The liver clears hormones, endotoxin, and metabolic waste, synthesizes Cholesterol, proteins, and bile salts, and stores glycogen. Mainstream hepatology treats cirrhosis, fatty liver, and enzyme leaks as organ-specific disease.

Ray Peat places liver function at the center of thyroid hormone conversion (T4 to T3), Estrogen inactivation, endotoxin clearance, and stress tolerance.[1][2]

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[3]

The liver converts cholesterol to bile salts for elimination; thyroid hormone speeds that pathway. Broda Barnes and Peat note hypothyroid patients often show elevated cholesterol and carotenemia (yellowish tint) when the liver clears carotene slowly.[4][5]

Impairing factors: alcohol, excess PUFA the liver cannot oxidize or store safely, iron overload, chronic Endotoxin from gut, and hypothyroid sluggishness. Hypothyroidism can cause enzyme leakage from liver and other organs on standard blood tests.[6]

Protective themes: Coffee, niacinamide, Gelatin/glycine and saturated fats (increase albumin, reduce fibrosis in models he cites), lowering endotoxin and PUFA, Aspirin in inflammatory contexts, adequate protein and thyroid support.[7][8]

Peat limits organ-meat liver to modest portions because of iron and phosphate load. Vitamin E may matter more for people who eat liver often, since vitamin E-deficient rats on a normal vitamin A diet built up more of the age pigment lipofuscin in the eye (rat study).[9] See Vitamin A, Cholesterol, Hypothyroidism, Iron, Harm reduction.

Alcohol, glutamate, and Kupffer cells

[edit]

Binge drinking upregulates hepatocyte VGLUT3, releasing glutamate that activates Kupffer-cell mGluR5/NOX2, driving nitric oxide–mediated inflammation and hepatocyte death, a direct hepatotransmitter pathway alongside gut LPS.[10]

Alcohol and saturated long-chain fats

[edit]

Alpha-tocopherol for six months improved steatosis, transaminases, and apoptosis markers in HIV patients with non-alcoholic steatohepatitis when newer antifibrotic trials exclude them.[11] In ethanol-fed mice, dietary palmitic and stearic acids reduce gut bacterial translocation and plasma endotoxin, preserve intestinal occludin and limit claudin-2 upregulation, reverse ethanol-induced dysbiosis (restoring Firmicutes and Lactobacillus), and protect against alcoholic steatohepatitis, whereas short-chain fatty acids improve barrier integrity but do not prevent liver injury.[12]

Amin A. Nanji's rat studies are the largest body of work on this specific substitution. Rats fed ethanol alongside tallow (largely saturated) developed none of the features of alcoholic liver disease, while rats fed the same ethanol dose alongside corn oil (largely PUFA) developed the full picture; lard, an intermediate mix, gave an intermediate result.[13] Switching rats already on a fish-oil/ethanol diet to a saturated palm-oil-based diet after 6 weeks reduced hepatic lipid peroxidation and reversed the liver injury already present, framed by the authors as a first candidate dietary treatment for alcoholic liver disease rather than just a prevention strategy.[14] A later study in the same model found the saturated-fat diet down-regulated cyclooxygenase-2 and TNF-alpha and reversed existing fibrosis, tying the protective effect to lower inflammation rather than just less lipid peroxidation.[15] A companion study switched already-injured rats onto medium-chain triglycerides instead of a saturated long-chain source and got a faster, more complete result: near-normal histology within two weeks, clearly ahead of vitamin E alone over the same period, tracked to reduced lipid peroxidation.[16]

This animal work now has a human trial behind it. A 60-day randomized trial in patients with severe alcoholic hepatitis compared clarified butter (ghee, saturated) against soybean oil (PUFA) at matched calorie and protein intake. The saturated-fat group had markedly lower 60-day mortality (12.2% vs 33%), a shift toward favorable commensal gut bacteria, lower TNF-alpha and NF-κB, higher IL-10 and adiponectin, and better MELD, Child-Pugh, and FIB-4 scores at follow-up, the animal mechanism playing out directly in patients rather than just protecting rats.[17]

Endotoxin and HDL3

[edit]

Portal endotoxin from gut injury or dysbiosis drives hepatic inflammation when HDL3 production is reduced; HDL3 binds LPS and limits inflammatory activation in bowel-resection, high-fat-diet, and alcoholic liver disease models.[18]

Gut microbiota, NLRP12, and hepatocellular carcinoma

[edit]

NLRP12 suppresses liver-cancer-promoting JNK signaling in hepatocytes; without NLRP12, gut-derived LPS reaching the liver via the bloodstream drives JNK activation and tumor growth, and depleting gut bacteria with antibiotics dramatically reduced tumor growth in NLRP12-deficient mice.[19]

SHBG as metabolic biomarker

[edit]

Hepatic miR-93 promotes metabolic dysfunction-associated steatotic liver disease pathogenesis, linking microRNA signaling to NAD+-sensitive fatty-liver progression.[20]

IBD and systemic mitochondrial failure

[edit]

When enterocyte mitochondria fail, dietary fat accumulates in intestinal epithelium instead of reaching peripheral tissues, feeding hepatic lipid overload and central obesity.[21] Inflammatory bowel disease patients show reduced plasma TCA-cycle metabolites, respiratory-complex activity, and ATP; succinate and IDH2 fall with disease activity and CRP, indicating systemic bioenergetic collapse alongside gut inflammation.[22]

Blood endotoxin rose with NAFLD severity from simple steatosis through NASH and advanced fibrosis, correlating with BMI, CRP, and markers of metabolic and liver dysfunction.[23]

Roundup at doses far below regulatory limits perturbed rat hepatic gene expression toward lipotoxic and fibrotic pathology with mitochondrial respiratory-chain suppression.[24]

Cirrhosis and arachidonic metabolites

[edit]

Mitochondrial NAD+ content in hepatocytes gates regenerative capacity after partial hepatectomy; SLC25A51 controls the mitochondrial NAD+ pool in vivo.[25] In decompensated cirrhosis, elevated 20-HETE (an arachidonic-acid metabolite) tracks mitochondrial membrane depolarization, ROS, and ATP failure in peripheral leukocytes, linking PUFA-derived lipid mediators to organ failure rather than fibrosis alone.[26] Hepatic sex hormone-binding globulin (SHBG) production reflects liver metabolic state: monosaccharide-induced lipogenesis in hepatocytes suppresses SHBG gene expression, and this regulation is independent of circulating insulin levels; low SHBG therefore signals disordered hepatic sugar metabolism before overt liver disease.[27] SHBG and albumin are both liver-synthesized proteins; low levels of either predict adverse outcomes and correlate with insulin resistance and type 2 diabetes risk in epidemiological work cited alongside this mechanism.

Exhaustive eccentric exercise and liver stress

[edit]

Exhaustive eccentric exercise (e.g. prolonged running) raised liver enzymes and worsened lipid profiles in overweight women with NAFLD, and vitamin D supplementation partly protected against these exercise-induced liver changes, showing that "healthy" endurance exercise can acutely stress an already-compromised liver.[28]

Herbal and dietary supplement liver injury

[edit]

UNOS registry data for liver-transplant waitlist patients from 1995 to 2020 show herbal and dietary supplements accounted for a rapidly growing share of non-acetaminophen drug-induced acute liver failure, rising from about 3% of such cases in the earliest study period to roughly a quarter of them by 2016-2020.[29] The trend tracks the growth of the supplement industry itself and is a reminder that "natural" products are not automatically liver-safe, especially concentrated botanical extracts taken outside clinical supervision. Milk thistle (Silybum marianum) extract (silibinin), commonly promoted for liver support, is one example. Herbal preparations including milk thistle can irritate the intestine; the cited account describes a case where someone's liver function worsened while taking it.[30] Separately, silibinin has been studied as a possible treatment for Cushing's disease and high cortisol.[31]

Ketogenic diet and liver enzymes

[edit]

A published case report followed a 57-year-old woman with obesity who started a ketogenic diet of eggs, cheese, butter, oil, nuts, and leafy greens; four months later her liver enzymes and LDL cholesterol had risen sharply and abdominal ultrasound showed a heterogenous, echogenic liver indicating non-alcoholic fatty liver disease. Stopping the diet brought a modest improvement within two weeks, with liver enzymes normalizing over eight months and LDL over a year.[32] A single case does not establish how often a ketogenic diet provokes this pattern, but it documents that a high-fat, carbohydrate-free diet can measurably stress the liver in a previously stable patient.

Oral contraceptives and mitochondrial fine structure

[edit]

Women taking oral contraceptives for 12 to 30 months showed liver-cell mitochondrial shape change, enlargement, and crystalline inclusions on electron microscopy; 1 to 6 months of use showed mainly increased smooth endoplasmic reticulum without those mitochondrial changes. Mitochondrial change did not track liver-function test abnormalities.[33] See Birth control, Mitochondria.

Glycogen, thyroid, and fasting

[edit]

During fasting, liver glycogen first supplies the glucose that keeps T4 to T3 conversion going; once glycogen runs out, mobilized fatty acids interfere with glucose use and tissue breaks down for fuel.[34]

Ammonia

[edit]

Ammonia is a nitrogen waste from amino acid breakdown. Every amino acid can contribute to ammonia load; the body clears it largely via the urea cycle (with CO2 as a reactant) and kidney excretion. In a bioenergetic frame it is a normal cost of protein turnover, not a free-standing "toxin to detox," but excess amino acid load without balanced nutrition can add stress.

Protein balance

[edit]

Glycine is non-toxic when the kidneys are working, "since any amino acid will contribute to the production of ammonia."[35]

Muscle-meat-heavy protein (high tryptophan and cysteine relative to gelatinous cuts) reproduces a stress amino acid pattern: more serotonin drive, more cortisol signaling, and thyroid suppression from those amino acids, versus traditional whole-animal eating with skin, connective tissue, and broths.[35] See Gelatin, Tryptophan, Serotonin.

Energy context

[edit]

High stress and low sugar oxidation push more reliance on protein breakdown for fuel, which increases nitrogen waste along with the hormonal cost. Supporting oxidative metabolism (thyroid, carbohydrate, lower PUFA, gut care) reduces the need to run the body on continuous amino acid catabolism. See Metabolism, Cortisol, Krebs cycle.

Stress, carbon dioxide and the brain

[edit]

The liver turns ammonia into urea by combining it with CO2, but stress raises ammonia formation while lowering the carbon dioxide available; ammonia also activates the NMDA system and intensifies stress.[36] Urea synthesis consumes aspartic acid and depends on carbon dioxide from normal mitochondrial function.[37]

Exhaustive exercise, high oxygen concentrations, high estrogen and hypothyroidism can each produce hyperammonemia, which tends to come with excess lactic acid because ammonia stimulates glycolysis.[38]

Hypoxia alone sharply increases ammonia production, and any energy deficit raises tissue ammonia. Ammonia disturbs carbon dioxide's regulation of brain circulation, its conversion to glutamine consumes ATP, and it rises during migraine attacks, which may explain part of progesterone's effect on migraine.[39]

Practice

[edit]

Prefer mixed animal protein with gelatin/collagen-rich foods; do not treat ammonia with aggressive "detox" stacks. Kidney disease and documented hyperammonemia are clinical problems, not wiki DIY. Labs that report ammonia can be useful in that medical context and misleading if over-interpreted in isolation: in cirrhosis patients, a plasma ammonia cutoff predicted 28-day mortality with 68% sensitivity and 67% specificity, useful but far from a definitive single-number diagnosis.[40]

Cirrhosis

[edit]

Cirrhosis is scarring (fibrosis) of liver tissue that progressively impairs function, from chronic alcohol use, viral hepatitis, fatty liver disease, or other causes. Ray Peat grouped it with other fibrotic diseases as sharing a common underlying process.

Shared fibrotic mechanism

[edit]

Liver cirrhosis, scleroderma, and organ fibrosis share a common driver, PUFA oxidation-driven inflammation, and treatments targeting that shared mechanism, not organ-specific fixes alone, as what actually work.[41]

Scleroderma, liver cirrhosis, fibrosis of the lungs, heart, and other organs, and all the diseases in which fibrous tissue becomes dense and progressively contracts, involve similar processes, and the treatments which are successful are those that stop the inflammation produced by the oxidation of the polyunsaturated fatty acids.

— Ray Peat[42]

His broader argument connects this to stress-driven arachidonic acid release causing blood vessel leakage, letting fibrin escape into tissue and drive fibrosis across whatever organ is under load, the liver in cirrhosis, lungs or heart in other fibrotic diseases.

A rat model of nonalcoholic steatohepatitis found dietary PUFA dose drove exactly this progression: raising dietary corn oil from 5% to 70% of the diet over 21 days shifted liver and serum fat composition from mostly saturated/monounsaturated fats toward linoleic acid, and this shift accompanied the disease's advance from simple fat accumulation through inflammation and necrosis to fibrosis.[43]

Practice (cirrhosis)

[edit]

Reducing PUFA intake is this framework's general lever for fibrotic disease broadly; it does not replace medical management of the underlying cause (alcohol cessation, antiviral treatment, etc.) or monitoring for cirrhosis complications. See Liver, PUFA, Hepatitis.

Large-dose testosterone propionate plus thiamine produced "clinical cure" in 60% of 700 cirrhosis cases in one protocol: intramuscular testosterone propionate (starting 50mg every other day, escalating to 100mg daily over 10 weeks) with thiamine (50-100mg, 2-3x/week), continued at least 3 years past symptom disappearance. The proposed mechanism: a deficiency of hepatic hyaluronidase activity may drive the excess connective-tissue growth in cirrhosis, and androgenic hormones (testosterone propionate performing best in the protocol) have anticirrhotic activity.[44]

Fatty liver

[edit]

Fructose is often blamed for fatty liver on the assumption that only the liver can metabolize it, but other organs metabolize fructose too, and the liver simply has the highest capacity for it. PUFA (linoleic acid) is the better-supported cause: it's required for experimental liver damage to develop at all.

Low thyroid function and endotoxin load add to the PUFA mechanism above. Practical support: cut seed oils and alcohol, support thyroid and protein, choline-rich foods, and aspirin for its anti-inflammatory, anti-endotoxin effect where appropriate.

In a meta-analysis of observational studies, primary hypothyroidism was linked to higher odds of fatty liver disease and of its inflamed or scarred forms.[45]

In the PIVENS trial, 800 IU/day of vitamin E for 96 weeks in non-diabetic adults with non-alcoholic steatohepatitis (NASH) met the study's primary histological improvement endpoint far more often than placebo (43% vs. 19%), with significant reductions in hepatocyte ballooning and lobular inflammation; fibrosis itself did not significantly improve with either vitamin E or the comparison drug pioglitazone.[46]

Both experimental and epidemiological studies show dietary linoleic acid (PUFA) is required for alcoholic liver damage to develop too. Animals fed tallow (a saturated fat) with ethanol had no liver injury, but even 0.7-2.5% linoleic acid combined with ethanol caused fatty liver, necrosis, and inflammation.[47]

Vitamins E and C

[edit]

In a cross-sectional study of 789 adults, people who ate the most vitamin E and vitamin C from food had less severe fatty liver disease, with lower odds of NASH, the inflamed form.[48] This is an association and cannot show that the vitamins caused the difference.

In a small randomized trial in people with biopsy-proven fatty liver, six months of vitamin E plus vitamin C lowered liver enzymes about as well as a standard bile-acid drug; ALT returned to normal in about 6 of 10 patients on the vitamins.[49] The gap between the two treatments was not significant, and the trial had no placebo group.

Whole oranges

[edit]

In adults with MASLD, 400 g/day of whole oranges for 4 weeks reduced fatty-liver prevalence on CAP imaging versus non-citrus fruit, independent of body-weight change. Liver stiffness and most liver enzymes were unchanged; GGT decreased.[50] See Orange.

Orange juice in mice

[edit]

Blood orange juice prevented high-fat-diet liver triglyceride accumulation better than blond juice in mice: blond juice weakly lowered liver triglycerides, while blood juice matched standard-diet levels.[51] Moro orange juice likewise opposed diet-induced fatty liver in mice over 12 weeks.[52] Mouse data only.

Endotoxin

[edit]

In a small human pilot study, people with fatty liver had higher blood endotoxin than controls and ate more fructose, despite similar total calories, fat and carbohydrate.[53] In mice on a high-fat diet, oleuropein from olive oil tightened the gut lining, lowered blood endotoxin and reduced liver fat.[54] See Endotoxin.

Coffee

[edit]

In rats fed a high-fat diet, decaffeinated coffee added to drinking water for 8 weeks reduced liver fat, liver scarring (collagen) and liver inflammation; its polyphenol and melanoidin fractions each carried part of the effect.[55]

In a meta-analysis of observational studies, coffee drinkers had about a quarter lower risk of fatty liver disease, and coffee-drinking patients with fatty liver had less fibrosis.[56]

Gallbladder

[edit]

The gallbladder stores and concentrates bile for fat digestion. Sludge and stones track estrogen, low thyroid, and irregular fat intake; removal is common, after which fat digestion needs some dietary adaptation.

Thyroid and estrogen effects

[edit]

Thyroxine and T3 have a direct prorelaxing effect on the sphincter of Oddi, the muscle valve that opens to let bile into the small intestine. In pig sphincter rings, physiological thyroxine cut acetylcholine-driven contractions by a mean of 37–44% and histamine-driven contractions by 54–56%, while cortisol, estrogen, and testosterone had no such effect; T3 matched thyroxine.[57] Human sphincter tissue responds the same way, through thyroid hormone receptor β isoforms and a transcriptional path that activates K+ channels.[58] In eight women studied while hypothyroid and again after thyroxine replacement, hepatic clearance of a bile tracer was lower at 45 and 60 minutes and hilum-to-duodenum transit was about 31% slower in the hypothyroid stage. Without that prorelaxing effect, biliary emptying slows.[59]

Separately, hormone replacement therapy with estrogen has been found to roughly triple gallbladder disease rates in women. Unopposed by progesterone, estrogen promotes fluid retention and tissue congestion.[60]

Gallstones

[edit]

Gallstones are concretions in the gallbladder, commonly cholesterol-rich; biliary colic and pancreatitis are complications. Rapid weight loss and very low-calorie diets raise risk; this is not a seed-oil puzzle alone. Fat intolerance after an attack needs medical advice.

Practice (gallbladder)

[edit]

Medical care for acute biliary disease (sudden severe pain, jaundice). Support thyroid function and eat regular meals with adequate fat to keep bile moving rather than stagnating. See Liver, Estrogen, Thyroid, Digestion, Saturated fat.

References

[edit]
  1. ↑ "Thyroid: Therapies, Confusion, and Fraud," Ray Peat article
  2. ↑ "Ray Peat, PhD on Endotoxin"
  3. ↑ "Leakiness, aging, and cancer," Ray Peat article
  4. ↑ "Thyroid: Therapies, Confusion, and Fraud," Ray Peat article
  5. ↑ "The Cholesterol and Thyroid Connection"
  6. ↑ "Leakiness, aging, and cancer," Ray Peat article
  7. ↑ "Leakiness, aging, and cancer," Ray Peat article
  8. ↑ "Ray Peat, PhD on Endotoxin"
  9. ↑ Herrmann RK, Robison WG Jr, Bieri JG. "Deficiencies of vitamins E and A in the rat: lipofuscin accumulation in the choroid," Invest Ophthalmol Vis Sci. 1984;25(4):429-433. No DOI. PMID 6706506.
  10. ↑ Yang S, Kim W, Ryu D, et al. "Binge drinking, VGLUT3 glutamate, and hepatic inflammation," Nat Commun. 2025. doi:10.1038/s41467-025-60820-3.
  11. ↑ Sebastiani G, Saeed S, Lebouche B, et al. "Vitamin E is an effective treatment for nonalcoholic steatohepatitis in HIV mono-infected patients," AIDS. 2020;34(2):237-244. doi:10.1097/QAD.0000000000002412. PMID 31651429.
  12. ↑ Chen P, Torralba M, Tan J, et al. "Supplementation of saturated long-chain fatty acids maintains intestinal eubiosis and reduces ethanol-induced liver injury in mice," Gastroenterology. 2015;148(1):203-214.e16. doi:10.1053/j.gastro.2014.09.014. PMID 25239591.
  13. ↑ Nanji AA, Mendenhall CL, French SW. "Beef fat prevents alcoholic liver disease in the rat," Alcohol Clin Exp Res. 1989;13(1):15-19. PMID 2646971.
  14. ↑ Nanji AA, Sadrzadeh SM, Yang EK, Fogt F, Meydani M, Dannenberg AJ. "Dietary saturated fatty acids: a novel treatment for alcoholic liver disease," Gastroenterology. 1995;109(2):547-554. PMID 7615205.
  15. ↑ Nanji AA, Zakim D, Rahemtulla A, et al. "Dietary saturated fatty acids down-regulate cyclooxygenase-2 and tumor necrosis factor alfa and reverse fibrosis in alcohol-induced liver disease in the rat," Hepatology. 1997;26(6):1538-1545. PMID 9397995.
  16. ↑ Nanji AA, Yang EK, Fogt F, Sadrzadeh SM, Dannenberg AJ. "Medium chain triglycerides and vitamin E reduce the severity of established experimental alcoholic liver disease," J Pharmacol Exp Ther. 1996;277(3):1694-1700. PMID 8667240.
  17. ↑ Tripathi H, Benjamin J, Sharma S, et al. "Saturated fat favorably alters the gut microbiota and improves survival in patients with severe alcoholic hepatitis: a randomized controlled trial," abstract, The Liver Meeting (AASLD), Boston, MA, 2023.
  18. ↑ Han YH, Onufer EJ, Huang LH, et al., Randolph GJ. "Enterically derived high-density lipoprotein restrains liver injury through the portal vein," Science. 2021;373(6553):eabe6729. doi:10.1126/science.abe6729. PMID 34437091.
  19. ↑ Udden SMN, Kwak YT, Zaki H, et al. "NLRP12 suppresses hepatocellular carcinoma via downregulation of cJun N-terminal kinase activation in the hepatocyte," eLife. 2019. doi:10.7554/eLife.40396.
  20. ↑ Lee S, et al. "Hepatic miR-93 in MASLD," Metabolism. 2025. doi:10.1016/j.metabol.2025.156266.
  21. ↑ Moschandrea C, Kondylis V, Evangelakos I, et al. "Mitochondrial dysfunction abrogates dietary lipid processing in enterocytes," Nature. 2024. doi:10.1038/s41586-023-06857-0. PMID 38123683.
  22. ↑ Dudzińska M, et al. "Mitochondrial dysfunction in inflammatory bowel disease," J Inflamm Res. 2025. doi:10.2147/JIR.S487349.
  23. ↑ Soppert J, et al. "Blood Endotoxin Levels as Biomarker of Nonalcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis," Clin Gastroenterol Hepatol. 2023. PMID 36470528.
  24. ↑ Mesnage R, et al. "Transcriptome effects of ultra-low dose Roundup," Environ Health. 2015. doi:10.1186/s12940-015-0056-1.
  25. ↑ Mukherjee S, Baur JA, et al. "Mitochondrial NAD+ limits liver regeneration," Nat Metab. 2025. doi:10.1038/s42255-025-01408-5.
  26. ↑ López-Vicario C, et al. "Lipid mediator-mitochondrial network in cirrhosis," Nat Commun. 2026. doi:10.1038/s41467-026-73386-5.
  27. ↑ Selva DM, et al. "Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone-binding globulin gene," J Clin Invest. 2007;117(12):3979-3987. PMID 17992261.
  28. ↑ Rahimpour S, Hoseini R, Behpour N, et al. "Alterations of liver enzymes and lipid profile in response to exhaustive eccentric exercise: vitamin D supplementation trial in overweight females with non-alcoholic fatty liver disease," BMC Gastroenterol. 2022. doi:10.1186/s12876-022-02457-w.
  29. ↑ Ghabril M, Ma J, Patidar KR, et al. "Eight-Fold Increase in Dietary Supplement-Related Liver Failure Leading to Transplant Waitlisting Over the Last Quarter Century in the United States," Liver Transpl. 2022;28(2):169-179. doi:10.1002/lt.26246. PMID 34331346.
  30. ↑ Ray Peat, Email Wiki, "Milk Thistle Liver Effects."
  31. ↑ "Milk Thistle (Silibinin) May Treat Cushing Disease and High Cortisol."
  32. ↑ Anekwe CV, Chandrasekaran P, Stanford FC. "Ketogenic Diet-induced Elevated Cholesterol, Elevated Liver Enzymes and Potential Non-alcoholic Fatty Liver Disease," Cureus. 2020;12(1):e6605. doi:10.7759/cureus.6605. PMID 32064187.
  33. ↑ Perez V, Gorosdisch S, De Martire J, Nicholson R, Di Paola G. "Oral contraceptives: long-term use produces fine structural changes in liver mitochondria," Science. 1969;165(3895):805-807. doi:10.1126/science.165.3895.805. PMID 5796555.
  34. ↑ Ray Peat, "Mary Shomon Interview."
  35. ↑ 35.0 35.1 Ray Peat, "Gelatin, stress, longevity," raypeat.com.
  36. ↑ Ray Peat, Sugar, Stress, and the Degenerative Diseases, newsletter.
  37. ↑ Ray Peat, "Epilepsy and progesterone," raypeat.com.
  38. ↑ Ray Peat, "Fatigue, aging, and recuperation," raypeat.com.
  39. ↑ Ray Peat, Estrogen, Aging, Radiation, Migraine and Energy, newsletter.
  40. ↑ Shalimar, Sheikh MF, Mookerjee RP, Agarwal B, Acharya SK, Jalan R, "Prognostic Role of Ammonia in Patients With Cirrhosis," Hepatology. 2019;70(3):982-994. PMID 30703853.
  41. ↑ Ray Peat, "Fats and degeneration," raypeat.com.
  42. ↑ Fats and degeneration, Ray Peat newsletter
  43. ↑ Wu X, Tong Y, Shankar K, et al. "Lipid fatty acid profile analyses in liver and serum in rats with nonalcoholic steatohepatitis using improved gas chromatography-mass spectrometry methodology," J Agric Food Chem. 2011;59(2):747-754.
  44. ↑ Haidut. "Vitamin B1 (Thiamine) and Testosterone can Cure Liver Cirrhosis." Ray Peat Forum.
  45. ↑ Association between primary hypothyroidism and metabolic dysfunction-associated steatotic liver disease: an updated meta-analysis Meta-analysis; 24 cross-sectional and 4 longitudinal studies, ~76.5 million people; prevalent MASLD OR 1.43; MASH or advanced fibrosis OR 2.84 (2.07-3.90); incident MASLD HR 1.39 (0.98-1.97, not significant). Observational, so causation is not shown. doi:10.1136/gutjnl-2024-332491. PMID 38782564.
  46. ↑ Sanyal AJ, Chalasani N, Kowdley KV, et al. "Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis," N Engl J Med, 2010;362(18):1675-1685. PMID 20427778.
  47. ↑ Peat, Raymond. "Oils in Context."
  48. ↑ Ivancovsky-Wajcman D, Fliss-Isakov N, Salomone F, Webb M, Shibolet O, Kariv R, Zelber-Sagi S. "Dietary vitamin E and C intake is inversely associated with the severity of nonalcoholic fatty liver disease." Dig Liver Dis. 2019;51(12):1698-1705. doi:10.1016/j.dld.2019.06.005. PMID Dietary vitamin E and C intake is inversely associated with the severity of nonalcoholic fatty liver disease. Cross-sectional (observational); Tel Aviv colonoscopy cohort; intake by food frequency questionnaire, NAFLD by ultrasound, NASH and fibrosis by FibroMax (n=714 with reliable FibroMax). Top vs bottom tertile of vitamin E per 1000 kcal and NASH: OR 0.64 (95% CI 0.43-0.94,; meeting the recommended vitamin E intake and NASH: OR 0.48 (0.30-0.77,. Top tertile of vitamin C: NAFLD OR 0.68 (0.47-0.99,, NASH OR 0.57 (0.38-0.84,. Association only; cannot show cause.
  49. ↑ Ersöz G, Günşar F, Karasu Z, Akay S, Batur Y, Akarca US. "Management of fatty liver disease with vitamin E and C compared to ursodeoxycholic acid treatment." Turk J Gastroenterol. 2005;16(3):124-128. PMID Management of fatty liver disease with vitamin E and C compared to ursodeoxycholic acid treatment (no DOI). Open-label, prospective, randomized; 57 patients with chronically raised ALT despite 3 months of diet; vitamin E 600 IU/day + vitamin C 500 mg/day (n=28) vs ursodeoxycholic acid 10 mg/kg/day (n=29) for 6 months. ALT normalized in 17/27 (63%) vs 16/29 (55%); difference between groups not significant. GGT fell only with ursodeoxycholic acid. No placebo arm, no repeat biopsy.
  50. ↑ 70.9% still above CAP threshold vs 100% of controls, p < 0.004. Notarnicola M, et al. "Daily Orange Consumption Reduces Hepatic Steatosis Prevalence in Patients with Metabolic Dysfunction-Associated Steatotic Liver Disease: Exploratory Outcomes of a Randomized Clinical Trial," Nutrients. 2024;16(18):3191. PMID 39339791.
  51. ↑ Sorrenti V, et al. "Blond and blood juice supplementation in high fat diet fed mice: effect on antioxidant status and DDAH/ADMA pathway," RSC Adv. 2019;9(20):11406-11412. PMID 35520248.
  52. ↑ Salamone F, et al. "Moro orange juice prevents fatty liver in mice," World J Gastroenterol. 2012;18(29):3862-3868. PMID 22876038.
  53. ↑ Thuy S, Ladurner R, Volynets V, et al. "Nonalcoholic fatty liver disease in humans is associated with increased plasma endotoxin and plasminogen activator inhibitor 1 concentrations and with fructose intake," J Nutr. 2008;138(8):1452-1455. doi:10.1093/jn/138.8.1452. PMID 18641190. Pilot case-control study; 12 NAFLD patients vs 6 controls; higher plasma endotoxin, PAI-1 and hepatic TLR4 mRNA in NAFLD; plasma PAI-1 correlated with endotoxin (Spearman r = 0.83).
  54. ↑ Schirone L, Overi D, Carpino G, et al. "Oleuropein, a Component of Extra Virgin Olive Oil, Improves Liver Steatosis and Lobular Inflammation by Lipopolysaccharides-TLR4 Axis Downregulation," Int J Mol Sci. 2024;25(11):5580. doi:10.3390/ijms25115580. PMID 38891768. Mouse study; 6 µg/day oleuropein for 30 days; lower serum LPS and zonulin, restored intestinal occludin, fewer hepatic TLR4+ macrophages.
  55. ↑ Vitaglione P, Morisco F, Mazzone G, et al. "Coffee reduces liver damage in a rat model of steatohepatitis: the underlying mechanisms and the role of polyphenols and melanoidins," Hepatology. 2010;52(5):1652-1661. doi:10.1002/hep.23902. PMID 21038411. Rat study; 1.5 mL/day decaffeinated coffee, polyphenols or melanoidins for 8 weeks after 4 weeks of high-fat diet; lower serum ALT and triglycerides, higher reduced/oxidized glutathione ratio, lower hepatic TNF-α and interferon-γ.
  56. ↑ Hayat U, Siddiqui AA, Okut H, Afroz S, Tasleem S, Haris A. "The effect of coffee consumption on the non-alcoholic fatty liver disease and liver fibrosis: A meta-analysis of 11 epidemiological studies," Ann Hepatol. 2021;20:100254. doi:10.1016/j.aohep.2020.08.071. PMID 32920163. Meta-analysis of 11 observational studies; NAFLD RR 0.77; fibrosis in NAFLD patients RR 0.68 (CI as published 0.68-0.79).
  57. ↑ Inkinen J, Sand J, Arvola P, Pörsti I, Nordback I. "Direct effect of thyroxine on pig sphincter of Oddi contractility," Dig Dis Sci. 2001;46(1):182-186. doi:10.1023/a:1005674211976. PMID 11270783. Ex vivo pig tissue.
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