibre fifth had 41% lower risk than the lowest."}]},{"from":"sx_colectomy","to":"diverticular_disease","level":"established","effect":"helps","note":"Removing the affected segment treats repeated or complicated diverticulitis."},{"from":"hpylori","to":"peptic_ulcer","level":"established","effect":"harms","note":"H. pylori causes most stomach and duodenal ulcers that are not due to painkillers."},{"from":"hpylori","to":"gastric_cancer","level":"established","effect":"harms","note":"Long-term H. pylori infection is the main cause of stomach cancer worldwide."},{"from":"peptic_ulcer","to":"s_stomach","level":"established","effect":"affects","note":"Stomach ulcers form in the stomach lining."},{"from":"peptic_ulcer","to":"s_duodenum","level":"established","effect":"affects","note":"Most peptic ulcers are in the first part of the duodenum."},{"from":"peptic_ulcer","to":"bp_internal_organs","level":"established","effect":"affects","note":"Ulcers affect the stomach and duodenum."},{"from":"peptic_ulcer","to":"d_abdominal_pain","level":"established","effect":"harms","note":"Ulcers typically cause burning or gnawing pain in the upper belly."},{"from":"gastric_cancer","to":"s_stomach","level":"established","effect":"affects","note":"The cancer grows from the stomach lining."},{"from":"h_hpylori_eradication","to":"hpylori","level":"established","effect":"helps","note":"The antibiotic combination clears the infection in most people; a follow-up test checks it worked."},{"from":"h_hpylori_eradication","to":"peptic_ulcer","level":"proven","effect":"helps","note":"Clearing H. pylori healed duodenal ulcers better and stopped far more ulcers coming back than no treatment, in many trials.","sources":[{"id":"pmid:27092708","citation":"Ford AC et al., Cochrane Database Syst Rev","year":2016,"design":"meta-analysis","finding":"In 55 RCTs, eradication improved duodenal ulcer healing and greatly reduced duodenal (RR 0.20) and gastric (RR 0.31) ulcer recurrence versus no treatment."}]},{"from":"h_hpylori_eradication","to":"gastric_cancer","level":"proven","effect":"helps","note":"In trials in healthy people with H. pylori, mostly in Asia, clearing it led to about a third fewer stomach cancers.","sources":[{"id":"pmid:24846275","citation":"Ford AC et al., BMJ","year":2014,"design":"meta-analysis","finding":"In 6 RCTs (about 6500 people), eradication lowered gastric cancer incidence (RR 0.66); data mainly from Asian populations."}]},{"from":"h_ppi","to":"peptic_ulcer","level":"established","effect":"helps","note":"Suppressing acid lets ulcers heal."},{"from":"sx_gastrectomy","to":"gastric_cancer","level":"established","effect":"helps","note":"Removing part or all of the stomach is the main curative treatment for stomach cancer that has not spread."},{"from":"hypertension","to":"stroke","level":"association","effect":"harms","note":"Higher blood pressure goes with more strokes at every age, and it is the biggest single modifiable stroke risk worldwide.","sources":[{"id":"pmid:12493255","citation":"Lewington S et al. (Prospective Studies Collaboration), Lancet","year":2002,"design":"cohort","finding":"One million adults in 61 cohort studies: higher usual blood pressure was linked to steadily higher death rates from stroke and heart disease at every age, with no threshold down to normal levels."},{"id":"pmid:27431356","citation":"O'Donnell MJ et al. (INTERSTROKE), Lancet","year":2016,"design":"case-control","finding":"In 32 countries, ten modifiable factors (led by high blood pressure, then lack of regular exercise, blood fats, diet, waist, stress, smoking, heart causes, heavy alcohol and diabetes) accounted for about 90% of stroke risk."}]},{"from":"hypertension","to":"coronary_artery_disease","level":"association","effect":"harms","note":"Higher blood pressure goes with steadily more deaths from coronary heart disease.","sources":[{"id":"pmid:12493255","citation":"Lewington S et al. (Prospective Studies Collaboration), Lancet","year":2002,"design":"cohort","finding":"One million adults in 61 cohort studies: higher usual blood pressure was linked to steadily higher death rates from stroke and heart disease at every age, with no threshold down to normal levels."}]},{"from":"hypertension","to":"heart_failure","level":"established","effect":"harms","note":"Years of high pressure thicken and stiffen the left ventricle, a leading cause of heart failure."},{"from":"hypertension","to":"atrial_fibrillation","level":"association","effect":"harms","note":"High blood pressure independently raised the chance of developing atrial fibrillation in the Framingham study.","sources":[{"id":"pmid:8114238","citation":"Benjamin EJ et al., JAMA (Framingham)","year":1994,"design":"cohort","finding":"Over up to 38 years, high blood pressure, diabetes, heart failure, valve disease and (in men) heart attack independently raised the risk of developing atrial fibrillation."}]},{"from":"type2_diabetes","to":"atrial_fibrillation","level":"association","effect":"harms","note":"Diabetes independently raised the chance of developing atrial fibrillation in the Framingham study.","sources":[{"id":"pmid:8114238","citation":"Benjamin EJ et al., JAMA (Framingham)","year":1994,"design":"cohort","finding":"Over up to 38 years, high blood pressure, diabetes, heart failure, valve disease and (in men) heart attack independently raised the risk of developing atrial fibrillation."}]},{"from":"atrial_fibrillation","to":"stroke","level":"association","effect":"harms","note":"Clots formed in the quivering left atrium can travel to the brain; AF raised stroke risk nearly fivefold in Framingham.","sources":[{"id":"pmid:1866765","citation":"Wolf PA, Abbott RD, Kannel WB, Stroke (Framingham)","year":1991,"design":"cohort","finding":"Over 34 years, atrial fibrillation was linked to a near fivefold rise in stroke, hypertension to a more than threefold rise and heart failure to a fourfold rise; AF's effect did not fade with age."}]},{"from":"heart_attack","to":"heart_failure","level":"established","effect":"harms","note":"A heart attack scars the left ventricle, which can leave it too weak to pump well."},{"from":"h_bp_medicines","to":"hypertension","level":"proven","effect":"helps","note":"In randomised trials, blood-pressure medicines lowered blood pressure.","sources":[{"id":"pmid:26724178","citation":"Ettehad D et al., Lancet","year":2016,"design":"meta-analysis","finding":"123 randomised trials (613,815 people): each step down in systolic blood pressure cut major cardiovascular events, coronary heart disease, stroke and heart failure in proportion to the fall."}]},{"from":"h_bp_medicines","to":"stroke","level":"proven","effect":"helps","note":"In randomised trials, lowering blood pressure cut strokes in proportion to how far it fell.","sources":[{"id":"pmid:26724178","citation":"Ettehad D et al., Lancet","year":2016,"design":"meta-analysis","finding":"123 randomised trials (613,815 people): each step down in systolic blood pressure cut major cardiovascular events, coronary heart disease, stroke and heart failure in proportion to the fall."}]},{"from":"h_bp_medicines","to":"heart_failure","level":"proven","effect":"helps","note":"In randomised trials, lowering blood pressure cut new heart failure.","sources":[{"id":"pmid:26724178","citation":"Ettehad D et al., Lancet","year":2016,"design":"meta-analysis","finding":"123 randomised trials (613,815 people): each step down in systolic blood pressure cut major cardiovascular events, coronary heart disease, stroke and heart failure in proportion to the fall."}]},{"from":"h_statins","to":"stroke","level":"proven","effect":"helps","note":"In randomised trials, lowering LDL cholesterol with statins reduced strokes from blocked arteries.","sources":[{"id":"pmid:21067804","citation":"Cholesterol Treatment Trialists' Collaboration, Lancet","year":2010,"design":"meta-analysis","finding":"In 26 randomised statin trials (about 170,000 people), lowering LDL cholesterol reduced heart attacks, artery-opening procedures and ischaemic strokes, in proportion to how far LDL fell."}]},{"from":"h_anticoagulants","to":"stroke","level":"proven","effect":"helps","note":"In randomised trials in atrial fibrillation, warfarin cut strokes by about two-thirds, with a small rise in serious bleeding.","scope":["atrial_fibrillation"],"sources":[{"id":"pmid:17577005","citation":"Hart RG, Pearce LA, Aguilar MI, Ann Intern Med","year":2007,"design":"meta-analysis","finding":"29 randomised trials in atrial fibrillation: adjusted-dose warfarin cut stroke by 64% and aspirin-type drugs by 22%, with small absolute increases in major bleeding."}]},{"from":"h_compression_stockings","to":"dvt","level":"proven","effect":"helps","note":"In randomised trials of passengers on long flights, compression stockings greatly reduced symptomless deep vein clots.","sources":[{"id":"pmid:33878207","citation":"Clarke MJ et al., Cochrane Database Syst Rev","year":2021,"design":"meta-analysis","finding":"12 randomised trials of passengers on long flights: compression stockings greatly reduced symptomless deep vein clots (high certainty) and probably leg swelling; too few events to judge pulmonary embolism."}]},{"from":"hypertension","to":"ckd","level":"association","effect":"harms","note":"Higher blood pressure went with a steadily higher chance of kidney failure over 16 years.","sources":[{"id":"pmid:7494564","citation":"Klag MJ et al., N Engl J Med (MRFIT)","year":1996,"design":"cohort","finding":"In about 330,000 men followed for 16 years, higher blood pressure was linked to a strong, graded rise in kidney failure, independent of other risk factors."}]},{"from":"ckd","to":"hypertension","level":"established","effect":"harms","note":"Damaged kidneys hold on to salt and water and release more pressure-raising hormone (renin), so kidney disease raises blood pressure."},{"from":"dvt","to":"pulmonary_embolism","level":"established","effect":"harms","note":"A piece of a leg-vein clot can break off and lodge in the lung arteries."},{"from":"h_anticoagulants","to":"dvt","level":"proven","effect":"helps","note":"In a randomised trial, continuing a blood thinner after a first vein or lung clot sharply cut repeat clots compared with placebo.","sources":[{"id":"pmid:23216615","citation":"Agnelli G et al. (AMPLIFY-EXT), N Engl J Med","year":2013,"design":"RCT","finding":"After 6-12 months of treatment for a vein clot or lung clot, continuing apixaban for another year cut recurrent clots compared with placebo without raising major bleeding."}]},{"from":"s_spleen_hilum","to":"s_spleen","level":"established","effect":"located","note":"Part of the spleen: the slit on its inner surface where its vessels enter and leave."},{"from":"mu_temporalis","to":"s_muscle","level":"established","effect":"located","note":"The temporalis is one of the body's skeletal muscles."},{"from":"mu_temporalis","to":"bp_face_jaw","level":"established","effect":"located","note":"The temporalis lies in, or moves, the face and jaw."},{"from":"mu_masseter","to":"s_muscle","level":"established","effect":"located","note":"The masseter is one of the body's skeletal muscles."},{"from":"mu_masseter","to":"bp_face_jaw","level":"established","effect":"located","note":"The masseter lies in, or moves, the face and jaw."},{"from":"mu_medial_pterygoid","to":"s_muscle","level":"established","effect":"located","note":"The medial pterygoid is one of the body's skeletal muscles."},{"from":"mu_medial_pterygoid","to":"bp_face_jaw","level":"established","effect":"located","note":"The medial pterygoid lies in, or moves, the face and jaw."},{"from":"mu_lateral_pterygoid","to":"s_muscle","level":"established","effect":"located","note":"The lateral pterygoid is one of the body's skeletal muscles."},{"from":"mu_lateral_pterygoid","to":"bp_face_jaw","level":"established","effect":"located","note":"The lateral pterygoid lies in, or moves, the face and jaw."},{"from":"mu_buccinator","to":"s_muscle","level":"established","effect":"located","note":"The buccinator is one of the body's skeletal muscles."},{"from":"mu_buccinator","to":"bp_face_jaw","level":"established","effect":"located","note":"The buccinator lies in, or moves, the face and jaw."},{"from":"mu_zygomaticus_major","to":"s_muscle","level":"established","effect":"located","note":"The zygomaticus major is one of the body's skeletal muscles."},{"from":"mu_zygomaticus_major","to":"bp_face_jaw","level":"established","effect":"located","note":"The zygomaticus major lies in, or moves, the face and jaw."},{"from":"mu_levator_labii_superioris","to":"s_muscle","level":"established","effect":"located","note":"The levator labii superioris is one of the body's skeletal muscles."},{"from":"mu_levator_labii_superioris","to":"bp_face_jaw","level":"established","effect":"located","note":"The levator labii superioris lies in, or moves, the face and jaw."},{"from":"mu_depressor_anguli_oris","to":"s_muscle","level":"established","effect":"located","note":"The depressor anguli oris is one of the body's skeletal muscles."},{"from":"mu_depressor_anguli_oris","to":"bp_face_jaw","level":"established","effect":"located","note":"The depressor anguli oris lies in, or moves, the face and jaw."},{"from":"mu_orbicularis_oris","to":"s_muscle","level":"established","effect":"located","note":"The orbicularis oris is one of the body's skeletal muscles."},{"from":"mu_orbicularis_oris","to":"bp_face_jaw","level":"established","effect":"located","note":"The orbicularis oris lies in, or moves, the face and jaw."},{"from":"mu_orbicularis_oculi","to":"s_muscle","level":"established","effect":"located","note":"The orbicularis oculi is one of the body's skeletal muscles."},{"from":"mu_orbicularis_oculi","to":"bp_face_jaw","level":"established","effect":"located","note":"The orbicularis oculi lies in, or moves, the face and jaw."},{"from":"mu_orbicularis_oculi","to":"bp_eyes","level":"established","effect":"located","note":"The orbicularis oculi lies in, or moves, the eye region."},{"from":"mu_frontalis","to":"s_muscle","level":"established","effect":"located","note":"The frontalis is one of the body's skeletal muscles."},{"from":"mu_frontalis","to":"bp_head_brain","level":"established","effect":"located","note":"The frontalis lies in, or moves, the head."},{"from":"mu_frontalis","to":"bp_face_jaw","level":"established","effect":"located","note":"The frontalis lies in, or moves, the face and jaw."},{"from":"mu_occipitalis","to":"s_muscle","level":"established","effect":"located","note":"The occipitalis is one of the body's skeletal muscles."},{"from":"mu_occipitalis","to":"bp_head_brain","level":"established","effect":"located","note":"The occipitalis lies in, or moves, the head."},{"from":"mu_platysma","to":"s_muscle","level":"established","effect":"located","note":"The platysma is one of the body's skeletal muscles."},{"from":"mu_platysma","to":"bp_cervical_spine","level":"established","effect":"located","note":"The platysma lies in, or moves, the neck."},{"from":"mu_platysma","to":"bp_face_jaw","level":"established","effect":"located","note":"The platysma lies in, or moves, the face and jaw."},{"from":"mu_sternocleidomastoid","to":"s_muscle","level":"established","effect":"located","note":"The sternocleidomastoid is one of the body's skeletal muscles."},{"from":"mu_sternocleidomastoid","to":"bp_cervical_spine","level":"established","effect":"located","note":"The sternocleidomastoid lies in, or moves, the neck."},{"from":"mu_scalenes","to":"s_muscle","level":"established","effect":"located","note":"The scalene muscles is one of the body's skeletal muscles."},{"from":"mu_scalenes","to":"bp_cervical_spine","level":"established","effect":"located","note":"The scalene muscles lies in, or moves, the neck."},{"from":"mu_sternohyoid","to":"s_muscle","level":"established","effect":"located","note":"The sternohyoid is one of the body's skeletal muscles."},{"from":"mu_sternohyoid","to":"bp_cervical_spine","level":"established","effect":"located","note":"The sternohyoid lies in, or moves, the neck."},{"from":"mu_splenius_capitis","to":"s_muscle","level":"established","effect":"located","note":"The splenius capitis is one of the body's skeletal muscles."},{"from":"mu_splenius_capitis","to":"bp_cervical_spine","level":"established","effect":"located","note":"The splenius capitis lies in, or moves, the neck."},{"from":"mu_levator_scapulae","to":"s_muscle","level":"established","effect":"located","note":"The levator scapulae is one of the body's skeletal muscles."},{"from":"mu_levator_scapulae","to":"bp_cervical_spine","level":"established","effect":"located","note":"The levator scapulae lies in, or moves, the neck."},{"from":"mu_levator_scapulae","to":"bp_shoulders","level":"established","effect":"located","note":"The levator scapulae lies in, or moves, the shoulder."},{"from":"mu_trapezius_upper","to":"s_muscle","level":"established","effect":"located","note":"The trapezius (upper fibres) is one of the body's skeletal muscles."},{"from":"mu_trapezius_upper","to":"bp_cervical_spine","level":"established","effect":"located","note":"The trapezius (upper fibres) lies in, or moves, the neck."},{"from":"mu_trapezius_upper","to":"bp_shoulders","level":"established","effect":"located","note":"The trapezius (upper fibres) lies in, or moves, the shoulder."},{"from":"mu_trapezius_middle","to":"s_muscle","level":"established","effect":"located","note":"The trapezius (middle fibres) is one of the body's skeletal muscles."},{"from":"mu_trapezius_middle","to":"bp_thoracic_spine","level":"established","effect":"located","note":"The trapezius (middle fibres) lies in, or moves, the mid back."},{"from":"mu_trapezius_middle","to":"bp_shoulders","level":"established","effect":"located","note":"The trapezius (middle fibres) lies in, or moves, the shoulder."},{"from":"mu_trapezius_lower","to":"s_muscle","level":"established","effect":"located","note":"The trapezius (lower fibres) is one of the body's skeletal muscles."},{"from":"mu_trapezius_lower","to":"bp_thoracic_spine","level":"established","effect":"located","note":"The trapezius (lower fibres) lies in, or moves, the mid back."},{"from":"mu_trapezius_lower","to":"bp_shoulders","level":"established","effect":"located","note":"The trapezius (lower fibres) lies in, or moves, the shoulder."},{"from":"mu_rhomboid_minor","to":"s_muscle","level":"established","effect":"located","note":"The rhomboid minor is one of the body's skeletal muscles."},{"from":"mu_rhomboid_minor","to":"bp_thoracic_spine","level":"established","effect":"located","note":"The rhomboid minor lies in, or moves, the mid back."},{"from":"mu_rhomboid_major","to":"s_muscle","level":"established","effect":"located","note":"The rhomboid major is one of the body's skeletal muscles."},{"from":"mu_rhomboid_major","to":"bp_thoracic_spine","level":"established","effect":"located","note":"The rhomboid major lies in, or moves, the mid back."},{"from":"mu_pectoralis_major","to":"s_muscle","level":"established","effect":"located","note":"The pectoralis major is one of the body's skeletal muscles."},{"from":"mu_pectoralis_major","to":"bp_chest_ribs","level":"established","effect":"located","note":"The pectoralis major lies in, or moves, the chest wall."},{"from":"mu_pectoralis_major","to":"bp_shoulders","level":"established","effect":"located","note":"The pectoralis major lies in, or moves, the shoulder."},{"from":"mu_pectoralis_minor","to":"s_muscle","level":"established","effect":"located","note":"The pectoralis minor is one of the body's skeletal muscles."},{"from":"mu_pectoralis_minor","to":"bp_chest_ribs","level":"established","effect":"located","note":"The pectoralis minor lies in, or moves, the chest wall."},{"from":"mu_pectoralis_minor","to":"bp_shoulders","level":"established","effect":"located","note":"The pectoralis minor lies in, or moves, the shoulder."},{"from":"mu_serratus_anterior","to":"s_muscle","level":"established","effect":"located","note":"The serratus anterior is one of the body's skeletal muscles."},{"from":"mu_serratus_anterior","to":"bp_chest_ribs","level":"established","effect":"located","note":"The serratus anterior lies in, or moves, the chest wall."},{"from":"mu_serratus_anterior","to":"bp_shoulders","level":"established","effect":"located","note":"The serratus anterior lies in, or moves, the shoulder."},{"from":"mu_subclavius","to":"s_muscle","level":"established","effect":"located","note":"The subclavius is one of the body's skeletal muscles."},{"from":"mu_subclavius","to":"bp_chest_ribs","level":"established","effect":"located","note":"The subclavius lies in, or moves, the chest wall."},{"from":"mu_subclavius","to":"bp_shoulders","level":"established","effect":"located","note":"The subclavius lies in, or moves, the shoulder."},{"from":"mu_rectus_abdominis","to":"s_muscle","level":"established","effect":"located","note":"The rectus abdominis is one of the body's skeletal muscles."},{"from":"mu_rectus_abdominis","to":"bp_abdomen","level":"established","effect":"located","note":"The rectus abdominis lies in, or moves, the belly wall and groin."},{"from":"mu_external_oblique","to":"s_muscle","level":"established","effect":"located","note":"The external oblique is one of the body's skeletal muscles."},{"from":"mu_external_oblique","to":"bp_abdomen","level":"established","effect":"located","note":"The external oblique lies in, or moves, the belly wall and groin."},{"from":"inguinal_hernia","to":"mu_external_oblique","level":"established","effect":"affects","note":"The external oblique's tendon sheet forms the front wall of the groin canal that an inguinal hernia pushes through."},{"from":"mu_internal_oblique","to":"s_muscle","level":"established","effect":"located","note":"The internal oblique is one of the body's skeletal muscles."},{"from":"mu_internal_oblique","to":"bp_abdomen","level":"established","effect":"located","note":"The internal oblique lies in, or moves, the belly wall and groin."},{"from":"inguinal_hernia","to":"mu_internal_oblique","level":"established","effect":"affects","note":"The internal oblique forms the roof of the groin canal that an inguinal hernia pushes through."},{"from":"mu_transversus_abdominis","to":"s_muscle","level":"established","effect":"located","note":"The transversus abdominis is one of the body's skeletal muscles."},{"from":"mu_transversus_abdominis","to":"bp_abdomen","level":"established","effect":"located","note":"The transversus abdominis lies in, or moves, the belly wall and groin."},{"from":"mu_transversus_abdominis","to":"bp_lumbar_spine","level":"established","effect":"located","note":"The transversus abdominis lies in, or moves, the low back."},{"from":"inguinal_hernia","to":"mu_transversus_abdominis","level":"established","effect":"affects","note":"The transversus abdominis and its fascia form the back wall of the groin canal that an inguinal hernia pushes through."},{"from":"mu_iliocostalis","to":"s_muscle","level":"established","effect":"located","note":"The iliocostalis is one of the body's skeletal muscles."},{"from":"mu_iliocostalis","to":"bp_thoracic_spine","level":"established","effect":"located","note":"The iliocostalis lies in, or moves, the mid back."},{"from":"mu_iliocostalis","to":"bp_lumbar_spine","level":"established","effect":"located","note":"The iliocostalis lies in, or moves, the low back."},{"from":"mu_longissimus","to":"s_muscle","level":"established","effect":"located","note":"The longissimus is one of the body's skeletal muscles."},{"from":"mu_longissimus","to":"bp_thoracic_spine","level":"established","effect":"located","note":"The longissimus lies in, or moves, the mid back."},{"from":"mu_longissimus","to":"bp_lumbar_spine","level":"established","effect":"located","note":"The longissimus lies in, or moves, the low back."},{"from":"mu_spinalis","to":"s_muscle","level":"established","effect":"located","note":"The spinalis is one of the body's skeletal muscles."},{"from":"mu_spinalis","to":"bp_thoracic_spine","level":"established","effect":"located","note":"The spinalis lies in, or moves, the mid back."},{"from":"mu_multifidus","to":"s_muscle","level":"established","effect":"located","note":"The multifidus is one of the body's skeletal muscles."},{"from":"mu_multifidus","to":"bp_lumbar_spine","level":"established","effect":"located","note":"The multifidus lies in, or moves, the low back."},{"from":"mu_quadratus_lumborum","to":"s_muscle","level":"established","effect":"located","note":"The quadratus lumborum is one of the body's skeletal muscles."},{"from":"mu_quadratus_lumborum","to":"bp_lumbar_spine","level":"established","effect":"located","note":"The quadratus lumborum lies in, or moves, the low back."},{"from":"mu_deltoid","to":"s_muscle","level":"established","effect":"located","note":"The deltoid is one of the body's skeletal muscles."},{"from":"mu_deltoid","to":"bp_shoulders","level":"established","effect":"located","note":"The deltoid lies in, or moves, the shoulder."},{"from":"mu_supraspinatus","to":"s_muscle","level":"established","effect":"located","note":"The supraspinatus is one of the body's skeletal muscles."},{"from":"mu_supraspinatus","to":"bp_shoulders","level":"established","effect":"located","note":"The supraspinatus lies in, or moves, the shoulder."},{"from":"rotator_cuff","to":"mu_supraspinatus","level":"established","effect":"affects","note":"The supraspinatus tendon is the rotator cuff tendon most often inflamed or torn."},{"from":"mu_infraspinatus","to":"s_muscle","level":"established","effect":"located","note":"The infraspinatus is one of the body's skeletal muscles."},{"from":"mu_infraspinatus","to":"bp_shoulders","level":"established","effect":"located","note":"The infraspinatus lies in, or moves, the shoulder."},{"from":"rotator_cuff","to":"mu_infraspinatus","level":"established","effect":"affects","note":"The infraspinatus is one of the four rotator cuff muscles that cuff disease affects."},{"from":"mu_teres_minor","to":"s_muscle","level":"established","effect":"located","note":"The teres minor is one of the body's skeletal muscles."},{"from":"mu_teres_minor","to":"bp_shoulders","level":"established","effect":"located","note":"The teres minor lies in, or moves, the shoulder."},{"from":"rotator_cuff","to":"mu_teres_minor","level":"established","effect":"affects","note":"The teres minor is one of the four rotator cuff muscles that cuff disease affects."},{"from":"mu_subscapularis","to":"s_muscle","level":"established","effect":"located","note":"The subscapularis is one of the body's skeletal muscles."},{"from":"mu_subscapularis","to":"bp_shoulders","level":"established","effect":"located","note":"The subscapularis lies in, or moves, the shoulder."},{"from":"rotator_cuff","to":"mu_subscapularis","level":"established","effect":"affects","note":"The subscapularis is one of the four rotator cuff muscles that cuff disease affects."},{"from":"mu_teres_major","to":"s_muscle","level":"established","effect":"located","note":"The teres major is one of the body's skeletal muscles."},{"from":"mu_teres_major","to":"bp_shoulders","level":"established","effect":"located","note":"The teres major lies in, or moves, the shoulder."},{"from":"mu_latissimus_dorsi","to":"s_muscle","level":"established","effect":"located","note":"The latissimus dorsi is one of the body's skeletal muscles."},{"from":"mu_latissimus_dorsi","to":"bp_thoracic_spine","level":"established","effect":"located","note":"The latissimus dorsi lies in, or moves, the mid back."},{"from":"mu_latissimus_dorsi","to":"bp_shoulders","level":"established","effect":"located","note":"The latissimus dorsi lies in, or moves, the shoulder."},{"from":"mu_coracobrachialis","to":"s_muscle","level":"established","effect":"located","note":"The coracobrachialis is one of the body's skeletal muscles."},{"from":"mu_coracobrachialis","to":"bp_shoulders","level":"established","effect":"located","note":"The coracobrachialis lies in, or moves, the shoulder."},{"from":"mu_biceps_brachii","to":"s_muscle","level":"established","effect":"located","note":"The biceps brachii is one of the body's skeletal muscles."},{"from":"mu_biceps_brachii","to":"bp_elbows","level":"established","effect":"located","note":"The biceps brachii lies in, or moves, the elbow."},{"from":"mu_biceps_brachii","to":"bp_shoulders","level":"established","effect":"located","note":"The biceps brachii lies in, or moves, the shoulder."},{"from":"mu_brachialis","to":"s_muscle","level":"established","effect":"located","note":"The brachialis is one of the body's skeletal muscles."},{"from":"mu_brachialis","to":"bp_elbows","level":"established","effect":"located","note":"The brachialis lies in, or moves, the elbow."},{"from":"mu_triceps_brachii","to":"s_muscle","level":"established","effect":"located","note":"The triceps brachii is one of the body's skeletal muscles."},{"from":"mu_triceps_brachii","to":"bp_elbows","level":"established","effect":"located","note":"The triceps brachii lies in, or moves, the elbow."},{"from":"mu_triceps_brachii","to":"bp_shoulders","level":"established","effect":"located","note":"The triceps brachii lies in, or moves, the shoulder."},{"from":"mu_pronator_teres","to":"s_muscle","level":"established","effect":"located","note":"The pronator teres is one of the body's skeletal muscles."},{"from":"mu_pronator_teres","to":"bp_elbows","level":"established","effect":"located","note":"The pronator teres lies in, or moves, the elbow."},{"from":"mu_pronator_teres","to":"bp_wrists_hands","level":"established","effect":"located","note":"The pronator teres lies in, or moves, the wrist and hand."},{"from":"epicondylitis","to":"mu_pronator_teres","level":"established","effect":"affects","note":"Golfer's elbow involves the shared flexor-pronator origin at the inner elbow, where this muscle starts."},{"from":"mu_flexor_carpi_radialis","to":"s_muscle","level":"established","effect":"located","note":"The flexor carpi radialis is one of the body's skeletal muscles."},{"from":"mu_flexor_carpi_radialis","to":"bp_wrists_hands","level":"established","effect":"located","note":"The flexor carpi radialis lies in, or moves, the wrist and hand."},{"from":"mu_flexor_carpi_radialis","to":"bp_elbows","level":"established","effect":"located","note":"The flexor carpi radialis lies in, or moves, the elbow."},{"from":"epicondylitis","to":"mu_flexor_carpi_radialis","level":"established","effect":"affects","note":"Golfer's elbow is overload of the shared flexor tendon at the inner elbow, where this muscle starts."},{"from":"mu_palmaris_longus","to":"s_muscle","level":"established","effect":"located","note":"The palmaris longus is one of the body's skeletal muscles."},{"from":"mu_palmaris_longus","to":"bp_wrists_hands","level":"established","effect":"located","note":"The palmaris longus lies in, or moves, the wrist and hand."},{"from":"mu_flexor_digitorum_superficialis","to":"s_muscle","level":"established","effect":"located","note":"The flexor digitorum superficialis is one of the body's skeletal muscles."},{"from":"mu_flexor_digitorum_superficialis","to":"bp_wrists_hands","level":"established","effect":"located","note":"The flexor digitorum superficialis lies in, or moves, the wrist and hand."},{"from":"mu_flexor_digitorum_superficialis","to":"bp_fingers","level":"established","effect":"located","note":"The flexor digitorum superficialis lies in, or moves, the fingers."},{"from":"mu_flexor_carpi_ulnaris","to":"s_muscle","level":"established","effect":"located","note":"The flexor carpi ulnaris is one of the body's skeletal muscles."},{"from":"mu_flexor_carpi_ulnaris","to":"bp_wrists_hands","level":"established","effect":"located","note":"The flexor carpi ulnaris lies in, or moves, the wrist and hand."},{"from":"mu_flexor_carpi_ulnaris","to":"bp_elbows","level":"established","effect":"located","note":"The flexor carpi ulnaris lies in, or moves, the elbow."},{"from":"mu_flexor_digitorum_profundus","to":"s_muscle","level":"established","effect":"located","note":"The flexor digitorum profundus is one of the body's skeletal muscles."},{"from":"mu_flexor_digitorum_profundus","to":"bp_wrists_hands","level":"established","effect":"located","note":"The flexor digitorum profundus lies in, or moves, the wrist and hand."},{"from":"mu_flexor_digitorum_profundus","to":"bp_fingers","level":"established","effect":"located","note":"The flexor digitorum profundus lies in, or moves, the fingers."},{"from":"mu_flexor_pollicis_longus","to":"s_muscle","level":"established","effect":"located","note":"The flexor pollicis longus is one of the body's skeletal muscles."},{"from":"mu_flexor_pollicis_longus","to":"bp_wrists_hands","level":"established","effect":"located","note":"The flexor pollicis longus lies in, or moves, the wrist and hand."},{"from":"mu_flexor_pollicis_longus","to":"bp_fingers","level":"established","effect":"located","note":"The flexor pollicis longus lies in, or moves, the fingers."},{"from":"mu_brachioradialis","to":"s_muscle","level":"established","effect":"located","note":"The brachioradialis is one of the body's skeletal muscles."},{"from":"mu_brachioradialis","to":"bp_elbows","level":"established","effect":"located","note":"The brachioradialis lies in, or moves, the elbow."},{"from":"mu_brachioradialis","to":"bp_wrists_hands","level":"established","effect":"located","note":"The brachioradialis lies in, or moves, the wrist and hand."},{"from":"mu_extensor_carpi_radialis_longus","to":"s_muscle","level":"established","effect":"located","note":"The extensor carpi radialis longus is one of the body's skeletal muscles."},{"from":"mu_extensor_carpi_radialis_longus","to":"bp_wrists_hands","level":"established","effect":"located","note":"The extensor carpi radialis longus lies in, or moves, the wrist and hand."},{"from":"mu_extensor_carpi_radialis_longus","to":"bp_elbows","level":"established","effect":"located","note":"The extensor carpi radialis longus lies in, or moves, the elbow."},{"from":"mu_extensor_carpi_radialis_brevis","to":"s_muscle","level":"established","effect":"located","note":"The extensor carpi radialis brevis is one of the body's skeletal muscles."},{"from":"mu_extensor_carpi_radialis_brevis","to":"bp_elbows","level":"established","effect":"located","note":"The extensor carpi radialis brevis lies in, or moves, the elbow."},{"from":"mu_extensor_carpi_radialis_brevis","to":"bp_wrists_hands","level":"established","effect":"located","note":"The extensor carpi radialis brevis lies in, or moves, the wrist and hand."},{"from":"epicondylitis","to":"mu_extensor_carpi_radialis_brevis","level":"established","effect":"affects","note":"Tennis elbow is overload of this muscle's tendon where it attaches to the outer elbow."},{"from":"mu_extensor_digitorum","to":"s_muscle","level":"established","effect":"located","note":"The extensor digitorum is one of the body's skeletal muscles."},{"from":"mu_extensor_digitorum","to":"bp_wrists_hands","level":"established","effect":"located","note":"The extensor digitorum lies in, or moves, the wrist and hand."},{"from":"mu_extensor_digitorum","to":"bp_fingers","level":"established","effect":"located","note":"The extensor digitorum lies in, or moves, the fingers."},{"from":"mu_extensor_carpi_ulnaris","to":"s_muscle","level":"established","effect":"located","note":"The extensor carpi ulnaris is one of the body's skeletal muscles."},{"from":"mu_extensor_carpi_ulnaris","to":"bp_wrists_hands","level":"established","effect":"located","note":"The extensor carpi ulnaris lies in, or moves, the wrist and hand."},{"from":"mu_anconeus","to":"s_muscle","level":"established","effect":"located","note":"The anconeus is one of the body's skeletal muscles."},{"from":"mu_anconeus","to":"bp_elbows","level":"established","effect":"located","note":"The anconeus lies in, or moves, the elbow."},{"from":"mu_supinator","to":"s_muscle","level":"established","effect":"located","note":"The supinator is one of the body's skeletal muscles."},{"from":"mu_supinator","to":"bp_elbows","level":"established","effect":"located","note":"The supinator lies in, or moves, the elbow."},{"from":"mu_supinator","to":"bp_wrists_hands","level":"established","effect":"located","note":"The supinator lies in, or moves, the wrist and hand."},{"from":"mu_abductor_pollicis_longus","to":"s_muscle","level":"established","effect":"located","note":"The abductor pollicis longus is one of the body's skeletal muscles."},{"from":"mu_abductor_pollicis_longus","to":"bp_wrists_hands","level":"established","effect":"located","note":"The abductor pollicis longus lies in, or moves, the wrist and hand."},{"from":"mu_abductor_pollicis_longus","to":"bp_fingers","level":"established","effect":"located","note":"The abductor pollicis longus lies in, or moves, the fingers."},{"from":"mu_extensor_pollicis_brevis","to":"s_muscle","level":"established","effect":"located","note":"The extensor pollicis brevis is one of the body's skeletal muscles."},{"from":"mu_extensor_pollicis_brevis","to":"bp_wrists_hands","level":"established","effect":"located","note":"The extensor pollicis brevis lies in, or moves, the wrist and hand."},{"from":"mu_extensor_pollicis_brevis","to":"bp_fingers","level":"established","effect":"located","note":"The extensor pollicis brevis lies in, or moves, the fingers."},{"from":"mu_extensor_pollicis_longus","to":"s_muscle","level":"established","effect":"located","note":"The extensor pollicis longus is one of the body's skeletal muscles."},{"from":"mu_extensor_pollicis_longus","to":"bp_wrists_hands","level":"established","effect":"located","note":"The extensor pollicis longus lies in, or moves, the wrist and hand."},{"from":"mu_extensor_pollicis_longus","to":"bp_fingers","level":"established","effect":"located","note":"The extensor pollicis longus lies in, or moves, the fingers."},{"from":"mu_thenar","to":"s_muscle","level":"established","effect":"located","note":"The thenar muscles is one of the body's skeletal muscles."},{"from":"mu_thenar","to":"bp_wrists_hands","level":"established","effect":"located","note":"The thenar muscles lies in, or moves, the wrist and hand."},{"from":"mu_thenar","to":"bp_fingers","level":"established","effect":"located","note":"The thenar muscles lies in, or moves, the fingers."},{"from":"carpal_tunnel","to":"mu_thenar","level":"established","effect":"affects","note":"The median nerve squeezed in carpal tunnel syndrome supplies the ball-of-thumb muscles, which can waste in severe cases."},{"from":"mu_hypothenar","to":"s_muscle","level":"established","effect":"located","note":"The hypothenar muscles is one of the body's skeletal muscles."},{"from":"mu_hypothenar","to":"bp_wrists_hands","level":"established","effect":"located","note":"The hypothenar muscles lies in, or moves, the wrist and hand."},{"from":"mu_hypothenar","to":"bp_fingers","level":"established","effect":"located","note":"The hypothenar muscles lies in, or moves, the fingers."},{"from":"mu_interossei","to":"s_muscle","level":"established","effect":"located","note":"The interossei is one of the body's skeletal muscles."},{"from":"mu_interossei","to":"bp_wrists_hands","level":"established","effect":"located","note":"The interossei lies in, or moves, the wrist and hand."},{"from":"mu_interossei","to":"bp_fingers","level":"established","effect":"located","note":"The interossei lies in, or moves, the fingers."},{"from":"mu_levator_ani","to":"s_muscle","level":"established","effect":"located","note":"The levator ani is one of the body's skeletal muscles."},{"from":"mu_levator_ani","to":"bp_abdomen","level":"established","effect":"located","note":"The levator ani lies in, or moves, the belly wall and groin."},{"from":"mu_levator_ani","to":"bp_hips","level":"established","effect":"located","note":"The levator ani lies in, or moves, the hip and groin."},{"from":"pelvic","to":"mu_levator_ani","level":"established","effect":"helps","note":"Pelvic-floor training is exercise of this muscle group, which keeps urine and stool in."},{"from":"mu_piriformis","to":"s_muscle","level":"established","effect":"located","note":"The piriformis is one of the body's skeletal muscles."},{"from":"mu_piriformis","to":"bp_hips","level":"established","effect":"located","note":"The piriformis lies in, or moves, the hip and groin."},{"from":"mu_gluteus_maximus","to":"s_muscle","level":"established","effect":"located","note":"The gluteus maximus is one of the body's skeletal muscles."},{"from":"mu_gluteus_maximus","to":"bp_hips","level":"established","effect":"located","note":"The gluteus maximus lies in, or moves, the hip and groin."},{"from":"mu_gluteus_medius","to":"s_muscle","level":"established","effect":"located","note":"The gluteus medius is one of the body's skeletal muscles."},{"from":"mu_gluteus_medius","to":"bp_hips","level":"established","effect":"located","note":"The gluteus medius lies in, or moves, the hip and groin."},{"from":"mu_gluteus_minimus","to":"s_muscle","level":"established","effect":"located","note":"The gluteus minimus is one of the body's skeletal muscles."},{"from":"mu_gluteus_minimus","to":"bp_hips","level":"established","effect":"located","note":"The gluteus minimus lies in, or moves, the hip and groin."},{"from":"mu_psoas_major","to":"s_muscle","level":"established","effect":"located","note":"The psoas major is one of the body's skeletal muscles."},{"from":"mu_psoas_major","to":"bp_hips","level":"established","effect":"located","note":"The psoas major lies in, or moves, the hip and groin."},{"from":"mu_psoas_major","to":"bp_lumbar_spine","level":"established","effect":"located","note":"The psoas major lies in, or moves, the low back."},{"from":"mu_iliacus","to":"s_muscle","level":"established","effect":"located","note":"The iliacus is one of the body's skeletal muscles."},{"from":"mu_iliacus","to":"bp_hips","level":"established","effect":"located","note":"The iliacus lies in, or moves, the hip and groin."},{"from":"mu_tensor_fasciae_latae","to":"s_muscle","level":"established","effect":"located","note":"The tensor fasciae latae is one of the body's muscle-and-tendon structures."},{"from":"mu_tensor_fasciae_latae","to":"bp_hips","level":"established","effect":"located","note":"The tensor fasciae latae lies in, or moves, the hip and groin."},{"from":"mu_tensor_fasciae_latae","to":"bp_knees","level":"established","effect":"located","note":"The tensor fasciae latae lies in, or moves, the knee."},{"from":"mu_pectineus","to":"s_muscle","level":"established","effect":"located","note":"The pectineus is one of the body's skeletal muscles."},{"from":"mu_pectineus","to":"bp_hips","level":"established","effect":"located","note":"The pectineus lies in, or moves, the hip and groin."},{"from":"mu_adductor_longus","to":"s_muscle","level":"established","effect":"located","note":"The adductor longus is one of the body's skeletal muscles."},{"from":"mu_adductor_longus","to":"bp_hips","level":"established","effect":"located","note":"The adductor longus lies in, or moves, the hip and groin."},{"from":"mu_adductor_brevis","to":"s_muscle","level":"established","effect":"located","note":"The adductor brevis is one of the body's skeletal muscles."},{"from":"mu_adductor_brevis","to":"bp_hips","level":"established","effect":"located","note":"The adductor brevis lies in, or moves, the hip and groin."},{"from":"mu_adductor_magnus","to":"s_muscle","level":"established","effect":"located","note":"The adductor magnus is one of the body's skeletal muscles."},{"from":"mu_adductor_magnus","to":"bp_hips","level":"established","effect":"located","note":"The adductor magnus lies in, or moves, the hip and groin."},{"from":"mu_adductor_magnus","to":"bp_knees","level":"established","effect":"located","note":"The adductor magnus lies in, or moves, the knee."},{"from":"mu_gracilis","to":"s_muscle","level":"established","effect":"located","note":"The gracilis is one of the body's skeletal muscles."},{"from":"mu_gracilis","to":"bp_hips","level":"established","effect":"located","note":"The gracilis lies in, or moves, the hip and groin."},{"from":"mu_gracilis","to":"bp_knees","level":"established","effect":"located","note":"The gracilis lies in, or moves, the knee."},{"from":"mu_rectus_femoris","to":"s_muscle","level":"established","effect":"located","note":"The rectus femoris is one of the body's skeletal muscles."},{"from":"mu_rectus_femoris","to":"bp_knees","level":"established","effect":"located","note":"The rectus femoris lies in, or moves, the knee."},{"from":"mu_rectus_femoris","to":"bp_hips","level":"established","effect":"located","note":"The rectus femoris lies in, or moves, the hip and groin."},{"from":"mu_vastus_lateralis","to":"s_muscle","level":"established","effect":"located","note":"The vastus lateralis is one of the body's skeletal muscles."},{"from":"mu_vastus_lateralis","to":"bp_knees","level":"established","effect":"located","note":"The vastus lateralis lies in, or moves, the knee."},{"from":"mu_vastus_medialis","to":"s_muscle","level":"established","effect":"located","note":"The vastus medialis is one of the body's skeletal muscles."},{"from":"mu_vastus_medialis","to":"bp_knees","level":"established","effect":"located","note":"The vastus medialis lies in, or moves, the knee."},{"from":"mu_vastus_intermedius","to":"s_muscle","level":"established","effect":"located","note":"The vastus intermedius is one of the body's skeletal muscles."},{"from":"mu_vastus_intermedius","to":"bp_knees","level":"established","effect":"located","note":"The vastus intermedius lies in, or moves, the knee."},{"from":"mu_sartorius","to":"s_muscle","level":"established","effect":"located","note":"The sartorius is one of the body's skeletal muscles."},{"from":"mu_sartorius","to":"bp_hips","level":"established","effect":"located","note":"The sartorius lies in, or moves, the hip and groin."},{"from":"mu_sartorius","to":"bp_knees","level":"established","effect":"located","note":"The sartorius lies in, or moves, the knee."},{"from":"mu_biceps_femoris_long_head","to":"s_muscle","level":"established","effect":"located","note":"The biceps femoris (long head) is one of the body's skeletal muscles."},{"from":"mu_biceps_femoris_long_head","to":"bp_knees","level":"established","effect":"located","note":"The biceps femoris (long head) lies in, or moves, the knee."},{"from":"mu_biceps_femoris_long_head","to":"bp_hips","level":"established","effect":"located","note":"The biceps femoris (long head) lies in, or moves, the hip and groin."},{"from":"mu_biceps_femoris_short_head","to":"s_muscle","level":"established","effect":"located","note":"The biceps femoris (short head) is one of the body's skeletal muscles."},{"from":"mu_biceps_femoris_short_head","to":"bp_knees","level":"established","effect":"located","note":"The biceps femoris (short head) lies in, or moves, the knee."},{"from":"mu_semitendinosus","to":"s_muscle","level":"established","effect":"located","note":"The semitendinosus is one of the body's skeletal muscles."},{"from":"mu_semitendinosus","to":"bp_knees","level":"established","effect":"located","note":"The semitendinosus lies in, or moves, the knee."},{"from":"mu_semitendinosus","to":"bp_hips","level":"established","effect":"located","note":"The semitendinosus lies in, or moves, the hip and groin."},{"from":"mu_semimembranosus","to":"s_muscle","level":"established","effect":"located","note":"The semimembranosus is one of the body's skeletal muscles."},{"from":"mu_semimembranosus","to":"bp_knees","level":"established","effect":"located","note":"The semimembranosus lies in, or moves, the knee."},{"from":"mu_semimembranosus","to":"bp_hips","level":"established","effect":"located","note":"The semimembranosus lies in, or moves, the hip and groin."},{"from":"mu_popliteus","to":"s_muscle","level":"established","effect":"located","note":"The popliteus is one of the body's skeletal muscles."},{"from":"mu_popliteus","to":"bp_knees","level":"established","effect":"located","note":"The popliteus lies in, or moves, the knee."},{"from":"mu_patellar_tendon","to":"s_muscle","level":"established","effect":"located","note":"The patellar tendon is one of the body's muscle-and-tendon structures."},{"from":"mu_patellar_tendon","to":"bp_knees","level":"established","effect":"located","note":"The patellar tendon lies in, or moves, the knee."},{"from":"mu_gastrocnemius","to":"s_muscle","level":"established","effect":"located","note":"The gastrocnemius is one of the body's skeletal muscles."},{"from":"mu_gastrocnemius","to":"bp_ankles_feet","level":"established","effect":"located","note":"The gastrocnemius lies in, or moves, the ankle and foot."},{"from":"mu_gastrocnemius","to":"bp_knees","level":"established","effect":"located","note":"The gastrocnemius lies in, or moves, the knee."},{"from":"mu_soleus","to":"s_muscle","level":"established","effect":"located","note":"The soleus is one of the body's skeletal muscles."},{"from":"mu_soleus","to":"bp_ankles_feet","level":"established","effect":"located","note":"The soleus lies in, or moves, the ankle and foot."},{"from":"mu_achilles_tendon","to":"s_muscle","level":"established","effect":"located","note":"The achilles tendon is one of the body's muscle-and-tendon structures."},{"from":"mu_achilles_tendon","to":"bp_ankles_feet","level":"established","effect":"located","note":"The achilles tendon lies in, or moves, the ankle and foot."},{"from":"mu_tibialis_anterior","to":"s_muscle","level":"established","effect":"located","note":"The tibialis anterior is one of the body's skeletal muscles."},{"from":"mu_tibialis_anterior","to":"bp_ankles_feet","level":"established","effect":"located","note":"The tibialis anterior lies in, or moves, the ankle and foot."},{"from":"mu_peroneus_longus","to":"s_muscle","level":"established","effect":"located","note":"The peroneus (fibularis) longus is one of the body's skeletal muscles."},{"from":"mu_peroneus_longus","to":"bp_ankles_feet","level":"established","effect":"located","note":"The peroneus (fibularis) longus lies in, or moves, the ankle and foot."},{"from":"mu_peroneus_brevis","to":"s_muscle","level":"established","effect":"located","note":"The peroneus (fibularis) brevis is one of the body's skeletal muscles."},{"from":"mu_peroneus_brevis","to":"bp_ankles_feet","level":"established","effect":"located","note":"The peroneus (fibularis) brevis lies in, or moves, the ankle and foot."},{"from":"mu_extensor_digitorum_longus","to":"s_muscle","level":"established","effect":"located","note":"The extensor digitorum longus is one of the body's skeletal muscles."},{"from":"mu_extensor_digitorum_longus","to":"bp_ankles_feet","level":"established","effect":"located","note":"The extensor digitorum longus lies in, or moves, the ankle and foot."},{"from":"mu_extensor_hallucis_longus","to":"s_muscle","level":"established","effect":"located","note":"The extensor hallucis longus is one of the body's skeletal muscles."},{"from":"mu_extensor_hallucis_longus","to":"bp_ankles_feet","level":"established","effect":"located","note":"The extensor hallucis longus lies in, or moves, the ankle and foot."},{"from":"mu_tibialis_posterior","to":"s_muscle","level":"established","effect":"located","note":"The tibialis posterior is one of the body's skeletal muscles."},{"from":"mu_tibialis_posterior","to":"bp_ankles_feet","level":"established","effect":"located","note":"The tibialis posterior lies in, or moves, the ankle and foot."},{"from":"mu_flexor_digitorum_longus","to":"s_muscle","level":"established","effect":"located","note":"The flexor digitorum longus is one of the body's skeletal muscles."},{"from":"mu_flexor_digitorum_longus","to":"bp_ankles_feet","level":"established","effect":"located","note":"The flexor digitorum longus lies in, or moves, the ankle and foot."},{"from":"mu_flexor_hallucis_longus","to":"s_muscle","level":"established","effect":"located","note":"The flexor hallucis longus is one of the body's skeletal muscles."},{"from":"mu_flexor_hallucis_longus","to":"bp_ankles_feet","level":"established","effect":"located","note":"The flexor hallucis longus lies in, or moves, the ankle and foot."},{"from":"mu_extensor_digitorum_brevis","to":"s_muscle","level":"established","effect":"located","note":"The extensor digitorum brevis is one of the body's skeletal muscles."},{"from":"mu_extensor_digitorum_brevis","to":"bp_ankles_feet","level":"established","effect":"located","note":"The extensor digitorum brevis lies in, or moves, the ankle and foot."},{"from":"mu_abductor_hallucis","to":"s_muscle","level":"established","effect":"located","note":"The abductor hallucis is one of the body's skeletal muscles."},{"from":"mu_abductor_hallucis","to":"bp_ankles_feet","level":"established","effect":"located","note":"The abductor hallucis lies in, or moves, the ankle and foot."},{"from":"mu_flexor_digitorum_brevis","to":"s_muscle","level":"established","effect":"located","note":"The flexor digitorum brevis is one of the body's skeletal muscles."},{"from":"mu_flexor_digitorum_brevis","to":"bp_ankles_feet","level":"established","effect":"located","note":"The flexor digitorum brevis lies in, or moves, the ankle and foot."},{"from":"mu_abductor_digiti_minimi","to":"s_muscle","level":"established","effect":"located","note":"The abductor digiti minimi (foot) is one of the body's skeletal muscles."},{"from":"mu_abductor_digiti_minimi","to":"bp_ankles_feet","level":"established","effect":"located","note":"The abductor digiti minimi (foot) lies in, or moves, the ankle and foot."},{"from":"mu_plantar_fascia","to":"s_muscle","level":"established","effect":"located","note":"The plantar fascia is one of the body's muscle-and-tendon structures."},{"from":"mu_plantar_fascia","to":"bp_ankles_feet","level":"established","effect":"located","note":"The plantar fascia lies in, or moves, the ankle and foot."},{"from":"n_trigeminal","to":"s_brainstem","level":"established","effect":"located","note":"This nerve attaches to the side of the pons."},{"from":"n_trigeminal","to":"s_jaw_tmj","level":"established","effect":"helps","note":"Its lower branch works the chewing muscles that move the jaw."},{"from":"n_trigeminal","to":"s_cornea","level":"established","effect":"helps","note":"Carries feeling from the surface of the eye and triggers the protective blink."},{"from":"headache","to":"n_trigeminal","level":"established","effect":"located","note":"Pain from the coverings and blood vessels of the brain travels in the trigeminal nerve, which is why it is central to migraine and other headaches."},{"from":"n_facial","to":"s_brainstem","level":"established","effect":"located","note":"This nerve leaves the brainstem where the pons meets the medulla."},{"from":"n_facial","to":"s_eyelids","level":"established","effect":"helps","note":"Works the muscle that closes the eye and protects it."},{"from":"n_facial","to":"s_lacrimal","level":"established","effect":"helps","note":"Carries the signals that make tears."},{"from":"n_facial","to":"s_salivary_glands","level":"established","effect":"helps","note":"Drives saliva from the glands under the jaw and tongue."},{"from":"n_facial","to":"s_tongue","level":"established","effect":"helps","note":"Carries taste from the front two-thirds of the tongue."},{"from":"trigeminal_neuralgia","to":"n_trigeminal","level":"established","effect":"affects","note":"Usually an artery pressing on the trigeminal nerve root where it leaves the brainstem."},{"from":"trigeminal_neuralgia","to":"pain","level":"established","effect":"harms","note":"Causes sudden stabbing face pain, often set off by touch or chewing.","sources":[{"id":"pmid:30860637","citation":"Bendtsen et al., Eur J Neurol","year":2019,"design":"review","finding":"European Academy of Neurology guideline: MRI to look for a vessel touching the nerve or other causes; carbamazepine or oxcarbazepine for long-term treatment; microvascular decompression for suitable people."}]},{"from":"trigeminal_neuralgia","to":"bp_face_jaw","level":"established","effect":"affects","note":"The pain is in the face and jaw, in the areas served by the trigeminal nerve."},{"from":"ms","to":"trigeminal_neuralgia","level":"established","effect":"harms","note":"A multiple-sclerosis patch where the nerve enters the brainstem is one cause of trigeminal neuralgia, especially in younger people."},{"from":"bells_palsy","to":"n_facial","level":"established","effect":"affects","note":"Swelling of the facial nerve in its bony canal weakens one side of the face."},{"from":"bells_palsy","to":"bp_face_jaw","level":"established","effect":"affects","note":"Causes a drooping face on one side."},{"from":"bells_palsy","to":"dry_eye","level":"established","effect":"harms","note":"When the eyelid cannot close, the eye dries out and can be damaged."},{"from":"h_oral_corticosteroids","to":"bells_palsy","level":"proven","effect":"helps","note":"Steroid tablets started within three days of onset raised the chance of full recovery in trials; adding antivirals has uncertain extra benefit.","sources":[{"id":"pmid:17942873","citation":"Sullivan et al., N Engl J Med","year":2007,"design":"RCT","finding":"In a placebo-controlled trial of people treated within three days of Bell's palsy onset, prednisolone raised full recovery of facial function at 3 and 9 months; acyclovir alone or added gave no clear benefit."},{"id":"pmid:31486071","citation":"Gagyor et al., Cochrane Database Syst Rev","year":2019,"design":"meta-analysis","finding":"Review of antivirals for Bell's palsy, noting that corticosteroid benefit is established and that the added benefit of antivirals on top of steroids is uncertain."}]},{"from":"n_olfactory","to":"s_smell","level":"established","effect":"located","note":"The olfactory nerve is the first part of the smell system, from nose to brain."},{"from":"n_olfactory","to":"br_olfactory_bulb","level":"established","effect":"helps","note":"The olfactory nerve carries smell signals from the nose into the olfactory bulb."},{"from":"smell","to":"n_olfactory","level":"established","effect":"located","note":"Smell loss can start in the nose's smell nerve fibres (after viral infections or head injury) or further in, in the bulb and brain, as in Parkinson's."},{"from":"wi_head_impacts","to":"n_olfactory","level":"established","effect":"harms","note":"A blow to the head can tear the fine smell fibres where they pass through the bone under the brain, causing lasting smell loss."},{"from":"n_oculomotor","to":"s_brainstem","level":"established","effect":"located","note":"This nerve starts from nuclei in the midbrain."},{"from":"n_oculomotor","to":"s_eye_muscles","level":"established","effect":"helps","note":"Works four of the six muscles that move the eye, and the eyelid-lifting muscle."},{"from":"n_oculomotor","to":"s_iris","level":"established","effect":"helps","note":"Carries the signals that narrow the pupil in bright light and for close focus."},{"from":"diplopia","to":"n_oculomotor","level":"established","effect":"located","note":"Weakness of this nerve is one cause of double vision, often with a drooping eyelid."},{"from":"n_trochlear","to":"s_brainstem","level":"established","effect":"located","note":"This nerve leaves the back of the midbrain."},{"from":"n_trochlear","to":"s_eye_muscles","level":"established","effect":"helps","note":"Works the superior oblique muscle, which turns the eye down and in."},{"from":"diplopia","to":"n_trochlear","level":"established","effect":"located","note":"Weakness of this nerve causes tilted double vision, worst looking down."},{"from":"n_abducens","to":"s_brainstem","level":"established","effect":"located","note":"This nerve leaves the brainstem between the pons and medulla."},{"from":"n_abducens","to":"s_eye_muscles","level":"established","effect":"helps","note":"Works the lateral rectus muscle, which turns the eye outward."},{"from":"diplopia","to":"n_abducens","level":"established","effect":"located","note":"Weakness of this nerve causes side-by-side double vision."},{"from":"n_spinal_roots","to":"s_spinal","level":"established","effect":"located","note":"The roots are where each spinal nerve leaves the cord."},{"from":"low_back_disc","to":"n_spinal_roots","level":"established","effect":"affects","note":"A slipped disc in the lower back presses on a nerve root, causing sciatica."},{"from":"cervical_radiculopathy","to":"n_spinal_roots","level":"established","effect":"affects","note":"A disc or bony spur in the neck presses on a nerve root, sending pain or tingling down the arm."},{"from":"vzv","to":"n_spinal_roots","level":"established","effect":"harms","note":"The chickenpox virus lies dormant in the sensory ganglia of the nerve roots and can reactivate as shingles."},{"from":"n_cauda_equina","to":"s_spinal","level":"established","effect":"located","note":"The bundle of nerve roots that carries on down the spinal canal below the end of the cord."},{"from":"n_cauda_equina","to":"s_bladder","level":"established","effect":"helps","note":"Nerves in the cauda equina control emptying and holding urine."},{"from":"bp_lumbar_spine","to":"n_cauda_equina","level":"established","effect":"located","note":"The cauda equina runs down the canal of the lower back, where a large disc can squash it."},{"from":"n_dermatomes","to":"n_spinal_roots","level":"established","effect":"located","note":"Each dermatome is the strip of skin served by one nerve root.","sources":[{"id":"pmid:18470936","citation":"Lee et al., Clin Anat","year":2008,"design":"review","finding":"A systematic review found standard textbook dermatome maps inconsistent and based on flawed studies, and built an evidence-based map stressing that neighbouring dermatomes overlap and vary between people."}]},{"from":"n_cervical_plexus","to":"s_peripheral","level":"established","effect":"located","note":"Part of the peripheral nervous system, formed by the upper neck nerves."},{"from":"n_phrenic","to":"n_cervical_plexus","level":"established","effect":"located","note":"The phrenic nerve comes mainly from the third to fifth neck nerves."},{"from":"n_phrenic","to":"s_diaphragm","level":"established","effect":"helps","note":"The phrenic nerve is the only motor nerve of the diaphragm, the main breathing muscle."},{"from":"bp_chest_ribs","to":"n_intercostal","level":"established","effect":"located","note":"A nerve runs under each rib; rib fractures and chest surgery can irritate it."},{"from":"vzv","to":"shingles","level":"established","effect":"harms","note":"Shingles is the chickenpox virus waking up in a nerve ganglion."},{"from":"vaccine","to":"shingles","level":"proven","effect":"helps","note":"The adjuvanted subunit shingles vaccine prevented about 97% of shingles in a large placebo-controlled trial in adults aged 50 and over.","sources":[{"id":"pmid:25916341","citation":"Lal et al., N Engl J Med","year":2015,"design":"RCT","finding":"In a placebo-controlled trial in over 15,000 adults aged 50 and over, the adjuvanted subunit zoster vaccine cut shingles by about 97% over about 3 years, with similar efficacy at 70 and over."}]},{"from":"shingles","to":"n_spinal_roots","level":"established","effect":"affects","note":"The virus reactivates in a sensory ganglion beside the spinal cord (or the trigeminal ganglion) and travels along that nerve."},{"from":"shingles","to":"pain","level":"established","effect":"harms","note":"Causes burning nerve pain, which can persist after the rash heals (postherpetic neuralgia)."},{"from":"n_brachial_plexus","to":"s_peripheral","level":"established","effect":"located","note":"Part of the peripheral nervous system: the junction box of the arm nerves."},{"from":"bp_shoulders","to":"n_brachial_plexus","level":"established","effect":"located","note":"The arm nerves pass under the collarbone and through the armpit, near the shoulder."},{"from":"wi_vehicle","to":"n_brachial_plexus","level":"established","effect":"harms","note":"Vehicle and especially motorcycle crashes are a leading cause of brachial plexus tears from the head and shoulder being forced apart."},{"from":"n_median","to":"n_brachial_plexus","level":"established","effect":"located","note":"One of the five main nerves leaving the brachial plexus."},{"from":"n_ulnar","to":"n_brachial_plexus","level":"established","effect":"located","note":"One of the five main nerves leaving the brachial plexus."},{"from":"n_radial","to":"n_brachial_plexus","level":"established","effect":"located","note":"One of the five main nerves leaving the brachial plexus."},{"from":"n_musculocutaneous","to":"n_brachial_plexus","level":"established","effect":"located","note":"One of the five main nerves leaving the brachial plexus."},{"from":"n_axillary","to":"n_brachial_plexus","level":"established","effect":"located","note":"One of the five main nerves leaving the brachial plexus."},{"from":"carpal_tunnel","to":"n_median","level":"established","effect":"affects","note":"Carpal tunnel syndrome is the median nerve being squeezed at the wrist."},{"from":"bp_wrists_hands","to":"n_median","level":"established","effect":"located","note":"The median and ulnar nerves cross the wrist, where they are squeezed or cut."},{"from":"bp_elbows","to":"n_ulnar","level":"established","effect":"located","note":"The ulnar nerve lies just under the skin behind the inner elbow."},{"from":"bp_shoulders","to":"n_axillary","level":"established","effect":"located","note":"The axillary nerve wraps round the top of the arm bone and is hurt in shoulder dislocations."},{"from":"wi_struck_caught","to":"n_median","level":"established","effect":"harms","note":"Cuts and crush injuries of the forearm and wrist are a common way the median and ulnar nerves are injured at work."},{"from":"cubital_tunnel","to":"n_ulnar","level":"established","effect":"affects","note":"The ulnar nerve is squeezed or stretched behind the elbow."},{"from":"cubital_tunnel","to":"bp_elbows","level":"established","effect":"affects","note":"A work-claimed elbow problem: the nerve sits behind the inner elbow."},{"from":"cubital_tunnel","to":"neuropathy","level":"established","effect":"harms","note":"Causes numbness and tingling in the little and ring fingers."},{"from":"n_sympathetic_chain","to":"s_autonomic","level":"established","effect":"located","note":"The sympathetic chain is the fight-or-flight half of the automatic nervous system."},{"from":"n_prevertebral_ganglia","to":"s_autonomic","level":"established","effect":"located","note":"These ganglia are the sympathetic relay stations for the belly organs."},{"from":"n_parasympathetic","to":"s_autonomic","level":"established","effect":"located","note":"The rest-and-digest half of the automatic nervous system."},{"from":"s_vagus","to":"n_parasympathetic","level":"established","effect":"located","note":"The vagus carries most of the parasympathetic outflow from the brainstem."},{"from":"n_sympathetic_chain","to":"s_heart","level":"established","effect":"helps","note":"Sympathetic nerves speed the heart and make it beat harder."},{"from":"n_sympathetic_chain","to":"s_iris","level":"established","effect":"helps","note":"Sympathetic nerves from the neck ganglia widen the pupil."},{"from":"oh","to":"n_sympathetic_chain","level":"established","effect":"located","note":"Dizziness on standing happens when sympathetic nerves fail to tighten blood vessels."},{"from":"n_parasympathetic","to":"s_bladder","level":"established","effect":"helps","note":"Sacral parasympathetic nerves contract the bladder to empty it."},{"from":"ed","to":"n_parasympathetic","level":"established","effect":"located","note":"Erection depends on sacral parasympathetic nerves, which pelvic surgery can damage."},{"from":"n_myenteric_plexus","to":"s_gut","level":"established","effect":"located","note":"Part of the gut's own nervous system, between the muscle layers of the wall."},{"from":"n_submucosal_plexus","to":"s_gut","level":"established","effect":"located","note":"Part of the gut's own nervous system, beneath the lining."},{"from":"n_myenteric_plexus","to":"m_motility","level":"established","effect":"helps","note":"This nerve net drives the squeezing waves that move food along."},{"from":"s_vagus","to":"n_myenteric_plexus","level":"established","effect":"helps","note":"The vagus talks to the gut mainly through the myenteric plexus."},{"from":"constipation","to":"n_myenteric_plexus","level":"established","effect":"located","note":"Slow movement of the bowel often reflects weak signalling in the gut-wall nerves."},{"from":"parkinsons","to":"n_myenteric_plexus","level":"association","effect":"affects","note":"Parkinson's-type alpha-synuclein deposits are found in gut-wall nerves of many people with Parkinson's, sometimes years before diagnosis, but biopsy tests also find them in people without Parkinson's, so this is not a reliable test and does not show where the disease starts.","sources":[{"id":"pmid:20306269","citation":"Beach et al., Acta Neuropathol","year":2010,"design":"case-control","finding":"In autopsies of 92 people, phosphorylated alpha-synuclein was most frequent in the spinal cord, then the sympathetic ganglia beside the spine, the vagus nerve and the gut, and was likely widespread in everyone with Parkinson's or Lewy body dementia; it was rare in other organs."},{"id":"pmid:27015771","citation":"Stokholm et al., Ann Neurol","year":2016,"design":"case-control","finding":"In archived gut tissue taken on average 7 years (up to 20 years) before a Parkinson's diagnosis, phosphorylated alpha-synuclein was found in 56% of people later diagnosed, more than in controls, but a second staining method showed no difference from controls."},{"id":"pmid:25589666","citation":"Visanji et al., Neurology","year":2015,"design":"case-control","finding":"Aggregated, phosphorylated alpha-synuclein was found in colon biopsies of all 11 people without Parkinson's as well as most with it, so colon biopsy was not a useful test."},{"id":"pmid:27044604","citation":"Corbillé et al., Acta Neuropathol Commun","year":2016,"design":"lab","finding":"Four expert labs' staining methods applied blind to the same colon biopsies all stained most control slides, and none reached 80% sensitivity and specificity for Parkinson's."}]},{"from":"parkinsons","to":"n_sympathetic_chain","level":"association","effect":"affects","note":"In autopsy studies the sympathetic ganglia beside the spine are among the places outside the brain where Parkinson's-type deposits are most often found.","sources":[{"id":"pmid:20306269","citation":"Beach et al., Acta Neuropathol","year":2010,"design":"case-control","finding":"In autopsies of 92 people, phosphorylated alpha-synuclein was most frequent in the spinal cord, then the sympathetic ganglia beside the spine, the vagus nerve and the gut, and was likely widespread in everyone with Parkinson's or Lewy body dementia; it was rare in other organs."}]},{"from":"n_vestibulocochlear","to":"s_cochlea","level":"established","effect":"helps","note":"Carries hearing signals from the cochlea to the brain."},{"from":"n_vestibulocochlear","to":"s_vestibular","level":"established","effect":"helps","note":"Carries balance signals from the inner-ear balance organs to the brain."},{"from":"vertigo","to":"n_vestibulocochlear","level":"established","effect":"located","note":"Inflammation or a tumour of the balance part of this nerve is one cause of vertigo."},{"from":"n_glossopharyngeal","to":"s_brainstem","level":"established","effect":"located","note":"This nerve leaves the medulla just above the vagus."},{"from":"n_glossopharyngeal","to":"s_throat","level":"established","effect":"helps","note":"Carries feeling from the throat, the trigger for the gag reflex and swallowing."},{"from":"n_glossopharyngeal","to":"s_tongue","level":"established","effect":"helps","note":"Carries taste and touch from the back third of the tongue."},{"from":"n_glossopharyngeal","to":"s_salivary_glands","level":"established","effect":"helps","note":"Drives saliva from the parotid gland in front of the ear."},{"from":"n_glossopharyngeal","to":"s_autonomic","level":"established","effect":"helps","note":"Carries blood-pressure and oxygen signals from sensors in the neck artery, which the brain uses to steady blood pressure."},{"from":"n_glossopharyngeal","to":"s_vagus","level":"established","effect":"helps","note":"Works together with the vagus for gagging, swallowing and blood-pressure reflexes; the two leave the skull side by side."},{"from":"n_accessory","to":"s_spinal","level":"established","effect":"located","note":"Its cells sit in the top of the spinal cord in the neck."},{"from":"n_accessory","to":"s_muscle","level":"established","effect":"helps","note":"Works the neck muscle that turns the head and the trapezius that shrugs the shoulder."},{"from":"bp_shoulders","to":"n_accessory","level":"established","effect":"located","note":"Injury to this nerve in the neck causes a drooping, weak and aching shoulder."},{"from":"n_hypoglossal","to":"s_brainstem","level":"established","effect":"located","note":"This nerve leaves the medulla."},{"from":"n_hypoglossal","to":"s_tongue","level":"established","effect":"helps","note":"Works all the muscles that move the tongue."},{"from":"swallow","to":"n_hypoglossal","level":"established","effect":"located","note":"The tongue pushes food back to start a swallow, so weakness of this nerve makes swallowing harder."},{"from":"n_lumbar_plexus","to":"s_peripheral","level":"established","effect":"located","note":"Part of the peripheral nervous system, formed by the upper lower-back nerves."},{"from":"n_sacral_plexus","to":"s_peripheral","level":"established","effect":"located","note":"Part of the peripheral nervous system, formed by the lowest back nerves."},{"from":"n_femoral","to":"n_lumbar_plexus","level":"established","effect":"located","note":"The largest branch of the lumbar plexus."},{"from":"n_obturator","to":"n_lumbar_plexus","level":"established","effect":"located","note":"A branch of the lumbar plexus."},{"from":"n_sciatic","to":"n_sacral_plexus","level":"established","effect":"located","note":"The main product of the sacral plexus."},{"from":"n_tibial","to":"n_sciatic","level":"established","effect":"located","note":"One of the two branches the sciatic nerve splits into above the knee."},{"from":"n_common_peroneal","to":"n_sciatic","level":"established","effect":"located","note":"One of the two branches the sciatic nerve splits into above the knee."},{"from":"n_sural","to":"n_tibial","level":"established","effect":"located","note":"Formed by skin branches of the tibial and common peroneal nerves."},{"from":"n_pudendal","to":"n_sacral_plexus","level":"established","effect":"located","note":"Comes from the lowest sacral nerves of the sacral plexus."},{"from":"low_back_disc","to":"n_sciatic","level":"established","effect":"affects","note":"In sciatica a pinched lower-back root sends pain and tingling along the course of the sciatic nerve."},{"from":"bp_hips","to":"n_sciatic","level":"established","effect":"located","note":"The sciatic nerve runs just behind the hip joint and can be hurt in hip dislocations."},{"from":"bp_knees","to":"n_common_peroneal","level":"established","effect":"located","note":"This nerve wraps round the bone just below the outer knee, where knee injuries and pressure damage it."},{"from":"bp_ankles_feet","to":"n_tibial","level":"established","effect":"located","note":"The tibial nerve runs behind the inner ankle into the sole (the tarsal tunnel)."},{"from":"sx_hip_replacement","to":"n_sciatic","level":"established","effect":"harms","note":"Injury to the sciatic nerve is an uncommon but known complication of hip replacement."},{"from":"neuropathy","to":"n_sural","level":"established","effect":"located","note":"Neuropathy affects the longest nerves first, and the sural nerve at the ankle is where tests usually find it."},{"from":"bp_sexual_function","to":"n_pudendal","level":"established","effect":"located","note":"The pudendal nerve carries genital feeling and the signals for orgasm and ejaculation."},{"from":"n_meissner","to":"s_skin","level":"established","effect":"located","note":"These touch receptors sit just under the outer layer of hairless skin."},{"from":"n_pacinian","to":"s_skin","level":"established","effect":"located","note":"These vibration receptors sit deep in the skin and around joints."},{"from":"n_nociceptors","to":"s_skin","level":"established","effect":"located","note":"Pain nerve endings are spread through the skin and most other tissues."},{"from":"pain","to":"n_nociceptors","level":"established","effect":"located","note":"Pain from injury or inflammation starts as signals from these nerve endings."},{"from":"n_nociceptors","to":"m_painproc","level":"established","effect":"helps","note":"These endings feed the pain-processing system in the spinal cord and brain."},{"from":"n_meissner","to":"s_peripheral","level":"established","effect":"located","note":"Sensory endings are the far tips of the peripheral nerves."},{"from":"n_pacinian","to":"s_peripheral","level":"established","effect":"located","note":"Sensory endings are the far tips of the peripheral nerves."},{"from":"n_nociceptors","to":"s_peripheral","level":"established","effect":"located","note":"Sensory endings are the far tips of the peripheral nerves."},{"from":"type2_diabetes","to":"neuropathy","level":"established","effect":"harms","note":"Years of high blood sugar damage the longest nerves first, causing numbness and burning in the feet; it is the most common cause of neuropathy."},{"from":"type2_diabetes","to":"s_peripheral","level":"established","effect":"affects","note":"Diabetes damages the peripheral nerves and their small blood vessels."},{"from":"guillain_barre","to":"s_peripheral","level":"established","effect":"affects","note":"The immune system attacks the peripheral nerves, stripping their insulation or damaging the fibres."},{"from":"guillain_barre","to":"s_spinal","level":"established","effect":"affects","note":"The attack also hits the nerve roots where they leave the spinal cord."},{"from":"guillain_barre","to":"neuropathy","level":"established","effect":"harms","note":"Usually starts with tingling and numbness in the feet and hands."},{"from":"guillain_barre","to":"breathless","level":"established","effect":"harms","note":"In severe cases the breathing muscles weaken and a ventilator is needed."},{"from":"campylobacter","to":"guillain_barre","level":"association","effect":"harms","note":"Recent Campylobacter food poisoning was found in about a quarter of people with Guillain–Barré, far more than in controls.","sources":[{"id":"pmid:7477117","citation":"Rees et al., N Engl J Med","year":1995,"design":"case-control","finding":"Recent Campylobacter jejuni infection was found in 26% of people with Guillain-Barré syndrome versus 1-2% of controls, and was linked to axonal damage and slower recovery."}]},{"from":"h_ivig_plasma_exchange","to":"guillain_barre","level":"proven","effect":"helps","note":"Plasma exchange speeds recovery compared with supportive care, and immunoglobulin by drip works about as well as plasma exchange.","sources":[{"id":"pmid:28241090","citation":"Chevret et al., Cochrane Database Syst Rev","year":2017,"design":"meta-analysis","finding":"In six trials (649 people), plasma exchange shortened the time to walk again and improved recovery compared with supportive care alone."},{"id":"pmid:25238327","citation":"Hughes et al., Cochrane Database Syst Rev","year":2014,"design":"meta-analysis","finding":"In randomised trials, intravenous immunoglobulin started within two weeks hastened recovery from Guillain-Barré syndrome about as much as plasma exchange."}]},{"from":"bn_clavicle","to":"s_bones","level":"established","effect":"located","note":"The clavicle (collarbone) is part of the skeleton."},{"from":"bn_clavicle","to":"bp_shoulders","level":"established","effect":"located","note":"The clavicle (collarbone) is in the shoulder."},{"from":"bn_clavicle","to":"bp_chest_ribs","level":"established","effect":"located","note":"The clavicle (collarbone) is in the chest."},{"from":"bn_scapula","to":"s_bones","level":"established","effect":"located","note":"The scapula (shoulder blade) is part of the skeleton."},{"from":"bn_scapula","to":"bp_shoulders","level":"established","effect":"located","note":"The scapula (shoulder blade) is in the shoulder."},{"from":"bn_scapula","to":"bp_thoracic_spine","level":"established","effect":"located","note":"The scapula (shoulder blade) is in the mid back."},{"from":"bn_humerus","to":"s_bones","level":"established","effect":"located","note":"The humerus is part of the skeleton."},{"from":"bn_humerus","to":"bp_shoulders","level":"established","effect":"located","note":"The humerus is in the shoulder."},{"from":"bn_humerus","to":"bp_elbows","level":"established","effect":"located","note":"The humerus is in the elbow."},{"from":"fracture","to":"bn_humerus","level":"established","effect":"located","note":"A break of the neck of the humerus is a typical fracture after a fall in older people with thin bones."},{"from":"bn_radius","to":"s_bones","level":"established","effect":"located","note":"The radius is part of the skeleton."},{"from":"bn_radius","to":"bp_wrists_hands","level":"established","effect":"located","note":"The radius is in the wrist and hand."},{"from":"bn_radius","to":"bp_elbows","level":"established","effect":"located","note":"The radius is in the elbow."},{"from":"fracture","to":"bn_radius","level":"established","effect":"located","note":"A broken wrist from a fall on the outstretched hand is usually a break of the lower radius."},{"from":"bn_ulna","to":"s_bones","level":"established","effect":"located","note":"The ulna is part of the skeleton."},{"from":"bn_ulna","to":"bp_elbows","level":"established","effect":"located","note":"The ulna is in the elbow."},{"from":"bn_ulna","to":"bp_wrists_hands","level":"established","effect":"located","note":"The ulna is in the wrist and hand."},{"from":"bn_carpals","to":"s_bones","level":"established","effect":"located","note":"The carpal bones is part of the skeleton."},{"from":"bn_carpals","to":"bp_wrists_hands","level":"established","effect":"located","note":"The carpal bones is in the wrist and hand."},{"from":"bn_scaphoid","to":"s_bones","level":"established","effect":"located","note":"The scaphoid is part of the skeleton."},{"from":"bn_scaphoid","to":"bn_carpals","level":"established","effect":"located","note":"The scaphoid is part of the carpal bones."},{"from":"bn_scaphoid","to":"bp_wrists_hands","level":"established","effect":"located","note":"The scaphoid is in the wrist and hand."},{"from":"bn_metacarpals","to":"s_bones","level":"established","effect":"located","note":"The metacarpals is part of the skeleton."},{"from":"bn_metacarpals","to":"bp_wrists_hands","level":"established","effect":"located","note":"The metacarpals is in the wrist and hand."},{"from":"bn_metacarpals","to":"bp_fingers","level":"established","effect":"located","note":"The metacarpals is in the fingers."},{"from":"bn_phalanges_hand","to":"s_bones","level":"established","effect":"located","note":"The phalanges of the hand is part of the skeleton."},{"from":"bn_phalanges_hand","to":"bp_fingers","level":"established","effect":"located","note":"The phalanges of the hand is in the fingers."},{"from":"bn_pelvis","to":"s_bones","level":"established","effect":"located","note":"The pelvis (hip bones) is part of the skeleton."},{"from":"bn_pelvis","to":"bp_hips","level":"established","effect":"located","note":"The pelvis (hip bones) is in the hip and pelvis."},{"from":"fracture","to":"bn_pelvis","level":"established","effect":"located","note":"Low-energy falls in older people can crack the pelvic ring, mainly the pubic rami."},{"from":"sx_hip_replacement","to":"bn_pelvis","level":"established","effect":"affects","note":"A hip replacement lines the socket in the pelvis with an artificial cup."},{"from":"bn_ilium","to":"s_bones","level":"established","effect":"located","note":"The ilium is part of the skeleton."},{"from":"bn_ilium","to":"bn_pelvis","level":"established","effect":"located","note":"The ilium is part of the pelvis (hip bones)."},{"from":"bn_ilium","to":"bp_hips","level":"established","effect":"located","note":"The ilium is in the hip and pelvis."},{"from":"bn_ischium","to":"s_bones","level":"established","effect":"located","note":"The ischium is part of the skeleton."},{"from":"bn_ischium","to":"bn_pelvis","level":"established","effect":"located","note":"The ischium is part of the pelvis (hip bones)."},{"from":"bn_ischium","to":"bp_hips","level":"established","effect":"located","note":"The ischium is in the hip and pelvis."},{"from":"bn_pubis","to":"s_bones","level":"established","effect":"located","note":"The pubis is part of the skeleton."},{"from":"bn_pubis","to":"bn_pelvis","level":"established","effect":"located","note":"The pubis is part of the pelvis (hip bones)."},{"from":"bn_pubis","to":"bp_hips","level":"established","effect":"located","note":"The pubis is in the hip and pelvis."},{"from":"bn_pubis","to":"bp_abdomen","level":"established","effect":"located","note":"The pubis is in the belly and groin."},{"from":"bn_femur","to":"s_bones","level":"established","effect":"located","note":"The femur is part of the skeleton."},{"from":"bn_femur","to":"bp_hips","level":"established","effect":"located","note":"The femur is in the hip and pelvis."},{"from":"bn_femur","to":"bp_knees","level":"established","effect":"located","note":"The femur is in the knee."},{"from":"fracture","to":"bn_femur","level":"established","effect":"located","note":"Hip fracture is a break of the top of the femur, the most serious common fracture after a fall."},{"from":"sx_hip_replacement","to":"bn_femur","level":"established","effect":"affects","note":"A hip replacement replaces the head and neck of the femur with an artificial ball on a stem."},{"from":"bn_patella","to":"s_bones","level":"established","effect":"located","note":"The patella (kneecap) is part of the skeleton."},{"from":"bn_patella","to":"bp_knees","level":"established","effect":"located","note":"The patella (kneecap) is in the knee."},{"from":"bn_tibia","to":"s_bones","level":"established","effect":"located","note":"The tibia (shinbone) is part of the skeleton."},{"from":"bn_tibia","to":"bp_knees","level":"established","effect":"located","note":"The tibia (shinbone) is in the knee."},{"from":"bn_tibia","to":"bp_ankles_feet","level":"established","effect":"located","note":"The tibia (shinbone) is in the ankle and foot."},{"from":"bn_fibula","to":"s_bones","level":"established","effect":"located","note":"The fibula is part of the skeleton."},{"from":"bn_fibula","to":"bp_knees","level":"established","effect":"located","note":"The fibula is in the knee."},{"from":"bn_fibula","to":"bp_ankles_feet","level":"established","effect":"located","note":"The fibula is in the ankle and foot."},{"from":"bn_tarsals","to":"s_bones","level":"established","effect":"located","note":"The tarsal bones is part of the skeleton."},{"from":"bn_tarsals","to":"bp_ankles_feet","level":"established","effect":"located","note":"The tarsal bones is in the ankle and foot."},{"from":"bn_talus","to":"s_bones","level":"established","effect":"located","note":"The talus is part of the skeleton."},{"from":"bn_talus","to":"bn_tarsals","level":"established","effect":"located","note":"The talus is part of the tarsal bones."},{"from":"bn_talus","to":"bp_ankles_feet","level":"established","effect":"located","note":"The talus is in the ankle and foot."},{"from":"bn_calcaneus","to":"s_bones","level":"established","effect":"located","note":"The calcaneus (heel bone) is part of the skeleton."},{"from":"bn_calcaneus","to":"bn_tarsals","level":"established","effect":"located","note":"The calcaneus (heel bone) is part of the tarsal bones."},{"from":"bn_calcaneus","to":"bp_ankles_feet","level":"established","effect":"located","note":"The calcaneus (heel bone) is in the ankle and foot."},{"from":"bn_metatarsals","to":"s_bones","level":"established","effect":"located","note":"The metatarsals is part of the skeleton."},{"from":"bn_metatarsals","to":"bp_ankles_feet","level":"established","effect":"located","note":"The metatarsals is in the ankle and foot."},{"from":"bn_phalanges_foot","to":"s_bones","level":"established","effect":"located","note":"The phalanges of the foot is part of the skeleton."},{"from":"bn_phalanges_foot","to":"bp_ankles_feet","level":"established","effect":"located","note":"The phalanges of the foot is in the ankle and foot."},{"from":"vn_superior_vena_cava","to":"s_veins","level":"established","effect":"located","note":"The superior vena cava is one of the body's named veins."},{"from":"vn_superior_vena_cava","to":"bp_heart_circulation","level":"established","effect":"located","note":"The superior vena cava is in the heart and circulation."},{"from":"vn_superior_vena_cava","to":"bp_chest_ribs","level":"established","effect":"located","note":"The superior vena cava is in the chest."},{"from":"vn_inferior_vena_cava","to":"s_veins","level":"established","effect":"located","note":"The inferior vena cava is one of the body's named veins."},{"from":"vn_inferior_vena_cava","to":"bp_heart_circulation","level":"established","effect":"located","note":"The inferior vena cava is in the heart and circulation."},{"from":"vn_inferior_vena_cava","to":"bp_abdomen","level":"established","effect":"located","note":"The inferior vena cava is in the belly and groin."},{"from":"vn_brachiocephalic","to":"s_veins","level":"established","effect":"located","note":"The brachiocephalic vein is one of the body's named veins."},{"from":"vn_brachiocephalic","to":"bp_heart_circulation","level":"established","effect":"located","note":"The brachiocephalic vein is in the heart and circulation."},{"from":"vn_brachiocephalic","to":"bp_chest_ribs","level":"established","effect":"located","note":"The brachiocephalic vein is in the chest."},{"from":"vn_internal_jugular","to":"s_veins","level":"established","effect":"located","note":"The internal jugular vein is one of the body's named veins."},{"from":"vn_internal_jugular","to":"bp_heart_circulation","level":"established","effect":"located","note":"The internal jugular vein is in the heart and circulation."},{"from":"vn_internal_jugular","to":"bp_cervical_spine","level":"established","effect":"located","note":"The internal jugular vein is in the neck."},{"from":"vn_subclavian","to":"s_veins","level":"established","effect":"located","note":"The subclavian vein is one of the body's named veins."},{"from":"vn_subclavian","to":"bp_heart_circulation","level":"established","effect":"located","note":"The subclavian vein is in the heart and circulation."},{"from":"vn_subclavian","to":"bp_shoulders","level":"established","effect":"located","note":"The subclavian vein is in the shoulder."},{"from":"vn_brachial","to":"s_veins","level":"established","effect":"located","note":"The brachial and axillary veins is one of the body's named veins."},{"from":"vn_brachial","to":"bp_heart_circulation","level":"established","effect":"located","note":"The brachial and axillary veins is in the heart and circulation."},{"from":"vn_brachial","to":"bp_shoulders","level":"established","effect":"located","note":"The brachial and axillary veins is in the shoulder."},{"from":"vn_brachial","to":"bp_elbows","level":"established","effect":"located","note":"The brachial and axillary veins is in the elbow."},{"from":"vn_cephalic","to":"s_veins","level":"established","effect":"located","note":"The cephalic vein is one of the body's named veins."},{"from":"vn_cephalic","to":"bp_heart_circulation","level":"established","effect":"located","note":"The cephalic vein is in the heart and circulation."},{"from":"vn_cephalic","to":"bp_elbows","level":"established","effect":"located","note":"The cephalic vein is in the elbow."},{"from":"vn_cephalic","to":"bp_shoulders","level":"established","effect":"located","note":"The cephalic vein is in the shoulder."},{"from":"vn_common_iliac","to":"s_veins","level":"established","effect":"located","note":"The common iliac vein is one of the body's named veins."},{"from":"vn_common_iliac","to":"bp_heart_circulation","level":"established","effect":"located","note":"The common iliac vein is in the heart and circulation."},{"from":"vn_common_iliac","to":"bp_hips","level":"established","effect":"located","note":"The common iliac vein is in the hip and pelvis."},{"from":"vn_common_iliac","to":"bp_abdomen","level":"established","effect":"located","note":"The common iliac vein is in the belly and groin."},{"from":"vn_external_iliac","to":"s_veins","level":"established","effect":"located","note":"The external iliac vein is one of the body's named veins."},{"from":"vn_external_iliac","to":"bp_heart_circulation","level":"established","effect":"located","note":"The external iliac vein is in the heart and circulation."},{"from":"vn_external_iliac","to":"bp_hips","level":"established","effect":"located","note":"The external iliac vein is in the hip and pelvis."},{"from":"vn_femoral","to":"s_veins","level":"established","effect":"located","note":"The femoral vein is one of the body's named veins."},{"from":"vn_femoral","to":"bp_heart_circulation","level":"established","effect":"located","note":"The femoral vein is in the heart and circulation."},{"from":"vn_femoral","to":"bp_hips","level":"established","effect":"located","note":"The femoral vein is in the hip and pelvis."},{"from":"vn_femoral","to":"bp_knees","level":"established","effect":"located","note":"The femoral vein is in the knee."},{"from":"vn_popliteal","to":"s_veins","level":"established","effect":"located","note":"The popliteal vein is one of the body's named veins."},{"from":"vn_popliteal","to":"bp_heart_circulation","level":"established","effect":"located","note":"The popliteal vein is in the heart and circulation."},{"from":"vn_popliteal","to":"bp_knees","level":"established","effect":"located","note":"The popliteal vein is in the knee."},{"from":"vn_great_saphenous","to":"s_veins","level":"established","effect":"located","note":"The great saphenous vein is one of the body's named veins."},{"from":"vn_great_saphenous","to":"bp_heart_circulation","level":"established","effect":"located","note":"The great saphenous vein is in the heart and circulation."},{"from":"vn_great_saphenous","to":"bp_knees","level":"established","effect":"located","note":"The great saphenous vein is in the knee."},{"from":"vn_great_saphenous","to":"bp_hips","level":"established","effect":"located","note":"The great saphenous vein is in the hip and pelvis."},{"from":"dvt","to":"vn_femoral","level":"established","effect":"affects","note":"Deep vein thrombosis is a clot in the deep leg veins such as the femoral vein."},{"from":"dvt","to":"vn_popliteal","level":"established","effect":"affects","note":"Deep vein thrombosis is a clot in the deep leg veins such as the popliteal vein."},{"from":"ar_ascending_aorta","to":"s_aorta","level":"established","effect":"located","note":"The ascending aorta is one segment of the aorta."},{"from":"ar_ascending_aorta","to":"bp_heart_circulation","level":"established","effect":"located","note":"The ascending aorta is in the heart and circulation."},{"from":"ar_ascending_aorta","to":"bp_chest_ribs","level":"established","effect":"located","note":"The ascending aorta is in the chest."},{"from":"ar_aortic_arch","to":"s_aorta","level":"established","effect":"located","note":"The aortic arch is one segment of the aorta."},{"from":"ar_aortic_arch","to":"bp_heart_circulation","level":"established","effect":"located","note":"The aortic arch is in the heart and circulation."},{"from":"ar_aortic_arch","to":"bp_chest_ribs","level":"established","effect":"located","note":"The aortic arch is in the chest."},{"from":"ar_descending_thoracic_aorta","to":"s_aorta","level":"established","effect":"located","note":"The descending thoracic aorta is one segment of the aorta."},{"from":"ar_descending_thoracic_aorta","to":"bp_heart_circulation","level":"established","effect":"located","note":"The descending thoracic aorta is in the heart and circulation."},{"from":"ar_descending_thoracic_aorta","to":"bp_thoracic_spine","level":"established","effect":"located","note":"The descending thoracic aorta is in the mid back."},{"from":"ar_abdominal_aorta","to":"s_aorta","level":"established","effect":"located","note":"The abdominal aorta is one segment of the aorta."},{"from":"ar_abdominal_aorta","to":"bp_heart_circulation","level":"established","effect":"located","note":"The abdominal aorta is in the heart and circulation."},{"from":"ar_abdominal_aorta","to":"bp_abdomen","level":"established","effect":"located","note":"The abdominal aorta is in the belly and groin."},{"from":"ar_brachiocephalic_trunk","to":"s_blood","level":"established","effect":"located","note":"The brachiocephalic trunk is one of the body's named arteries."},{"from":"ar_brachiocephalic_trunk","to":"bp_heart_circulation","level":"established","effect":"located","note":"The brachiocephalic trunk is in the heart and circulation."},{"from":"ar_brachiocephalic_trunk","to":"bp_chest_ribs","level":"established","effect":"located","note":"The brachiocephalic trunk is in the chest."},{"from":"ar_common_carotid","to":"s_blood","level":"established","effect":"located","note":"The common carotid artery is one of the body's named arteries."},{"from":"ar_common_carotid","to":"bp_heart_circulation","level":"established","effect":"located","note":"The common carotid artery is in the heart and circulation."},{"from":"ar_common_carotid","to":"bp_cervical_spine","level":"established","effect":"located","note":"The common carotid artery is in the neck."},{"from":"ar_internal_carotid","to":"s_blood","level":"established","effect":"located","note":"The internal carotid artery is one of the body's named arteries."},{"from":"ar_internal_carotid","to":"bp_heart_circulation","level":"established","effect":"located","note":"The internal carotid artery is in the heart and circulation."},{"from":"ar_internal_carotid","to":"bp_cervical_spine","level":"established","effect":"located","note":"The internal carotid artery is in the neck."},{"from":"ar_internal_carotid","to":"bp_head_brain","level":"established","effect":"located","note":"The internal carotid artery is in the head."},{"from":"ar_external_carotid","to":"s_blood","level":"established","effect":"located","note":"The external carotid artery is one of the body's named arteries."},{"from":"ar_external_carotid","to":"bp_heart_circulation","level":"established","effect":"located","note":"The external carotid artery is in the heart and circulation."},{"from":"ar_external_carotid","to":"bp_face_jaw","level":"established","effect":"located","note":"The external carotid artery is in the face and jaw."},{"from":"ar_external_carotid","to":"bp_cervical_spine","level":"established","effect":"located","note":"The external carotid artery is in the neck."},{"from":"ar_subclavian","to":"s_blood","level":"established","effect":"located","note":"The subclavian artery is one of the body's named arteries."},{"from":"ar_subclavian","to":"bp_heart_circulation","level":"established","effect":"located","note":"The subclavian artery is in the heart and circulation."},{"from":"ar_subclavian","to":"bp_shoulders","level":"established","effect":"located","note":"The subclavian artery is in the shoulder."},{"from":"ar_subclavian","to":"bp_cervical_spine","level":"established","effect":"located","note":"The subclavian artery is in the neck."},{"from":"ar_axillary","to":"s_blood","level":"established","effect":"located","note":"The axillary artery is one of the body's named arteries."},{"from":"ar_axillary","to":"bp_heart_circulation","level":"established","effect":"located","note":"The axillary artery is in the heart and circulation."},{"from":"ar_axillary","to":"bp_shoulders","level":"established","effect":"located","note":"The axillary artery is in the shoulder."},{"from":"ar_brachial","to":"s_blood","level":"established","effect":"located","note":"The brachial artery is one of the body's named arteries."},{"from":"ar_brachial","to":"bp_heart_circulation","level":"established","effect":"located","note":"The brachial artery is in the heart and circulation."},{"from":"ar_brachial","to":"bp_elbows","level":"established","effect":"located","note":"The brachial artery is in the elbow."},{"from":"ar_brachial","to":"bp_shoulders","level":"established","effect":"located","note":"The brachial artery is in the shoulder."},{"from":"ar_radial","to":"s_blood","level":"established","effect":"located","note":"The radial artery is one of the body's named arteries."},{"from":"ar_radial","to":"bp_heart_circulation","level":"established","effect":"located","note":"The radial artery is in the heart and circulation."},{"from":"ar_radial","to":"bp_wrists_hands","level":"established","effect":"located","note":"The radial artery is in the wrist and hand."},{"from":"ar_ulnar","to":"s_blood","level":"established","effect":"located","note":"The ulnar artery is one of the body's named arteries."},{"from":"ar_ulnar","to":"bp_heart_circulation","level":"established","effect":"located","note":"The ulnar artery is in the heart and circulation."},{"from":"ar_ulnar","to":"bp_wrists_hands","level":"established","effect":"located","note":"The ulnar artery is in the wrist and hand."},{"from":"ar_common_iliac","to":"s_blood","level":"established","effect":"located","note":"The common iliac artery is one of the body's named arteries."},{"from":"ar_common_iliac","to":"bp_heart_circulation","level":"established","effect":"located","note":"The common iliac artery is in the heart and circulation."},{"from":"ar_common_iliac","to":"bp_hips","level":"established","effect":"located","note":"The common iliac artery is in the hip and pelvis."},{"from":"ar_common_iliac","to":"bp_abdomen","level":"established","effect":"located","note":"The common iliac artery is in the belly and groin."},{"from":"ar_internal_iliac","to":"s_blood","level":"established","effect":"located","note":"The internal iliac artery is one of the body's named arteries."},{"from":"ar_internal_iliac","to":"bp_heart_circulation","level":"established","effect":"located","note":"The internal iliac artery is in the heart and circulation."},{"from":"ar_internal_iliac","to":"bp_hips","level":"established","effect":"located","note":"The internal iliac artery is in the hip and pelvis."},{"from":"ar_external_iliac","to":"s_blood","level":"established","effect":"located","note":"The external iliac artery is one of the body's named arteries."},{"from":"ar_external_iliac","to":"bp_heart_circulation","level":"established","effect":"located","note":"The external iliac artery is in the heart and circulation."},{"from":"ar_external_iliac","to":"bp_hips","level":"established","effect":"located","note":"The external iliac artery is in the hip and pelvis."},{"from":"ar_femoral","to":"s_blood","level":"established","effect":"located","note":"The femoral artery is one of the body's named arteries."},{"from":"ar_femoral","to":"bp_heart_circulation","level":"established","effect":"located","note":"The femoral artery is in the heart and circulation."},{"from":"ar_femoral","to":"bp_hips","level":"established","effect":"located","note":"The femoral artery is in the hip and pelvis."},{"from":"ar_femoral","to":"bp_knees","level":"established","effect":"located","note":"The femoral artery is in the knee."},{"from":"ar_popliteal","to":"s_blood","level":"established","effect":"located","note":"The popliteal artery is one of the body's named arteries."},{"from":"ar_popliteal","to":"bp_heart_circulation","level":"established","effect":"located","note":"The popliteal artery is in the heart and circulation."},{"from":"ar_popliteal","to":"bp_knees","level":"established","effect":"located","note":"The popliteal artery is in the knee."},{"from":"ar_anterior_tibial","to":"s_blood","level":"established","effect":"located","note":"The anterior tibial artery is one of the body's named arteries."},{"from":"ar_anterior_tibial","to":"bp_heart_circulation","level":"established","effect":"located","note":"The anterior tibial artery is in the heart and circulation."},{"from":"ar_anterior_tibial","to":"bp_ankles_feet","level":"established","effect":"located","note":"The anterior tibial artery is in the ankle and foot."},{"from":"ar_posterior_tibial","to":"s_blood","level":"established","effect":"located","note":"The posterior tibial artery is one of the body's named arteries."},{"from":"ar_posterior_tibial","to":"bp_heart_circulation","level":"established","effect":"located","note":"The posterior tibial artery is in the heart and circulation."},{"from":"ar_posterior_tibial","to":"bp_ankles_feet","level":"established","effect":"located","note":"The posterior tibial artery is in the ankle and foot."},{"from":"ar_dorsalis_pedis","to":"s_blood","level":"established","effect":"located","note":"The dorsalis pedis artery is one of the body's named arteries."},{"from":"ar_dorsalis_pedis","to":"bp_heart_circulation","level":"established","effect":"located","note":"The dorsalis pedis artery is in the heart and circulation."},{"from":"ar_dorsalis_pedis","to":"bp_ankles_feet","level":"established","effect":"located","note":"The dorsalis pedis artery is in the ankle and foot."},{"from":"ar_coeliac_trunk","to":"s_blood","level":"established","effect":"located","note":"The coeliac trunk is one of the body's named arteries."},{"from":"ar_coeliac_trunk","to":"bp_heart_circulation","level":"established","effect":"located","note":"The coeliac trunk is in the heart and circulation."},{"from":"ar_coeliac_trunk","to":"bp_internal_organs","level":"established","effect":"located","note":"The coeliac trunk is in the internal organs."},{"from":"s_liver_segment_1","to":"s_liver","level":"established","effect":"located","note":"The liver segment 1 (caudate lobe) is part of the liver."},{"from":"s_liver_segment_1","to":"bp_internal_organs","level":"established","effect":"located","note":"The liver segment 1 (caudate lobe) is one of the internal organs' parts."},{"from":"s_liver_segment_2","to":"s_liver","level":"established","effect":"located","note":"The liver segment 2 is part of the liver."},{"from":"s_liver_segment_2","to":"bp_internal_organs","level":"established","effect":"located","note":"The liver segment 2 is one of the internal organs' parts."},{"from":"s_liver_segment_3","to":"s_liver","level":"established","effect":"located","note":"The liver segment 3 is part of the liver."},{"from":"s_liver_segment_3","to":"bp_internal_organs","level":"established","effect":"located","note":"The liver segment 3 is one of the internal organs' parts."},{"from":"s_liver_segment_4","to":"s_liver","level":"established","effect":"located","note":"The liver segment 4 (quadrate area) is part of the liver."},{"from":"s_liver_segment_4","to":"bp_internal_organs","level":"established","effect":"located","note":"The liver segment 4 (quadrate area) is one of the internal organs' parts."},{"from":"s_liver_segment_5","to":"s_liver","level":"established","effect":"located","note":"The liver segment 5 is part of the liver."},{"from":"s_liver_segment_5","to":"bp_internal_organs","level":"established","effect":"located","note":"The liver segment 5 is one of the internal organs' parts."},{"from":"s_liver_segment_6","to":"s_liver","level":"established","effect":"located","note":"The liver segment 6 is part of the liver."},{"from":"s_liver_segment_6","to":"bp_internal_organs","level":"established","effect":"located","note":"The liver segment 6 is one of the internal organs' parts."},{"from":"s_liver_segment_7","to":"s_liver","level":"established","effect":"located","note":"The liver segment 7 is part of the liver."},{"from":"s_liver_segment_7","to":"bp_internal_organs","level":"established","effect":"located","note":"The liver segment 7 is one of the internal organs' parts."},{"from":"s_liver_segment_8","to":"s_liver","level":"established","effect":"located","note":"The liver segment 8 is part of the liver."},{"from":"s_liver_segment_8","to":"bp_internal_organs","level":"established","effect":"located","note":"The liver segment 8 is one of the internal organs' parts."},{"from":"s_hepatic_artery","to":"s_liver","level":"established","effect":"located","note":"The hepatic artery is part of the liver."},{"from":"s_hepatic_artery","to":"s_blood","level":"established","effect":"located","note":"The hepatic artery is one of the body's named arteries."},{"from":"s_hepatic_artery","to":"bp_internal_organs","level":"established","effect":"located","note":"The hepatic artery is one of the internal organs' parts."},{"from":"s_hepatic_veins","to":"s_liver","level":"established","effect":"located","note":"The hepatic veins is part of the liver."},{"from":"s_hepatic_veins","to":"s_veins","level":"established","effect":"located","note":"The hepatic veins is one of the body's named veins."},{"from":"s_hepatic_veins","to":"bp_internal_organs","level":"established","effect":"located","note":"The hepatic veins is one of the internal organs' parts."},{"from":"s_ligamentum_teres","to":"s_liver","level":"established","effect":"located","note":"The ligamentum teres (round ligament of the liver) is part of the liver."},{"from":"s_ligamentum_teres","to":"bp_internal_organs","level":"established","effect":"located","note":"The ligamentum teres (round ligament of the liver) is one of the internal organs' parts."},{"from":"s_hepatic_lobules","to":"s_liver","level":"established","effect":"located","note":"The hepatic lobules (liver cell plates) is part of the liver."},{"from":"s_hepatic_lobules","to":"bp_internal_organs","level":"established","effect":"located","note":"The hepatic lobules (liver cell plates) is one of the internal organs' parts."},{"from":"s_sinusoids","to":"s_liver","level":"established","effect":"located","note":"The hepatic sinusoids is part of the liver."},{"from":"s_sinusoids","to":"bp_internal_organs","level":"established","effect":"located","note":"The hepatic sinusoids is one of the internal organs' parts."},{"from":"s_gallbladder_fundus","to":"s_gallbladder","level":"established","effect":"located","note":"The gallbladder fundus is part of the gallbladder."},{"from":"s_gallbladder_fundus","to":"bp_internal_organs","level":"established","effect":"located","note":"The gallbladder fundus is one of the internal organs' parts."},{"from":"s_gallbladder_body","to":"s_gallbladder","level":"established","effect":"located","note":"The gallbladder body is part of the gallbladder."},{"from":"s_gallbladder_body","to":"bp_internal_organs","level":"established","effect":"located","note":"The gallbladder body is one of the internal organs' parts."},{"from":"s_gallbladder_neck","to":"s_gallbladder","level":"established","effect":"located","note":"The gallbladder neck (Hartmann's pouch) is part of the gallbladder."},{"from":"s_gallbladder_neck","to":"bp_internal_organs","level":"established","effect":"located","note":"The gallbladder neck (Hartmann's pouch) is one of the internal organs' parts."},{"from":"s_gallbladder_mucosa","to":"s_gallbladder","level":"established","effect":"located","note":"The gallbladder lining (mucosa) is part of the gallbladder."},{"from":"s_gallbladder_mucosa","to":"bp_internal_organs","level":"established","effect":"located","note":"The gallbladder lining (mucosa) is one of the internal organs' parts."},{"from":"s_cystic_duct","to":"s_gallbladder","level":"established","effect":"located","note":"The cystic duct is part of the gallbladder."},{"from":"s_cystic_duct","to":"s_bile_ducts","level":"established","effect":"located","note":"The cystic duct is part of the bile ducts."},{"from":"s_cystic_duct","to":"bp_internal_organs","level":"established","effect":"located","note":"The cystic duct is one of the internal organs' parts."},{"from":"s_common_hepatic_duct","to":"s_bile_ducts","level":"established","effect":"located","note":"The common hepatic duct is part of the bile ducts."},{"from":"s_common_hepatic_duct","to":"bp_internal_organs","level":"established","effect":"located","note":"The common hepatic duct is one of the internal organs' parts."},{"from":"s_common_bile_duct","to":"s_bile_ducts","level":"established","effect":"located","note":"The common bile duct is part of the bile ducts."},{"from":"s_common_bile_duct","to":"bp_internal_organs","level":"established","effect":"located","note":"The common bile duct is one of the internal organs' parts."},{"from":"s_cystic_artery","to":"s_gallbladder","level":"established","effect":"located","note":"The cystic artery is part of the gallbladder."},{"from":"s_cystic_artery","to":"s_blood","level":"established","effect":"located","note":"The cystic artery is one of the body's named arteries."},{"from":"s_cystic_artery","to":"bp_internal_organs","level":"established","effect":"located","note":"The cystic artery is one of the internal organs' parts."},{"from":"s_pancreas_head","to":"s_pancreas","level":"established","effect":"located","note":"The head of the pancreas is part of the pancreas (islets)."},{"from":"s_pancreas_head","to":"bp_internal_organs","level":"established","effect":"located","note":"The head of the pancreas is one of the internal organs' parts."},{"from":"s_pancreas_uncinate","to":"s_pancreas","level":"established","effect":"located","note":"The uncinate process is part of the pancreas (islets)."},{"from":"s_pancreas_uncinate","to":"bp_internal_organs","level":"established","effect":"located","note":"The uncinate process is one of the internal organs' parts."},{"from":"s_pancreas_neck","to":"s_pancreas","level":"established","effect":"located","note":"The neck of the pancreas is part of the pancreas (islets)."},{"from":"s_pancreas_neck","to":"bp_internal_organs","level":"established","effect":"located","note":"The neck of the pancreas is one of the internal organs' parts."},{"from":"s_pancreas_body","to":"s_pancreas","level":"established","effect":"located","note":"The body of the pancreas is part of the pancreas (islets)."},{"from":"s_pancreas_body","to":"bp_internal_organs","level":"established","effect":"located","note":"The body of the pancreas is one of the internal organs' parts."},{"from":"s_pancreas_tail","to":"s_pancreas","level":"established","effect":"located","note":"The tail of the pancreas is part of the pancreas (islets)."},{"from":"s_pancreas_tail","to":"bp_internal_organs","level":"established","effect":"located","note":"The tail of the pancreas is one of the internal organs' parts."},{"from":"s_pancreatic_duct","to":"s_pancreas","level":"established","effect":"located","note":"The main pancreatic duct (duct of Wirsung) is part of the pancreas (islets)."},{"from":"s_pancreatic_duct","to":"bp_internal_organs","level":"established","effect":"located","note":"The main pancreatic duct (duct of Wirsung) is one of the internal organs' parts."},{"from":"s_accessory_pancreatic_duct","to":"s_pancreas","level":"established","effect":"located","note":"The accessory pancreatic duct (duct of Santorini) is part of the pancreas (islets)."},{"from":"s_accessory_pancreatic_duct","to":"bp_internal_organs","level":"established","effect":"located","note":"The accessory pancreatic duct (duct of Santorini) is one of the internal organs' parts."},{"from":"s_ampulla_of_vater","to":"s_duodenum","level":"established","effect":"located","note":"The ampulla of Vater and sphincter of Oddi is part of the duodenum."},{"from":"s_ampulla_of_vater","to":"s_bile_ducts","level":"established","effect":"located","note":"The ampulla of Vater and sphincter of Oddi is part of the bile ducts."},{"from":"s_ampulla_of_vater","to":"bp_internal_organs","level":"established","effect":"located","note":"The ampulla of Vater and sphincter of Oddi is one of the internal organs' parts."},{"from":"s_splenic_artery","to":"s_spleen","level":"established","effect":"located","note":"The splenic artery is part of the spleen."},{"from":"s_splenic_artery","to":"s_blood","level":"established","effect":"located","note":"The splenic artery is one of the body's named arteries."},{"from":"s_splenic_artery","to":"bp_internal_organs","level":"established","effect":"located","note":"The splenic artery is one of the internal organs' parts."},{"from":"s_splenic_vein","to":"s_spleen","level":"established","effect":"located","note":"The splenic vein is part of the spleen."},{"from":"s_splenic_vein","to":"s_veins","level":"established","effect":"located","note":"The splenic vein is one of the body's named veins."},{"from":"s_splenic_vein","to":"bp_internal_organs","level":"established","effect":"located","note":"The splenic vein is one of the internal organs' parts."},{"from":"s_superior_mesenteric_artery","to":"s_small_intestine","level":"established","effect":"located","note":"The superior mesenteric artery is part of the small intestine."},{"from":"s_superior_mesenteric_artery","to":"s_blood","level":"established","effect":"located","note":"The superior mesenteric artery is one of the body's named arteries."},{"from":"s_superior_mesenteric_artery","to":"bp_internal_organs","level":"established","effect":"located","note":"The superior mesenteric artery is one of the internal organs' parts."},{"from":"s_superior_mesenteric_vein","to":"s_small_intestine","level":"established","effect":"located","note":"The superior mesenteric vein is part of the small intestine."},{"from":"s_superior_mesenteric_vein","to":"s_veins","level":"established","effect":"located","note":"The superior mesenteric vein is one of the body's named veins."},{"from":"s_superior_mesenteric_vein","to":"bp_internal_organs","level":"established","effect":"located","note":"The superior mesenteric vein is one of the internal organs' parts."},{"from":"s_pancreaticoduodenal_arteries","to":"s_pancreas","level":"established","effect":"located","note":"The gastroduodenal and pancreaticoduodenal arteries is part of the pancreas (islets)."},{"from":"s_pancreaticoduodenal_arteries","to":"s_duodenum","level":"established","effect":"located","note":"The gastroduodenal and pancreaticoduodenal arteries is part of the duodenum."},{"from":"s_pancreaticoduodenal_arteries","to":"s_blood","level":"established","effect":"located","note":"The gastroduodenal and pancreaticoduodenal arteries is one of the body's named arteries."},{"from":"s_pancreaticoduodenal_arteries","to":"bp_internal_organs","level":"established","effect":"located","note":"The gastroduodenal and pancreaticoduodenal arteries is one of the internal organs' parts."},{"from":"bn_skull","to":"s_bones","level":"established","effect":"located","note":"The skull is part of the skeleton."},{"from":"bn_skull","to":"bp_head_brain","level":"established","effect":"located","note":"The skull is in the head."},{"from":"bn_frontal","to":"s_bones","level":"established","effect":"located","note":"The frontal bone is part of the skeleton."},{"from":"bn_frontal","to":"bn_skull","level":"established","effect":"located","note":"The frontal bone is part of the skull."},{"from":"bn_frontal","to":"bp_head_brain","level":"established","effect":"located","note":"The frontal bone is in the head."},{"from":"bn_frontal","to":"bp_face_jaw","level":"established","effect":"located","note":"The frontal bone is in the face and jaw."},{"from":"bn_parietal","to":"s_bones","level":"established","effect":"located","note":"The parietal bone is part of the skeleton."},{"from":"bn_parietal","to":"bn_skull","level":"established","effect":"located","note":"The parietal bone is part of the skull."},{"from":"bn_parietal","to":"bp_head_brain","level":"established","effect":"located","note":"The parietal bone is in the head."},{"from":"bn_temporal","to":"s_bones","level":"established","effect":"located","note":"The temporal bone is part of the skeleton."},{"from":"bn_temporal","to":"bn_skull","level":"established","effect":"located","note":"The temporal bone is part of the skull."},{"from":"bn_temporal","to":"bp_head_brain","level":"established","effect":"located","note":"The temporal bone is in the head."},{"from":"bn_temporal","to":"bp_ears","level":"established","effect":"located","note":"The temporal bone is in the ear."},{"from":"bn_occipital","to":"s_bones","level":"established","effect":"located","note":"The occipital bone is part of the skeleton."},{"from":"bn_occipital","to":"bn_skull","level":"established","effect":"located","note":"The occipital bone is part of the skull."},{"from":"bn_occipital","to":"bp_head_brain","level":"established","effect":"located","note":"The occipital bone is in the head."},{"from":"bn_occipital","to":"bp_cervical_spine","level":"established","effect":"located","note":"The occipital bone is in the neck."},{"from":"bn_sphenoid","to":"s_bones","level":"established","effect":"located","note":"The sphenoid bone is part of the skeleton."},{"from":"bn_sphenoid","to":"bn_skull","level":"established","effect":"located","note":"The sphenoid bone is part of the skull."},{"from":"bn_sphenoid","to":"bp_head_brain","level":"established","effect":"located","note":"The sphenoid bone is in the head."},{"from":"bn_maxilla","to":"s_bones","level":"established","effect":"located","note":"The maxilla is part of the skeleton."},{"from":"bn_maxilla","to":"bn_skull","level":"established","effect":"located","note":"The maxilla is part of the skull."},{"from":"bn_maxilla","to":"bp_face_jaw","level":"established","effect":"located","note":"The maxilla is in the face and jaw."},{"from":"bn_maxilla","to":"bp_teeth","level":"established","effect":"located","note":"The maxilla is in the teeth."},{"from":"bn_zygomatic","to":"s_bones","level":"established","effect":"located","note":"The zygomatic bone is part of the skeleton."},{"from":"bn_zygomatic","to":"bn_skull","level":"established","effect":"located","note":"The zygomatic bone is part of the skull."},{"from":"bn_zygomatic","to":"bp_face_jaw","level":"established","effect":"located","note":"The zygomatic bone is in the face and jaw."},{"from":"bn_mandible","to":"s_bones","level":"established","effect":"located","note":"The mandible is part of the skeleton."},{"from":"bn_mandible","to":"bn_skull","level":"established","effect":"located","note":"The mandible is part of the skull."},{"from":"bn_mandible","to":"bp_face_jaw","level":"established","effect":"located","note":"The mandible is in the face and jaw."},{"from":"bn_mandible","to":"bp_teeth","level":"established","effect":"located","note":"The mandible is in the teeth."},{"from":"bn_vertebral_column","to":"s_bones","level":"established","effect":"located","note":"The vertebral column (spine) is part of the skeleton."},{"from":"bn_vertebral_column","to":"bp_cervical_spine","level":"established","effect":"located","note":"The vertebral column (spine) is in the neck."},{"from":"bn_vertebral_column","to":"bp_thoracic_spine","level":"established","effect":"located","note":"The vertebral column (spine) is in the mid back."},{"from":"bn_vertebral_column","to":"bp_lumbar_spine","level":"established","effect":"located","note":"The vertebral column (spine) is in the low back."},{"from":"bn_cervical_vertebrae","to":"s_bones","level":"established","effect":"located","note":"The cervical vertebrae (C1 to C7) is part of the skeleton."},{"from":"bn_cervical_vertebrae","to":"bn_vertebral_column","level":"established","effect":"located","note":"The cervical vertebrae (C1 to C7) is part of the vertebral column (spine)."},{"from":"bn_cervical_vertebrae","to":"bp_cervical_spine","level":"established","effect":"located","note":"The cervical vertebrae (C1 to C7) is in the neck."},{"from":"cervical_radiculopathy","to":"bn_cervical_vertebrae","level":"established","effect":"affects","note":"Cervical radiculopathy is a nerve root pinched where it leaves between the neck vertebrae."},{"from":"bn_atlas_c1","to":"s_bones","level":"established","effect":"located","note":"The atlas (C1) is part of the skeleton."},{"from":"bn_atlas_c1","to":"bn_cervical_vertebrae","level":"established","effect":"located","note":"The atlas (C1) is part of the cervical vertebrae (C1 to C7)."},{"from":"bn_atlas_c1","to":"bp_cervical_spine","level":"established","effect":"located","note":"The atlas (C1) is in the neck."},{"from":"bn_axis_c2","to":"s_bones","level":"established","effect":"located","note":"The axis (C2) is part of the skeleton."},{"from":"bn_axis_c2","to":"bn_cervical_vertebrae","level":"established","effect":"located","note":"The axis (C2) is part of the cervical vertebrae (C1 to C7)."},{"from":"bn_axis_c2","to":"bp_cervical_spine","level":"established","effect":"located","note":"The axis (C2) is in the neck."},{"from":"bn_thoracic_vertebrae","to":"s_bones","level":"established","effect":"located","note":"The thoracic vertebrae (T1 to T12) is part of the skeleton."},{"from":"bn_thoracic_vertebrae","to":"bn_vertebral_column","level":"established","effect":"located","note":"The thoracic vertebrae (T1 to T12) is part of the vertebral column (spine)."},{"from":"bn_thoracic_vertebrae","to":"bp_thoracic_spine","level":"established","effect":"located","note":"The thoracic vertebrae (T1 to T12) is in the mid back."},{"from":"fracture","to":"bn_thoracic_vertebrae","level":"established","effect":"located","note":"Osteoporotic compression fractures are most common in the thoracic vertebrae."},{"from":"bn_lumbar_vertebrae","to":"s_bones","level":"established","effect":"located","note":"The lumbar vertebrae (L1 to L5) is part of the skeleton."},{"from":"bn_lumbar_vertebrae","to":"bn_vertebral_column","level":"established","effect":"located","note":"The lumbar vertebrae (L1 to L5) is part of the vertebral column (spine)."},{"from":"bn_lumbar_vertebrae","to":"bp_lumbar_spine","level":"established","effect":"located","note":"The lumbar vertebrae (L1 to L5) is in the low back."},{"from":"fracture","to":"bn_lumbar_vertebrae","level":"established","effect":"located","note":"Osteoporotic compression fractures also often affect the upper lumbar vertebrae."},{"from":"low_back_disc","to":"bn_lumbar_vertebrae","level":"established","effect":"affects","note":"Disc herniations in the low back bulge from between the lumbar vertebrae, most often L4/L5 and L5/S1."},{"from":"bn_sacrum","to":"s_bones","level":"established","effect":"located","note":"The sacrum is part of the skeleton."},{"from":"bn_sacrum","to":"bn_vertebral_column","level":"established","effect":"located","note":"The sacrum is part of the vertebral column (spine)."},{"from":"bn_sacrum","to":"bp_lumbar_spine","level":"established","effect":"located","note":"The sacrum is in the low back."},{"from":"bn_sacrum","to":"bp_hips","level":"established","effect":"located","note":"The sacrum is in the hip and pelvis."},{"from":"bn_coccyx","to":"s_bones","level":"established","effect":"located","note":"The coccyx is part of the skeleton."},{"from":"bn_coccyx","to":"bn_vertebral_column","level":"established","effect":"located","note":"The coccyx is part of the vertebral column (spine)."},{"from":"bn_coccyx","to":"bp_lumbar_spine","level":"established","effect":"located","note":"The coccyx is in the low back."},{"from":"bn_coccyx","to":"bp_hips","level":"established","effect":"located","note":"The coccyx is in the hip and pelvis."},{"from":"bn_ribs","to":"s_bones","level":"established","effect":"located","note":"The ribs is part of the skeleton."},{"from":"bn_ribs","to":"bp_chest_ribs","level":"established","effect":"located","note":"The ribs is in the chest."},{"from":"bn_sternum","to":"s_bones","level":"established","effect":"located","note":"The sternum (breastbone) is part of the skeleton."},{"from":"bn_sternum","to":"bp_chest_ribs","level":"established","effect":"located","note":"The sternum (breastbone) is in the chest."},{"from":"s_arteries","to":"s_blood","level":"established","effect":"located","note":"The arteries are the outgoing half of the blood vessels."},{"from":"hypertension","to":"s_arteries","level":"established","effect":"affects","note":"Years of high pressure stiffen artery walls and speed up plaque build-up."},{"from":"br_vta","to":"s_brainstem","level":"established","effect":"located","note":"Part of the midbrain, the top of the brainstem."},{"from":"br_vta","to":"s_limbic","level":"established","effect":"located","note":"The dopamine source of the brain's reward circuit."},{"from":"br_vta","to":"m_reward","level":"established","effect":"helps","note":"Its dopamine cells drive the reward pathway to the nucleus accumbens and frontal brain."},{"from":"parkinsons","to":"br_vta","level":"association","effect":"affects","note":"Post-mortem studies find Parkinson's also thins out the VTA's dopamine cells, though less than the substantia nigra.","sources":[{"id":"pmid:26251824","citation":"Alberico SL et al., Basal Ganglia","year":2015,"design":"review","finding":"Reviewing post-mortem counts plus three new cases, the VTA degenerates in Parkinson's disease but less than the substantia nigra pars compacta."}]},{"from":"hm_leptin","to":"obesity","level":"established","effect":"helps","note":"Made by fat tissue to tell the brain you have enough stored energy; in obesity the brain often stops responding to it."},{"from":"hm_leptin","to":"br_hypothalamus","level":"established","effect":"helps","note":"Leptin acts on the hypothalamus to turn down appetite."},{"from":"hm_ghrelin","to":"br_hypothalamus","level":"established","effect":"helps","note":"Ghrelin from the empty stomach acts on the hypothalamus to raise hunger."},{"from":"hm_ghrelin","to":"nutrition","level":"established","effect":"helps","note":"Ghrelin drives appetite, so low levels can contribute to poor eating and weight loss."},{"from":"hm_glucagon","to":"type2_diabetes","level":"established","effect":"harms","note":"Glucagon tells the liver to release sugar; it is often too high in type 2 diabetes and adds to high blood sugar."},{"from":"hm_cortisol","to":"hypertension","level":"established","effect":"harms","note":"Long-term high cortisol, as in Cushing syndrome, raises blood pressure."},{"from":"pancreatitis","to":"nausea","level":"established","effect":"harms","note":"Inflamed pancreas commonly causes nausea and vomiting with belly pain."},{"from":"gallstones","to":"nausea","level":"established","effect":"harms","note":"Gallstone attacks often bring nausea with pain in the upper right belly."},{"from":"appendicitis","to":"nausea","level":"established","effect":"harms","note":"Nausea and loss of appetite are early signs of appendicitis."},{"from":"appendicitis","to":"d_abdominal_pain","level":"established","effect":"harms","note":"Pain that moves to the lower right belly is the classic sign of appendicitis."},{"from":"peptic_ulcer","to":"nausea","level":"established","effect":"harms","note":"Ulcers in the stomach or gut lining can cause nausea."},{"from":"pregnancy","to":"nausea","level":"established","effect":"harms","note":"Morning sickness is common in early pregnancy."},{"from":"gastric_cancer","to":"d_abdominal_pain","level":"established","effect":"harms","note":"Stomach cancer can cause upper belly pain or discomfort."},{"from":"colorectal_cancer","to":"d_abdominal_pain","level":"established","effect":"harms","note":"Bowel cancer can cause cramping belly pain."},{"from":"pancreatic_cancer","to":"d_abdominal_pain","level":"established","effect":"harms","note":"Pancreatic cancer often causes upper belly pain that spreads to the back."},{"from":"coeliac_disease","to":"d_abdominal_pain","level":"established","effect":"harms","note":"Gluten damage to the gut lining commonly causes belly pain."},{"from":"liver_cancer","to":"d_jaundice","level":"established","effect":"harms","note":"A liver tumour can block bile or reduce liver function, turning skin and eyes yellow."},{"from":"coeliac_disease","to":"d_bloating","level":"established","effect":"harms","note":"Gluten damage to the gut lining often causes bloating and wind."},{"from":"sibo","to":"d_bloating","level":"established","effect":"harms","note":"Extra bacteria in the small bowel ferment food and make gas."},{"from":"pancreatic_insufficiency","to":"d_bloating","level":"established","effect":"harms","note":"Undigested food reaching the colon is fermented into gas."},{"from":"cirrhosis","to":"d_bloating","level":"established","effect":"harms","note":"A scarred liver can cause fluid to build up in the belly (ascites), felt as swelling and bloating."},{"from":"pancreatic_insufficiency","to":"d_diarrhoea","level":"established","effect":"harms","note":"Without enough digestive enzymes, fat passes through as pale, greasy, loose stools."},{"from":"lactose_intolerance","to":"d_diarrhoea","level":"established","effect":"harms","note":"Undigested milk sugar draws water into the gut and is fermented, causing loose stools."},{"from":"sibo","to":"d_diarrhoea","level":"established","effect":"harms","note":"Overgrowth in the small bowel can upset fat absorption and cause loose stools."},{"from":"peptic_ulcer","to":"heartburn","level":"established","effect":"harms","note":"Ulcers and reflux often occur together, with burning upper belly or chest discomfort."},{"from":"colorectal_cancer","to":"constipation","level":"established","effect":"harms","note":"A growing bowel tumour can partly block the bowel and change bowel habit."},{"from":"hm_adrenaline","to":"d_palpitations","level":"established","effect":"harms","note":"Adrenaline speeds and strengthens the heartbeat, which can be felt as palpitations."},{"from":"hypertension","to":"m_bp","level":"established","effect":"harms","note":"Hypertension means blood pressure control is set too high."},{"from":"pulmonary_embolism","to":"d_chest_pain","level":"established","effect":"harms","note":"A clot in the lung artery can cause sharp chest pain, often worse on breathing in."},{"from":"pneumothorax","to":"d_chest_pain","level":"established","effect":"harms","note":"A collapsed lung typically causes sudden one-sided chest pain."},{"from":"gerd","to":"d_chest_pain","level":"established","effect":"harms","note":"Acid reflux can cause burning chest pain that feels like heart pain."},{"from":"heart_attack","to":"breathless","level":"established","effect":"harms","note":"A heart attack weakens the pump, which can cause breathlessness."},{"from":"coronary_artery_disease","to":"breathless","level":"established","effect":"harms","note":"Narrowed heart arteries can limit the heart so effort causes breathlessness."},{"from":"ckd","to":"d_leg_swelling","level":"established","effect":"harms","note":"Failing kidneys keep salt and water, which pools as swelling in the legs."},{"from":"cirrhosis","to":"d_leg_swelling","level":"established","effect":"harms","note":"A scarred liver makes less albumin and raises pressure in the veins, so fluid collects in the legs."},{"from":"pregnancy","to":"d_leg_swelling","level":"established","effect":"harms","note":"The growing womb presses on veins and the body holds extra fluid, so ankles often swell."},{"from":"pre_eclampsia","to":"d_leg_swelling","level":"established","effect":"harms","note":"Sudden swelling with high blood pressure in pregnancy is a warning sign."},{"from":"parkinsons","to":"br_stn","level":"established","effect":"affects","note":"Without dopamine the subthalamic nucleus becomes over-active, which adds to slowness and stiffness."},{"from":"parkinsons","to":"br_gp","level":"established","effect":"affects","note":"Loss of dopamine makes the globus pallidus over-brake movement."},{"from":"dystonia","to":"br_gp","level":"established","effect":"affects","note":"Abnormal output from the globus pallidus is linked to dystonia; it is a deep-brain stimulation target."},{"from":"essential_tremor","to":"br_dentate","level":"established","effect":"affects","note":"The dentate nucleus is part of the cerebellar loop thought to generate essential tremor."},{"from":"ptsd","to":"br_amygdala","level":"established","effect":"affects","note":"The amygdala, the brain fear alarm, is over-reactive in PTSD."},{"from":"depression_c","to":"br_amygdala","level":"established","effect":"affects","note":"The amygdala, which handles threat and emotion, is over-active in depression."},{"from":"coeliac_disease","to":"m_absorb","level":"established","effect":"harms","note":"Gluten damage flattens the gut lining so less nutrient is absorbed."},{"from":"pancreatic_insufficiency","to":"m_absorb","level":"established","effect":"harms","note":"Too few digestive enzymes means fats and other nutrients are not broken down well enough to absorb."},{"from":"crohns","to":"m_absorb","level":"established","effect":"harms","note":"Inflamed small bowel absorbs nutrients poorly."},{"from":"pancreatic_insufficiency","to":"nutrition","level":"established","effect":"harms","note":"Poor digestion of food leads to weight loss and nutrient shortage."},{"from":"m_absorb","to":"nutrition","level":"established","effect":"helps","note":"How well the gut absorbs food sets how well the body is nourished."},{"from":"crohns","to":"m_inflam","level":"established","effect":"harms","note":"Crohn disease is long-lasting inflammation of the gut wall."},{"from":"ulcerative_colitis","to":"m_inflam","level":"established","effect":"harms","note":"Ulcerative colitis is long-lasting inflammation of the colon lining."},{"from":"epilepsy","to":"m_excit","level":"established","effect":"harms","note":"Seizures arise when brain cells fire too easily and together."},{"from":"ptsd","to":"m_stress","level":"established","effect":"harms","note":"In PTSD the stress alarm stays switched on after the danger has passed."},{"from":"crps","to":"m_painproc","level":"established","effect":"harms","note":"In complex regional pain syndrome pain signalling stays amplified long after the injury."},{"from":"tourette","to":"m_cstc","level":"established","effect":"harms","note":"Tics are linked to over-active loops between the movement centres and the cortex."},{"from":"ocd_c","to":"m_cstc","level":"established","effect":"harms","note":"Obsessions and compulsions are linked to over-active loops between the frontal cortex and the movement centres."},{"from":"faecali","to":"crohns","level":"association","effect":"helps","note":"People with Crohn's disease tend to have less Faecalibacterium, and lower levels in the bowel lining went with the disease coming back after surgery.","sources":[{"id":"pmid:18936492","citation":"Sokol H et al., Proc Natl Acad Sci U S A","year":2008,"design":"cohort","finding":"Reduced F. prausnitzii on resected ileal Crohn's mucosa was associated with higher risk of postoperative recurrence; it was anti-inflammatory in cells and mice."}]},{"from":"roseburia","to":"ulcerative_colitis","level":"association","effect":"helps","note":"People with ulcerative colitis tend to have less Roseburia, a butyrate maker that feeds the bowel lining.","sources":[{"id":"pmid:24021287","citation":"Machiels K et al., Gut","year":2014,"design":"case-control","finding":"In 127 ulcerative colitis patients versus 87 controls, Roseburia hominis and F. prausnitzii were reduced and inversely linked to disease activity."}]},{"from":"sthermo","to":"lactose_intolerance","level":"proven","effect":"helps","note":"The live yogurt bacteria make their own lactase, so lactose in yogurt is digested better and causes fewer symptoms in people who lack lactase.","sources":[{"id":"pmid:25042846","citation":"de Vrese M et al., Clin Nutr","year":2015,"design":"RCT","finding":"In a randomised double-blind crossover trial in 24 lactose maldigesters, freeze-dried yogurt culture reduced breath hydrogen by 27% versus placebo."},{"id":"pmid:24695892","citation":"Savaiano DA, Am J Clin Nutr","year":2014,"design":"review","finding":"Lactose in yogurt is digested better than in other dairy because the bacterial lactase from L. bulgaricus and S. thermophilus stays active in the small intestine."}]},{"from":"wi_solvent_degreasing","to":"tx_hexane","level":"established","effect":"harms","note":"Solvent and degreasing work, and glue use in shoe and furniture making, is the classic way people breathe in n-hexane."},{"from":"wi_solvent_degreasing","to":"tx_toluene","level":"established","effect":"harms","note":"Toluene is a common industrial solvent in paints, thinners, glues and degreasers, so solvent work is a main way people are exposed."},{"from":"wi_pesticide_application","to":"tx_organochlorines","level":"established","effect":"harms","note":"Organochlorine insecticides such as DDT and dieldrin were widely sprayed on farms, so pesticide applicators were among the most exposed people."},{"from":"wi_pesticide_application","to":"tx_rotenone","level":"established","effect":"harms","note":"Rotenone is a plant-derived pesticide that was sprayed on crops and used in fish control, so pesticide applicators handled it directly."},{"from":"wi_welding_fumes","to":"tx_cadmium","level":"established","effect":"harms","note":"Smelting and welding or brazing cadmium-plated or cadmium-containing metal releases cadmium fumes that workers breathe in."},{"from":"wi_welding_fumes","to":"tx_arsenic","level":"established","effect":"harms","note":"Copper and other metal smelting releases arsenic into the air, and smelter workers are the classic group with high arsenic exposure."},{"from":"entero","to":"uti","level":"established","effect":"harms","note":"E. coli, a member of this family that lives in the bowel, causes most urinary tract infections."},{"from":"klebsiella","to":"uti","level":"established","effect":"harms","note":"Klebsiella is a common cause of urinary tract infections, especially hospital-acquired ones."},{"from":"borrelia","to":"s_conduction_system","level":"established","effect":"harms","note":"Lyme disease can inflame the heart and block its electrical signal (Lyme carditis)."},{"from":"trypanosoma","to":"heart_failure","level":"established","effect":"harms","note":"Years after infection, Chagas disease (T. cruzi) can damage the heart muscle and cause heart failure."},{"from":"enterovirus","to":"s_heart","level":"established","effect":"harms","note":"Some enteroviruses, especially coxsackie B viruses, are a common cause of viral inflammation of the heart muscle (myocarditis)."},{"from":"schistosoma","to":"s_liver","level":"established","effect":"harms","note":"Eggs of the gut-vein species (S. mansoni) lodge in the liver and cause scarring that raises pressure in the portal vein."},{"from":"entamoeba","to":"s_liver","level":"established","effect":"harms","note":"The amoeba can travel from the colon wall to the liver and form an abscess."},{"from":"toxo","to":"s_retina","level":"established","effect":"harms","note":"Toxoplasma is a common cause of infection and scarring in the retina, which can blur vision."},{"from":"cmv","to":"s_retina","level":"established","effect":"harms","note":"In people with very weak immunity, such as advanced HIV, CMV can infect the retina and threaten sight."},{"from":"flu","to":"heart_attack","level":"association","effect":"harms","note":"The risk of a heart attack rises about sixfold in the week after a confirmed flu infection.","sources":[{"id":"pmid:29365305","citation":"Kwong JC et al., N Engl J Med","year":2018,"design":"cohort","finding":"In a self-controlled case series, heart attack admissions were about 6 times more frequent in the 7 days after laboratory-confirmed influenza."}]},{"from":"tx_diesel","to":"lung_cancer","level":"association","effect":"harms","note":"Workers with heavy diesel exhaust exposure, such as miners and truck drivers, get more lung cancer; IARC lists diesel exhaust as a known human carcinogen.","sources":[{"id":"pmid:22946126","citation":"Benbrahim-Tallaa L et al., Lancet Oncol","year":2012,"design":"review","finding":"IARC classified diesel engine exhaust as carcinogenic to humans (Group 1), based on raised lung cancer in exposed workers such as miners and truck drivers."}]},{"from":"tx_arsenic","to":"lung_cancer","level":"association","effect":"harms","note":"Breathing in arsenic, as smelter workers did, raises lung cancer risk; IARC lists arsenic as a known cause.","sources":[{"id":"pmid:19418618","citation":"Straif K et al., Lancet Oncol","year":2009,"design":"review","finding":"IARC Monograph 100C working group confirmed arsenic and cadmium compounds as causes of lung cancer in people, based mainly on studies of exposed workers."}]},{"from":"tx_cadmium","to":"lung_cancer","level":"association","effect":"harms","note":"Workers who breathe cadmium fumes or dust have more lung cancer; IARC lists cadmium as a known cause.","sources":[{"id":"pmid:19418618","citation":"Straif K et al., Lancet Oncol","year":2009,"design":"review","finding":"IARC Monograph 100C working group confirmed arsenic and cadmium compounds as causes of lung cancer in people, based mainly on studies of exposed workers."}]},{"from":"wi_welding_fumes","to":"lung_cancer","level":"association","effect":"harms","note":"Welders get more lung cancer than other workers; IARC lists welding fumes as a known human carcinogen.","sources":[{"id":"pmid:28408286","citation":"Guha N et al., Lancet Oncol","year":2017,"design":"review","finding":"IARC classified welding fumes as carcinogenic to humans (Group 1), based on raised lung cancer in welders in many studies."}]},{"from":"tx_tobacco","to":"gastric_cancer","level":"association","effect":"harms","note":"Smoking raises the risk of stomach cancer.","sources":[{"id":"pmid:19891056","citation":"Secretan B et al., Lancet Oncol","year":2009,"design":"review","finding":"IARC Monograph 100E working group found sufficient human evidence that tobacco smoking causes cancers of the stomach, liver and colorectum, among others."}]},{"from":"tx_tobacco","to":"liver_cancer","level":"association","effect":"harms","note":"Smoking raises the risk of liver cancer.","sources":[{"id":"pmid:19891056","citation":"Secretan B et al., Lancet Oncol","year":2009,"design":"review","finding":"IARC Monograph 100E working group found sufficient human evidence that tobacco smoking causes cancers of the stomach, liver and colorectum, among others."}]},{"from":"tx_tobacco","to":"colorectal_cancer","level":"association","effect":"harms","note":"Smoking raises the risk of bowel (colorectal) cancer.","sources":[{"id":"pmid:19891056","citation":"Secretan B et al., Lancet Oncol","year":2009,"design":"review","finding":"IARC Monograph 100E working group found sufficient human evidence that tobacco smoking causes cancers of the stomach, liver and colorectum, among others."}]},{"from":"tx_tobacco","to":"type2_diabetes","level":"association","effect":"harms","note":"Smokers develop type 2 diabetes more often than non-smokers, with risk rising with how much they smoke.","sources":[{"id":"pmid:26388413","citation":"Pan A et al., Lancet Diabetes Endocrinol","year":2015,"design":"meta-analysis","finding":"Across 88 prospective studies, current smoking was linked to a 37% higher risk of type 2 diabetes, with a dose-response relation."}]},{"from":"hcv","to":"liver_cancer","level":"established","effect":"harms","note":"Long-term hepatitis C infection scars the liver and is a leading cause of liver cancer, like hepatitis B.","sources":[{"id":"pmid:19350698","citation":"Bouvard V et al., Lancet Oncol","year":2009,"design":"review","finding":"IARC Monograph 100B working group confirmed hepatitis C as a cause of liver cancer, Epstein-Barr virus as a cause of nasopharyngeal cancer and some lymphomas, and H. pylori as a cause of stomach cancer and stomach (MALT) lymphoma."}]},{"from":"ebv","to":"head_neck_cancer","level":"established","effect":"harms","note":"Epstein-Barr virus is a known cause of nasopharyngeal cancer, the cancer at the back of the nose, which is one of the head and neck cancers.","sources":[{"id":"pmid:19350698","citation":"Bouvard V et al., Lancet Oncol","year":2009,"design":"review","finding":"IARC Monograph 100B working group confirmed hepatitis C as a cause of liver cancer, Epstein-Barr virus as a cause of nasopharyngeal cancer and some lymphomas, and H. pylori as a cause of stomach cancer and stomach (MALT) lymphoma."}]},{"from":"hpylori","to":"lymphoma","level":"established","effect":"harms","note":"Long-term H. pylori infection can cause a slow-growing lymphoma in the stomach lining (MALT lymphoma), which often shrinks when the infection is cleared.","sources":[{"id":"pmid:19350698","citation":"Bouvard V et al., Lancet Oncol","year":2009,"design":"review","finding":"IARC Monograph 100B working group confirmed hepatitis C as a cause of liver cancer, Epstein-Barr virus as a cause of nasopharyngeal cancer and some lymphomas, and H. pylori as a cause of stomach cancer and stomach (MALT) lymphoma."}]},{"from":"fuso","to":"colorectal_cancer","level":"association","effect":"harms","note":"Fusobacterium nucleatum is found more often inside colorectal tumours than in nearby healthy bowel lining; whether it helps cause the cancer is not proven.","sources":[{"id":"pmid:22009990","citation":"Kostic AD et al., Genome Res","year":2012,"design":"case-control","finding":"Fusobacterium sequences were enriched in colorectal carcinomas compared with matched normal tissue in 95 tumour/normal pairs."}]},{"from":"wi_job_strain","to":"coronary_artery_disease","level":"association","effect":"harms","note":"People in high-demand, low-control jobs have somewhat more heart attacks and coronary heart disease.","sources":[{"id":"pmid:22981903","citation":"Kivimaki M et al., Lancet","year":2012,"design":"meta-analysis","finding":"In 13 European cohorts (197,473 workers), job strain was linked to a 23% higher risk of coronary heart disease."}]},{"from":"wi_shift_work","to":"type2_diabetes","level":"association","effect":"harms","note":"People who work shifts, especially rotating and night shifts, develop diabetes slightly more often.","sources":[{"id":"pmid:25030030","citation":"Gan Y et al., Occup Environ Med","year":2015,"design":"meta-analysis","finding":"Across 12 studies (226,652 people), ever working shifts was linked to a 9% higher risk of diabetes, more so in men."}]},{"from":"wi_noise","to":"hypertension","level":"association","effect":"harms","note":"Workers exposed to loud noise at work have high blood pressure more often, with more risk at higher noise levels.","sources":[{"id":"pmid:32872306","citation":"Bolm-Audorff U et al., Int J Environ Res Public Health","year":2020,"design":"meta-analysis","finding":"Occupational noise of 80 dB(A) or more was linked to a 1.75-fold risk of hypertension, with a dose-response relation."}]},{"from":"wi_heat","to":"aki","level":"association","effect":"harms","note":"Workers who regularly do heavy work in heat have kidney disease and sudden kidney injury more often, probably from repeated dehydration.","sources":[{"id":"pmid:30526938","citation":"Flouris AD et al., Lancet Planet Health","year":2018,"design":"meta-analysis","finding":"About 15% of people who regularly worked under heat stress had kidney disease or acute kidney injury."}]},{"from":"tx_lead","to":"hypertension","level":"association","effect":"harms","note":"Higher lead exposure is linked to higher blood pressure, and reviewers judged this link likely causal.","sources":[{"id":"pmid:17431501","citation":"Navas-Acien A et al., Environ Health Perspect","year":2007,"design":"review","finding":"Systematic review concluded the evidence is sufficient to infer a causal relationship between lead exposure and hypertension."}]},{"from":"apples","to":"lipid_transfer_proteins","level":"established","effect":"contains","note":"Apple skin contains an LTP, Mal d 3."},{"from":"cherries","to":"lipid_transfer_proteins","level":"established","effect":"contains","note":"Cherries contain an LTP, Pru av 3, close to the peach LTP Pru p 3."},{"from":"nuts","to":"lipid_transfer_proteins","level":"established","effect":"contains","note":"Hazelnut (Cor a 8) and walnut (Jug r 3) contain LTPs."},{"from":"peanuts","to":"lipid_transfer_proteins","level":"established","effect":"contains","note":"Peanut contains an LTP, Ara h 9, which matters most in Mediterranean peanut allergy."},{"from":"tomatoes","to":"lipid_transfer_proteins","level":"established","effect":"contains","note":"Tomato contains an LTP, Sola l 3, especially in the skin and seeds."},{"from":"grapes","to":"lipid_transfer_proteins","level":"established","effect":"contains","note":"Grapes contain an LTP, Vit v 1, which also survives into wine."},{"from":"cannabis","to":"lipid_transfer_proteins","level":"established","effect":"contains","note":"Cannabis leaves and pollen contain an LTP, Can s 3; sensitisation was found in about 8% of Spanish allergy patients, though symptoms from cannabis itself were uncommon.","sources":[{"id":"pmid:23921252","citation":"Larramendi CH et al., Int Arch Allergy Immunol","year":2013,"design":"cross-sectional (545 patients)","finding":"8% of Spanish allergy-clinic patients were skin-test sensitised to cannabis leaf (more among smokers), with an LTP among the main allergens; symptoms from cannabis itself were uncommon and mild."}]},{"from":"al_wheat","to":"lipid_transfer_proteins","level":"established","effect":"contains","note":"Wheat contains an LTP, Tri a 14, important both in flour asthma and in some wheat food allergy.","sources":[{"id":"pmid:17716720","citation":"Palacin A et al., J Allergy Clin Immunol","year":2007,"design":"lab (40 patients)","finding":"Baker's asthma is a frequent occupational allergy mainly caused by breathing cereal flour; 60% of 40 bakers with flour asthma had IgE to wheat LTP (Tri a 14)."}]},{"from":"al_pollen","to":"lipid_transfer_proteins","level":"established","effect":"contains","note":"Mugwort (Art v 3) and plane-tree (Pla a 3) pollen contain LTPs."},{"from":"lipid_transfer_proteins","to":"anaphylaxis","level":"association","effect":"harms","note":"LTP sensitisation carries a real risk of anaphylaxis to plant foods, higher with exercise, alcohol or anti-inflammatory painkillers.","sources":[{"id":"pmid:22994350","citation":"Pascal M et al., Clin Exp Allergy","year":2012,"design":"case series (45 patients)","finding":"In LTP syndrome, many unrelated plant foods caused reactions; 76% of patients had anaphylaxis, and about a third of those reactions needed a cofactor such as exercise or anti-inflammatory painkillers. All were sensitised to peach Pru p 3 and wheat Tri a 14."},{"id":"pmid:33341818","citation":"Ruano-Zaragoza M et al., Int Arch Allergy Immunol","year":2021,"design":"cross-sectional (421 patients)","finding":"Of 421 people sensitised to peach LTP (Pru p 3), 37% had had anaphylaxis; most were also sensitised to the LTPs of walnut, plane-tree pollen, peanut and hazelnut, and recognising five or more LTPs went with more anaphylaxis."}]},{"from":"lipid_transfer_proteins","to":"food_allergy","level":"association","effect":"harms","note":"LTP allergy often spreads across many unrelated fruits, nuts and vegetables, and cooking does not protect.","sources":[{"id":"pmid:22994350","citation":"Pascal M et al., Clin Exp Allergy","year":2012,"design":"case series (45 patients)","finding":"In LTP syndrome, many unrelated plant foods caused reactions; 76% of patients had anaphylaxis, and about a third of those reactions needed a cofactor such as exercise or anti-inflammatory painkillers. All were sensitised to peach Pru p 3 and wheat Tri a 14."},{"id":"pmid:33341818","citation":"Ruano-Zaragoza M et al., Int Arch Allergy Immunol","year":2021,"design":"cross-sectional (421 patients)","finding":"Of 421 people sensitised to peach LTP (Pru p 3), 37% had had anaphylaxis; most were also sensitised to the LTPs of walnut, plane-tree pollen, peanut and hazelnut, and recognising five or more LTPs went with more anaphylaxis."}]},{"from":"al_wheat","to":"occ_asthma","level":"established","effect":"harms","note":"Breathing flour dust is a leading cause of occupational asthma (baker's asthma) in bakers and millers.","sources":[{"id":"pmid:17716720","citation":"Palacin A et al., J Allergy Clin Immunol","year":2007,"design":"lab (40 patients)","finding":"Baker's asthma is a frequent occupational allergy mainly caused by breathing cereal flour; 60% of 40 bakers with flour asthma had IgE to wheat LTP (Tri a 14)."}]},{"from":"wi_isocyanates","to":"al_wheat","level":"established","effect":"affects","note":"Breathing flour dust at work in bakeries and mills is the main route to becoming sensitised to wheat and developing baker's asthma.","sources":[{"id":"pmid:17716720","citation":"Palacin A et al., J Allergy Clin Immunol","year":2007,"design":"lab (40 patients)","finding":"Baker's asthma is a frequent occupational allergy mainly caused by breathing cereal flour; 60% of 40 bakers with flour asthma had IgE to wheat LTP (Tri a 14)."}]},{"from":"al_pet_dander","to":"redmeat","level":"association","effect":"affects","note":"Being sensitised to cat can, uncommonly, bring allergic reactions to pork (pork-cat syndrome), because cat and pig blood albumin look alike; it differs from alpha-gal allergy in coming on quickly.","scope":["allergic_rhinitis","allergic_asthma"],"sources":[{"id":"pmid:9105522","citation":"Hilger C et al., Allergy","year":1997,"design":"lab and cohort","finding":"Cat and pig serum albumin cross-reacted; IgE to pork albumin sat within the IgE to cat albumin (cat came first); 14-23% of cat-allergic people were sensitised to cat albumin and about a third of those sensitised to pork albumin may react to pork."},{"id":"pmid:8086105","citation":"Drouet M et al., Allerg Immunol (Paris)","year":1994,"design":"case-control","finding":"Sensitisation to pork meat came with sensitisation to cat dander significantly more often than in a comparison group, suggesting cross-allergy between pork and cat."}]},{"from":"al_alpha_gal","to":"al_other_drugs","level":"association","effect":"affects","note":"Alpha-gal sensitisation from tick bites can bring reactions to medicines carrying alpha-gal, such as the cancer drug cetuximab and gelatin-based drips.","scope":["food_allergy"],"sources":[{"id":"pmid:18337601","citation":"Chung CH et al., N Engl J Med","year":2008,"design":"case-control","finding":"Allergic reactions to the cancer drug cetuximab were linked to IgE present before treatment against alpha-gal, a sugar on the drug, which was common in the US South-East."},{"id":"pmid:22480538","citation":"Mullins RJ et al., J Allergy Clin Immunol","year":2012,"design":"cohort","finding":"Most patients allergic to red meat were skin-test sensitised to gelatin and a subset reacted to both; alpha-gal was found in bovine gelatin used in intravenous fluids."}]},{"from":"al_peanut","to":"seed_storage_proteins","level":"established","effect":"contains","note":"True peanut allergy is mainly IgE to the storage proteins Ara h 1, 2, 3 and 6; Ara h 2 is the strongest marker.","sources":[{"id":"pmid:29377469","citation":"Uotila R et al., Clin Exp Allergy","year":2018,"design":"cohort (102 challenged children)","finding":"In peanut-sensitised children in a birch region, PR-10 (Bet v 1) sensitisation was equally common in peanut-allergic and peanut-tolerant children; IgE to the storage proteins Ara h 2 and Ara h 6 best told them apart, and storage-protein sensitisation to tree nuts was uncommon despite widespread tree-nut avoidance."}]},{"from":"al_tree_nuts","to":"seed_storage_proteins","level":"established","effect":"contains","note":"True tree-nut allergy is mainly IgE to storage proteins such as hazelnut Cor a 14, cashew Ana o 3 and walnut Jug r 1."},{"from":"al_sesame","to":"seed_storage_proteins","level":"established","effect":"contains","note":"Sesame allergy is mainly to its storage proteins, including the 2S albumin Ses i 1; these also end up in tahini, hummus and cold-pressed sesame oil."},{"from":"soy","to":"seed_storage_proteins","level":"established","effect":"contains","note":"Soy contains the storage proteins Gly m 5 and Gly m 6, which drive more persistent soy allergy."},{"from":"legumes","to":"seed_storage_proteins","level":"established","effect":"contains","note":"Lentils, beans and chickpeas contain related legume storage proteins (vicilins and legumins)."},{"from":"seed_storage_proteins","to":"anaphylaxis","level":"association","effect":"harms","note":"Sensitisation to these heat-stable storage proteins marks the peanut, nut and sesame allergies most likely to be severe.","sources":[{"id":"pmid:29377469","citation":"Uotila R et al., Clin Exp Allergy","year":2018,"design":"cohort (102 challenged children)","finding":"In peanut-sensitised children in a birch region, PR-10 (Bet v 1) sensitisation was equally common in peanut-allergic and peanut-tolerant children; IgE to the storage proteins Ara h 2 and Ara h 6 best told them apart, and storage-protein sensitisation to tree nuts was uncommon despite widespread tree-nut avoidance."},{"id":"pmid:31866098","citation":"Brough HA et al. (Pronuts), J Allergy Clin Immunol","year":2020,"design":"cohort (122 children, food challenges)","finding":"Among children with at least one confirmed nut or sesame allergy who were challenged with all the others, 61% had more than one such allergy; still, most could add many nuts back to their diet."}]},{"from":"al_peanut","to":"al_tree_nuts","level":"association","effect":"affects","note":"Many people with peanut allergy are also sensitised to tree nuts, but tests over-call it: food challenges found real allergy to another nut in some, not all, and most could still eat many nuts.","scope":["food_allergy"],"sources":[{"id":"pmid:31866098","citation":"Brough HA et al. (Pronuts), J Allergy Clin Immunol","year":2020,"design":"cohort (122 children, food challenges)","finding":"Among children with at least one confirmed nut or sesame allergy who were challenged with all the others, 61% had more than one such allergy; still, most could add many nuts back to their diet."},{"id":"pmid:29377469","citation":"Uotila R et al., Clin Exp Allergy","year":2018,"design":"cohort (102 challenged children)","finding":"In peanut-sensitised children in a birch region, PR-10 (Bet v 1) sensitisation was equally common in peanut-allergic and peanut-tolerant children; IgE to the storage proteins Ara h 2 and Ara h 6 best told them apart, and storage-protein sensitisation to tree nuts was uncommon despite widespread tree-nut avoidance."},{"id":"pmid:16580071","citation":"de Leon MP et al., Mol Immunol","year":2007,"design":"lab","finding":"IgE to the main peanut allergen Ara h 2 was blocked by almond and Brazil nut extracts, so Ara h 2 shares IgE targets with some tree-nut proteins."}]},{"from":"al_peanut","to":"al_sesame","level":"association","effect":"affects","note":"Peanut allergy and sesame allergy often occur together in children, though they involve different proteins.","scope":["food_allergy"],"sources":[{"id":"pmid:31866098","citation":"Brough HA et al. (Pronuts), J Allergy Clin Immunol","year":2020,"design":"cohort (122 children, food challenges)","finding":"Among children with at least one confirmed nut or sesame allergy who were challenged with all the others, 61% had more than one such allergy; still, most could add many nuts back to their diet."}]},{"from":"dairy","to":"milk_caseins_whey","level":"established","effect":"contains","note":"Milk, yoghurt and cheese contain casein and whey proteins; cheese is mostly casein."},{"from":"al_milk","to":"milk_caseins_whey","level":"established","effect":"contains","note":"Cow's milk allergy is IgE to casein, whey proteins or both."},{"from":"milk_caseins_whey","to":"food_allergy","level":"association","effect":"harms","note":"Casein keeps causing reactions after baking while whey mostly does not, so higher casein IgE goes with a more lasting milk allergy; goat and sheep milk caseins cross-react with cow's.","sources":[{"id":"pmid:18620743","citation":"Nowak-Wegrzyn A et al., J Allergy Clin Immunol","year":2008,"design":"cohort (100 children, food challenges)","finding":"Of 100 milk-allergic children, 68 tolerated extensively heated (baked) milk though not plain milk; those who reacted to baked milk had higher casein IgE."},{"id":"pmid:10383602","citation":"Restani P et al., Clin Exp Allergy","year":1999,"design":"lab","finding":"IgE from children allergic to cow's milk recognised most milk proteins of ewe, goat and buffalo, but not camel's milk."}]},{"from":"al_egg","to":"ovomucoid","level":"established","effect":"contains","note":"Egg allergy that persists through baking is mainly IgE to ovomucoid in the white."},{"from":"ovomucoid","to":"food_allergy","level":"association","effect":"harms","note":"Ovomucoid survives baking, so people with high ovomucoid IgE are more likely to react even to egg in baked goods.","sources":[{"id":"pmid:9275136","citation":"Urisu A et al., J Allergy Clin Immunol","year":1997,"design":"double-blind food challenges","finding":"Many egg-allergic people who reacted to raw (freeze-dried) egg white tolerated heated egg white, and 16 of 17 who reacted to heated egg white tolerated heated egg white with the ovomucoid removed."},{"id":"pmid:18851876","citation":"Lemon-Mule H et al., J Allergy Clin Immunol","year":2008,"design":"cohort (117 children, food challenges)","finding":"64 of 117 egg-allergic children tolerated extensively heated egg in baked goods; those who reacted to baked egg had higher ovomucoid IgE."}]},{"from":"al_pollen","to":"profilins","level":"established","effect":"contains","note":"Grass, birch, mugwort and ragweed pollens all contain profilins (Phl p 12, Bet v 2, Art v 4, Amb a 8)."},{"from":"al_latex","to":"profilins","level":"established","effect":"contains","note":"Latex contains a profilin, Hev b 8."},{"from":"bananas","to":"profilins","level":"established","effect":"contains","note":"Banana contains a profilin, Mus a 1."},{"from":"tomatoes","to":"profilins","level":"established","effect":"contains","note":"Tomato contains a profilin, Sola l 1."},{"from":"citrus","to":"profilins","level":"established","effect":"contains","note":"Oranges contain a profilin, Cit s 2."},{"from":"parsley_celery","to":"profilins","level":"established","effect":"contains","note":"Celery contains a profilin, Api g 4."},{"from":"profilins","to":"food_allergy","level":"association","effect":"harms","note":"Profilin sensitisation can cause mild mouth itching from many raw fruits and vegetables, which are usually tolerated cooked.","sources":[{"id":"pmid:18489029","citation":"Asero R et al., Clin Exp Allergy","year":2008,"design":"cohort (200 pollen-allergic patients)","finding":"30% of pollen-allergic patients were sensitised to profilin; most profilin-allergic patients had only mouth symptoms, reacted to several plant foods (including melon) and tolerated them cooked or processed."}]},{"from":"al_pollen","to":"bananas","level":"association","effect":"affects","note":"Being sensitised to ragweed pollen can bring mouth itching from banana and melons (the ragweed-melon-banana pattern).","scope":["allergic_rhinitis"],"sources":[{"id":"pmid:3584742","citation":"Enberg RN et al., J Allergy Clin Immunol","year":1987,"design":"lab (192 sera)","finding":"Most people with IgE to watermelon, melons or banana also had IgE to ragweed; watermelon and ragweed extracts shared allergens, and watermelon-sensitised people more often reported itching or swelling of the mouth after eating these foods."},{"id":"pmid:18489029","citation":"Asero R et al., Clin Exp Allergy","year":2008,"design":"cohort (200 pollen-allergic patients)","finding":"30% of pollen-allergic patients were sensitised to profilin; most profilin-allergic patients had only mouth symptoms, reacted to several plant foods (including melon) and tolerated them cooked or processed."}]},{"from":"al_pollen","to":"peppers","level":"lab","effect":"affects","note":"People with mugwort-related celery and spice allergy have IgE that also binds paprika proteins; mugwort pollen blocked it in the lab.","scope":["allergic_rhinitis"],"sources":[{"id":"pmid:9491227","citation":"Leitner A et al., Allergy","year":1998,"design":"lab (22 sera)","finding":"Sera from people with the mugwort-birch-celery-spice syndrome bound pepper and paprika proteins, and mugwort, birch and celery extracts blocked the binding; the shared proteins were not Bet v 1 or profilin."}]},{"from":"al_pollen","to":"black_pepper","level":"lab","effect":"affects","note":"People with mugwort-related celery and spice allergy have IgE that also binds black pepper proteins; mugwort pollen blocked it in the lab.","scope":["allergic_rhinitis"],"sources":[{"id":"pmid:9491227","citation":"Leitner A et al., Allergy","year":1998,"design":"lab (22 sera)","finding":"Sera from people with the mugwort-birch-celery-spice syndrome bound pepper and paprika proteins, and mugwort, birch and celery extracts blocked the binding; the shared proteins were not Bet v 1 or profilin."}]},{"from":"al_pollen","to":"pr10_proteins","level":"established","effect":"contains","note":"Birch pollen's main allergen, Bet v 1, is a PR-10 protein; alder, hazel and oak pollen carry close relatives."},{"from":"apples","to":"pr10_proteins","level":"established","effect":"contains","note":"Raw apple contains Mal d 1, a birch-like PR-10 protein, mostly in and under the skin; cooking destroys it."},{"from":"cherries","to":"pr10_proteins","level":"established","effect":"contains","note":"Cherries and other stone fruit contain birch-like PR-10 proteins (Pru av 1 in sweet cherry)."},{"from":"nuts","to":"pr10_proteins","level":"established","effect":"contains","note":"Hazelnuts contain Cor a 1, a birch-like PR-10 protein; roasting weakens it."},{"from":"carrots","to":"pr10_proteins","level":"established","effect":"contains","note":"Raw carrot contains Dau c 1, a birch-like PR-10 protein."},{"from":"parsley_celery","to":"pr10_proteins","level":"established","effect":"contains","note":"Celery contains Api g 1, a birch-like PR-10 protein."},{"from":"soy","to":"pr10_proteins","level":"established","effect":"contains","note":"Soy contains Gly m 4, a birch-like PR-10 protein; there is most of it in lightly processed soy drinks and protein powders."},{"from":"peanuts","to":"pr10_proteins","level":"established","effect":"contains","note":"Peanut contains Ara h 8, a birch-like PR-10 protein that usually causes only mild mouth itching."},{"from":"kiwifruit","to":"pr10_proteins","level":"established","effect":"contains","note":"Kiwi contains Act d 8, a birch-like PR-10 protein, alongside its other allergens."},{"from":"pr10_proteins","to":"food_allergy","level":"association","effect":"harms","note":"PR-10 proteins cause pollen-food syndrome: usually a quick itchy mouth from raw fruit, nuts or vegetables in birch-allergic people.","sources":[{"id":"pmid:35975576","citation":"Skypala IJ et al. (BSACI guideline), Clin Exp Allergy","year":2022,"design":"review","finding":"UK guideline: pollen food syndrome is a common allergy to raw plant foods in pollen-sensitised people, caused by unstable plant proteins that look like pollen allergens; symptoms are usually quick and in the mouth, but reactions to soya milk, nuts, peanuts or severe reactions need more testing."},{"id":"pmid:29377469","citation":"Uotila R et al., Clin Exp Allergy","year":2018,"design":"cohort (102 challenged children)","finding":"In peanut-sensitised children in a birch region, PR-10 (Bet v 1) sensitisation was equally common in peanut-allergic and peanut-tolerant children; IgE to the storage proteins Ara h 2 and Ara h 6 best told them apart, and storage-protein sensitisation to tree nuts was uncommon despite widespread tree-nut avoidance."}]},{"from":"al_pollen","to":"apples","level":"association","effect":"affects","note":"Being sensitised to birch pollen can bring an itchy mouth and throat from raw apple, often the first food to cause it.","scope":["allergic_rhinitis"],"sources":[{"id":"pmid:35975576","citation":"Skypala IJ et al. (BSACI guideline), Clin Exp Allergy","year":2022,"design":"review","finding":"UK guideline: pollen food syndrome is a common allergy to raw plant foods in pollen-sensitised people, caused by unstable plant proteins that look like pollen allergens; symptoms are usually quick and in the mouth, but reactions to soya milk, nuts, peanuts or severe reactions need more testing."}]},{"from":"al_pollen","to":"cherries","level":"association","effect":"affects","note":"Being sensitised to birch pollen can bring mouth itching from raw cherries and other stone fruit.","scope":["allergic_rhinitis"],"sources":[{"id":"pmid:35975576","citation":"Skypala IJ et al. (BSACI guideline), Clin Exp Allergy","year":2022,"design":"review","finding":"UK guideline: pollen food syndrome is a common allergy to raw plant foods in pollen-sensitised people, caused by unstable plant proteins that look like pollen allergens; symptoms are usually quick and in the mouth, but reactions to soya milk, nuts, peanuts or severe reactions need more testing."}]},{"from":"al_pollen","to":"nuts","level":"association","effect":"affects","note":"Being sensitised to birch pollen can bring mouth itching from raw hazelnut; this is usually milder than a true nut allergy, which involves other proteins.","scope":["allergic_rhinitis"],"sources":[{"id":"pmid:35975576","citation":"Skypala IJ et al. (BSACI guideline), Clin Exp Allergy","year":2022,"design":"review","finding":"UK guideline: pollen food syndrome is a common allergy to raw plant foods in pollen-sensitised people, caused by unstable plant proteins that look like pollen allergens; symptoms are usually quick and in the mouth, but reactions to soya milk, nuts, peanuts or severe reactions need more testing."},{"id":"pmid:29377469","citation":"Uotila R et al., Clin Exp Allergy","year":2018,"design":"cohort (102 challenged children)","finding":"In peanut-sensitised children in a birch region, PR-10 (Bet v 1) sensitisation was equally common in peanut-allergic and peanut-tolerant children; IgE to the storage proteins Ara h 2 and Ara h 6 best told them apart, and storage-protein sensitisation to tree nuts was uncommon despite widespread tree-nut avoidance."}]},{"from":"al_pollen","to":"carrots","level":"association","effect":"affects","note":"Being sensitised to birch pollen can bring mouth itching from raw carrot.","scope":["allergic_rhinitis"],"sources":[{"id":"pmid:35975576","citation":"Skypala IJ et al. (BSACI guideline), Clin Exp Allergy","year":2022,"design":"review","finding":"UK guideline: pollen food syndrome is a common allergy to raw plant foods in pollen-sensitised people, caused by unstable plant proteins that look like pollen allergens; symptoms are usually quick and in the mouth, but reactions to soya milk, nuts, peanuts or severe reactions need more testing."},{"id":"pmid:8911702","citation":"Bauer L et al., Clin Exp Allergy","year":1996,"design":"lab","finding":"In celery-allergic patients, IgE cross-reacted between birch pollen, mugwort pollen and celery through Bet v 1-like proteins, profilin and a third group of proteins."}]},{"from":"al_pollen","to":"parsley_celery","level":"association","effect":"affects","note":"Being sensitised to birch or mugwort pollen can bring reactions to celery; mugwort-linked celery allergy is more often severe.","scope":["allergic_rhinitis"],"sources":[{"id":"pmid:8911702","citation":"Bauer L et al., Clin Exp Allergy","year":1996,"design":"lab","finding":"In celery-allergic patients, IgE cross-reacted between birch pollen, mugwort pollen and celery through Bet v 1-like proteins, profilin and a third group of proteins."},{"id":"pmid:38763171","citation":"Ballmer-Weber BK et al., J Allergy Clin Immunol","year":2024,"design":"cross-sectional (79 patients)","finding":"Of 79 people with proven celery allergy, 80% were sensitised to birch and 77% to mugwort pollen; IgE to the celery protein Api g 7 tracked mugwort Art v 1 and carried about 6 times the odds of severe anaphylaxis rather than only mouth symptoms."},{"id":"pmid:35975576","citation":"Skypala IJ et al. (BSACI guideline), Clin Exp Allergy","year":2022,"design":"review","finding":"UK guideline: pollen food syndrome is a common allergy to raw plant foods in pollen-sensitised people, caused by unstable plant proteins that look like pollen allergens; symptoms are usually quick and in the mouth, but reactions to soya milk, nuts, peanuts or severe reactions need more testing."}]},{"from":"al_pollen","to":"soy","level":"association","effect":"affects","note":"Being sensitised to birch pollen can, rarely, bring sudden and sometimes severe reactions to soy protein drinks or powders.","scope":["allergic_rhinitis"],"sources":[{"id":"pmid:12417891","citation":"Kleine-Tebbe J et al., J Allergy Clin Immunol","year":2002,"design":"case series (20 patients)","finding":"Twenty mostly birch-allergic people reacted, some with anaphylaxis, the first time they took a soy protein drink; their IgE bound the soy PR-10 protein SAM22 (Gly m 4), and birch Bet v 1 blocked that binding."},{"id":"pmid:35975576","citation":"Skypala IJ et al. (BSACI guideline), Clin Exp Allergy","year":2022,"design":"review","finding":"UK guideline: pollen food syndrome is a common allergy to raw plant foods in pollen-sensitised people, caused by unstable plant proteins that look like pollen allergens; symptoms are usually quick and in the mouth, but reactions to soya milk, nuts, peanuts or severe reactions need more testing."}]},{"from":"al_latex","to":"hevein_chitinases","level":"established","effect":"contains","note":"Latex contains the Hev b proteins, including hevein (Hev b 6.02), the piece shared with fruit chitinases.","sources":[{"id":"pmid:10069887","citation":"Blanco C et al., J Allergy Clin Immunol","year":1999,"design":"lab (18 patients)","finding":"Class I chitinases, which carry a hevein-like domain, from chestnut and avocado gave positive skin tests in about 7 in 10 latex-fruit-allergic patients and cross-reacted with latex; chitinases without that domain did not."}]},{"from":"avocado","to":"hevein_chitinases","level":"established","effect":"contains","note":"Avocado contains a class I chitinase (Prs a 1) with a hevein-like piece.","sources":[{"id":"pmid:10069887","citation":"Blanco C et al., J Allergy Clin Immunol","year":1999,"design":"lab (18 patients)","finding":"Class I chitinases, which carry a hevein-like domain, from chestnut and avocado gave positive skin tests in about 7 in 10 latex-fruit-allergic patients and cross-reacted with latex; chitinases without that domain did not."},{"id":"pmid:10887324","citation":"Sanchez-Monge R et al., J Allergy Clin Immunol","year":2000,"design":"lab","finding":"Class I chitinases are the panallergens of the latex-fruit syndrome (avocado, banana, chestnut); their allergenic activity is induced by ethylene (used to ripen fruit) and inactivated by heating."}]},{"from":"bananas","to":"hevein_chitinases","level":"established","effect":"contains","note":"Banana contains a class I chitinase with a hevein-like piece; there is more of it in fruit ripened with ethylene.","sources":[{"id":"pmid:10887324","citation":"Sanchez-Monge R et al., J Allergy Clin Immunol","year":2000,"design":"lab","finding":"Class I chitinases are the panallergens of the latex-fruit syndrome (avocado, banana, chestnut); their allergenic activity is induced by ethylene (used to ripen fruit) and inactivated by heating."}]},{"from":"hevein_chitinases","to":"food_allergy","level":"association","effect":"harms","note":"The hevein-like chitinases shared by latex and some fruits cause latex-fruit reactions, which are often more than just mouth symptoms.","sources":[{"id":"pmid:10069887","citation":"Blanco C et al., J Allergy Clin Immunol","year":1999,"design":"lab (18 patients)","finding":"Class I chitinases, which carry a hevein-like domain, from chestnut and avocado gave positive skin tests in about 7 in 10 latex-fruit-allergic patients and cross-reacted with latex; chitinases without that domain did not."},{"id":"pmid:39064262","citation":"Gromek W et al., J Clin Med","year":2024,"design":"review","finding":"Across studies, 4 to 88% of latex-allergic people had latex-fruit syndrome; banana, avocado, kiwi and papaya were the commonest fruits, and most reported fruit reactions were systemic rather than local."}]},{"from":"al_latex","to":"bananas","level":"association","effect":"affects","note":"Being sensitised to latex can bring allergic reactions to banana, one of the commonest latex-fruit foods.","sources":[{"id":"pmid:39064262","citation":"Gromek W et al., J Clin Med","year":2024,"design":"review","finding":"Across studies, 4 to 88% of latex-allergic people had latex-fruit syndrome; banana, avocado, kiwi and papaya were the commonest fruits, and most reported fruit reactions were systemic rather than local."},{"id":"pmid:10887324","citation":"Sanchez-Monge R et al., J Allergy Clin Immunol","year":2000,"design":"lab","finding":"Class I chitinases are the panallergens of the latex-fruit syndrome (avocado, banana, chestnut); their allergenic activity is induced by ethylene (used to ripen fruit) and inactivated by heating."}]},{"from":"al_latex","to":"avocado","level":"association","effect":"affects","note":"Being sensitised to latex can bring allergic reactions to avocado through a shared hevein-like protein.","sources":[{"id":"pmid:39064262","citation":"Gromek W et al., J Clin Med","year":2024,"design":"review","finding":"Across studies, 4 to 88% of latex-allergic people had latex-fruit syndrome; banana, avocado, kiwi and papaya were the commonest fruits, and most reported fruit reactions were systemic rather than local."},{"id":"pmid:10069887","citation":"Blanco C et al., J Allergy Clin Immunol","year":1999,"design":"lab (18 patients)","finding":"Class I chitinases, which carry a hevein-like domain, from chestnut and avocado gave positive skin tests in about 7 in 10 latex-fruit-allergic patients and cross-reacted with latex; chitinases without that domain did not."}]},{"from":"al_latex","to":"kiwifruit","level":"association","effect":"affects","note":"Being sensitised to latex can bring allergic reactions to kiwi.","sources":[{"id":"pmid:39064262","citation":"Gromek W et al., J Clin Med","year":2024,"design":"review","finding":"Across studies, 4 to 88% of latex-allergic people had latex-fruit syndrome; banana, avocado, kiwi and papaya were the commonest fruits, and most reported fruit reactions were systemic rather than local."}]},{"from":"wi_isocyanates","to":"al_latex","level":"association","effect":"affects","note":"Wearing and breathing powder from latex gloves at work was the main route to latex allergy in health workers; it fell after a switch to powder-free low-protein gloves.","sources":[{"id":"pmid:12170275","citation":"Allmers H et al., J Allergy Clin Immunol","year":2002,"design":"cohort (national registry)","finding":"After German health care switched to low-protein powder-free latex gloves, suspected occupational latex allergy cases, which had risen until 1998, declined steadily."}]},{"from":"shellfish","to":"tropomyosin","level":"established","effect":"contains","note":"Shrimp, crab, lobster and molluscs contain tropomyosin, their main allergen, which survives cooking.","sources":[{"id":"pmid:7963157","citation":"Leung PS et al., J Allergy Clin Immunol","year":1994,"design":"lab","finding":"The major heat-stable shrimp allergen was cloned and found to be tropomyosin."}]},{"from":"al_shellfish","to":"tropomyosin","level":"established","effect":"contains","note":"Shellfish allergy is mainly IgE to tropomyosin.","sources":[{"id":"pmid:10474029","citation":"Reese G et al., Int Arch Allergy Immunol","year":1999,"design":"review","finding":"Tropomyosin is the major allergen of shrimp, crab, lobster and crawfish and is also allergenic in dust mites, cockroaches and molluscs such as squid, making it a likely cross-sensitising pan-allergen; tropomyosin from vertebrates is not allergenic."}]},{"from":"al_dust_mite","to":"tropomyosin","level":"established","effect":"contains","note":"House dust mites contain a tropomyosin (Der p 10) very like shellfish tropomyosin.","sources":[{"id":"pmid:10474029","citation":"Reese G et al., Int Arch Allergy Immunol","year":1999,"design":"review","finding":"Tropomyosin is the major allergen of shrimp, crab, lobster and crawfish and is also allergenic in dust mites, cockroaches and molluscs such as squid, making it a likely cross-sensitising pan-allergen; tropomyosin from vertebrates is not allergenic."}]},{"from":"al_cockroach","to":"tropomyosin","level":"established","effect":"contains","note":"Cockroaches contain a tropomyosin (Bla g 7) very like shellfish tropomyosin.","sources":[{"id":"pmid:10474029","citation":"Reese G et al., Int Arch Allergy Immunol","year":1999,"design":"review","finding":"Tropomyosin is the major allergen of shrimp, crab, lobster and crawfish and is also allergenic in dust mites, cockroaches and molluscs such as squid, making it a likely cross-sensitising pan-allergen; tropomyosin from vertebrates is not allergenic."}]},{"from":"tropomyosin","to":"food_allergy","level":"association","effect":"harms","note":"Tropomyosin causes most shellfish allergy, a usually lifelong allergy that can be severe.","sources":[{"id":"pmid:10474029","citation":"Reese G et al., Int Arch Allergy Immunol","year":1999,"design":"review","finding":"Tropomyosin is the major allergen of shrimp, crab, lobster and crawfish and is also allergenic in dust mites, cockroaches and molluscs such as squid, making it a likely cross-sensitising pan-allergen; tropomyosin from vertebrates is not allergenic."}]},{"from":"al_dust_mite","to":"shellfish","level":"association","effect":"affects","note":"Being sensitised to dust mites can bring sensitisation, and sometimes reactions, to shrimp and other shellfish through shared tropomyosin, even in people who have never eaten shellfish.","scope":["allergic_rhinitis","allergic_asthma"],"sources":[{"id":"pmid:12859453","citation":"Fernandes J et al., Clin Exp Allergy","year":2003,"design":"lab (9 people)","finding":"Orthodox Jewish people who had never eaten shellfish but were dust-mite allergic had positive shrimp skin tests, and their IgE to shrimp tropomyosin was blocked by mite or cockroach extract."},{"id":"pmid:10474029","citation":"Reese G et al., Int Arch Allergy Immunol","year":1999,"design":"review","finding":"Tropomyosin is the major allergen of shrimp, crab, lobster and crawfish and is also allergenic in dust mites, cockroaches and molluscs such as squid, making it a likely cross-sensitising pan-allergen; tropomyosin from vertebrates is not allergenic."}]},{"from":"al_cockroach","to":"shellfish","level":"lab","effect":"affects","note":"Cockroach tropomyosin cross-reacts with shrimp tropomyosin in lab tests, so cockroach sensitisation can show up as shrimp sensitisation.","scope":["allergic_asthma"],"sources":[{"id":"pmid:12859453","citation":"Fernandes J et al., Clin Exp Allergy","year":2003,"design":"lab (9 people)","finding":"Orthodox Jewish people who had never eaten shellfish but were dust-mite allergic had positive shrimp skin tests, and their IgE to shrimp tropomyosin was blocked by mite or cockroach extract."},{"id":"pmid:10474029","citation":"Reese G et al., Int Arch Allergy Immunol","year":1999,"design":"review","finding":"Tropomyosin is the major allergen of shrimp, crab, lobster and crawfish and is also allergenic in dust mites, cockroaches and molluscs such as squid, making it a likely cross-sensitising pan-allergen; tropomyosin from vertebrates is not allergenic."}]},{"from":"al_fish","to":"parvalbumin","level":"established","effect":"contains","note":"Fish allergy is mainly IgE to parvalbumin, shared by most bony fish.","sources":[{"id":"pmid:11971005","citation":"Swoboda I et al., J Immunol","year":2002,"design":"lab","finding":"Carp parvalbumin bound IgE from all 60 fish-allergic patients tested and carried about 70% of the IgE targets in cod, tuna and salmon extracts: it is the main cross-reactive fish allergen."}]},{"from":"parvalbumin","to":"food_allergy","level":"association","effect":"harms","note":"Because parvalbumin is shared, people allergic to one fish usually react to several kinds of fish.","sources":[{"id":"pmid:11971005","citation":"Swoboda I et al., J Immunol","year":2002,"design":"lab","finding":"Carp parvalbumin bound IgE from all 60 fish-allergic patients tested and carried about 70% of the IgE targets in cod, tuna and salmon extracts: it is the main cross-reactive fish allergen."},{"id":"pmid:16337465","citation":"Van Do T et al., J Allergy Clin Immunol","year":2005,"design":"lab (10 patients)","finding":"Parvalbumins of cod, salmon, pollack, herring and wolffish cross-reacted strongly in fish-allergic people, while tuna, mackerel, halibut and flounder cross-reacted least."}]},{"from":"al_shellfish","to":"occ_asthma","level":"association","effect":"harms","note":"Breathing steam and aerosols from crab and prawn processing causes occupational asthma in seafood workers.","sources":[{"id":"pmid:11511741","citation":"Jeebhay MF et al., Occup Environ Med","year":2001,"design":"review","finding":"Seafood-processing workers breathe aerosols from crab, prawn, mussel and fish processing and handle seafood; occupational asthma affects 7 to 36% and protein contact dermatitis 3 to 11% of exposed workers."}]},{"from":"al_fish","to":"occ_asthma","level":"association","effect":"harms","note":"Breathing aerosols from fish processing and fishmeal production can cause occupational asthma.","sources":[{"id":"pmid:11511741","citation":"Jeebhay MF et al., Occup Environ Med","year":2001,"design":"review","finding":"Seafood-processing workers breathe aerosols from crab, prawn, mussel and fish processing and handle seafood; occupational asthma affects 7 to 36% and protein contact dermatitis 3 to 11% of exposed workers."}]},{"from":"wi_isocyanates","to":"al_shellfish","level":"association","effect":"affects","note":"Seafood processing at work, breathing cooking steam and handling shellfish, is a route to becoming sensitised to shellfish.","sources":[{"id":"pmid:11511741","citation":"Jeebhay MF et al., Occup Environ Med","year":2001,"design":"review","finding":"Seafood-processing workers breathe aerosols from crab, prawn, mussel and fish processing and handle seafood; occupational asthma affects 7 to 36% and protein contact dermatitis 3 to 11% of exposed workers."}]},{"from":"wi_isocyanates","to":"al_fish","level":"association","effect":"affects","note":"Fish processing and fishmeal work is a route to becoming sensitised to fish.","sources":[{"id":"pmid:11511741","citation":"Jeebhay MF et al., Occup Environ Med","year":2001,"design":"review","finding":"Seafood-processing workers breathe aerosols from crab, prawn, mussel and fish processing and handle seafood; occupational asthma affects 7 to 36% and protein contact dermatitis 3 to 11% of exposed workers."}]},{"from":"m_allergy","to":"m_ige_sensitisation","level":"established","effect":"helps","note":"Regulatory T cells trained by oral tolerance stop B cells from making IgE against a harmless protein."},{"from":"m_allergy","to":"m_type2","level":"established","effect":"helps","note":"Regulatory T cells release calming signals that hold back the allergic (type-2) helper cells."},{"from":"m_type2","to":"m_ige_sensitisation","level":"established","effect":"helps","note":"IL-4 and IL-13 from type-2 cells are the signals that switch B cells to making allergy IgE; less of them, less IgE."},{"from":"m_type2","to":"m_eosinophils","level":"established","effect":"helps","note":"IL-5 from type-2 cells makes and sustains eosinophils, so a calmer type-2 response means fewer of them."},{"from":"m_type2","to":"m_late_phase","level":"established","effect":"helps","note":"Type-2 helper cells drive the slow second wave of an allergic reaction."},{"from":"m_type2","to":"m_skin_barrier","level":"lab","effect":"helps","note":"In skin cells grown in the lab, IL-4 and IL-13 lowered filaggrin, so allergic inflammation itself can weaken the skin barrier.","sources":[{"id":"pmid:17512043","citation":"Howell MD et al., J Allergy Clin Immunol","year":2007,"design":"lab","finding":"Filaggrin was reduced in eczema skin, and keratinocytes grown with IL-4 and IL-13 made much less filaggrin."}]},{"from":"m_ige_sensitisation","to":"m_mast_cells","level":"established","effect":"helps","note":"Allergy IgE is what arms mast cells and basophils; without it, the allergen cannot set them off."},{"from":"m_mast_cells","to":"m_late_phase","level":"established","effect":"helps","note":"Chemicals from mast cells call in the cells of the late-phase reaction hours later."},{"from":"m_eosinophils","to":"m_late_phase","level":"established","effect":"helps","note":"Eosinophils arriving in the lining are a main cause of the slow second wave."},{"from":"m_skin_barrier","to":"m_ige_sensitisation","level":"association","effect":"helps","note":"People born with weaker filaggrin skin protein are more likely to become allergic to peanut, which fits allergens getting in through broken skin.","sources":[{"id":"pmid:21377035","citation":"Brown SJ et al., J Allergy Clin Immunol","year":2011,"design":"case-control","finding":"Filaggrin loss-of-function variants were strongly associated with challenge-proven peanut allergy, replicated in a second population, and still after allowing for eczema."},{"id":"pmid:16550169","citation":"Palmer CN et al., Nat Genet","year":2006,"design":"case-control","finding":"Common filaggrin loss-of-function variants were a major predisposing factor for atopic eczema."}]},{"from":"m_skin_barrier","to":"m_type2","level":"established","effect":"helps","note":"Damaged skin cells release alarm signals (TSLP, IL-33) that switch on allergic type-2 cells."},{"from":"m_airway_barrier","to":"m_type2","level":"established","effect":"helps","note":"Damaged airway lining cells release alarm signals (TSLP, IL-33, IL-25) that switch on allergic type-2 cells."},{"from":"m_skin_barrier","to":"s_skin","level":"established","effect":"located","note":"The barrier is the outermost layer of the skin."},{"from":"m_airway_barrier","to":"s_airways","level":"established","effect":"located","note":"The lining of the windpipe and bronchi."},{"from":"m_airway_barrier","to":"s_nose","level":"established","effect":"located","note":"The same lining covers the nose and sinuses."},{"from":"m_mast_cells","to":"s_immune","level":"established","effect":"located","note":"Mast cells are immune cells that live in the skin and the linings of the airways and gut."},{"from":"al_pollen","to":"allergic_conjunctivitis","level":"established","effect":"harms","note":"Pollen landing on the eye is the commonest cause of seasonal itchy, watery eyes."},{"from":"al_pet_dander","to":"allergic_conjunctivitis","level":"established","effect":"harms","note":"Cat and dog allergen often makes the eyes itch and swell around animals."},{"from":"al_dust_mite","to":"allergic_conjunctivitis","level":"established","effect":"harms","note":"Dust-mite allergy causes year-round itchy eyes as well as a blocked nose."},{"from":"allergic_conjunctivitis","to":"itchy_nose_eyes","level":"established","effect":"harms","note":"Itchy, red, watery eyes are the core symptom."},{"from":"allergic_conjunctivitis","to":"s_eyes","level":"established","effect":"affects","note":"Inflames the clear lining of the eye and inner eyelids."},{"from":"al_penicillin","to":"drug_allergy","level":"established","effect":"harms","note":"Penicillins are the commonest cause of drug allergy, though most people with the label turn out not to be allergic when tested.","sources":[{"id":"pmid:30558872","citation":"Blumenthal KG et al., Lancet","year":2019,"design":"review","finding":"Antibiotics are the commonest cause of serious immune drug reactions, but most patients labelled penicillin-allergic are not allergic when risk-stratified, tested and re-challenged."}]},{"from":"al_other_drugs","to":"drug_allergy","level":"established","effect":"harms","note":"Anaesthetic drugs, chlorhexidine, painkillers and other medicines can all cause drug allergy."},{"from":"drug_allergy","to":"anaphylaxis","level":"established","effect":"harms","note":"Medicines are a leading cause of anaphylaxis in adults."},{"from":"drug_allergy","to":"hives","level":"established","effect":"harms","note":"Hives are the commonest sign of an immediate drug allergy."},{"from":"drug_allergy","to":"s_immune","level":"established","effect":"affects","note":"An immune reaction, by IgE (fast) or T cells (delayed), against a medicine."},{"from":"al_venom","to":"venom_allergy","level":"established","effect":"harms","note":"Venom proteins from bees, wasps, hornets and fire ants are what the allergy is aimed at."},{"from":"venom_allergy","to":"anaphylaxis","level":"established","effect":"harms","note":"A sting can cause whole-body anaphylaxis in people with venom allergy.","sources":[{"id":"pmid:23076950","citation":"Boyle RJ et al., Cochrane Database Syst Rev","year":2012,"design":"meta-analysis","finding":"About 40% of untreated people with a previous sting reaction had a whole-body reaction to a later sting, versus under 3% after venom immunotherapy."}]},{"from":"venom_allergy","to":"angioedema","level":"established","effect":"harms","note":"Stings can cause large swellings around the sting or swelling of the face and throat."},{"from":"venom_allergy","to":"s_immune","level":"established","effect":"affects","note":"An IgE allergy to venom proteins."},{"from":"al_alpha_gal","to":"alpha_gal_syndrome","level":"established","effect":"harms","note":"IgE against the alpha-gal sugar, made after tick bites, causes the syndrome.","sources":[{"id":"pmid:21453959","citation":"Commins SP et al., J Allergy Clin Immunol","year":2011,"design":"cohort","finding":"IgE to alpha-gal rose 20-fold or more after tick bites and tracked with tick-bite history and lone star tick exposure."}]},{"from":"alpha_gal_syndrome","to":"anaphylaxis","level":"established","effect":"harms","note":"Anaphylaxis can start three to six hours after eating red meat, often at night, which makes the cause easy to miss.","sources":[{"id":"pmid:19070355","citation":"Commins SP et al., J Allergy Clin Immunol","year":2009,"design":"cohort","finding":"Patients with IgE to alpha-gal had delayed anaphylaxis, angioedema or hives three to six hours after eating beef, pork or lamb."}]},{"from":"alpha_gal_syndrome","to":"hives","level":"established","effect":"harms","note":"Delayed hives after red meat are a common sign."},{"from":"alpha_gal_syndrome","to":"d_abdominal_pain","level":"established","effect":"harms","note":"Some people get only delayed belly pain and diarrhoea after red meat."},{"from":"alpha_gal_syndrome","to":"s_immune","level":"established","effect":"affects","note":"An IgE allergy to a sugar rather than a protein."},{"from":"d_itch","to":"s_skin","level":"established","effect":"located","note":"Itch nerve endings sit in the top layers of the skin."},{"from":"atopic_eczema","to":"d_itch","level":"established","effect":"harms","note":"Itch is the main symptom of eczema, and scratching keeps the rash going."},{"from":"urticaria","to":"d_itch","level":"established","effect":"harms","note":"Hives are intensely itchy because histamine stimulates itch nerves."},{"from":"contact_dermatitis","to":"d_itch","level":"established","effect":"harms","note":"Allergic contact rashes are itchy where the skin touched the trigger."},{"from":"hives","to":"d_itch","level":"established","effect":"harms","note":"Each wheal itches as histamine stimulates the skin's itch nerves."},{"from":"food_allergy","to":"nausea","level":"established","effect":"harms","note":"Vomiting soon after eating is a common sign of a food allergic reaction, especially in babies."},{"from":"food_allergy","to":"d_abdominal_pain","level":"established","effect":"harms","note":"Cramping belly pain can come within minutes to two hours of eating the food."},{"from":"anaphylaxis","to":"nausea","level":"established","effect":"harms","note":"Vomiting and belly cramps are common in anaphylaxis, especially from foods and stings."},{"from":"eoe","to":"heartburn","level":"established","effect":"harms","note":"EoE can feel like reflux: burning or pain behind the breastbone that acid medicine may not fully relieve."},{"from":"eoe","to":"d_abdominal_pain","level":"established","effect":"harms","note":"Children with EoE often have belly pain, vomiting and feeding problems rather than food sticking."},{"from":"h_ras_blockers","to":"angioedema","level":"established","effect":"harms","note":"ACE-inhibitor medicines can rarely cause sudden lip, tongue or throat swelling, even after years; it comes from bradykinin, not histamine, so antihistamines and adrenaline work poorly."},{"from":"atopic_eczema","to":"allergic_rhinitis","level":"association","effect":"harms","note":"Children with persistent eczema often develop hay fever later, but most children with eczema do not follow a set 'march'.","sources":[{"id":"pmid:25335105","citation":"Belgrave DC et al., PLoS Med","year":2014,"design":"cohort","finding":"In two UK birth cohorts, persistent eczema with later-onset rhinitis was a distinct pattern, but only about 7% of children with symptoms followed an atopic-march-like sequence."}]},{"from":"h_allergen_immunotherapy","to":"allergic_rhinitis","level":"proven","effect":"helps","note":"Injections or under-the-tongue allergen treatment reduced hay-fever symptoms and medicine use in many placebo-controlled trials.","sources":[{"id":"pmid:17253469","citation":"Calderon MA et al., Cochrane Database Syst Rev","year":2007,"design":"meta-analysis","finding":"In 51 trials, injection immunotherapy for seasonal hay fever reduced symptom and medication scores against placebo; serious reactions were rare and there were no deaths."},{"id":"pmid:21154351","citation":"Radulovic S et al., Cochrane Database Syst Rev","year":2010,"design":"meta-analysis","finding":"In 49 pooled trials, under-the-tongue immunotherapy reduced hay-fever symptoms and medication needs against placebo, with no anaphylaxis reported."}]},{"from":"h_allergen_immunotherapy","to":"allergic_asthma","level":"proven","effect":"helps","note":"A house-dust-mite tablet under the tongue lowered the risk of moderate or severe asthma attacks in mite-allergic adults.","sources":[{"id":"pmid:27115376","citation":"Virchow JC et al., JAMA","year":2016,"design":"RCT","finding":"In 834 adults with mite-allergic asthma, the mite tablet reduced the risk of a moderate or severe asthma attack by about 30% against placebo while inhaled steroids were reduced."}]},{"from":"h_allergen_immunotherapy","to":"m_allergy","level":"established","effect":"helps","note":"Works by retraining tolerance: more regulatory T cells and 'blocking' IgG4 antibodies."},{"from":"h_oral_immunotherapy","to":"food_allergy","level":"proven","effect":"helps","note":"Daily, slowly increased amounts of peanut let most treated children eat more peanut without reacting, but usually do not cure the allergy.","sources":[{"id":"pmid:30449234","citation":"PALISADE Group (Vickery BP et al.), N Engl J Med","year":2018,"design":"RCT","finding":"67% of children on peanut oral immunotherapy tolerated a meaningful amount of peanut protein at the exit challenge versus 4% on placebo; most had side effects."}]},{"from":"h_oral_immunotherapy","to":"anaphylaxis","level":"proven","effect":"harms","note":"During treatment, oral immunotherapy roughly tripled the chance of anaphylaxis compared with simply avoiding peanut.","scope":["food_allergy"],"sources":[{"id":"pmid:31030987","citation":"Chu DK et al., Lancet","year":2019,"design":"meta-analysis","finding":"In 12 trials, peanut oral immunotherapy raised anaphylaxis risk (risk ratio about 3.1), adrenaline use and serious adverse events versus avoidance or placebo (high certainty)."}]},{"from":"h_early_allergen_intro","to":"food_allergy","level":"proven","effect":"helps","note":"Babies at high risk who ate peanut regularly from infancy were far less likely to have peanut allergy at five, and trials of several foods point the same way.","sources":[{"id":"pmid:25705822","citation":"Du Toit G et al., N Engl J Med","year":2015,"design":"RCT","finding":"In high-risk infants, regular peanut eating from 4 to 11 months reduced peanut allergy at 5 years from 13.7% to 1.9% (skin-test-negative group)."},{"id":"pmid:36972063","citation":"Scarpone R et al., JAMA Pediatr","year":2023,"design":"meta-analysis","finding":"Moderate-certainty evidence from trials that introducing multiple allergenic foods between 2 and 12 months reduced IgE food allergy (risk ratio 0.49)."}]},{"from":"h_early_allergen_intro","to":"m_allergy","level":"proven","effect":"helps","note":"Eating the food early and regularly builds oral tolerance; in LEAP the protected children made more blocking IgG4 and less peanut IgE.","sources":[{"id":"pmid:25705822","citation":"Du Toit G et al., N Engl J Med","year":2015,"design":"RCT","finding":"Peanut-specific IgG4 rose mainly in the peanut-eating group, while more of the avoidance group had raised peanut IgE."}]},{"from":"h_antihistamines","to":"urticaria","level":"proven","effect":"helps","note":"Non-drowsy antihistamines reduce hives and itch better than placebo and are the first treatment for chronic hives.","sources":[{"id":"pmid:25397904","citation":"Sharma M et al., Cochrane Database Syst Rev","year":2014,"design":"meta-analysis","finding":"Several H1-antihistamines at standard doses were effective against placebo for chronic spontaneous urticaria, though evidence was mostly low quality and no single drug stood out."}]},{"from":"h_antihistamines","to":"allergic_rhinitis","level":"proven","effect":"helps","note":"Antihistamine tablets relieve sneezing, itch and runny nose in hay fever, but help a blocked nose less.","sources":[{"id":"pmid:41707943","citation":"Vieira RJ et al., J Allergy Clin Immunol Pract","year":2026,"design":"meta-analysis","finding":"Network meta-analysis of 74 RCTs of second-generation oral antihistamines for allergic rhinitis; several improved nasal symptoms, serious adverse events were rare, certainty mostly low."}]},{"from":"h_nasal_steroids","to":"allergic_rhinitis","level":"proven","effect":"helps","note":"Steroid nasal sprays reduce sneezing, runny and blocked nose in hay fever better than placebo.","sources":[{"id":"pmid:37288109","citation":"Soe KK et al., Front Pharmacol","year":2023,"design":"meta-analysis","finding":"Network meta-analysis of 26 RCTs (about 9,500 patients): licensed intranasal corticosteroids improved total nasal symptom scores versus placebo in seasonal and perennial allergic rhinitis."}]},{"from":"h_nasal_steroids","to":"insomnia","level":"proven","effect":"helps","note":"In people with hay fever, steroid nasal sprays improved sleep quality in pooled trials.","scope":["allergic_rhinitis"],"sources":[{"id":"pmid:39471798","citation":"Tabata K et al., Int Arch Allergy Immunol","year":2025,"design":"meta-analysis","finding":"In 18 RCTs (6,019 participants) intranasal corticosteroids improved the sleep domain of rhinitis quality-of-life scores; daytime sleepiness did not change significantly."}]},{"from":"h_adrenaline_autoinjector","to":"anaphylaxis","level":"established","effect":"helps","note":"Adrenaline is the first and most important treatment for anaphylaxis; antihistamines are not a substitute."},{"from":"h_adrenaline_autoinjector","to":"hm_adrenaline","level":"established","effect":"helps","note":"The pen delivers the body's own fast stress hormone, adrenaline, into the muscle."},{"from":"h_anti_ige","to":"allergic_asthma","level":"proven","effect":"helps","note":"Anti-IgE injections reduced asthma attacks in moderate-to-severe allergic asthma.","sources":[{"id":"pmid:24414989","citation":"Normansell R et al., Cochrane Database Syst Rev","year":2014,"design":"meta-analysis","finding":"In 25 trials, omalizumab added to inhaled steroids reduced asthma exacerbations (odds ratio 0.55) and allowed steroid reduction."}]},{"from":"h_anti_ige","to":"urticaria","level":"proven","effect":"helps","note":"Anti-IgE injections reduced itch and hives in chronic hives not controlled by antihistamines.","sources":[{"id":"pmid:23432142","citation":"Maurer M et al., N Engl J Med","year":2013,"design":"RCT","finding":"Omalizumab reduced weekly itch-severity scores and hives against placebo in chronic spontaneous urticaria not controlled by antihistamines."}]},{"from":"h_anti_ige","to":"food_allergy","level":"proven","effect":"helps","note":"In children with several food allergies, anti-IgE let two-thirds eat a small amount of peanut without reacting, against 7% on placebo.","sources":[{"id":"pmid:38407394","citation":"Wood RA et al., N Engl J Med","year":2024,"design":"RCT","finding":"67% of omalizumab-treated children and adolescents with multiple food allergies tolerated the peanut challenge versus 7% on placebo, with similar gains for cashew, milk and egg."}]},{"from":"h_anti_il4r","to":"atopic_eczema","level":"proven","effect":"helps","note":"Blocking IL-4 and IL-13 cleared or nearly cleared moderate-to-severe eczema in more than a third of patients, against about one in ten on placebo.","sources":[{"id":"pmid:27690741","citation":"Simpson EL et al., N Engl J Med","year":2016,"design":"RCT","finding":"In SOLO 1 and SOLO 2 (about 1,400 adults), 36-38% on dupilumab reached clear or almost clear skin at 16 weeks versus 8-10% on placebo."}]},{"from":"h_anti_il4r","to":"allergic_asthma","level":"proven","effect":"helps","note":"Anti-IL-4 receptor injections roughly halved severe asthma attacks in uncontrolled moderate-to-severe asthma.","sources":[{"id":"pmid:29782217","citation":"Castro M et al., N Engl J Med","year":2018,"design":"RCT","finding":"Dupilumab lowered the annual rate of severe asthma exacerbations by about 48% versus placebo and improved lung function."}]},{"from":"h_anti_il4r","to":"eoe","level":"proven","effect":"helps","note":"Anti-IL-4 receptor injections healed the oesophagus lining in about six in ten people with EoE, against about one in twenty on placebo.","sources":[{"id":"pmid:36546624","citation":"Dellon ES et al., N Engl J Med","year":2022,"design":"RCT","finding":"Weekly dupilumab gave histologic remission in about 60% of adults and adolescents with EoE versus 5-6% on placebo, and improved swallowing."}]},{"from":"h_allergen_immunotherapy","to":"venom_allergy","level":"proven","effect":"helps","note":"Venom immunotherapy cut whole-body reactions to a later sting from about 40% to under 3% in pooled trials.","sources":[{"id":"pmid:23076950","citation":"Boyle RJ et al., Cochrane Database Syst Rev","year":2012,"design":"meta-analysis","finding":"In 7 trials, venom immunotherapy reduced systemic reactions to later stings (3 of 113 treated vs 37 of 93 untreated) and improved quality of life."}]},{"from":"h_emollients","to":"atopic_eczema","level":"proven","effect":"helps","note":"Regular moisturisers reduce eczema severity and flares and cut the amount of steroid cream needed.","sources":[{"id":"pmid:28166390","citation":"van Zuuren EJ et al., Cochrane Database Syst Rev","year":2017,"design":"meta-analysis","finding":"In 77 studies, moisturisers lowered investigator-assessed eczema severity, reduced flares (risk ratio 0.33) and steroid use, and worked better combined with active treatment."}]},{"from":"h_emollients_from_birth","to":"atopic_eczema","level":"failed","effect":"helps","note":"Daily moisturiser from birth did not prevent eczema in two large trials.","sources":[{"id":"pmid:32087126","citation":"Chalmers JR et al., Lancet","year":2020,"design":"RCT","finding":"In 1,394 high-risk newborns, daily emollient in the first year did not reduce eczema at age 2 (23% vs 25%) and increased skin infections."},{"id":"pmid:32087121","citation":"Skjerven HO et al., Lancet","year":2020,"design":"RCT","finding":"In 2,397 infants, regular skin emollients did not reduce atopic dermatitis by 12 months."},{"id":"pmid:36373988","citation":"Kelleher MM et al., Cochrane Database Syst Rev","year":2022,"design":"meta-analysis","finding":"Skin care interventions in the first year probably do not prevent eczema, may increase food allergy and probably increase skin infection."}]},{"from":"h_emollients_from_birth","to":"food_allergy","level":"failed","effect":"helps","note":"Emollients from birth did not lower food allergy and may slightly raise it.","sources":[{"id":"pmid:36373988","citation":"Kelleher MM et al., Cochrane Database Syst Rev","year":2022,"design":"meta-analysis","finding":"Skin care interventions in infancy may increase the risk of food allergy (low certainty)."}]},{"from":"h_breastfeeding","to":"allergic_asthma","level":"association","effect":"helps","note":"Children breastfed for longer had somewhat less asthma in population studies; this may partly reflect other family differences.","sources":[{"id":"pmid:26192405","citation":"Lodge CJ et al., Acta Paediatr","year":2015,"design":"meta-analysis","finding":"More breastfeeding was associated with less asthma at 5-18 years, weakly with less eczema under 2, and not with food allergy; evidence quality was low."}]},{"from":"h_breastfeeding","to":"atopic_eczema","level":"association","effect":"helps","note":"Exclusive breastfeeding for three to four months was weakly linked with less eczema under two, mostly from low-quality studies.","sources":[{"id":"pmid:26192405","citation":"Lodge CJ et al., Acta Paediatr","year":2015,"design":"meta-analysis","finding":"Exclusive breastfeeding for 3-4 months was associated with reduced eczema at 2 years or younger, mainly from cross-sectional studies of low quality."}]},{"from":"h_farm_pets_early","to":"allergic_asthma","level":"association","effect":"helps","note":"Children growing up on traditional farms, surrounded by more varied microbes, have less asthma.","sources":[{"id":"pmid:21345099","citation":"Ege MJ et al., N Engl J Med","year":2011,"design":"cohort","finding":"Farm children had less asthma and atopy and greater microbial exposure; microbial diversity was inversely related to asthma risk."},{"id":"pmid:27518660","citation":"Stein MM et al., N Engl J Med","year":2016,"design":"cohort","finding":"Amish children had 4 and 6 times lower asthma and sensitisation than Hutterite children, with much higher house-dust endotoxin; Amish dust protected mice from allergic airway disease."}]},{"from":"h_farm_pets_early","to":"m_allergy","level":"association","effect":"helps","note":"Babies living with two or more dogs or cats were less likely to become sensitised to allergens later in childhood.","sources":[{"id":"pmid:12190366","citation":"Ownby DR et al., JAMA","year":2002,"design":"cohort","finding":"Exposure to 2 or more dogs or cats in the first year roughly halved skin-prick and IgE sensitisation at 6-7 years."},{"id":"pmid:30566481","citation":"Hesselmar B et al., PLoS One","year":2018,"design":"cohort","finding":"Allergic disease at 7-9 years fell in a dose-dependent way with the number of household cats and dogs in the first year."}]},{"from":"h_allergen_avoidance","to":"food_allergy","level":"established","effect":"helps","note":"For someone with a confirmed food allergy, avoiding the food is what prevents reactions; avoiding foods that are not allergens can cause harm."},{"from":"h_allergen_avoidance","to":"allergic_asthma","level":"failed","effect":"helps","note":"Mattress covers and other house-dust-mite control measures did not improve asthma in pooled trials.","sources":[{"id":"pmid:18425868","citation":"Gotzsche PC, Johansen HK, Cochrane Database Syst Rev","year":2008,"design":"meta-analysis","finding":"In 54 trials, physical and chemical dust-mite control measures had no effect on asthma symptoms, peak flow or medication use."}]},{"from":"vitd","to":"allergic_asthma","level":"mixed","effect":"helps","note":"Vitamin D supplements did not reduce attacks in people who already have asthma, but high-dose vitamin D in pregnancy probably lowered wheeze in their children.","sources":[{"id":"pmid:36744416","citation":"Williamson A et al., Cochrane Database Syst Rev","year":2023,"design":"meta-analysis","finding":"In 20 trials, vitamin D supplementation did not reduce asthma exacerbations needing steroids or improve asthma control."},{"id":"pmid:40792481","citation":"Patchen BK et al., Cochrane Database Syst Rev","year":2025,"design":"meta-analysis","finding":"Evidence that early-life vitamin D prevents childhood asthma is limited, but high-dose vitamin D in pregnancy likely helps prevent childhood wheeze (moderate certainty)."}]},{"from":"tx_tobacco","to":"allergic_asthma","level":"association","effect":"harms","note":"Children exposed to smoke before or after birth develop asthma and wheeze more often.","sources":[{"id":"pmid:22430451","citation":"Burke H et al., Pediatrics","year":2012,"design":"meta-analysis","finding":"In 79 prospective studies, pre- or postnatal passive smoke exposure raised incident wheeze by 30-70% and incident asthma by 21-85%."}]},{"from":"tx_pm25","to":"allergic_asthma","level":"association","effect":"harms","note":"Long-term exposure to air pollution, especially fine particles, is linked with children developing asthma.","sources":[{"id":"pmid:32233861","citation":"Thurston GD et al., Ann Am Thorac Soc","year":2020,"design":"review","finding":"An ATS workshop concluded long-term air pollution exposure is a cause of childhood asthma, while evidence for adult-onset asthma remains insufficient."}]},{"from":"exercise","to":"anaphylaxis","level":"association","effect":"harms","note":"In people with food allergy, exercising soon after eating the food can turn a mild reaction into anaphylaxis, especially with wheat.","scope":["food_allergy"],"sources":[{"id":"pmid:36990430","citation":"Dolle-Bierke S et al., J Allergy Clin Immunol Pract","year":2023,"design":"cohort","finding":"In 3,427 food anaphylaxis cases, exercise was strongly associated with wheat anaphylaxis and raised the odds of severe peanut anaphylaxis."}]},{"from":"tx_alcohol","to":"anaphylaxis","level":"association","effect":"harms","note":"In people with food allergy, drinking alcohol around the meal was linked with more severe reactions.","scope":["food_allergy"],"sources":[{"id":"pmid:36990430","citation":"Dolle-Bierke S et al., J Allergy Clin Immunol Pract","year":2023,"design":"cohort","finding":"Alcohol intake was associated with about three times the odds of severe wheat-induced anaphylaxis."}]},{"from":"flu","to":"allergic_asthma","level":"established","effect":"harms","note":"Flu and other respiratory viruses are among the commonest triggers of asthma attacks."},{"from":"atopic_eczema","to":"insomnia","level":"association","effect":"harms","note":"Children with active eczema have worse sleep quality, mostly from itch and scratching at night.","sources":[{"id":"pmid:30830151","citation":"Ramirez FD et al., JAMA Pediatr","year":2019,"design":"cohort","finding":"In 13,988 children followed to 16, active eczema was linked with about 50% higher odds of sleep-quality disturbances, worse with severe disease, though total sleep time was similar."}]},{"from":"allergic_rhinitis","to":"insomnia","level":"association","effect":"harms","note":"A blocked, itchy nose disturbs sleep, more so when hay fever is severe.","sources":[{"id":"pmid:16983053","citation":"Leger D et al., Arch Intern Med","year":2006,"design":"cohort","finding":"In 591 patients, all dimensions of sleep were impaired by allergic rhinitis, most with the severe form (cross-sectional, with controls)."}]},{"from":"atopic_eczema","to":"depression","level":"association","effect":"harms","note":"Adults with eczema were more likely to be diagnosed with depression, more so with severe eczema.","sources":[{"id":"pmid:31479767","citation":"Schonmann Y et al., J Allergy Clin Immunol Pract","year":2020,"design":"cohort","finding":"Among 526,808 adults with eczema, new depression was 14% more common (26% with severe eczema) and new anxiety 17% more common than in matched controls."}]},{"from":"atopic_eczema","to":"anxiety","level":"association","effect":"harms","note":"Adults with eczema were somewhat more likely to be diagnosed with anxiety.","sources":[{"id":"pmid:31479767","citation":"Schonmann Y et al., J Allergy Clin Immunol Pract","year":2020,"design":"cohort","finding":"Atopic eczema was associated with increased incidence of anxiety (hazard ratio 1.17)."}]},{"from":"faecali","to":"allergic_asthma","level":"association","effect":"helps","note":"Babies whose gut held less Faecalibacterium and three other bacteria in the first 100 days were more often at risk of asthma later.","sources":[{"id":"pmid:26424567","citation":"Arrieta MC et al., Sci Transl Med","year":2015,"design":"cohort","finding":"Infants at risk of asthma had less Lachnospira, Veillonella, Faecalibacterium and Rothia and less faecal acetate in early life; giving these bacteria to germ-free mice reduced airway inflammation in their offspring."}]},{"from":"allergic_rhinitis","to":"parkinsons","level":"association","effect":"harms","note":"People with hay fever had a slightly higher chance of a later Parkinson's diagnosis in large Asian health records; early Parkinson's nose and smell changes could be part of this, so it is not shown to be a cause.","sources":[{"id":"pmid:42091590","citation":"Chang HJ et al., NPJ Parkinsons Dis","year":2026,"design":"cohort","finding":"In 5 million Korean adults, allergic rhinitis (HR 1.18) and asthma (HR 1.16) were associated with incident Parkinson's, rising with severity and number of allergic conditions; atopic dermatitis was not."},{"id":"pmid:40907323","citation":"Yang TH et al., Parkinsonism Relat Disord","year":2025,"design":"case-control","finding":"Prior allergic rhinitis was more common in 16,611 people with Parkinson's than in matched controls (adjusted OR 1.40)."}]},{"from":"allergic_asthma","to":"parkinsons","level":"association","effect":"harms","note":"Asthma was linked with a slightly higher chance of a later Parkinson's diagnosis in one large cohort; this is a link, not proof of cause.","sources":[{"id":"pmid:42091590","citation":"Chang HJ et al., NPJ Parkinsons Dis","year":2026,"design":"cohort","finding":"Asthma was associated with a 16% higher incidence of Parkinson's over about 10 years in Korean adults aged 40 and over."}]},{"from":"fibre","to":"gb_bacteroides","level":"established","effect":"helps","note":"Plant fibre is what these bacteria are built to eat."},{"from":"gb_bacteroides","to":"m_micro","level":"established","effect":"helps","note":"Ferments fibre into acetate and propionate."},{"from":"gb_bvulgatus","to":"m_micro","level":"established","effect":"helps","note":"Ferments plant fibre into acetate and propionate."},{"from":"gb_bfragilis","to":"m_allergy","level":"lab","effect":"helps","note":"Its capsule sugar helped germ-free mice build the calming side of the immune system; not tested in people.","sources":[{"id":"pmid:16009137","citation":"Mazmanian et al., Cell","year":2005,"design":"lab","finding":"A polysaccharide from Bacteroides fragilis directed maturation of the immune system in germ-free mice."}]},{"from":"gb_pcopri","to":"m_micro","level":"established","effect":"helps","note":"Ferments fibre and starch into short-chain fatty acids."},{"from":"fibre","to":"gb_pcopri","level":"association","effect":"helps","note":"People carrying more of this bacterium got the biggest blood-sugar improvement from a barley-fibre meal.","sources":[{"id":"pmid:26552345","citation":"Kovatcheva-Datchary et al., Cell Metabolism","year":2015,"design":"cohort","finding":"Improvement in glucose metabolism after barley kernel bread was linked to higher gut abundance of Prevotella copri."}]},{"from":"gb_blautia","to":"m_micro","level":"established","effect":"helps","note":"Makes acetate, which the butyrate makers then use."},{"from":"gb_anaerostipes","to":"m_micro","level":"established","effect":"helps","note":"Turns lactate from other bacteria into butyrate."},{"from":"gb_ehallii","to":"m_micro","level":"established","effect":"helps","note":"Makes butyrate and propionate from lactate."},{"from":"gb_coprococcus","to":"depression_c","level":"association","effect":"helps","note":"Found at lower levels in people with depression in two large population studies; direction of cause unknown.","sources":[{"id":"pmid:30718848","citation":"Valles-Colomer et al., Nature Microbiology","year":2019,"design":"cohort","finding":"Coprococcus and Dialister were depleted in depression in two population cohorts."}]},{"from":"gb_dialister","to":"depression_c","level":"association","effect":"helps","note":"Found at lower levels in people with depression in two large population studies; direction of cause unknown.","sources":[{"id":"pmid:30718848","citation":"Valles-Colomer et al., Nature Microbiology","year":2019,"design":"cohort","finding":"Coprococcus and Dialister were depleted in depression in two population cohorts."}]},{"from":"gb_clostridia_clusters","to":"m_allergy","level":"lab","effect":"helps","note":"A defined mixture of human Clostridia strains built up regulatory T cells in mice; not tested in people.","sources":[{"id":"pmid:23842501","citation":"Atarashi et al., Nature","year":2013,"design":"lab","finding":"A rationally selected mixture of 17 human Clostridia strains induced regulatory T cells in the mouse colon."}]},{"from":"gb_clostridia_clusters","to":"m_inflam","level":"lab","effect":"helps","note":"The same Clostridia mixture calmed colitis in mice.","sources":[{"id":"pmid:23842501","citation":"Atarashi et al., Nature","year":2013,"design":"lab","finding":"The Clostridia mixture reduced colitis in mouse models."}]},{"from":"fibre","to":"gb_clostridia_clusters","level":"established","effect":"helps","note":"Fibre is the food that keeps this whole group going."},{"from":"gb_msmithii","to":"m_micro","level":"established","effect":"helps","note":"Removing hydrogen lets the other bacteria keep fermenting fibre."},{"from":"gb_msmithii","to":"constipation","level":"association","effect":"harms","note":"People with constipation and methane on the breath carry more of this archaeon; whether it is cause or consequence is unclear.","sources":[{"id":"pmid:22573345","citation":"Kim et al., Digestive Diseases and Sciences","year":2012,"design":"case-control","finding":"Methanobrevibacter smithii counts were significantly higher in constipation-predominant IBS patients with breath methane than in non-methane IBS patients."}]},{"from":"gb_msmithii","to":"ibs","level":"association","effect":"harms","note":"Higher levels in the constipation-predominant form of IBS.","sources":[{"id":"pmid:22573345","citation":"Kim et al., Digestive Diseases and Sciences","year":2012,"design":"case-control","finding":"M. smithii was the predominant methanogen and was raised in constipation-predominant IBS with breath methane."}]},{"from":"gb_ecoli_commensal","to":"vitk","level":"established","effect":"helps","note":"Gut bacteria including E. coli make vitamin K2; leafy greens still supply most of what the body uses."},{"from":"gb_ecoli_commensal","to":"b12","level":"established","effect":"helps","note":"Gut bacteria make B12, but they make it in the colon, past the point where the body can absorb it, so it does not count towards your intake."},{"from":"fibre","to":"gb_bifido_longum","level":"established","effect":"helps","note":"Inulin-type fibre from onions, chicory and wheat feeds it."},{"from":"gb_bifido_longum","to":"m_micro","level":"established","effect":"helps","note":"Makes lactate and acetate, which butyrate makers use."},{"from":"fibre","to":"gb_bifido_adolescentis","level":"established","effect":"helps","note":"Resistant starch and inulin-type fibre feed it."},{"from":"fibre","to":"gb_bacteroides_plebeius","level":"established","effect":"helps","note":"Seaweed fibre is its speciality."},{"from":"gb_phascolarctobacterium","to":"m_micro","level":"established","effect":"helps","note":"Turns succinate into propionate."},{"from":"christensenella","to":"obesity","level":"association","effect":"helps","note":"People who carry this bacterium tend to be leaner; it is one of the most inherited members of the gut community.","sources":[{"id":"pmid:31660948","citation":"Waters & Ley, BMC Biology","year":2019,"design":"review","finding":"Christensenellaceae are heritable, widespread and consistently associated with lower body mass index and markers of health."}]},{"from":"fibre","to":"gb_eubacterium_eligens","level":"established","effect":"helps","note":"Pectin from fruit and vegetables is its food."},{"from":"gb_eubacterium_eligens","to":"m_micro","level":"established","effect":"helps","note":"Ferments pectin into short-chain fatty acids."},{"from":"fibre","to":"gb_bacteroides_uniformis","level":"established","effect":"helps","note":"Breaks down many kinds of plant fibre."},{"from":"gb_bacteroides_uniformis","to":"m_micro","level":"established","effect":"helps","note":"Makes acetate and propionate from fibre."},{"from":"al_milk","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Milk proteins (casein, whey) are the commonest food target for IgE in babies."},{"from":"al_egg","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Egg-white proteins are a common IgE target in young children, especially those with eczema."},{"from":"al_wheat","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Wheat proteins can sensitise through the gut, skin or, for bakers, the airways."},{"from":"al_soy","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Soy proteins can become an IgE target, usually in young children."},{"from":"al_fish","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Fish parvalbumin is a stable protein that the immune system can make IgE against."},{"from":"al_shellfish","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Shellfish tropomyosin is a common IgE target in adults."},{"from":"al_peanut","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Peanut storage proteins are strong triggers of IgE sensitisation, often first met through inflamed skin."},{"from":"al_tree_nuts","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Tree-nut proteins are frequent targets of IgE sensitisation."},{"from":"al_sesame","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Sesame proteins are a growing cause of IgE sensitisation."},{"from":"al_alpha_gal","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Tick bites make the body produce IgE against the alpha-gal sugar."},{"from":"al_latex","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Latex proteins sensitised many health workers through gloves, skin and breathed-in powder."},{"from":"al_pollen","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Pollen proteins landing on the nose and eyes are the commonest airborne cause of IgE sensitisation."},{"from":"al_dust_mite","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Dust-mite proteins are the commonest year-round cause of IgE sensitisation worldwide."},{"from":"al_pet_dander","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Cat and dog proteins carried on dust and clothes commonly sensitise, even in homes without pets."},{"from":"al_mould","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Mould spores carry proteins that can sensitise through the airways."},{"from":"al_cockroach","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Cockroach proteins in household dust sensitise many children in crowded city housing."},{"from":"al_venom","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"A sting can lead the body to make IgE against venom proteins."},{"from":"al_penicillin","to":"m_ige_sensitisation","level":"established","effect":"harms","note":"Penicillin binds to body proteins, and the immune system can make IgE against the combination."},{"from":"al_dust_mite","to":"m_airway_barrier","level":"established","effect":"harms","note":"Dust-mite allergen is an enzyme that cuts the seals between airway lining cells, letting itself and other allergens in."},{"from":"al_other_drugs","to":"m_mast_cells","level":"established","effect":"harms","note":"Some medicines (certain antibiotics, opioids, muscle relaxants, contrast dyes) can make mast cells release histamine directly, without IgE."},{"from":"al_venom","to":"m_mast_cells","level":"established","effect":"harms","note":"Venom contains peptides that open mast cells directly, on top of any IgE allergy."},{"from":"m_ige_sensitisation","to":"food_allergy","level":"established","effect":"helps","note":"No IgE sensitisation, no IgE food allergy: sensitisation is the first step, though a positive test alone is not allergy."},{"from":"m_ige_sensitisation","to":"allergic_rhinitis","level":"established","effect":"helps","note":"Hay fever needs IgE against the pollen, mite or animal protein first."},{"from":"m_mast_cells","to":"anaphylaxis","level":"established","effect":"helps","note":"Anaphylaxis is mast cells and basophils emptying all over the body at once; calmer cells mean less risk."},{"from":"m_mast_cells","to":"urticaria","level":"established","effect":"helps","note":"Hives are skin mast cells releasing histamine."},{"from":"m_eosinophils","to":"eoe","level":"established","effect":"helps","note":"EoE is defined by eosinophils building up in the oesophagus lining."},{"from":"m_eosinophils","to":"allergic_asthma","level":"established","effect":"helps","note":"Eosinophils in the airways drive attacks and long-term airway damage in many people with allergic asthma."},{"from":"m_type2","to":"atopic_eczema","level":"established","effect":"helps","note":"Type-2 signals (IL-4, IL-13, IL-31) keep eczema skin inflamed and itchy."},{"from":"m_skin_barrier","to":"atopic_eczema","level":"established","effect":"helps","note":"A leaky skin barrier is one of the two roots of eczema."},{"from":"m_skin_barrier","to":"contact_dermatitis","level":"established","effect":"helps","note":"An intact skin barrier keeps irritants and contact allergens out; a damaged one lets them in."},{"from":"m_airway_barrier","to":"allergic_asthma","level":"established","effect":"helps","note":"A sealed, well-cleared airway lining keeps allergens away from immune cells."},{"from":"m_late_phase","to":"allergic_rhinitis","level":"established","effect":"helps","note":"The late phase causes the blocked nose that lasts hours after pollen exposure."},{"from":"wi_wet_work","to":"m_skin_barrier","level":"established","effect":"harms","note":"Repeated wetting, soap and detergents strip the skin fats that seal the barrier."},{"from":"tx_tobacco","to":"m_airway_barrier","level":"established","effect":"harms","note":"Smoke damages the airway lining and its cleaning hairs (cilia)."},{"from":"hm_cortisol","to":"m_type2","level":"established","effect":"helps","note":"The body's own cortisol damps allergic inflammation; steroid medicines copy this effect."},{"from":"h_anti_ige","to":"m_mast_cells","level":"established","effect":"helps","note":"Mopping up IgE leaves mast cells and basophils with fewer armed receptors, so they fire less."},{"from":"h_anti_il4r","to":"m_type2","level":"established","effect":"helps","note":"Blocks the receptor for IL-4 and IL-13, the main type-2 signals."},{"from":"tx_diesel","to":"m_ige_sensitisation","level":"lab","effect":"harms","note":"In small nose-challenge experiments in volunteers, diesel particles boosted allergy IgE and even started a new IgE allergy; real-world effects are less certain.","sources":[{"id":"pmid:9036991","citation":"Diaz-Sanchez D et al., J Immunol","year":1997,"design":"lab","finding":"Nasal challenge with diesel exhaust particles plus ragweed raised ragweed-specific IgE and type-2 cytokines far more than ragweed alone in sensitised volunteers."},{"id":"pmid:10588999","citation":"Diaz-Sanchez D et al., J Allergy Clin Immunol","year":1999,"design":"lab","finding":"9 of 15 atopic volunteers given diesel particles before a new protein (KLH) made IgE against it, versus none of 10 given KLH alone."}]},{"from":"gb_gastric_residents","to":"s_stomach","level":"established","effect":"helps","note":"These bacteria live in the stomach's mucus; part of the stomach's normal defences."},{"from":"h_ppi","to":"gb_gastric_residents","level":"association","effect":"harms","note":"With less acid, the stomach and upper gut community changes and more mouth bacteria survive the journey down.","sources":[{"id":"pmid:26657899","citation":"Imhann et al., Gut","year":2016,"design":"cohort","finding":"Proton pump inhibitor users showed a clear shift in gut microbiome composition, including more oral and Streptococcaceae bacteria."}]},{"from":"fermented","to":"gb_lacto_plantarum","level":"established","effect":"contains","note":"Sauerkraut and kimchi are fermented by this bacterium."},{"from":"fermented","to":"gb_lacto_casei","level":"established","effect":"contains","note":"Found in cheese and fermented milk drinks."},{"from":"dairy","to":"gb_lacto_acidophilus","level":"established","effect":"contains","note":"Added to many live yoghurts."},{"from":"probiotics","to":"gb_lacto_rhamnosus","level":"established","effect":"helps","note":"One of the most used probiotic species."},{"from":"probiotics","to":"gb_lacto_reuteri","level":"established","effect":"helps","note":"A common ingredient of probiotic products."},{"from":"probiotics","to":"gb_bifido_breve","level":"established","effect":"helps","note":"A common ingredient of infant and adult probiotic products."},{"from":"gb_lacto_acidophilus","to":"m_micro","level":"established","effect":"helps","note":"Its lactate is turned into butyrate by colon bacteria further down."},{"from":"gb_lacto_plantarum","to":"m_micro","level":"established","effect":"helps","note":"Makes lactate that colon bacteria convert to short-chain fatty acids."},{"from":"gb_lacto_reuteri","to":"m_micro","level":"established","effect":"helps","note":"Makes lactate for the butyrate makers downstream."},{"from":"gb_lacto_casei","to":"m_micro","level":"established","effect":"helps","note":"Makes lactate for the butyrate makers downstream."},{"from":"gb_bifido_infantis","to":"m_micro","level":"established","effect":"helps","note":"Makes acetate and lactate from milk sugars."},{"from":"gb_bifido_breve","to":"m_micro","level":"established","effect":"helps","note":"Makes acetate and lactate."},{"from":"gb_bifido_bifidum","to":"m_micro","level":"established","effect":"helps","note":"Shares mucus and milk sugars with other short-chain fatty acid makers."},{"from":"gb_small_intestine_community","to":"s_small_intestine","level":"established","effect":"helps","note":"This is where these bacteria live; a normal, sparse community kept in check by acid, bile and movement."},{"from":"gb_lacto_gasseri","to":"m_micro","level":"established","effect":"helps","note":"Makes lactic acid, which lowers the local pH."},{"from":"hav","to":"s_liver","level":"established","effect":"harms","note":"Hepatitis A infects and inflames liver cells for a few weeks."},{"from":"hav","to":"d_jaundice","level":"established","effect":"harms","note":"Hepatitis A often turns the skin and eyes yellow, especially in adults."},{"from":"hav","to":"nausea","level":"established","effect":"harms","note":"Nausea, vomiting and loss of appetite are early signs of hepatitis A."},{"from":"hdv","to":"s_liver","level":"established","effect":"harms","note":"Hepatitis D adds to hepatitis B's damage to liver cells."},{"from":"hdv","to":"cirrhosis","level":"established","effect":"harms","note":"Hepatitis D with hepatitis B scars the liver into cirrhosis faster than hepatitis B alone."},{"from":"hev","to":"s_liver","level":"established","effect":"harms","note":"Hepatitis E infects and inflames liver cells."},{"from":"hev","to":"d_jaundice","level":"established","effect":"harms","note":"Hepatitis E often causes jaundice."},{"from":"hev","to":"pregnancy","level":"established","effect":"harms","note":"Hepatitis E caught late in pregnancy can cause liver failure in the mother and loss of the baby."},{"from":"sx_kidney_transplant","to":"hev","level":"established","effect":"harms","note":"On anti-rejection drugs, hepatitis E can become a long-lasting liver infection."},{"from":"hsv2","to":"s_reproductive","level":"established","effect":"harms","note":"Herpes simplex 2 causes painful blisters and sores on the genitals."},{"from":"hsv2","to":"n_spinal_roots","level":"established","effect":"harms","note":"After the first outbreak the virus sleeps in the sacral nerve roots and can reactivate."},{"from":"hsv2","to":"pain","level":"established","effect":"harms","note":"Genital herpes outbreaks are painful, often with burning or tingling first."},{"from":"hhv8","to":"kaposi_sarcoma","level":"established","effect":"harms","note":"Human herpesvirus 8 is the necessary cause of Kaposi sarcoma."},{"from":"hiv","to":"kaposi_sarcoma","level":"established","effect":"harms","note":"Untreated HIV lets human herpesvirus 8 cause Kaposi sarcoma."},{"from":"hiv","to":"hhv8","level":"established","effect":"harms","note":"Weakened immunity from HIV lets human herpesvirus 8 become active."},{"from":"htlv1","to":"lymphoma","level":"established","effect":"harms","note":"A small share of HTLV-1 carriers develop adult T-cell leukaemia/lymphoma decades later."},{"from":"htlv1","to":"s_spinal","level":"established","effect":"harms","note":"HTLV-1 can cause slow inflammation of the spinal cord, leading to stiff, weak legs."},{"from":"hpv_high_risk","to":"cervical_cancer","level":"established","effect":"harms","note":"Long-lasting high-risk HPV infection causes nearly all cervical cancers."},{"from":"hpv_high_risk","to":"anal_cancer","level":"established","effect":"harms","note":"Long-lasting high-risk HPV infection causes most anal cancers."},{"from":"hpv_high_risk","to":"head_neck_cancer","level":"established","effect":"harms","note":"HPV 16 causes a growing share of throat (oropharyngeal) cancers."},{"from":"hpv_high_risk","to":"s_cervix","level":"established","effect":"harms","note":"High-risk HPV infects the cells of the cervix where precancer starts."},{"from":"hpv_high_risk","to":"s_rectum_anus","level":"established","effect":"harms","note":"High-risk HPV infects the lining of the anal canal."},{"from":"hpv_low_risk","to":"s_skin","level":"established","effect":"harms","note":"Low-risk HPV types cause common, plantar and genital warts on the skin."},{"from":"hpv_low_risk","to":"s_larynx","level":"established","effect":"harms","note":"HPV 6 and 11 can cause wart-like growths in the voice box (recurrent respiratory papillomatosis)."},{"from":"cervical_cancer","to":"s_cervix","level":"established","effect":"affects","note":"Cervical cancer starts in the lining of the cervix."},{"from":"anal_cancer","to":"s_rectum_anus","level":"established","effect":"affects","note":"Anal cancer grows in the lining of the anal canal."},{"from":"kaposi_sarcoma","to":"s_skin","level":"established","effect":"affects","note":"Kaposi sarcoma shows as purple-brown patches or lumps on the skin."},{"from":"kaposi_sarcoma","to":"s_lymph","level":"established","effect":"affects","note":"Kaposi sarcoma can spread to lymph nodes and lymph vessels."},{"from":"h_hpv_vaccine","to":"hpv_high_risk","level":"proven","effect":"helps","note":"In trials, HPV vaccination prevents precancer of the cervix caused by high-risk types.","sources":[{"id":"pmid:41276263","citation":"Bergman H et al., Cochrane Database Syst Rev","year":2025,"design":"meta-analysis","finding":"In randomised trials, HPV vaccination reduced cervical precancer (CIN2+) and anogenital warts; the trials had no cancer outcome data."}]},{"from":"h_hpv_vaccine","to":"hpv_low_risk","level":"proven","effect":"helps","note":"Vaccines covering HPV 6 and 11 prevent genital warts in trials.","sources":[{"id":"pmid:41276263","citation":"Bergman H et al., Cochrane Database Syst Rev","year":2025,"design":"meta-analysis","finding":"In randomised trials, HPV vaccination reduced cervical precancer (CIN2+) and anogenital warts; the trials had no cancer outcome data."}]},{"from":"h_hpv_vaccine","to":"cervical_cancer","level":"association","effect":"helps","note":"Countries that vaccinate girls early see much less cervical cancer; trials were too short to count cancers.","sources":[{"id":"pmid:41276264","citation":"Henschke N et al., Cochrane Database Syst Rev","year":2025,"design":"review","finding":"Long-term population data from several countries consistently show less high-grade cervical precancer and cervical cancer in females vaccinated in early adolescence."}]},{"from":"h_hepb_vaccine","to":"hbv","level":"proven","effect":"helps","note":"Hepatitis B vaccination prevents infection in randomised trials.","sources":[{"id":"pmid:16235273","citation":"Chen W, Gluud C, Cochrane Database Syst Rev","year":2005,"design":"meta-analysis","finding":"In randomised trials in health-care workers, plasma-derived hepatitis B vaccine significantly prevented hepatitis B infection events."}]},{"from":"h_hepb_vaccine","to":"liver_cancer","level":"association","effect":"helps","note":"People vaccinated as babies in Taiwan have far less liver cancer as young adults.","sources":[{"id":"pmid:27269245","citation":"Chang MH et al., Gastroenterology","year":2016,"design":"cohort","finding":"In Taiwan, people vaccinated against hepatitis B as infants had much lower liver cancer rates as children and young adults than unvaccinated birth cohorts."}]},{"from":"h_hepb_vaccine","to":"hdv","level":"established","effect":"helps","note":"Hepatitis D cannot infect without hepatitis B, so preventing hepatitis B also prevents hepatitis D."},{"from":"h_hepa_vaccine","to":"hav","level":"proven","effect":"helps","note":"One dose prevented clinical hepatitis A in a placebo-controlled trial.","sources":[{"id":"pmid:1320740","citation":"Werzberger A et al., N Engl J Med","year":1992,"design":"RCT","finding":"In a placebo-controlled trial in children, one dose of inactivated hepatitis A vaccine prevented all clinically apparent hepatitis A from day 50 on."}]},{"from":"h_condoms","to":"hiv","level":"association","effect":"helps","note":"Consistent condom use was linked with about 80% less HIV infection in couples studies.","sources":[{"id":"pmid:11869658","citation":"Weller S, Davis K, Cochrane Database Syst Rev","year":2002,"design":"meta-analysis","finding":"In observational cohorts of couples where one partner had HIV, consistent condom use was linked with about 80% less HIV infection."}]},{"from":"h_condoms","to":"hsv2","level":"association","effect":"helps","note":"Condoms were linked with less genital herpes, but protection is partial.","sources":[{"id":"pmid:15356939","citation":"Holmes KK et al., Bull World Health Organ","year":2004,"design":"review","finding":"Consistent condom use was associated with less gonorrhoea, chlamydia, genital herpes, syphilis and trichomoniasis; partial protection still substantially reduces spread."}]},{"from":"h_prep","to":"hiv","level":"proven","effect":"helps","note":"Taking anti-HIV medicine before exposure prevented most new HIV infections in trials.","sources":[{"id":"pmid:22784037","citation":"Baeten JM et al., N Engl J Med","year":2012,"design":"RCT","finding":"Daily oral antiretroviral pills taken by HIV-negative partners (PrEP) cut new HIV infections by about two-thirds or more versus placebo."}]},{"from":"greens","to":"gb_rothia","level":"established","effect":"helps","note":"Leafy greens supply the nitrate these tongue bacteria use."},{"from":"nitrate","to":"gb_rothia","level":"established","effect":"helps","note":"Dietary nitrate is the substance it reduces to nitrite."},{"from":"nitrate","to":"gb_neisseria_commensal","level":"established","effect":"helps","note":"Dietary nitrate is the substance it reduces to nitrite."},{"from":"gb_rothia","to":"m_bp","level":"established","effect":"helps","note":"It does the first step, nitrate to nitrite; whether that lowers blood pressure is graded mixed on the mouth nitrate-reducers node."},{"from":"gb_neisseria_commensal","to":"m_bp","level":"established","effect":"helps","note":"Also turns nitrate into nitrite, the step before nitric oxide."},{"from":"tx_tobacco","to":"gb_neisseria_commensal","level":"association","effect":"harms","note":"Smokers' mouths carry fewer of these oxygen-using bacteria.","sources":[{"id":"pmid:27015003","citation":"Wu et al., ISME Journal","year":2016,"design":"cohort","finding":"Current smokers had depleted Proteobacteria, including Neisseria, and enriched Streptococcus in the oral microbiome; former smokers resembled never-smokers."}]},{"from":"gb_rothia","to":"periodontitis","level":"lab","effect":"helps","note":"Adding nitrate and a nitrate-reducing Rothia strain to plaque from gum-disease patients shifted it towards a healthier mix in the laboratory.","sources":[{"id":"pmid:37330520","citation":"Mazurel et al., npj Biofilms and Microbiomes","year":2023,"design":"lab","finding":"Nitrate, alone and with a nitrate-reducing Rothia aeria strain, reduced biofilm mass and shifted subgingival biofilms from periodontitis patients towards a health-associated composition."}]},{"from":"gb_veillonella_oral","to":"m_micro","level":"established","effect":"helps","note":"Turns lactate into propionate instead of letting acid build up."},{"from":"gb_strep_oralis","to":"bb_strep_mutans","level":"lab","effect":"helps","note":"The hydrogen peroxide these commensals make held back S. mutans and Candida on a laboratory tooth surface.","sources":[{"id":"pmid:42159380","citation":"Shao et al., Applied and Environmental Microbiology","year":2026,"design":"lab","finding":"Hydrogen-peroxide-producing commensal Streptococcus oralis strains disrupted Streptococcus mutans and Candida albicans synergism on saliva-coated hydroxyapatite discs."}]},{"from":"gb_strep_oralis","to":"caries","level":"lab","effect":"helps","note":"A plaque dominated by these peroxide makers is less acid-forming in laboratory models.","sources":[{"id":"pmid:42159380","citation":"Shao et al., Applied and Environmental Microbiology","year":2026,"design":"lab","finding":"Commensal streptococci antagonised the cariogenic S. mutans-C. albicans biofilm."}]},{"from":"sugar","to":"bb_strep_mutans","level":"established","effect":"harms","note":"Sugar is what this bacterium turns into tooth-dissolving acid and sticky plaque glue."},{"from":"bb_strep_mutans","to":"caries","level":"established","effect":"harms","note":"Its acid dissolves enamel; children who share its strains more are more likely to have cavities.","sources":[{"id":"pmid:33662253","citation":"Manchanda et al., Pediatric Dentistry","year":2021,"design":"meta-analysis","finding":"Pooled observational studies showed horizontal transmission of S. mutans between young children, with caries-free children less likely to share genotypes."}]},{"from":"bb_tannerella","to":"periodontitis","level":"association","effect":"harms","note":"One of the three red-complex bacteria found together in deep, bleeding gum pockets.","sources":[{"id":"pmid:15853938","citation":"Holt & Ebersole, Periodontology 2000","year":2005,"design":"review","finding":"Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia form the red complex consistently associated with destructive periodontal disease."}]},{"from":"bb_tdenticola","to":"periodontitis","level":"association","effect":"harms","note":"The third red-complex bacterium; it breaks down proteins in the inflamed gum pocket.","sources":[{"id":"pmid:15853938","citation":"Holt & Ebersole, Periodontology 2000","year":2005,"design":"review","finding":"The red complex, including Treponema denticola, is a prototype polybacterial community associated with periodontitis."}]},{"from":"bb_aggregatibacter","to":"periodontitis","level":"association","effect":"harms","note":"Its white-cell toxin is linked with the rapid bone loss of aggressive gum disease in young people.","sources":[{"id":"pmid:28879247","citation":"Burgess et al., JDR Clinical and Translational Research","year":2017,"design":"case-control","finding":"83 percent of young people with localised aggressive periodontitis carried the highly leukotoxic JP2 sequence of A. actinomycetemcomitans."}]},{"from":"bb_prevotella_intermedia","to":"gingivitis","level":"association","effect":"harms","note":"Becomes prominent in inflamed, bleeding gums, including gum swelling in pregnancy.","sources":[{"id":"pmid:15853938","citation":"Holt & Ebersole, Periodontology 2000","year":2005,"design":"review","finding":"Prevotella intermedia is part of the orange complex that precedes and accompanies red-complex periodontal disease."}]},{"from":"gb_strep_salivarius","to":"s_tongue","level":"established","effect":"helps","note":"A dominant, harmless resident of the tongue and saliva from the first days of life."},{"from":"gb_coryne_matruchotii","to":"s_mouth","level":"established","effect":"helps","note":"Forms the scaffold that ordinary, stable dental plaque is built on."},{"from":"gb_dolosigranulum","to":"bb_spneumo","level":"lab","effect":"helps","note":"Grown together with pneumococcus in the laboratory, it slowed its growth, and did so more strongly alongside nose Corynebacterium.","sources":[{"id":"pmid:40445193","citation":"Cisneros et al., Microbiology Spectrum","year":2025,"design":"lab","finding":"Dolosigranulum pigrum and Corynebacterium pseudodiphtheriticum inhibited Streptococcus pneumoniae growth in co-culture, synergistically when combined."}]},{"from":"gb_coryne_nose","to":"bb_spneumo","level":"lab","effect":"helps","note":"Slowed pneumococcal growth in co-culture, most of all together with Dolosigranulum.","sources":[{"id":"pmid:40445193","citation":"Cisneros et al., Microbiology Spectrum","year":2025,"design":"lab","finding":"C. pseudodiphtheriticum inhibited pneumococcal growth in vitro, synergistically with D. pigrum."}]},{"from":"gb_dolosigranulum","to":"s_nose","level":"association","effect":"helps","note":"Babies whose nose community was dominated by these harmless bacteria had fewer respiratory infections in their first year.","sources":[{"id":"pmid:28665684","citation":"Bosch et al., American Journal of Respiratory and Critical Care Medicine","year":2017,"design":"cohort","finding":"Infant nasopharyngeal profiles dominated by Corynebacterium and Dolosigranulum were associated with fewer respiratory tract infections, while Moraxella and Haemophilus profiles went with more."}]},{"from":"gb_coryne_nose","to":"s_nose","level":"association","effect":"helps","note":"Part of the same commensal-dominated nose profile that went with fewer infant respiratory infections.","sources":[{"id":"pmid:28665684","citation":"Bosch et al., American Journal of Respiratory and Critical Care Medicine","year":2017,"design":"cohort","finding":"Corynebacterium and Dolosigranulum dominated profiles were associated with respiratory health in infancy."}]},{"from":"bb_spneumo","to":"otitis_media","level":"established","effect":"harms","note":"One of the three nose bacteria behind most middle-ear infections; it has to be carried before it can cause one."},{"from":"bb_spneumo","to":"s_throat","level":"established","effect":"harms","note":"The nose and throat are where it is carried, usually without symptoms."},{"from":"bb_moraxella","to":"otitis_media","level":"established","effect":"harms","note":"A standard cause of middle-ear infection in young children."},{"from":"bb_hinfluenzae","to":"otitis_media","level":"established","effect":"harms","note":"A standard cause of middle-ear and sinus infection; the Hib vaccine does not cover this type."},{"from":"bb_hinfluenzae","to":"copd","level":"established","effect":"harms","note":"It settles in damaged airways and is a common trigger of flare-ups."},{"from":"bb_moraxella","to":"copd","level":"established","effect":"harms","note":"Another common trigger of flare-ups in long-standing lung disease."},{"from":"gb_throat_commensals","to":"strep","level":"established","effect":"helps","note":"These harmless streptococci occupy the throat surface that group A strep would need."},{"from":"gb_lung_commensals","to":"s_lungs","level":"established","effect":"helps","note":"Healthy airways carry a thin community breathed down from the mouth and cleared again."},{"from":"gb_lung_commensals","to":"m_inflam","level":"association","effect":"harms","note":"When mouth bacteria build up in the lower airway, inflammatory cells there rise with them.","sources":[{"id":"pmid:24450871","citation":"Segal et al., Microbiome","year":2013,"design":"cohort","finding":"Lungs enriched with supraglottic (oral) taxa such as Prevotella and Veillonella showed increased lymphocyte and neutrophil inflammation."}]},{"from":"bb_pseudomonas","to":"s_lungs","level":"established","effect":"harms","note":"Settles permanently in airways already damaged by cystic fibrosis or bronchiectasis."},{"from":"bb_pseudomonas","to":"copd","level":"established","effect":"harms","note":"Chronic carriage in damaged airways goes with more frequent flare-ups."},{"from":"gb_conjunctival_residents","to":"s_eyes","level":"lab","effect":"helps","note":"An eye-surface commensal kept protective immune cells on standby in the mouse eye, which helped it resist infection.","sources":[{"id":"pmid:28709803","citation":"St Leger et al., Immunity","year":2017,"design":"lab","finding":"Corynebacterium mastitidis on the ocular surface drove an interleukin-17 response from mucosal gamma-delta T cells that protected mice against corneal infection."}]},{"from":"gb_cutibacterium","to":"s_skin","level":"established","effect":"helps","note":"The main resident of healthy oily skin, living on sebum inside hair follicles."},{"from":"gb_cutibacterium","to":"bb_staph_aureus","level":"established","effect":"helps","note":"The propionic acid it makes keeps the skin surface acidic, which Staphylococcus aureus does not like."},{"from":"gb_cutibacterium","to":"acne","level":"association","effect":"harms","note":"The facial community differs between adolescents with and without acne, but everyone carries this bacterium, so it is not a simple cause.","sources":[{"id":"pmid:41370181","citation":"Witkam et al., British Journal of Dermatology","year":2026,"design":"cohort","finding":"In 399 adolescents with physician-diagnosed acne and 527 controls, facial bacterial microbiota composition differed significantly between groups after adjustment for confounders."}]},{"from":"gb_staph_epidermidis","to":"s_skin","level":"established","effect":"helps","note":"The commonest bacterium on human skin."},{"from":"gb_staph_epidermidis","to":"bb_staph_aureus","level":"lab","effect":"helps","note":"Makes substances that interfere with Staphylococcus aureus on the skin surface.","sources":[{"id":"pmid:28228596","citation":"Nakatsuji et al., Science Translational Medicine","year":2017,"design":"lab","finding":"Antimicrobial peptides from commensal Staphylococcus epidermidis and S. hominis killed S. aureus and were deficient on the skin of people with atopic dermatitis."}]},{"from":"gb_staph_hominis","to":"bb_staph_aureus","level":"lab","effect":"helps","note":"Some strains make small molecules that specifically block Staphylococcus aureus.","sources":[{"id":"pmid:28228596","citation":"Nakatsuji et al., Science Translational Medicine","year":2017,"design":"lab","finding":"S. hominis strains producing antimicrobial peptides killed S. aureus; applying them to human skin reduced S. aureus."}]},{"from":"gb_staph_hominis","to":"atopic_eczema","level":"lab","effect":"helps","note":"People with eczema carry fewer of the strains that make these antibacterials; putting them back on the skin lowered Staphylococcus aureus in a small study.","sources":[{"id":"pmid:28228596","citation":"Nakatsuji et al., Science Translational Medicine","year":2017,"design":"lab","finding":"Commensal antimicrobial peptides were deficient in atopic dermatitis, and autologous commensal application decreased S. aureus colonisation."}]},{"from":"bb_staph_aureus","to":"atopic_eczema","level":"association","effect":"harms","note":"The more heavily the skin is colonised, the worse the eczema tends to be; treating the eczema usually reduces the bacterium too.","sources":[{"id":"pmid:42183252","citation":"Jin et al., Frontiers in Immunology","year":2026,"design":"meta-analysis","finding":"Pooling seven randomised controlled trials with 929 participants found a moderate positive correlation between S. aureus colonisation and atopic dermatitis severity."}]},{"from":"bb_staph_aureus","to":"s_skin","level":"established","effect":"harms","note":"The main cause of boils, infected cuts and infected eczema."},{"from":"gb_coryne_skin","to":"s_skin","level":"established","effect":"helps","note":"A normal resident of the armpit and other moist folds."},{"from":"gb_skin_dry","to":"s_skin","level":"established","effect":"helps","note":"The thin, changeable community of dry skin on the forearms and palms."},{"from":"bb_malassezia","to":"seborrhoeic_dermatitis","level":"association","effect":"harms","note":"Found at higher levels on affected scalp than on healthy scalp; everyone carries it, so susceptibility matters as much as the yeast.","sources":[{"id":"pmid:41591389","citation":"Gupta et al., Medical Mycology","year":2026,"design":"case-control","finding":"In 60 patients with scalp seborrhoeic dermatitis and 30 healthy controls, Malassezia and Staphylococcus were associated with lesional scalp sites."}]},{"from":"bb_candida","to":"s_mouth","level":"established","effect":"harms","note":"Overgrowth on the tongue and palate is oral thrush, most often after antibiotics, inhaled steroids or with a dry mouth."},{"from":"bb_candida","to":"s_vagina","level":"established","effect":"harms","note":"Overgrowth in the vagina is thrush, with itching and a thick discharge."},{"from":"flu_b","to":"s_airways","level":"established","effect":"harms","note":"Influenza B infects and inflames the lining of the airways."},{"from":"flu_b","to":"d_fever","level":"established","effect":"harms","note":"Influenza B usually causes sudden fever and aches."},{"from":"flu_b","to":"pneumonia_infection","level":"established","effect":"harms","note":"Flu can lead to viral pneumonia or a bacterial pneumonia on top."},{"from":"flu","to":"pneumonia_infection","level":"established","effect":"harms","note":"Influenza A can cause viral pneumonia or open the way for a bacterial one."},{"from":"flu","to":"d_fever","level":"established","effect":"harms","note":"Influenza A usually causes sudden fever and aches."},{"from":"sarscov2","to":"pneumonia_infection","level":"established","effect":"harms","note":"SARS-CoV-2 can infect the air sacs and cause COVID pneumonia."},{"from":"rsv","to":"s_airways","level":"established","effect":"harms","note":"RSV infects the smallest airways, which swell and clog with mucus."},{"from":"rsv","to":"wheeze","level":"established","effect":"harms","note":"RSV bronchiolitis causes wheeze and fast breathing in babies."},{"from":"rsv","to":"pneumonia_infection","level":"established","effect":"harms","note":"RSV causes pneumonia in babies and older adults."},{"from":"rhinovirus","to":"s_nose","level":"established","effect":"harms","note":"Rhinovirus infects the lining of the nose, causing a runny, blocked nose."},{"from":"rhinovirus","to":"d_sore_throat","level":"established","effect":"harms","note":"Colds often start with a scratchy sore throat."},{"from":"rhinovirus","to":"allergic_asthma","level":"established","effect":"harms","note":"Cold viruses, rhinovirus most of all, are the commonest trigger of asthma attacks."},{"from":"adenovirus","to":"s_throat","level":"established","effect":"harms","note":"Adenovirus causes sore throat with fever."},{"from":"adenovirus","to":"s_eyes","level":"established","effect":"harms","note":"Some adenovirus types cause conjunctivitis (pink eye)."},{"from":"adenovirus","to":"d_diarrhoea","level":"established","effect":"harms","note":"Some adenovirus types cause diarrhoea in young children."},{"from":"parainfluenza","to":"s_larynx","level":"established","effect":"harms","note":"Parainfluenza swells the voice box and windpipe, causing croup."},{"from":"parainfluenza","to":"d_cough","level":"established","effect":"harms","note":"Croup causes a barking cough in young children."},{"from":"hmpv","to":"s_airways","level":"established","effect":"harms","note":"Human metapneumovirus infects the airways like RSV."},{"from":"hmpv","to":"wheeze","level":"established","effect":"harms","note":"hMPV can cause bronchiolitis with wheeze."},{"from":"seasonal_cov","to":"s_nose","level":"established","effect":"harms","note":"Common-cold coronaviruses infect the lining of the nose and throat."},{"from":"norovirus","to":"gastroenteritis","level":"established","effect":"harms","note":"Norovirus is the commonest cause of gastroenteritis."},{"from":"norovirus","to":"nausea","level":"established","effect":"harms","note":"Norovirus causes sudden, forceful vomiting."},{"from":"norovirus","to":"d_diarrhoea","level":"established","effect":"harms","note":"Norovirus causes watery diarrhoea for a few days."},{"from":"rotavirus","to":"s_small_intestine","level":"established","effect":"harms","note":"Rotavirus damages the lining cells of the small intestine."},{"from":"rotavirus","to":"gastroenteritis","level":"established","effect":"harms","note":"Rotavirus causes severe gastroenteritis in babies and young children."},{"from":"rotavirus","to":"d_diarrhoea","level":"established","effect":"harms","note":"Rotavirus causes watery diarrhoea that can dehydrate a child fast."},{"from":"astrovirus","to":"gastroenteritis","level":"established","effect":"harms","note":"Astrovirus causes milder gastroenteritis in children and older people."},{"from":"gastroenteritis","to":"s_gut","level":"established","effect":"affects","note":"Gastroenteritis inflames the lining of the stomach and intestine."},{"from":"gastroenteritis","to":"d_diarrhoea","level":"established","effect":"harms","note":"Gastroenteritis causes diarrhoea."},{"from":"gastroenteritis","to":"nausea","level":"established","effect":"harms","note":"Gastroenteritis causes nausea and vomiting."},{"from":"pneumonia_infection","to":"s_alveoli","level":"established","effect":"affects","note":"Pneumonia fills the air sacs with fluid and pus."},{"from":"pneumonia_infection","to":"d_cough","level":"established","effect":"harms","note":"Pneumonia causes cough, often with phlegm."},{"from":"pneumonia_infection","to":"breathless","level":"established","effect":"harms","note":"Pneumonia makes breathing fast and hard."},{"from":"pneumonia_infection","to":"d_fever","level":"established","effect":"harms","note":"Pneumonia usually causes fever and chills."},{"from":"h_flu_vaccine","to":"flu","level":"proven","effect":"helps","note":"In trials, flu vaccines cut confirmed influenza in healthy adults by more than half; protection in older adults is less certain.","sources":[{"id":"pmid:29388196","citation":"Demicheli V et al., Cochrane Database Syst Rev","year":2018,"design":"meta-analysis","finding":"In randomised trials in healthy adults, inactivated flu vaccines probably reduce laboratory-confirmed influenza from about 2.3% to 0.9% in a season."}]},{"from":"h_flu_vaccine","to":"flu_b","level":"proven","effect":"helps","note":"Seasonal flu vaccines include influenza B strains and reduce confirmed flu in trials.","sources":[{"id":"pmid:29388196","citation":"Demicheli V et al., Cochrane Database Syst Rev","year":2018,"design":"meta-analysis","finding":"In randomised trials in healthy adults, inactivated flu vaccines probably reduce laboratory-confirmed influenza from about 2.3% to 0.9% in a season."}]},{"from":"h_covid_vaccine","to":"sarscov2","level":"proven","effect":"helps","note":"COVID-19 vaccines prevented most symptomatic COVID-19 in placebo-controlled trials.","sources":[{"id":"pmid:33301246","citation":"Polack FP et al., N Engl J Med","year":2020,"design":"RCT","finding":"Two doses of the BNT162b2 mRNA vaccine gave 95% protection against symptomatic COVID-19 versus placebo, with fewer severe cases."}]},{"from":"h_rsv_vaccine","to":"rsv","level":"proven","effect":"helps","note":"RSV vaccines prevented RSV lung infection in older adults and in babies of vaccinated mothers.","sources":[{"id":"pmid:36791160","citation":"Papi A et al., N Engl J Med","year":2023,"design":"RCT","finding":"One dose of an RSV prefusion F vaccine prevented RSV lower respiratory tract disease, including severe disease, in adults aged 60 or older."},{"id":"pmid:37018474","citation":"Kampmann B et al., N Engl J Med","year":2023,"design":"RCT","finding":"RSV vaccination during pregnancy protected infants against medically attended severe RSV lower respiratory tract illness."}]},{"from":"h_rota_vaccine","to":"rotavirus","level":"proven","effect":"helps","note":"Rotavirus vaccines prevent rotavirus diarrhoea in babies in trials.","sources":[{"id":"pmid:34788488","citation":"Bergman H et al., Cochrane Database Syst Rev","year":2021,"design":"meta-analysis","finding":"Rotavirus vaccines in use prevent rotavirus diarrhoea in children in randomised trials, with no increase in serious adverse events."}]},{"from":"h_hand_washing","to":"gastroenteritis","level":"proven","effect":"helps","note":"Promoting hand washing cut diarrhoea episodes by about a third in trials.","sources":[{"id":"pmid:33539552","citation":"Ejemot-Nwadiaro RI et al., Cochrane Database Syst Rev","year":2021,"design":"meta-analysis","finding":"Hand-washing promotion probably reduces diarrhoea episodes by about 30% in child day-care centres and in low- and middle-income communities."},{"id":"pmid:36715243","citation":"Jefferson T et al., Cochrane Database Syst Rev","year":2023,"design":"meta-analysis","finding":"In randomised trials, hand hygiene is likely to modestly reduce respiratory illness."}]},{"from":"h_safe_water","to":"gastroenteritis","level":"proven","effect":"helps","note":"Household water filters and disinfection reduced diarrhoea in trials.","sources":[{"id":"pmid:26488938","citation":"Clasen TF et al., Cochrane Database Syst Rev","year":2015,"design":"meta-analysis","finding":"In mostly cluster-randomised trials, household water filters and disinfection reduced diarrhoea (filters by about half), though most trials were not blinded."}]},{"from":"h_safe_water","to":"hev","level":"established","effect":"helps","note":"Hepatitis E outbreaks spread through stool-contaminated drinking water, so safe water prevents them."},{"from":"h_safe_water","to":"hav","level":"established","effect":"helps","note":"Hepatitis A spreads through contaminated water and food, so safe water lowers the risk."},{"from":"bb_rumino_gnavus","to":"crohns","level":"association","effect":"harms","note":"A particular branch of this bacterium is enriched during flares of inflammatory bowel disease.","sources":[{"id":"pmid:29183332","citation":"Hall et al., Genome Medicine","year":2017,"design":"cohort","finding":"A novel Ruminococcus gnavus clade was enriched in patients with inflammatory bowel disease and expanded during disease flares."}]},{"from":"bb_rumino_gnavus","to":"m_inflam","level":"association","effect":"harms","note":"It blooms when the bowel is inflamed and its sugar polymer provokes inflammatory signals.","sources":[{"id":"pmid:29183332","citation":"Hall et al., Genome Medicine","year":2017,"design":"cohort","finding":"R. gnavus expansion tracked inflammatory bowel disease activity."}]},{"from":"redmeat","to":"bb_bilophila","level":"lab","effect":"harms","note":"Animal fat means more bile, and the taurine in bile is this bacterium's food; shown with high-fat diets in mice.","sources":[{"id":"pmid:30022049","citation":"Natividad et al., Nature Communications","year":2018,"design":"lab","finding":"Bilophila wadsworthia expanded on and aggravated high-fat-diet-induced metabolic dysfunction in mice."}]},{"from":"bb_bilophila","to":"m_barrier","level":"lab","effect":"harms","note":"The hydrogen sulfide it releases irritated the gut lining in mice.","sources":[{"id":"pmid:30022049","citation":"Natividad et al., Nature Communications","year":2018,"design":"lab","finding":"B. wadsworthia worsened intestinal barrier function and inflammation in high-fat-diet mice."}]},{"from":"bb_bilophila","to":"m_inflam","level":"lab","effect":"harms","note":"Added to gut and whole-body inflammation in mice on a fatty diet.","sources":[{"id":"pmid:30022049","citation":"Natividad et al., Nature Communications","year":2018,"design":"lab","finding":"B. wadsworthia aggravated inflammation and metabolic dysfunction in mice."}]},{"from":"bb_enterococcus","to":"uti","level":"established","effect":"harms","note":"A recognised cause of urine infections, especially after catheters or antibiotics."},{"from":"bb_sgallolyticus","to":"colorectal_cancer","level":"association","effect":"harms","note":"Found more often in people with bowel tumours, and sometimes the first clue to one; cause is not established.","sources":[{"id":"pmid:39703539","citation":"Warner & Mehta, Gut Microbiome","year":2024,"design":"review","finding":"Reviews the consistent association between Streptococcus gallolyticus subsp. gallolyticus infection and colorectal cancer and the proposed mechanisms."}]},{"from":"bb_ecoli_aiec","to":"crohns","level":"association","effect":"harms","note":"These strains are found more often in the bowel lining in Crohn's disease.","sources":[{"id":"pmid:42472818","citation":"Mohammed Abdelhadi et al., Gut Pathogens","year":2026,"design":"review","finding":"Reviews evidence that adherent-invasive E. coli is enriched in the ileal mucosa in Crohn's disease and strategies aimed at it."}]},{"from":"bb_ecoli_aiec","to":"m_barrier","level":"lab","effect":"harms","note":"These strains stick to and invade the cells of the gut lining in laboratory models.","sources":[{"id":"pmid:42472818","citation":"Mohammed Abdelhadi et al., Gut Pathogens","year":2026,"design":"review","finding":"AIEC adheres to and invades intestinal epithelial cells and survives in macrophages."}]},{"from":"h_antibiotics","to":"cdiff","level":"established","effect":"harms","note":"Clearing out the normal colon bacteria is what lets C. difficile take over; this link means antibiotics give it its opening."},{"from":"h_antibiotics","to":"bb_enterococcus","level":"established","effect":"harms","note":"Enterococci survive many antibiotics and expand into the space left behind."},{"from":"h_antibiotics","to":"bifido","level":"association","effect":"harms","note":"Bifidobacteria were among the groups still depleted months after a course in healthy adults.","sources":[{"id":"pmid:30349083","citation":"Palleja et al., Nature Microbiology","year":2018,"design":"cohort","finding":"After a four-day broad-spectrum antibiotic course in healthy men, the gut microbiota largely recovered by six months but several common species, including Bifidobacterium, remained missing."}]},{"from":"h_antibiotics","to":"faecali","level":"association","effect":"harms","note":"Butyrate makers are slow to come back after a course of antibiotics.","sources":[{"id":"pmid:30349083","citation":"Palleja et al., Nature Microbiology","year":2018,"design":"cohort","finding":"Butyrate-producing species were depleted and slow to recover after antibiotic exposure in healthy adults."}]},{"from":"h_antibiotics","to":"uti","level":"established","effect":"helps","note":"Antibiotics are the treatment for a bacterial urine infection."},{"from":"h_fmt","to":"cdiff","level":"proven","effect":"helps","note":"In a randomised trial, donor stool cured far more people with repeatedly returning C. difficile than antibiotics alone, and the trial was stopped early for that reason.","sources":[{"id":"pmid:23323867","citation":"van Nood et al., New England Journal of Medicine","year":2013,"design":"RCT","finding":"Duodenal infusion of donor faeces resolved recurrent Clostridium difficile infection in 81 percent of patients versus 31 percent with vancomycin alone; the trial was stopped early."}]},{"from":"h_breastfeeding","to":"bifido","level":"established","effect":"helps","note":"Human milk sugars are indigestible to the baby and feed bifidobacteria almost exclusively."},{"from":"sx_caesarean","to":"bifido","level":"association","effect":"harms","note":"Babies born by caesarean start out with fewer bifidobacteria; the gap narrows over the first year.","sources":[{"id":"pmid:31534227","citation":"Shao et al., Nature","year":2019,"design":"cohort","finding":"Caesarean-born newborns had reduced Bifidobacterium and Bacteroides and more opportunistic hospital-associated bacteria; differences largely resolved by the end of infancy."}]},{"from":"sx_caesarean","to":"bb_enterococcus","level":"association","effect":"harms","note":"Caesarean-born babies were more often colonised early by hospital-type bacteria including enterococci.","sources":[{"id":"pmid:31534227","citation":"Shao et al., Nature","year":2019,"design":"cohort","finding":"Caesarean birth was associated with colonisation by opportunistic pathogens including Enterococcus, Enterobacter and Klebsiella."}]},{"from":"tx_alcohol","to":"entero","level":"association","effect":"harms","note":"Heavy drinkers' colon samples carried more of these bacteria.","sources":[{"id":"pmid:22241860","citation":"Mutlu et al., American Journal of Physiology: Gastrointestinal and Liver Physiology","year":2012,"design":"case-control","finding":"Colonic mucosal microbiome in alcoholics showed dysbiosis with lower Bacteroidetes and higher Proteobacteria."}]},{"from":"tx_alcohol","to":"prevotella","level":"association","effect":"harms","note":"Heavy drinkers had less of the Bacteroidetes group, which Prevotella and Bacteroides belong to.","sources":[{"id":"pmid:22241860","citation":"Mutlu et al., American Journal of Physiology: Gastrointestinal and Liver Physiology","year":2012,"design":"case-control","finding":"A subset of alcoholics had reduced Bacteroidetes and increased Proteobacteria in colonic mucosal biopsies."}]},{"from":"gb_lacto_crispatus","to":"s_vagina","level":"established","effect":"helps","note":"Its lactic acid holds the vaginal pH low, which most other bacteria cannot tolerate."},{"from":"gb_lacto_crispatus","to":"bacterial_vaginosis","level":"association","effect":"helps","note":"Communities dominated by this species are the most stable and the least likely to tip into bacterial vaginosis.","sources":[{"id":"pmid:20534435","citation":"Ravel et al., Proceedings of the National Academy of Sciences","year":2011,"design":"cohort","finding":"Vaginal communities of reproductive-age women fell into five groups, four dominated by Lactobacillus species, with differing pH and stability."},{"id":"pmid:22553250","citation":"Gajer et al., Science Translational Medicine","year":2012,"design":"cohort","finding":"Sampling women twice weekly showed L. crispatus-dominated communities were comparatively stable while others changed rapidly."}]},{"from":"gb_lacto_crispatus","to":"bb_gardnerella","level":"established","effect":"helps","note":"A pH around four, kept there by its lactic acid, holds back Gardnerella and its partners."},{"from":"gb_lacto_iners","to":"s_vagina","level":"established","effect":"helps","note":"Also a lactic-acid maker, and the commonest vaginal lactobacillus, but a weaker guardian."},{"from":"gb_lacto_iners","to":"bacterial_vaginosis","level":"association","effect":"harms","note":"Compared with crispatus-dominated communities, iners-dominated ones more often tip into bacterial vaginosis.","sources":[{"id":"pmid:36729966","citation":"Carter et al., Sexually Transmitted Diseases","year":2023,"design":"meta-analysis","finding":"A series of systematic reviews and meta-analyses found L. iners-dominated vaginal microbiota associated with higher odds of bacterial vaginosis and several sexually transmitted infections than L. crispatus-dominated microbiota."}]},{"from":"gb_lacto_jensenii","to":"s_vagina","level":"established","effect":"helps","note":"Another lactic-acid maker of the vaginal community."},{"from":"bb_gardnerella","to":"bacterial_vaginosis","level":"established","effect":"harms","note":"The central bacterium of the condition, forming the film on the vaginal wall that others join."},{"from":"bb_fannyhessea","to":"bacterial_vaginosis","level":"association","effect":"harms","note":"Found with Gardnerella in the film, and its presence goes with the condition returning.","sources":[{"id":"pmid:20534435","citation":"Ravel et al., Proceedings of the National Academy of Sciences","year":2011,"design":"cohort","finding":"Communities low in Lactobacillus contained Atopobium, Prevotella and other anaerobes and had higher pH."}]},{"from":"bb_prevotella_bivia","to":"bacterial_vaginosis","level":"association","effect":"harms","note":"One of the mixed anaerobes that expand when lactobacilli thin out; it makes the amines behind the smell.","sources":[{"id":"pmid:20534435","citation":"Ravel et al., Proceedings of the National Academy of Sciences","year":2011,"design":"cohort","finding":"Prevotella was among the anaerobes characterising low-Lactobacillus, higher-pH vaginal communities."}]},{"from":"bb_gbs","to":"s_vagina","level":"established","effect":"harms","note":"Carried in the vagina and bowel of a large minority of women, usually with no symptoms at all."},{"from":"bb_gbs","to":"pregnancy","level":"established","effect":"harms","note":"It matters only around birth, when a baby can pick it up; pooled studies put carriage in pregnancy near one in five.","sources":[{"id":"pmid:42811015","citation":"Toh et al., Emerging Infectious Diseases","year":2026,"design":"meta-analysis","finding":"Pooled prevalence of group B streptococcus rectovaginal colonisation among 978,150 pregnant women in the Asia-Pacific region was 18 percent."}]},{"from":"gb_urinary_lacto","to":"s_bladder","level":"association","effect":"helps","note":"Lactobacilli were the commonest bacteria cultured straight from the bladder in women without urgency symptoms.","sources":[{"id":"pmid:25006228","citation":"Pearce et al., mBio","year":2014,"design":"case-control","finding":"Urine collected directly from the bladder contained a distinct microbiome; Lactobacillus was common in women without urgency urinary incontinence, while women with it carried a different mix."}]},{"from":"bb_upec","to":"uti","level":"established","effect":"harms","note":"These strains from a person's own bowel cause most urine infections."},{"from":"bb_staph_saprophyticus","to":"uti","level":"established","effect":"harms","note":"The second commonest cause of simple bladder infection in young women."},{"from":"bb_proteus","to":"uti","level":"established","effect":"harms","note":"Makes the urine alkaline, which is how struvite stones form; common with long-term catheters."},{"from":"mumps","to":"s_salivary_glands","level":"established","effect":"harms","note":"Mumps makes the salivary glands, mostly in front of the ears, swell painfully."},{"from":"mumps","to":"s_testes","level":"established","effect":"harms","note":"After puberty, mumps can inflame the testicles (orchitis)."},{"from":"mumps","to":"meningitis","level":"established","effect":"harms","note":"Mumps can cause a usually mild viral meningitis."},{"from":"rubella","to":"d_rash","level":"established","effect":"harms","note":"Rubella causes a pink rash that spreads from the face."},{"from":"rubella","to":"congenital_infection","level":"established","effect":"harms","note":"Rubella in early pregnancy can cause deafness, cataracts and heart defects in the baby."},{"from":"measles","to":"d_rash","level":"established","effect":"harms","note":"Measles causes a blotchy rash that starts behind the ears and spreads down."},{"from":"parvovirus_b19","to":"s_marrow","level":"established","effect":"harms","note":"Parvovirus B19 briefly stops the marrow making red blood cells."},{"from":"parvovirus_b19","to":"d_rash","level":"established","effect":"harms","note":"Parvovirus B19 causes bright red cheeks and a lacy rash in children."},{"from":"parvovirus_b19","to":"congenital_infection","level":"established","effect":"harms","note":"In pregnancy, parvovirus B19 can cause severe anaemia in the baby."},{"from":"poliovirus","to":"s_spinal","level":"established","effect":"harms","note":"Poliovirus destroys motor nerve cells in the spinal cord."},{"from":"poliovirus","to":"s_muscle","level":"established","effect":"harms","note":"Loss of those nerve cells leaves muscles paralysed and wasted."},{"from":"ev_d68","to":"s_spinal","level":"established","effect":"harms","note":"Enterovirus D68 can damage spinal cord motor cells, causing sudden limb weakness."},{"from":"ev_d68","to":"wheeze","level":"established","effect":"harms","note":"Enterovirus D68 causes colds with wheeze, worst in children with asthma."},{"from":"coxsackie","to":"s_mouth","level":"established","effect":"harms","note":"Coxsackie viruses cause painful mouth ulcers."},{"from":"coxsackie","to":"d_rash","level":"established","effect":"harms","note":"Hand, foot and mouth disease causes spots on the hands and feet."},{"from":"dengue","to":"s_blood","level":"established","effect":"harms","note":"Severe dengue makes blood vessels leak and platelets fall, risking bleeding."},{"from":"dengue","to":"d_fever","level":"established","effect":"harms","note":"Dengue causes sudden high fever."},{"from":"dengue","to":"pain","level":"established","effect":"harms","note":"Dengue causes severe muscle, bone and eye pain."},{"from":"chikungunya","to":"pain","level":"established","effect":"harms","note":"Chikungunya causes severe joint pain that can last months."},{"from":"chikungunya","to":"d_fever","level":"established","effect":"harms","note":"Chikungunya starts with sudden high fever."},{"from":"yellow_fever","to":"s_liver","level":"established","effect":"harms","note":"Severe yellow fever attacks the liver."},{"from":"yellow_fever","to":"d_jaundice","level":"established","effect":"harms","note":"Yellow fever is named for the jaundice it causes."},{"from":"jev","to":"encephalitis","level":"established","effect":"harms","note":"Japanese encephalitis virus inflames the brain in a small share of infections."},{"from":"jev","to":"s_bg","level":"established","effect":"harms","note":"Japanese encephalitis damages the thalamus and basal ganglia, which can leave movement problems."},{"from":"tbev","to":"encephalitis","level":"established","effect":"harms","note":"Tick-borne encephalitis virus can inflame the brain."},{"from":"tbev","to":"meningitis","level":"established","effect":"harms","note":"Tick-borne encephalitis virus can cause meningitis."},{"from":"rabies","to":"encephalitis","level":"established","effect":"harms","note":"Rabies causes a brain inflammation that is almost always fatal once symptoms start."},{"from":"rabies","to":"s_brainstem","level":"established","effect":"harms","note":"Rabies travels up nerves to the brainstem, causing spasms of swallowing and breathing."},{"from":"westnile","to":"encephalitis","level":"established","effect":"harms","note":"West Nile virus causes encephalitis in about 1 in 150 infections, most often in older people."},{"from":"hsv1","to":"encephalitis","level":"established","effect":"harms","note":"Herpes simplex 1 is the commonest cause of sporadic viral encephalitis."},{"from":"hsv2","to":"meningitis","level":"established","effect":"harms","note":"Herpes simplex 2 can cause viral meningitis, sometimes recurring."},{"from":"mpox","to":"d_rash","level":"established","effect":"harms","note":"Mpox causes a blistering rash that crusts over."},{"from":"mpox","to":"swollen_nodes","level":"established","effect":"harms","note":"Mpox typically causes swollen lymph nodes."},{"from":"molluscum","to":"s_skin","level":"established","effect":"harms","note":"Molluscum causes small pearly bumps on the skin."},{"from":"ebola","to":"s_blood","level":"established","effect":"harms","note":"Ebola damages vessel linings and blood clotting."},{"from":"ebola","to":"d_diarrhoea","level":"established","effect":"harms","note":"Ebola causes severe vomiting and diarrhoea with fluid loss."},{"from":"hantavirus","to":"s_kidneys","level":"established","effect":"harms","note":"European and Asian hantaviruses cause fever with kidney failure."},{"from":"hantavirus","to":"s_lungs","level":"established","effect":"harms","note":"American hantaviruses make the lungs fill with fluid."},{"from":"bk_virus","to":"s_kidneys","level":"established","effect":"harms","note":"Reactivated BK virus can damage a transplanted kidney."},{"from":"sx_kidney_transplant","to":"bk_virus","level":"established","effect":"harms","note":"Anti-rejection drugs after kidney transplant let BK virus reactivate."},{"from":"sx_kidney_transplant","to":"cmv","level":"established","effect":"harms","note":"Cytomegalovirus is the commonest serious virus after transplant, because anti-rejection drugs let it reactivate."},{"from":"sx_liver_transplant","to":"cmv","level":"established","effect":"harms","note":"Anti-rejection drugs after liver transplant let cytomegalovirus reactivate."},{"from":"zika","to":"congenital_infection","level":"established","effect":"harms","note":"Zika in pregnancy can cause a small head (microcephaly) and brain damage in the baby."},{"from":"cmv","to":"congenital_infection","level":"established","effect":"harms","note":"Cytomegalovirus passed in pregnancy is the commonest infectious cause of childhood deafness."},{"from":"toxo","to":"congenital_infection","level":"established","effect":"harms","note":"Toxoplasma caught in pregnancy can damage the baby's eyes and brain."},{"from":"treponema","to":"congenital_infection","level":"established","effect":"harms","note":"Untreated syphilis in pregnancy can cause stillbirth and congenital syphilis."},{"from":"meningitis","to":"headache","level":"established","effect":"harms","note":"Meningitis causes a severe headache with stiff neck."},{"from":"meningitis","to":"d_fever","level":"established","effect":"harms","note":"Meningitis usually causes fever."},{"from":"meningitis","to":"seizures","level":"established","effect":"harms","note":"Meningitis can cause seizures."},{"from":"encephalitis","to":"s_cortex","level":"established","effect":"affects","note":"Encephalitis inflames the brain tissue itself."},{"from":"encephalitis","to":"seizures","level":"established","effect":"harms","note":"Encephalitis often causes seizures."},{"from":"encephalitis","to":"memory","level":"established","effect":"harms","note":"Survivors of encephalitis, especially herpes encephalitis, may have lasting memory loss."},{"from":"encephalitis","to":"alzheimers","level":"association","effect":"harms","note":"In national biobanks, viral encephalitis was the infection most strongly linked with later Alzheimer's disease; this does not prove cause.","sources":[{"id":"pmid:36669485","citation":"Levine KS et al., Neuron","year":2023,"design":"cohort","finding":"In Finnish and UK biobanks, viral encephalitis was most strongly linked with later Alzheimer's disease, and influenza with pneumonia with five of six neurodegenerative diseases studied."}]},{"from":"h_mmr_vaccine","to":"measles","level":"proven","effect":"helps","note":"Measles vaccine prevents measles, about 95% after one dose.","sources":[{"id":"pmid:5902680","citation":"Medical Research Council Measles Vaccines Committee, Br Med J","year":1966,"design":"controlled trial","finding":"A controlled clinical trial of live measles vaccine in British children compared vaccinated with unvaccinated children for later measles."},{"id":"pmid:34806766","citation":"Di Pietrantonj C et al., Cochrane Database Syst Rev","year":2021,"design":"meta-analysis","finding":"In cohort studies MMR vaccine was about 95% effective against measles after one dose and also protected against mumps and rubella, with no link to autism."}]},{"from":"h_mmr_vaccine","to":"mumps","level":"association","effect":"helps","note":"MMR protected against mumps in cohort studies, though protection can wane.","sources":[{"id":"pmid:34806766","citation":"Di Pietrantonj C et al., Cochrane Database Syst Rev","year":2021,"design":"meta-analysis","finding":"In cohort studies MMR vaccine was about 95% effective against measles after one dose and also protected against mumps and rubella, with no link to autism."}]},{"from":"h_mmr_vaccine","to":"rubella","level":"association","effect":"helps","note":"MMR protected against rubella in cohort studies, preventing congenital rubella.","sources":[{"id":"pmid:34806766","citation":"Di Pietrantonj C et al., Cochrane Database Syst Rev","year":2021,"design":"meta-analysis","finding":"In cohort studies MMR vaccine was about 95% effective against measles after one dose and also protected against mumps and rubella, with no link to autism."}]},{"from":"h_polio_vaccine","to":"poliovirus","level":"proven","effect":"helps","note":"Polio vaccine prevented paralytic polio in the 1954 placebo-controlled field trial.","sources":[{"id":"pmid:16281456","citation":"Burke DS, Clin Trials","year":2004,"design":"review","finding":"Reviews the 1954 placebo-controlled field trial that showed inactivated polio vaccine prevents paralytic polio."}]},{"from":"gb_subdoligranulum","to":"m_micro","level":"established","effect":"helps","note":"Makes butyrate."},{"from":"gb_butyricicoccus","to":"m_micro","level":"established","effect":"helps","note":"Makes butyrate."},{"from":"gb_odoribacter","to":"m_micro","level":"established","effect":"helps","note":"Makes propionate."},{"from":"fibre","to":"gb_lachnospira","level":"established","effect":"helps","note":"Pectin, the fibre in apples and citrus, is its food."},{"from":"gb_lachnospira","to":"m_micro","level":"established","effect":"helps","note":"Breaks pectin down into short-chain fatty acids."},{"from":"gb_bacteroides","to":"vitk","level":"established","effect":"helps","note":"Bacteroides are among the gut bacteria that make vitamin K2."},{"from":"gb_cscindens","to":"cdiff","level":"lab","effect":"helps","note":"The secondary bile acids it makes blocked C. difficile growth in mice and went with resistance in people's stool samples.","sources":[{"id":"pmid:25337874","citation":"Buffie et al., Nature","year":2015,"design":"lab","finding":"Clostridium scindens, via secondary bile acid production, restored resistance to Clostridium difficile in mice."}]},{"from":"gb_bfragilis","to":"vitk","level":"established","effect":"helps","note":"Another of the gut bacteria that make vitamin K2."},{"from":"p_falciparum","to":"s_blood","level":"established","effect":"harms","note":"Falciparum malaria destroys red blood cells, causing anaemia."},{"from":"p_falciparum","to":"d_fever","level":"established","effect":"harms","note":"Malaria causes waves of high fever and chills when infected cells burst."},{"from":"p_falciparum","to":"seizures","level":"established","effect":"harms","note":"Cerebral malaria causes seizures and coma, especially in children."},{"from":"p_falciparum","to":"s_kidneys","level":"established","effect":"harms","note":"Severe falciparum malaria can cause kidney failure."},{"from":"p_falciparum","to":"pregnancy","level":"established","effect":"harms","note":"Malaria in pregnancy infects the placenta and causes low birth weight."},{"from":"p_vivax","to":"s_liver","level":"established","effect":"harms","note":"Vivax leaves dormant forms in the liver that cause relapses."},{"from":"p_vivax","to":"d_fever","level":"established","effect":"harms","note":"Vivax malaria causes repeated bouts of fever."},{"from":"p_vivax","to":"s_spleen","level":"established","effect":"harms","note":"Vivax malaria enlarges the spleen, which can rarely rupture."},{"from":"plasmodium","to":"d_fever","level":"established","effect":"harms","note":"All malaria species cause fever when infected red cells burst."},{"from":"babesia","to":"s_blood","level":"established","effect":"harms","note":"Babesia infects and bursts red blood cells."},{"from":"sx_splenectomy","to":"babesia","level":"established","effect":"harms","note":"Without a spleen, babesiosis can become severe and life-threatening."},{"from":"trichomonas","to":"s_vagina","level":"established","effect":"harms","note":"Trichomonas inflames the vagina, causing discharge and itch."},{"from":"trichomonas","to":"s_urethra","level":"established","effect":"harms","note":"Trichomonas infects the urethra in both sexes."},{"from":"leishmania_visceral","to":"s_spleen","level":"established","effect":"harms","note":"Visceral leishmaniasis makes the spleen enormous."},{"from":"leishmania_visceral","to":"s_marrow","level":"established","effect":"harms","note":"Visceral leishmaniasis infects the bone marrow, causing anaemia and low white cells."},{"from":"leishmania_visceral","to":"d_fever","level":"established","effect":"harms","note":"Visceral leishmaniasis causes months of fever."},{"from":"hiv","to":"leishmania_visceral","level":"established","effect":"harms","note":"HIV makes visceral leishmaniasis more common, more severe and more likely to relapse."},{"from":"leishmania_cutaneous","to":"s_skin","level":"established","effect":"harms","note":"Cutaneous leishmaniasis leaves a slow-healing ulcer and scar."},{"from":"cyclospora","to":"s_small_intestine","level":"established","effect":"harms","note":"Cyclospora infects the lining of the small intestine."},{"from":"cyclospora","to":"d_diarrhoea","level":"established","effect":"harms","note":"Cyclospora causes long-lasting watery diarrhoea."},{"from":"naegleria","to":"meningitis","level":"established","effect":"harms","note":"Naegleria causes a rapidly fatal meningoencephalitis."},{"from":"naegleria","to":"n_olfactory","level":"established","effect":"harms","note":"Naegleria enters the brain along the smell nerve from the nose."},{"from":"acanthamoeba","to":"s_cornea","level":"established","effect":"harms","note":"Acanthamoeba infects the cornea in contact-lens wearers."},{"from":"crypto","to":"d_diarrhoea","level":"established","effect":"harms","note":"Cryptosporidium causes watery diarrhoea, long-lasting with weak immunity."},{"from":"hiv","to":"crypto","level":"established","effect":"harms","note":"With advanced HIV, Cryptosporidium can cause severe, lasting diarrhoea."},{"from":"entamoeba","to":"d_diarrhoea","level":"established","effect":"harms","note":"Entamoeba histolytica causes bloody diarrhoea (amoebic dysentery)."},{"from":"toxo","to":"encephalitis","level":"established","effect":"harms","note":"With advanced HIV, toxoplasma can reactivate and cause brain abscesses."},{"from":"h_bed_nets","to":"plasmodium","level":"proven","effect":"helps","note":"Insecticide-treated nets cut malaria episodes and child deaths in trials.","sources":[{"id":"pmid:30398672","citation":"Pryce J et al., Cochrane Database Syst Rev","year":2018,"design":"meta-analysis","finding":"In randomised trials, insecticide-treated bed nets reduce child deaths and malaria episodes."}]},{"from":"h_bed_nets","to":"p_falciparum","level":"proven","effect":"helps","note":"Most bed-net trials were in African areas of falciparum malaria.","sources":[{"id":"pmid:30398672","citation":"Pryce J et al., Cochrane Database Syst Rev","year":2018,"design":"meta-analysis","finding":"In randomised trials, insecticide-treated bed nets reduce child deaths and malaria episodes."}]},{"from":"h_malaria_vaccine","to":"p_falciparum","level":"proven","effect":"helps","note":"The RTS,S vaccine prevented many cases of falciparum malaria in African children in a trial.","sources":[{"id":"pmid:25913272","citation":"RTS,S Clinical Trials Partnership, Lancet","year":2015,"design":"RCT","finding":"The RTS,S/AS01 malaria vaccine prevented many cases of clinical malaria over 3-4 years in African infants and children."}]},{"from":"h_condoms","to":"trichomonas","level":"association","effect":"helps","note":"Condom use was associated with less trichomoniasis in women.","sources":[{"id":"pmid:15356939","citation":"Holmes KK et al., Bull World Health Organ","year":2004,"design":"review","finding":"Consistent condom use was associated with less gonorrhoea, chlamydia, genital herpes, syphilis and trichomoniasis; partial protection still substantially reduces spread."}]},{"from":"h_safe_water","to":"crypto","level":"established","effect":"helps","note":"Cryptosporidium resists chlorine and spreads in water, so filtered or boiled water prevents it."},{"from":"staph_aureus","to":"s_skin","level":"established","effect":"harms","note":"Staph aureus causes boils, impetigo, cellulitis and wound infections."},{"from":"staph_aureus","to":"sepsis","level":"established","effect":"harms","note":"Staph aureus in the blood is a common cause of sepsis."},{"from":"staph_aureus","to":"s_heart","level":"established","effect":"harms","note":"Staph aureus in the blood can infect heart valves (endocarditis)."},{"from":"staph_aureus","to":"s_bones","level":"established","effect":"harms","note":"Staph aureus is the commonest cause of bone infection (osteomyelitis)."},{"from":"staph_aureus","to":"pneumonia_infection","level":"established","effect":"harms","note":"Staph aureus can cause severe pneumonia, often after flu."},{"from":"mrsa","to":"s_skin","level":"established","effect":"harms","note":"MRSA causes skin abscesses and wound infections that resist common antibiotics."},{"from":"mrsa","to":"sepsis","level":"established","effect":"harms","note":"MRSA bloodstream infection is harder to treat than ordinary staph."},{"from":"pneumococcus","to":"pneumonia_infection","level":"established","effect":"harms","note":"Pneumococcus is the commonest bacterial cause of pneumonia."},{"from":"pneumococcus","to":"meningitis","level":"established","effect":"harms","note":"Pneumococcus is a leading cause of bacterial meningitis in adults."},{"from":"pneumococcus","to":"otitis_media","level":"established","effect":"harms","note":"Pneumococcus is a common cause of middle-ear infection in children."},{"from":"pneumococcus","to":"sepsis","level":"established","effect":"harms","note":"Pneumococcus can invade the blood and cause sepsis."},{"from":"pneumococcus","to":"opsi","level":"established","effect":"harms","note":"Pneumococcus causes most overwhelming infections after spleen removal."},{"from":"sx_splenectomy","to":"pneumococcus","level":"established","effect":"harms","note":"Without a spleen, pneumococcus in the blood is cleared poorly."},{"from":"sx_splenectomy","to":"meningococcus","level":"established","effect":"harms","note":"Without a spleen, meningococcal blood infection is more dangerous."},{"from":"sx_splenectomy","to":"hib","level":"established","effect":"harms","note":"Without a spleen, Hib is cleared poorly from the blood."},{"from":"flu","to":"pneumococcus","level":"established","effect":"harms","note":"Flu damages the airway lining and opens the way to pneumococcal pneumonia."},{"from":"hiv","to":"pneumococcus","level":"established","effect":"harms","note":"HIV greatly raises the risk of invasive pneumococcal disease."},{"from":"meningococcus","to":"meningitis","level":"established","effect":"harms","note":"Meningococcus causes meningitis that can kill within hours."},{"from":"meningococcus","to":"sepsis","level":"established","effect":"harms","note":"Meningococcal sepsis can cause shock and loss of limbs."},{"from":"meningococcus","to":"d_rash","level":"established","effect":"harms","note":"Meningococcal sepsis causes a rash that does not fade when pressed."},{"from":"meningococcus","to":"opsi","level":"established","effect":"harms","note":"Meningococcus is a cause of overwhelming infection after spleen removal."},{"from":"hib","to":"meningitis","level":"established","effect":"harms","note":"Before vaccination Hib was the main cause of meningitis in young children."},{"from":"hib","to":"s_larynx","level":"established","effect":"harms","note":"Hib can cause epiglottitis, swelling above the voice box that blocks breathing."},{"from":"hib","to":"opsi","level":"established","effect":"harms","note":"Hib is a cause of overwhelming infection after spleen removal."},{"from":"pseudomonas","to":"pneumonia_infection","level":"established","effect":"harms","note":"Pseudomonas causes pneumonia in people on ventilators and with damaged lungs."},{"from":"pseudomonas","to":"s_ears","level":"established","effect":"harms","note":"Pseudomonas is a common cause of swimmer's ear (outer ear infection)."},{"from":"legionella","to":"pneumonia_infection","level":"established","effect":"harms","note":"Legionella causes a severe pneumonia, Legionnaires' disease."},{"from":"mycoplasma","to":"pneumonia_infection","level":"established","effect":"harms","note":"Mycoplasma causes a milder \"walking\" pneumonia in young people."},{"from":"bordetella","to":"d_cough","level":"established","effect":"harms","note":"Whooping cough causes weeks of violent coughing fits."},{"from":"bordetella","to":"s_airways","level":"established","effect":"harms","note":"Bordetella toxins paralyse the cleaning hairs of the windpipe lining."},{"from":"diphtheria","to":"s_throat","level":"established","effect":"harms","note":"Diphtheria forms a grey membrane in the throat that can block breathing."},{"from":"diphtheria","to":"s_heart","level":"established","effect":"harms","note":"Diphtheria toxin can damage the heart muscle."},{"from":"gbs","to":"sepsis","level":"established","effect":"harms","note":"Group B strep passed at birth causes newborn sepsis."},{"from":"gbs","to":"meningitis","level":"established","effect":"harms","note":"Group B strep is a leading cause of meningitis in newborns."},{"from":"sepsis","to":"s_blood","level":"established","effect":"affects","note":"Sepsis disturbs blood pressure, clotting and oxygen delivery throughout the body."},{"from":"sepsis","to":"aki","level":"established","effect":"harms","note":"Sepsis is the commonest cause of acute kidney injury in hospital."},{"from":"sepsis","to":"d_fever","level":"established","effect":"harms","note":"Sepsis usually causes fever, though older people may instead be cold."},{"from":"sepsis","to":"cognition","level":"association","effect":"harms","note":"Older survivors of severe sepsis often have lasting new problems with memory and thinking.","sources":[{"id":"pmid:20978258","citation":"Iwashyna TJ et al., JAMA","year":2010,"design":"cohort","finding":"Older survivors of severe sepsis had substantial, persistent new cognitive impairment and disability compared with their state before."}]},{"from":"uti","to":"sepsis","level":"established","effect":"harms","note":"Kidney infection is a common source of sepsis, especially in older people."},{"from":"pneumonia_infection","to":"sepsis","level":"established","effect":"harms","note":"Pneumonia is the commonest source of sepsis."},{"from":"type2_diabetes","to":"mtb","level":"association","effect":"harms","note":"People with diabetes had about three times the risk of active tuberculosis.","sources":[{"id":"pmid:18630984","citation":"Jeon CY, Murray MB, PLoS Med","year":2008,"design":"meta-analysis","finding":"Across 13 observational studies, diabetes was associated with about three times the risk of active tuberculosis."}]},{"from":"h_pcv_vaccine","to":"pneumococcus","level":"proven","effect":"helps","note":"Pneumococcal vaccines prevent invasive disease and pneumonia from the covered types in trials.","sources":[{"id":"pmid:25785969","citation":"Bonten MJ et al., N Engl J Med","year":2015,"design":"RCT","finding":"In adults 65 and over, the PCV13 conjugate vaccine prevented vaccine-type pneumococcal pneumonia and invasive disease, but not pneumonia from all causes."},{"id":"pmid:23440780","citation":"Moberley S et al., Cochrane Database Syst Rev","year":2013,"design":"meta-analysis","finding":"Pneumococcal polysaccharide vaccine protects adults against invasive pneumococcal disease; evidence for all-cause pneumonia is weak."}]},{"from":"h_men_vaccine","to":"meningococcus","level":"proven","effect":"helps","note":"Meningococcal vaccine protected against meningitis from the covered group in trials.","sources":[{"id":"pmid:15674874","citation":"Patel M, Lee CK, Cochrane Database Syst Rev","year":2005,"design":"meta-analysis","finding":"In trials, serogroup A meningococcal polysaccharide vaccine protected against serogroup A meningitis, most clearly in children over five."}]},{"from":"h_hib_vaccine","to":"hib","level":"proven","effect":"helps","note":"Hib vaccine prevented nearly all Hib meningitis in a randomised trial.","sources":[{"id":"pmid:9130939","citation":"Mulholland K et al., Lancet","year":1997,"design":"RCT","finding":"In Gambian infants, Hib conjugate vaccine prevented nearly all Hib meningitis and Hib pneumonia, and about a fifth of all X-ray-confirmed pneumonia."}]},{"from":"h_dtp_vaccine","to":"bordetella","level":"proven","effect":"helps","note":"Acellular pertussis vaccines prevent whooping cough in children in trials.","sources":[{"id":"pmid:25228233","citation":"Zhang L et al., Cochrane Database Syst Rev","year":2014,"design":"meta-analysis","finding":"Multi-component acellular pertussis vaccines are effective at preventing whooping cough in children in randomised trials."}]},{"from":"h_bcg","to":"mtb","level":"proven","effect":"helps","note":"BCG at birth reduced tuberculosis by over half on average, most in young children.","sources":[{"id":"pmid:7596718","citation":"Colditz GA et al., Pediatrics","year":1995,"design":"meta-analysis","finding":"BCG vaccination of newborns and infants reduced tuberculosis by over half on average across trials and case-control studies."}]},{"from":"pinworm","to":"s_rectum_anus","level":"established","effect":"harms","note":"Female pinworms lay eggs around the anus at night."},{"from":"pinworm","to":"d_itch","level":"established","effect":"harms","note":"Pinworms cause itch around the anus, worst at night."},{"from":"h_hand_washing","to":"pinworm","level":"established","effect":"helps","note":"Washing hands and keeping nails short stops swallowed eggs re-infecting the person and family."},{"from":"whipworm","to":"s_colon","level":"established","effect":"harms","note":"Whipworms embed in the wall of the caecum and colon."},{"from":"whipworm","to":"d_diarrhoea","level":"established","effect":"harms","note":"Heavy whipworm infection causes bloody diarrhoea in children."},{"from":"echinococcus","to":"s_liver","level":"established","effect":"harms","note":"Echinococcus larvae grow into fluid-filled cysts in the liver."},{"from":"echinococcus","to":"s_lungs","level":"established","effect":"harms","note":"Hydatid cysts also form in the lungs."},{"from":"taenia_saginata","to":"s_small_intestine","level":"established","effect":"harms","note":"The beef tapeworm lives in the small intestine."},{"from":"fish_tapeworm","to":"s_small_intestine","level":"established","effect":"harms","note":"The fish tapeworm lives in the small intestine."},{"from":"fish_tapeworm","to":"b12","level":"established","effect":"harms","note":"The fish tapeworm takes up vitamin B12, which can cause deficiency."},{"from":"liver_fluke","to":"s_bile_ducts","level":"established","effect":"harms","note":"Liver flukes live in and inflame the bile ducts."},{"from":"liver_fluke","to":"cholangiocarcinoma","level":"established","effect":"harms","note":"Long liver fluke infection causes bile-duct cancer."},{"from":"fasciola","to":"s_bile_ducts","level":"established","effect":"harms","note":"Fasciola flukes settle in the bile ducts after crossing the liver."},{"from":"fasciola","to":"s_liver","level":"established","effect":"harms","note":"Young Fasciola flukes burrow through the liver."},{"from":"paragonimus","to":"s_lungs","level":"established","effect":"harms","note":"Lung flukes form cysts in the lungs."},{"from":"paragonimus","to":"d_cough","level":"established","effect":"harms","note":"Lung fluke infection causes chronic cough with blood-stained phlegm."},{"from":"trichinella","to":"s_muscle","level":"established","effect":"harms","note":"Trichinella larvae burrow into and encyst in muscle."},{"from":"trichinella","to":"pain","level":"established","effect":"harms","note":"Trichinosis causes muscle pain and tenderness."},{"from":"onchocerca","to":"s_eyes","level":"established","effect":"harms","note":"Onchocerca larvae in the eye cause inflammation and blindness."},{"from":"onchocerca","to":"d_itch","level":"established","effect":"harms","note":"Onchocerca larvae moving through the skin cause intense itch."},{"from":"loa_loa","to":"s_eyes","level":"established","effect":"harms","note":"Adult Loa loa worms can be seen crossing the white of the eye."},{"from":"loa_loa","to":"s_skin","level":"established","effect":"harms","note":"Loa loa causes itchy passing swellings under the skin."},{"from":"anisakis","to":"s_stomach","level":"established","effect":"harms","note":"Anisakis larvae burrow into the stomach wall."},{"from":"anisakis","to":"d_abdominal_pain","level":"established","effect":"harms","note":"Anisakis causes sudden severe stomach pain hours after eating raw fish."},{"from":"angiostrongylus","to":"meningitis","level":"established","effect":"harms","note":"Rat lungworm larvae cause eosinophilic meningitis."},{"from":"angiostrongylus","to":"headache","level":"established","effect":"harms","note":"Rat lungworm meningitis causes severe headache."},{"from":"scabies","to":"d_itch","level":"established","effect":"harms","note":"Scabies causes intense itch, worse at night."},{"from":"scabies","to":"s_skin","level":"established","effect":"harms","note":"Scabies mites burrow in the top layer of skin."},{"from":"head_lice","to":"d_itch","level":"established","effect":"harms","note":"Head lice cause scalp itch."},{"from":"body_lice","to":"d_itch","level":"established","effect":"harms","note":"Body lice cause itch and skin thickening."},{"from":"pubic_lice","to":"d_itch","level":"established","effect":"harms","note":"Pubic lice cause itch in the groin."},{"from":"taenia","to":"neurocysticercosis","level":"established","effect":"harms","note":"Swallowed pork tapeworm eggs form cysts in the brain."},{"from":"neurocysticercosis","to":"epilepsy","level":"established","effect":"harms","note":"Neurocysticercosis is a leading cause of adult-onset epilepsy worldwide."},{"from":"neurocysticercosis","to":"seizures","level":"established","effect":"harms","note":"Dying brain cysts inflame the brain and trigger seizures."},{"from":"neurocysticercosis","to":"s_cortex","level":"established","effect":"affects","note":"Cysts most often lodge in the outer brain (cortex)."},{"from":"cholangiocarcinoma","to":"s_bile_ducts","level":"established","effect":"affects","note":"Cholangiocarcinoma grows from the lining of the bile ducts."},{"from":"cholangiocarcinoma","to":"d_jaundice","level":"established","effect":"harms","note":"Bile-duct cancer often shows as painless jaundice when the duct blocks."},{"from":"cholangiocarcinoma","to":"d_itch","level":"established","effect":"harms","note":"Blocked bile ducts make bile salts build up and cause itch."}]}