Gut

Main pages: Candida (yeast overgrowth), SIBO (small intestinal bacterial overgrowth), Digestion (stomach acid, reflux, enzymes). Also standalone: Constipation, IBS.

The gut (intestinal tract) digests food, absorbs nutrients, and, in mainstream medicine, hosts a large microbiome. In Ray Peat's writing, the gut is also the main entry route for bacterial Endotoxin (LPS) when barrier function or motility fails, making intestinal health central to systemic Inflammation, hormone balance, and mitochondrial function. Germ-free animals, raised with no gut bacteria at all, show what's at stake: they eat more calories than conventionally colonized animals yet stay leaner and don't develop the same anxiety, which Peat took as evidence the bacteria themselves, not the food, are the source of the damage (see Endotoxin).

Endotoxin and the liver

The liver is the major source of the acute phase proteins, and it is constantly burdened by toxins absorbed from the bowel; disinfection of the bowel is known to accelerate recovery from stress.

— Ray Peat

When endotoxin enters blood, it impairs cytochrome oxidase and synergizes with stored PUFA, Peat's explanation for why gut irritation can produce thyroid suppression, estrogen elevation, and stress-hormone cascades.

Animal data: rats on high-PUFA diets show greater endotoxin-induced vascular leak than EFA-deficient rats. Pigs fed linoleic or fish oil had worse lung injury with LPS than pigs on palmitic acid.

Serotonin and the gut

~90% of body serotonin is produced in the gut (see Serotonin). Peat ties fermentable fibers, bacterial toxins, and slow transit to increased serotonin and endotoxin absorption, overlapping with Histamine and mast-cell activation in allergy and stress.

Intestinal sensation and consciousness

The intestine is powerfully related to consciousness, affecting not only our moods but even the way we feel ourselves in relation to our surrounding space. For example, motion sickness demonstrates the way our sense of movement in space is attached to our stomach and intestine - if we are on a ship, looking at things inside the ship that aren't moving in relation to our body, the real motion sensed by our body conflicts with what our eyes are seeing, and we interpret the inner movement as nausea, but if we just glance at the horizon, the inner sensation of motion suddenly is interpreted accurately as our body moving through space, and the nausea disappears. When there are actual forces being applied to our intestine from the inside, created by bacterial growth, gas, and toxins, our consciousness tries to make sense of it, and the result can be dizziness, a sense of disorientation or falling, so that our sense of location can seem ambiguous or confused.

— Ray Peat

Intestinal gas, bacterial growth, and toxins can contribute to dizziness and spatial disorientation. Looking at the horizon can resolve the visual-motion conflict of motion sickness; reducing intestinal disturbance addresses internally generated signals.

In a mouse study, fatty substances made by gut bacteria switched on sensory nerves supplying the gut, and these nerves raised dopamine in the brain's reward area during running; mice whose gut bacteria were wiped out with antibiotics ran about half as much. No people were studied. See Exercise.

Gut microbiome and psychiatric disease

Bacterial products from the gut reach the brain through the pathways above, and mendelian-randomization and case-control studies extend Peat's endotoxin/stress framework to depression, bipolar disorder, and schizophrenia.

Faecal microbiota transplantation case reports in bipolar disorder, and a 2026 pilot RCT with no MADRS difference between donor and own-stool FMT, are on Bipolar disorder#Faecal microbiota transplantation. A mouse study transferring ADHD human microbiota is on ADHD#Gut microbiota. An open-label autism trial of vancomycin plus donor microbiota ("Microbiota Transfer Therapy") in 18 children, with no control group and a two-year follow-up, is on Autism#Gut microbiota.

Therapies that have been successful in treating “schizophrenia” include penicillin, sleep therapy, hyperbaric oxygen, carbon dioxide therapy, thyroid, acetazolamide, lithium and vitamins. These all make fundamental contributions to the restoration of biological energy. Antibiotics, for example, lower endotoxin formation in the intestine, protect against the induction by endotoxin of serotonin, histamine, estrogen, and cortisol.

— Ray Peat

A systematic review of 44 observational studies (2,510 psychiatric cases, 2,407 controls) found no consistent difference in the number of gut bacteria between psychiatric patients and controls, but consistent shifts in which bacteria were present: depleted short-chain-fatty-acid producers, excess lactic-acid-producing bacteria, and altered taxa tied to glutamate and GABA metabolism, across major depressive disorder, bipolar disorder, and schizophrenia. A parallel review of the human bipolar disorder and depression literature reported the same pattern, reduced beneficial bacteria and increased pathogenic taxa correlating with mood-episode severity.

Mendelian-randomization studies, which use genetic variants to test causal direction rather than mere correlation, show gut microbiome composition and schizophrenia risk are bidirectionally causal: nine bacterial taxa raise risk and six lower it, acting through immune, tryptophan-metabolism, vagal, and short-chain-fatty-acid pathways. Genetic susceptibility to major depression raises irritable bowel syndrome risk in a one-directional analysis. A five-disorder mediation analysis found depression's effect on irritable bowel syndrome was partly mediated by reduced acetate and by insomnia, and schizophrenia's effect was over half mediated by elevated β-hydroxybutyrate, a ketone body.

A case-control study of 132 schizophrenia patients found altered bacterial tyrosine biosynthesis correlating with cognitive dysfunction; tyrosine is the amino-acid precursor for both thyroid hormone and dopamine, tying a gut-bacterial finding directly to Peat's thyroid/dopamine framework. Reviews of the field caution that psychotropic medication itself substantially alters gut microbial composition, confounding cause and effect in cross-sectional psychiatric-microbiome studies.

See Schizophrenia, Depression.

In 672 Korean adults, gut bacteria differed slightly by personality: high neuroticism went with more Proteobacteria, and conscientiousness with more butyrate makers.

Gut-skin axis

A 2021 Clinics in Dermatology review frames bidirectional signaling between gut and skin microbiomes (the gut-skin axis) for cutaneous diseases including rosacea, atopic dermatitis / eczema, psoriasis, acne vulgaris, photoaging, and cutaneous wounds. That paper is a narrative review, not a primary trial.

Disease-specific primary evidence is on Rosacea, Eczema, Psoriasis, and Acne: SIBO eradication and gut transit in rosacea, pediatric oral probiotic SCORAD trials in eczema, psoriasis gut-taxa shifts plus a probiotic PASI-75 RCT, and acne fecal community shifts plus Lactobacillus rhamnosus SP1.

Substances for gut healing

Mastic gum

Mastic gum, a resin from Pistacia lentiscus, has demonstrated ulcer-healing effects. A double-blind placebo-controlled trial (n=38, endoscopically proven duodenal ulcer) found that 1 g/day of mastic for 14 days achieved endoscopic healing in 70% of patients vs 22% with placebo. Symptomatic relief occurred in 80% of the mastic group vs 50% in controls. Mastic is also used traditionally for SIBO and upper gut disinfection; its antibacterial properties against H. pylori are documented.

NSAIDs and gut permeability

NSAIDs (ibuprofen, naproxen, aspirin at high doses) increase intestinal permeability within hours of a single dose, not just after prolonged use. A review of the human data found that all conventional NSAIDs increase intestinal permeability within 24 hours of ingestion, equally evident with short-term and long-term use. This drug-induced leakiness can allow endotoxin and other luminal contents to enter the bloodstream, compounding the metabolic burden on the liver and amplifying the endotoxin/inflammation cycle central to chronic disease in that framework.

Intestinal barrier

The intestinal barrier is the mucosa and tight junctions that keep gut contents out of blood; when it fails, endotoxin enters portal and systemic blood, triggering cytokines and stress hormones. See Leaky gut for the full mechanism and Harm reduction for practical support.

In a double-blind controlled-feeding study of healthy adults, 7 people eating 15 g/day of the emulsifier carboxymethylcellulose for 11 days, against 9 on an emulsifier-free diet, had modestly more postprandial abdominal discomfort, lower gut microbiota diversity and lower fecal short-chain fatty acids and free amino acids. Two of the seven showed bacteria encroaching into the normally sterile inner mucus layer, a central feature of gut inflammation.

Deoxynivalenol (DON), a Fusarium mold toxin in wheat and maize, shortens the villi (the finger-like folds that absorb food) and weakens the seals between gut-lining cells in pig and gut-cell studies; see Mold.

Tissue memory (extracellular matrix)

The gut lining renews itself completely every three to five days, the fastest turnover rate in the body, but the scaffold those cells sit on does not reset the same way. In mouse colitis models, an acute injury reshapes the intestinal extracellular matrix (ECM) through accumulation of collagen XVIII, and this altered "modECM" persists for over a year after the original inflammation resolves, trapping signaling molecules and steering intestinal stem cells toward a wound-associated, pro-inflammatory state instead of normal regeneration. Silencing collagen XVIII prevented the ECM damage from becoming irreversible and blocked the chronic disease state entirely, identifying it as a specific, targetable driver of persistent gut dysfunction rather than a passive scar. This gives a structural, non-bacterial mechanism for why gut symptoms can outlast the endotoxin/serotonin trigger that started them, complementing rather than replacing the endotoxin/serotonin drivers. See IBS.

Peat on reducing gut inflammation

Asked how to reduce deep gut inflammation: "The main thing is to reduce the fermentable grains, nuts, vegetables, starches, and use the foods that are easily, quickly digested and absorbed. Milk, meat, eggs, and sweet fruit such as oranges are quickly digested and so they don't support so much bacterial growth. And there are some fibrous foods that are also antiseptic." He listed raw carrot, bamboo shoots, and cooked mushrooms as fibrous foods with antiseptic properties that can be kept in the diet.

Peat diagnostic orientation to gut health

Peat organized GI health around four interacting factors:

1. Gut transit time - Slow transit allows bacterial overgrowth, endotoxin absorption, and estrogen recirculation; fast transit indicates adequate thyroid and digestive function.
2. Stomach acid - Low acid (common in hypothyroidism) impairs protein digestion and mineral absorption, allowing bacterial survival into the small intestine.
3. Bile - Adequate bile flow is needed for fat digestion and endotoxin clearance; bile stagnation increases LPS absorption.
4. Diet - Avoid foods and irritants that cannot be digested; add insoluble fibers (raw carrot, bamboo shoots, cooked mushrooms), antimicrobial foods (coconut oil), and bile stimulants.

When these four are in balance, the small intestine remains relatively sterile and endotoxin load stays low. When any one fails, the others tend to follow, producing the characteristic endotoxin/serotonin/estrogen cascade.

Practical approaches discussed

Raw carrot fiber lowers endotoxin absorption, but its natural antibiotics call for occasional vitamin K or servings of liver or broccoli with regular use.

Peat and FunctionalPS discuss:

• Raw carrot salad (fiber + vinegar/oil) to reduce endotoxin reabsorption and estrogen recirculation
• Easily digested foods; caution with fermentable Starch and resistant fibers in sensitive people
• Coffee, Gelatin/broth, Aspirin, and (context-specific) antibiotics
• Supporting Thyroid and Liver clearance

See Roadmap/04 - Gut health for the full practical protocol.

Oatmeal and potatoes do provide fiber, but they are good food for bacteria, and bacterial endotoxin is usually the basic problem causing hormone imbalance, by being a chronic burden for the liver, keeping it from storing enough sugar to process thyroid and the other hormones effectively.

— Ray Peat

See Intestinal barrier, Leaky gut, Harm reduction, Walter C. Alvarez.

Bloating

Bloating is gas and abdominal distension, usually from bacterial fermentation of undigested carbohydrate or fiber in the gut. Ray Peat distinguished fermentable fiber, which feeds gas-producing bacteria, from antibacterial fibrous foods, which don't.

Fermentable vs. antibacterial fiber

Peat's practical recommendation was to avoid fiber and starch that resists quick digestion (and therefore ferments), while favoring specific fibrous foods with antibacterial properties:

Besides avoiding foods containing fermentable fibers and starches that resist quick digestion, eating fibrous foods that contain antibacterial chemicals, such as bamboo shoots or raw carrots, helps to reduce endotoxin and serotonin.

— Ray Peat

Gut bacteria adapt over time: people who lack sufficient lactase to digest lactose well produce progressively less hydrogen gas from milk after weeks of regular exposure, as their intestinal flora adjusts. A controlled crossover trial confirmed this: after 10 days of daily lactose feeding, lactose-maldigesting adults showed 50% less flatus frequency and severity on a repeat lactose challenge, with breath hydrogen output falling from 385 to 9 parts per million-hours.

Practice

Favor raw carrots and bamboo shoots as fiber sources over fermentable fibers and resistant starch. Chronic bloating is treated in this framework as a bacterial/endotoxin issue as much as a mechanical digestion one. See Endotoxin, Fiber, Digestion, Lactose intolerance.

Carrageenan

Carrageenan is a seaweed polysaccharide used to thicken dairy, deli meats, and prepared foods. Regulators class it as safe because large molecules are assumed not to absorb.

In Ray Peat's account, carrageenan-containing foods caused him colitis and anaphylaxis; he classed it as a laboratory-grade inflammatory agent that enters the gut through persorption and adds to the harm of Endotoxin.

Carrageenan has been found to cause colitis and anaphylaxis in humans, but it is often present in baby "formulas" and a wide range of milk products, with the result that many people have come to believe that it was the milk-product that was responsible for their allergic symptoms.

— Ray Peat

Persorption and gut barrier failure

Even the normal intestine is able to permit the passage of large molecules and particles, in many cases particles larger than the cells that line the intestine.

— Ray Peat

Stress reduces intestinal blood flow; local irritation and inflammation increase permeability. Carrageenan is used to produce granulomas, arthritis, and immunodeficiency in animal models Peat cited. In humans, a small randomized trial found ulcerative colitis relapse over 12 months in 30% of patients on a carrageenan-free diet versus 60% on their usual diet. It can disappear macrophages and suppress liver cytochrome P450 detox enzymes.

Gerhard Volkheimer's persorption work showed starch grains and other hard particles in blood and urine after ingestion; mice fed raw starch aged faster with starch-blocked arterioles throughout organs.

Synergy with endotoxin and metabolism

Carrageenan and endotoxin together raise nitric oxide, prostaglandins, free radicals, and energy production. Energy failure increases intestinal permeability in a vicious circle, a theme of the bowel, liver, immune, and brain articles.

Tissues accumulating linoleic acid alter mitochondrial cardiolipin and thyroid hormone response; that theme links carrageenan damage to stored PUFA and Estrogen chemistry in the same article. Baby formulas and milk products often contain carrageenan despite human colitis reports Peat cited.

Nixtamalization and practical avoidance

Peat's students in Mexico ate only nixtamalized corn (atole, tamales, tortillas) for breakfast; none found starch grains in centrifuged blood or urine afterward, unlike raw starch persorption. That led him to favor alkali-treated corn products when possible.

Peat avoided carrageenan in cream, cider, hot dogs, ice cream, and sauces when listed on labels, and suspected unlabeled presence in composite ingredients because regulators treat it as safe natural material. He compared carrageenan regulation to delayed sulfite warnings where manufacturers knew of deadly reactions but information was suppressed. See Intestinal barrier, Endotoxin, Harm reduction.

Laxatives

A laxative relieves constipation by stimulating bowel movement. Different classes work through different mechanisms, and some support metabolism while others work against it.

Cascara sagrada ("sacred bark") is the dried bark of the buckthorn tree (Frangula purshiana), used traditionally as a laxative. Its main active component is emodin, an anthraquinone compound also found in rhubarb and aloe. Ray Peat's article "Cascara, Energy, Cancer and the FDA's Laxative Abuse" covers cascara and emodin at length, with effects well beyond a simple laxative action.

Mechanism

Emodin's laxative effect is one part of its broader antiinflammatory action. Since bacterial endotoxin drives nitric oxide production in the cells lining the gut, which impairs their respiration and the smooth muscle's ability to contract, an agent that inhibits that nitric oxide can restore normal peristalsis directly.

Emodin inhibits the formation of nitric oxide, increases mitochondrial respiration, inhibits angiogenesis and invasiveness, inhibits fatty acid synthase, inhibits HER-2 neu and tyrosine phosphorylases, and promotes cellular differentiation in cancer cells.

— Ray Peat

In an animal inflammation model, emodin dose-dependently suppressed nitric oxide production by inhibiting iNOS, and produced a 65-68% reduction in carrageenan-induced paw oedema at 40 mg/kg.

Peat contrasts emodin with tegaserod (Zelnorm), a since-withdrawn prescription drug that worked by increasing the bowel's sensitivity to serotonin. Since serotonin slows metabolism and increases free radical production, a serotonin-mimicking laxative works in the opposite direction from emodin, which raises mitochondrial oxygen consumption and ATP synthesis while lowering oxidative damage.

Regulatory history

The FDA's 2002 "Final rule" on OTC laxative ingredients found cascara sagrada (along with aloe) "not generally recognized as safe and effective," removing it from the approved OTC monograph effective November 2002, less than three months before the FDA approved Zelnorm. Zelnorm was later withdrawn from the market in 2007 after being linked to heart attacks and intestinal ischemia.

Sourcing and use

Peat's preferred source was bulk cascara powder from an Italian supplier (Farmalabor); US customs can complicate importing it, and a US co-op sells it premixed with glycerine as an acceptable alternative. He named lowering nitric oxide as its most important effect; raw carrot (see Roadmap: Gut health) or bamboo shoots have a similar, milder effect through the same mechanism. On a gentler alternative: "Milk of magnesia is very safe, but cascara has many protective biological effects."

A separate compiled bioenergetic guide describes taking it at night to produce a bowel movement the following morning, following whatever dose is listed on the product.

Emergency use

Sugar, aspirin, naloxone or naltrexone, antibiotics, and laxatives have been named as supportive measures for septic shock, helping to clear endotoxin from the gut.

Emodin-based laxatives

Emodin, the active compound in Cascara, has a laxative effect that helps lower nitric oxide, histamine, and serotonin, in contrast to laxative approaches that work by irritating the gut and raising serotonin.

Serotonin-irritant laxatives

Fiber sources such as pectin and stimulant compounds such as those in castor oil work by irritating the intestine, which raises serotonin release, a mechanism Peat generally viewed as working against metabolism compared to emodin's approach.

Castor oil

Castor oil's active component, ricinoleic acid, disrupts normal intestinal muscle activity. It desynchronizes the myoelectric impulses of the colon, an effect examined experimentally in cats in 1972. Ricinoleic acid acts on the EP3 prostanoid receptor for prostaglandin E2, similar to how emodin (from Cascara) increases prostaglandin synthesis, an effect blocked by indomethacin. Historically, castor oil was described as blistering the bowel from the inside once it reached the alkaline intestinal medium, splitting into its irritant components.

Celiac

Celiac disease is an autoimmune reaction to gluten that damages the small intestine lining, impairing nutrient absorption. It is more common in women. A meta-analysis pooling 275,818 people worldwide found a global seroprevalence of 1.4% (0.7% when confirmed by biopsy), with disease significantly more common in females than males (0.6% vs. 0.4%) and in children than adults (0.9% vs. 0.5%).

Gelatin as historical supportive treatment

Concentrated gelatinous broth has a long history of use for celiac disease alongside other digestive conditions:

The use of gelatin, especially in the form of a concentrated gelatinous beef broth, for colitis, dysentery, ulcers, celiac disease, and other diseases of the digestive system, goes far back in medical history.

— Ray Peat

This is a historical/supportive-care note, not a substitute for strict gluten avoidance, which is the only established treatment for the underlying autoimmune reaction in confirmed celiac disease.

Practice (celiac)

Strict gluten elimination is medically necessary for diagnosed celiac disease. Gelatin/bone broth may support gut healing during recovery from the intestinal damage, but does not address the autoimmune trigger itself. See Gluten, Gelatin, Digestion.

Inflammatory bowel disease

Crohn's disease is chronic inflammation of the intestine. Its incidence has risen for decades in industrialized countries, alongside rising liver disease. Canadian hospital records for 1971 to 1986 show discharges for Crohn's disease up 148% in males and 192% in females, with the 1986 rate for females 48% higher than for males.

Gut permeability

Intestinal permeability lets bacteria and endotoxin reach the blood, and this is much more dangerous when phagocytic cells are weakened. Carrageenan poisoning is one known cause of macrophage loss, adding to the immune damage from radiation, unsaturated fats and estrogens.

Mitochondria and the Paneth cell

In ileal tissue from Crohn's patients, inflammation correlated with fewer lysozyme granules in Paneth cells and lower Lgr5, a stem-cell marker, in the crypts. These changes persisted in non-inflamed tissue and predicted the risk of disease recurrence after surgical resection. Mouse experiments that disrupted mitochondrial function linked it to the abnormal Paneth cell type, and dichloroacetate, which blocks glycolysis and forces cells toward mitochondrial respiration, improved stem-cell niche function and restored crypt growth in organoids from inflamed mice.

Lactoferrin case report

A 22-year-old man with Crohn's colitis (disease activity index 415) reached clinical remission (index 50) on granulocyte apheresis, mesalazine and adalimumab. After his last adalimumab injection in April 2012 he took 1 g of bovine lactoferrin daily with no other treatment. His index was 35 in January 2013, blood tests in September 2015 showed no sign of recurrence, and colonoscopy in October 2015 showed almost complete mucosal healing. This is a single case.

Diarrhea

Diarrhea is loose or frequent stool, from infection, food intolerance, inflammatory bowel disease, or gut irritants. Ray Peat's framework points at endotoxin and gut-irritant food additives as underappreciated drivers of chronic bowel symptoms.

Carrageenan and endotoxin

Peat documented carrageenan (a common food thickener made from seaweed) causing colitis in humans, and described it as synergizing with endotoxin to disrupt gut cell energy production:

Carrageenan has been found to cause colitis and anaphylaxis in humans.

— Ray Peat

Carrageenan and endotoxin synergize in many ways, including their effects on nitric oxide, prostaglandins, toxic free radicals, and the defensive enzyme systems.

— Ray Peat

In a small randomized trial, ulcerative colitis patients on a carrageenan-free diet relapsed half as often over a year as those on their usual diet. The difference was not statistically significant. The underlying problem is an energy failure at the cell level, beyond local irritation:

The continuing efficient production of energy is a basic aspect of metabolic defense, and this is interrupted by carrageenan and endotoxin.

— Ray Peat

Practice (diarrhea)

Check food labels for carrageenan (common in dairy alternatives, deli meat, and some dairy products) and eliminate it if bowel symptoms are chronic. Address underlying endotoxin load through gut health and thyroid support rather than treating chronic diarrhea as purely infectious. Acute or bloody diarrhea, or diarrhea with dehydration, needs medical evaluation.

Leaky gut

Leaky gut (increased intestinal permeability) is the failure of the mucosa and tight junctions that normally keep gut contents out of blood. Bacterial endotoxin (LPS) crosses into portal and systemic blood, triggering cytokines and stress hormones.

Cellular energy metabolism is the basis for maintaining the barrier functions. Energy depletion causes the endothelial cells lining blood vessels to become excessively permeable.

— Ray Peat

Causes

Intense or prolonged exercise diverts blood away from the gut toward working muscle and skin, causing splanchnic hypoperfusion in the intestinal wall. When exercise ends and blood flow returns, the reperfusion generates reactive oxygen species through xanthine oxidase, damaging tight-junction proteins such as claudin-1; blocking xanthine oxidase directly prevents the resulting rise in permeability, confirming this as the mechanism rather than the exercise itself.

IL-1β and TNF-α activate myosin light-chain kinase, contracting the actin-myosin ring around gut epithelial cells and pulling tight junctions apart; this inflammatory route does not need a cut in blood flow.

The effect scales with intensity and duration rather than exercise as such. Moderate aerobic exercise raises beneficial gut bacteria such as Akkermansia; high-intensity or prolonged exercise (military training, ultra-endurance events) shifts the microbiota toward dysbiosis and directly raises intestinal permeability. A 90-minute run at a demanding pace raises intestinal permeability and serum I-FABP regardless of whether the runner develops GI symptoms. Heat compounds the damage more than duration does: exercise above 23°C substantially raises gut damage markers compared to a thermoneutral environment. See Harm reduction for a practical training protocol and Testosterone and exercise for the hormonal side of overtraining. In a 2021 review, an hour or more of endurance exercise at 70% or more of maximum work capacity was judged to raise gut permeability and let bacterial endotoxin into the blood, more so in heat, at altitude or when dehydrated, though the authors note a firm threshold is not yet established.

Deoxynivalenol (DON), a mold toxin common in wheat and maize, made human and pig gut-lining cells leakier in culture and lowered claudins, the proteins that seal the gaps between those cells, in the cultures and in piglets fed contaminated feed; see Mold.

Consequences

Chronic endotoxin absorption burdens the liver, impairs thyroid hormone conversion, and raises estrogen and cortisol. Rats on high-PUFA diets show greater endotoxin-induced vascular leak than EFA-deficient rats. See Gut for the full barrier mechanism.

Practical approaches

Raw carrot salad, a low-PUFA diet, Coffee, Gelatin/broth, and context-specific Aspirin or antibiotics appear in barrier-support notes. For exercise-induced permeability specifically, zinc carnosine or bovine colostrum truncated the rise by up to 70%, and 1g ascorbic acid (vitamin C) abolished the endotoxin/nitrite increase after strenuous exercise. Glutamine is used by some for this purpose, though stressed tissue preferentially consumes it as fuel rather than directing it to barrier repair; see Glutamine. See Harm reduction.

In athletes with elevated baseline permeability, 500 mg/day of bovine colostrum for 20 days brought the lactulose/mannitol ratio back into the normal range and lowered stool zonulin, both changes significantly greater than placebo.

Pancreas

The pancreas secretes digestive enzymes and the hormones insulin and glucagon. Blood sugar control and protein/fat digestion both depend on it.

PUFA and pancreatic function

In Ray Peat's framework, free PUFA damages pancreatic function at two separate levels: blocking the Krebs cycle in tissue (producing insulin resistance) and directly stressing the insulin-secreting beta cells themselves.

Free fatty acids can block the Krebs cycle, with relative insulin action resistance resulting.

— Ray Peat

Impaired glucose-induced insulin secretion could also be related to chronic exposure of pancreatic beta cells to elevated plasma free fatty acid levels.

— Ray Peat

He cited Ephraim Racker's finding that free unsaturated fatty acids inhibit mitochondrial respiration directly, with linoleic and linolenic acid specifically acting as intracellular signals through protein kinase C. In this framing, the same PUFA mechanism that produces tissue-level insulin resistance (resembling type 2 diabetes) can also impair or damage the beta cells' own insulin output (resembling type 1), depending on which tissue bears the exposure.

A 4-day controlled lipid-infusion trial in people genetically predisposed to type 2 diabetes (13 with a family history vs. 8 without) showed exactly this beta-cell-level damage directly: raising plasma free fatty acids into the range seen in diabetes (about 500 to 800 μmol/L) cut first-phase insulin secretion by 60% in the genetically susceptible group, while the same fatty-acid elevation increased first-phase secretion by 75% in the control group without that predisposition.

Practice (pancreas)

Low PUFA intake, adequate thyroid function, and sugar eaten with protein keep the organ from running in a chronic stress-adaptation mode. Digestive enzyme insufficiency shows up as bloating after protein- and fat-heavy meals rather than as a blood sugar problem.

Parasites

Parasitic infections (intestinal protozoa such as Giardia and Cryptosporidium, and helminths such as roundworms and pinworms) sit alongside bacterial overgrowth as a source of gut-derived endotoxin and chronic low-grade inflammation. Slow digestion generally goes with a build-up of putrefactive bacteria and opportunistic organisms, one reason Ray Peat favored short-transit-time, easily digested foods and occasional short courses of antimicrobials over long-term tolerance of a sluggish gut.

Two drugs come up repeatedly in this context: ivermectin and nitazoxanide. Both are approved antiparasitics that have since been investigated for broader antiviral and anticancer activity, a repurposing pattern common to older, cheap, well-characterized drugs.

Nitazoxanide

Nitazoxanide is a thiazolide antiparasitic, FDA-approved for diarrhea caused by Cryptosporidium parvum and Giardia lamblia. Its action is broader than the approved label: nitazoxanide and its active metabolite tizoxanide block post-translational maturation of viral glycoproteins, and have shown antiviral activity in cell culture against influenza A and B, several coronaviruses (including SARS-CoV-2 and the seasonal human coronaviruses), RSV, rotavirus, norovirus, and hepatitis B and C. A phase 2b/3 influenza trial found reduced symptoms and viral shedding at 600 mg twice daily versus placebo, and an early-treatment COVID-19 trial reported a shorter time to symptom resolution with a high-dose regimen. A phase 1 high-dose trial (1,500 mg twice daily for 7 days) reported no significant adverse events.

Separately, nitazoxanide has drawn interest as a repurposed cancer drug: it interferes with the unfolded protein response, autophagy, and c-Myc signaling, and has shown activity against gastric, colorectal, and triple-negative breast cancer cell lines. As with ivermectin's own preclinical cancer findings, this is cell-line and early-stage evidence, not a demonstrated human cancer treatment.

Context

On nitazoxanide's safety, Ray Peat: "It seems to be safe to use for a few days." It is mainly sold for parasites, but its action is broad.

Ulcers

Peptic ulcer is a break in the lining of the stomach or the first part of the small intestine (duodenum). The two best-established causes are infection with Helicobacter pylori and regular use of anti-inflammatory painkillers such as NSAIDs and aspirin. Acid, stress, endotoxin and low repair energy in the lining are the other drivers this site tracks. Bleeding or black stools need urgent medical care.

Causes (ulcers)

A 2017 Lancet review describes peptic ulcer as much less common than two decades earlier, because H. pylori infection has declined and acid-suppressing drugs are widely used, and adds that ulcers unrelated to either now pose their own diagnostic and treatment problems. The two main causes stack. A meta-analysis of seven case-control studies found upper gastrointestinal bleeding about twice as likely in low-dose aspirin users who were infected with H. pylori than in those who were not. Testing for and treating the infection is the standard step, and the Maastricht V consensus of 43 experts from 24 countries sets out how.

Stress

In the restraint model of stress ulcer, an animal held immobile quickly develops an ulcer, with lactic acid, histamine and serotonin released, while an animal in the same restraint that has something to bite is the contrast case. Supporting thyroid function, adequate food and the gut barrier is the usual approach on this site, alongside medical treatment.

Acid blockers

Acid blockers work. A meta-analysis of 849 randomised trials with 142,485 participants found that they cut endoscopic ulcer development by about three-quarters and raised ulcer healing more than threefold compared with control, although small-study bias may have inflated the benefit. The cost is in long-term use of proton pump inhibitors, where reviews link it to kidney disease, fractures, infections, and deficiencies of magnesium, B12 and calcium, and recommend deprescribing when there is no clear indication.

Vinegar

Vinegar is dilute acetic acid used in food. Small amounts with meals appear in glycemic research. Not a fat-loss miracle.

Acetate and atherosclerosis

In ApoE-deficient mice given oral sodium acetate for 12 weeks, plaque area and necrotic-core size in the aortic root were significantly smaller than in vehicle-treated mice, with acetate activating AMPK in plaque macrophages via the GPR43 receptor, reducing macrophage proliferation, inflammatory cytokine release (MCP-1, TNF-α, IL-1β), and oxidative stress. This is a mouse model given purified sodium acetate, not a human trial of dietary vinegar, but it identifies acetate (the active compound in vinegar) as a plausible mechanism worth further human study.

Practice (vinegar)

Food use. See Digestion, Sugar, Diabetes.