Cortisol

Abbreviation F
Molecular formula C₂₁H₃₀O₅
Type Glucocorticoid steroid hormone
Administration Endogenous (produced by adrenal cortex); supplemental forms include oral hydrocortisone (Cortef), prednisone, dexamethasone
Bioavailability Oral: ~96% for hydrocortisone; cortisol is slightly more water soluble than progesterone
Synonyms Hydrocortisone, Compound F
Source Produced by the adrenal cortex from cholesterol via pregnenolone → progesterone pathway; body makes ~`20 mg` daily
Ray's verdict Generally hurts
Negative, fundamentally catabolic and aging, necessary for short-term survival but harmful when chronically elevated


Cortisol is the main catabolic steroid in the human organism. In addition to tissue catabolism, cortisol plays a key role in virtually all chronic degenerative conditions, and the aging process in general.

It belongs to the glucocorticoid class of steroid hormones, synthesized in the adrenal cortex from cholesterol via the pregnenolone-progesterone pathway. Cortisol is the thing which has a short-term defensive reaction against stress. One of its main effects is to turn protein into sugar so that the sugar can be used for energy to increase adaptive ability to handle the stress.

History

Etymology

The name comes from Latin cortex ("bark" or "outer layer"), referring to the adrenal cortex, the outer layer of the adrenal gland that produces it, plus the "-ol" suffix for an alcohol group.

Edward Kendall isolated cortisol in 1949 and shared the 1950 Nobel Prize in Physiology or Medicine for characterizing adrenal cortex hormones and their anti-inflammatory effects.

The understanding of cortisol emerged from Hans Selye's pioneering stress research in the mid-20th century. The whole stress hormone system, the things that Hans Selye popularized and studied for many years, he was concentrating on the steroid system, and that's the most powerful stress-induced system.

Hans Selye had the concept of catatoxic steroids. They destroyed the toxin effect. The distinction matters: catatoxic steroids protect the organism by blocking toxin effects, without destroying the toxin directly.

Selye's adrenalectomy experiments demonstrated that animals without adrenal glands became acutely stress-sensitive: When Hans Selye was experimenting with removing adrenals, he found that after the tissue-stored steroids had dissipated, just a moderate amount of stress would kill the animals because they didn't have the adrenal resilience to meet the stress.

Felix Meerson later extended Selye's work to the mitochondrial level, exploring stress-limiting systems. Meerson's idea was that we have many layers of stress-limiting signals and hormones and processes, and it happens that the steroids are one major stress-limiting system where cortisol and serotonin and nitric oxide and estrogen activate the short-term stress reactions that can stimulate brief defense. If those continue, they destroy the organism.

Structure/Chemical properties

  • Molecular formula: C₂₁H₃₀O₅
  • Type: Glucocorticoid steroid (21-carbon structure)
  • Solubility: Cortisol is a little more water soluble than progesterone, and a diurnal cycle can be seen in the saliva.

Biosynthesis pathway: The pituitary senses something wrong in the organism, increases its ACTH, which drives the adrenal glands in particular to take up cholesterol and to synthesize cholesterol from raw materials, and to direct the cholesterol into the mitochondrion to turn it into pregnenolone, progesterone, DHEA, and finally cortisol.

Before the cortisol stage of stress, the continuously activated adrenal tissue will be first producing pregnenolone, progesterone, and DHEA, and it's only when those aren't enough to handle the stress that the progesterone will be further converted into the cortisol.

Stress and cancer metastasis

Pre-deployment cortisol and testosterone jointly predicted later PTSD symptoms in soldiers: elevated cortisol increased PTSD risk mainly when testosterone was low, supporting testosterone–cortisol mutual suppression in stress vulnerability.[1] Glucocorticoid-receptor positivity predicted poor outcome in triple-negative breast cancer; androgen-receptor positivity associated with lower grade and reduced recurrence risk, and DHT blocked dexamethasone-driven migration in GR/AR double-positive cells.[2] Chronic stress-driven glucocorticoid signaling couples to hepatic tryptophan kynurenine metabolism and liver cancer promotion in murine models.[3] Chronic stress elevates glucocorticoids, increases neutrophil extracellular trap formation, and creates a lung microenvironment that multiplies metastatic colonization; blocking neutrophil glucocorticoid receptors or digesting NETs with DNase I abolishes the effect.[4]

Function/Mechanism of Action

Three weeks of physiological-dose corticosterone in mouse drinking water reproduced chronic-stress depression phenotypes and mPFC dendritic spine loss; ketamine rapidly restored many of the same synapses it had eliminated.[5] Calorie restriction raised total urinary cortisol output and calorie monitoring increased perceived stress, suggesting chronic dieting itself can elevate glucocorticoid burden.[6] Stress hormones acting through β2-adrenergic receptors on neutrophils released S100A8/A9 and oxidized lipids that reactivated dormant tumor cells via FGFR signaling; beta-blockade blocked awakening.[7] Post-infarction patients months after recovery maintained high resting cortisol and exaggerated stress catecholamine surges despite healed lesions, consistent with chronic HPA overdrive as a cardiovascular risk trait.[8] In type 2 diabetes, flatter diurnal cortisol profiles correlated with higher glucose levels independent of BMI, supporting glucocorticoid dysregulation as a direct contributor to hyperglycemia.[9] Early-life poverty blunted pubertal testosterone trajectories and hippocampal volume growth, linking chronic stress-related HPA/HPG dysregulation to adult mood and regulatory deficits.[10] COVID-19 inpatients with baseline cortisol above 744 nmol/L had mean survival of 15 days versus 36 days below that threshold, with levels exceeding those seen after major surgery.[11] Ten days of corticosterone or dexamethasone in rats raised hippocampal and cerebellar 5-lipoxygenase mRNA and protein with membrane translocation, linking glucocorticoid exposure to upregulated leukotriene synthesis in brain.[12] Glucocorticoid therapy increased cyclooxygenase-2 expression in nasal polyps in vivo, contradicting the assumption that steroids uniformly suppress COX-2 and suggesting rebound inflammatory potential after withdrawal.[13] Stress-induced cortisol signaling upregulated decidual FKBP51, which inhibited progesterone-receptor function and precipitated idiopathic preterm birth in mice and human tissue models.[14] Glucocorticoid receptor signaling in liver induced Hes1 and hepatic steatosis, linking cortisol excess to non-alcoholic fatty liver and dyslipidemia.[15] Glucocorticoids and DHT both suppressed gastric ILC2 IL-13 and CSF2, but only androgen receptor signaling reversed established gastric metaplasia without the atrophic pre-cancerous changes seen with chronic cortisol.[16] After acute stress, higher salivary cortisol predicted reduced charitable giving, especially in people with strong mentalizing ability, with corresponding changes in dorsolateral prefrontal donation signals on fMRI.[17] Nicotinamide with D-ribose supplementation for one week significantly reduced salivary cortisol while raising NAD+ and improving glucose tolerance in middle-aged adults.[18] Hormonal contraceptive users maintained elevated ACTH after a social stress-recovery period when untreated women showed normal cortisol-axis downregulation, consistent with chronic HPA activation from progesterone suppression.[19] Dexamethasone raises amyloid-β production in neuronal and fibroblast models through glucocorticoid-driven 5-lipoxygenase upregulation; 5-LO blockade or genetic deletion abolishes the glucocorticoid-dependent Aβ increase.[20]

Glucocorticoid receptor antagonism and lifespan

Mifepristone (glucocorticoid/progesterone receptor antagonist) extends mated female Drosophila lifespan via mitophagy and reduced midgut hypertrophy, acting through a pathway shared with rapamycin.[21] Wobbler mice (ALS model) show marked corticosterone elevation in adrenal glands, plasma, brain, and spinal cord alongside hypothalamic-pituitary-gonadal suppression.[22] Primary functions:

  1. Blood sugar maintenance: When the adrenaline reaches a certain level and can't get the blood sugar up out of your storage, then you turn on the cortisol and that's the classic stress that can be harmful because the cortisol dissolves first tissues like the thymus which are very fragile that starts turning to sugar just immediately when you run out of stored glycogen.
  2. Protein → glucose conversion: If your liver didn't have the glycogen stored to release glucose under the influence of adrenaline, then you depend on cortisol to keep your blood sugar steady, and cortisol activates the conversion of protein to sugar and fat.
  3. Anti-inflammatory (acute): Progesterone and cortisol both prevent leakiness of capillaries and are antiinflammatory, though they are antagonists in other situations. They both stabilize mast cells, decreasing histamine and serotonin, and inhibit phospholipase and prostaglandin formation and release of various inflammatory cytokines, and protect the glycocalyx.
  4. Detoxification (at physiologic levels): A physiologically balanced amount of cortisol induces enzymes of detoxification, for example in the intestine.

Receptor mechanism: Prednisolone, dexamethasone, and cortisol are all glucocorticoid receptor agonists. The cortisol-GR complex translocates to the cell nucleus to exert systemic effects.

Glucocorticoid receptor sulfhydryl groups

Beta-lapachone competitively inhibits glucocorticoid binding at the receptor ligand site without triggering the activation conformation, acting as a silent glucocorticoid-receptor antagonist; its inhibition is reversed by reducing agents (DTT, mercaptoethanol), consistent with interaction at sulfhydryl groups required for receptor activation.[23]

Catalytic concentrations of adrenal cortical hormones inhibit reduced diphosphopyridine nucleotide (DPNH) oxidation in heart sarcosomes at the DPNH-cytochrome c reductase step; α-tocopherol competitively reverses this inhibition.[24]

Hair follicle stem cells

Chronic stress elevates corticosterone (cortisol in humans), which keeps hair follicle stem cells in extended quiescence without re-entering growth phase; removing adrenal stress hormones restores regeneration even in aged mice.[25]

Fasting and steroidogenesis (women)

Low-carbohydrate feeding in obese men shifted hepatic cortisol metabolism toward higher 11β-HSD1 regeneration and lower cortisol inactivation, independent of weight loss, linking macronutrient restriction to higher tissue glucocorticoid exposure.[26] In male athletes, a low-carbohydrate diet (about 30% of daily intake) during three consecutive days of intensive training (70-75% VO2max, 60 minutes per day) dropped the free testosterone:cortisol ratio 43% by the day after training, while a moderate-to-high carbohydrate diet (about 60% of intake) produced no significant change.[27] A meta-analysis of 27 studies found low- versus high-carbohydrate diets raise post-exercise cortisol, especially after exercise lasting 20 minutes or more, and that high-protein, low-carbohydrate diets lower both resting and post-exercise total testosterone.[28] A 48-hour fast in healthy young women increased progestogen metabolites but lowered relative mineralocorticoid, glucocorticoid, and androgen end-products; serum aldosterone rose while CYP17A1 and 5α-reductase activities fell, with a non-significant trend toward higher 11β-HSD1 activity (cortisol activation).[29]

Peripheral regeneration and 11β-HSD1

Six weeks of daily treadmill training doubled pulmonary 11β-HSD1 expression in lean and obese mice, increasing local glucocorticoid activation.[30] In human carotid atheroma, 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) expression is two- to tenfold higher than in adjacent intact tissue; cortisol and cortisone stimulate further 11β-HSD1 expression in lipid-storing vascular smooth muscle cells, creating local cortisol auto-amplification that promotes collagen deposition and inflammatory gene expression independent of circulating adrenal output.[31] Transgenic overexpression of 11β-HSD1 in adipose tissue produces visceral obesity, hyperglycemia, and hypertension in mice.[32]

Glucose vs. insulin: opposite inflammatory effects

In type 1 diabetes patients, glucose infusion induced Toll-like receptor and HMGB1 (pro-inflammatory) expression in mononuclear cells, while insulin infusion suppressed the same markers, a direct experimental demonstration that insulin is anti-inflammatory and unopposed glucose (as occurs when insulin signaling is blocked by stress hormones like cortisol) is pro-inflammatory.[33]

Medical uses/Effects

Acute stress depleted hair-follicle melanocyte stem cells through sympathetic-noradrenaline signaling, directly linking stress hormones to premature hair graying.[34] Self-collected earwax over weeks gives a more stable cortisol readout than single blood or saliva samples and resists short-term fluctuations from exercise, alcohol, or venipuncture stress.[35] Chronic prednisolone raises hepatic NF-κB, iNOS, and nitrosative injury markers; vitamin D3 repletion normalizes these changes and lowers liver aminotransferases in rodent models.[36]

Medical Uses/Effects

Legitimate uses:

  • Addison's disease: Addison's disease, with adrenal cortex degeneration, can cause cortisol deficiency, in which case progesterone would compensate.
  • Acute shock/stress: Short-term cortisol maintains capillary integrity and provides emergency fuel.
  • ACTH suppression: Since ACTH can interfere with ovarian function, cortisol can sometimes help the ovaries to make progesterone, by suppressing ACTH.

Conversion relationships:

Cortisol works in the body although the body can convert cortisol to cortisone. Synthetic cortisol-like drugs, such as prednisone are more like cortisol. Also, hydrocortisone is a drug that acts like cortisol.

Dosing

Endogenous production:

The body makes 20 mg of cortisol daily.

Synthetic equivalence:

Taking 10 mg of prednisone is equivalent to about 50 mg of cortisol or 2.5 times the daily amount made in-vitro. Cortef is Hydrocortisone which acts like cortisol.

Ray Peat's caution on supplementation:

William Jefferies' book created a lot of interest in cortisol supplementation (Cortef). "I don't think his arguments are correct. The amounts he sometimes prescribed weren't always safe." He knew people who followed Jefferies' prescription and got Cushing's symptoms.[37]

Diurnal rhythm:

Cortisol peaks ~8am and reaches its lowest between midnight and 4am.

Side/Adverse effects

Tissue catabolism (the hallmark problem):

The main features of aging can be produced directly by administering excessive amounts of cortisol. These features include atrophy of skin, arteries, muscle, bone, immune system, and parts of the brain, loss of pigment (melanin), deposition of fat in certain areas, and slowed conduction velocity of nerves. The physiology of aging (especially reproductive aging) overlaps the physiology of stress.

— Ray Peat

[38]

Thymus destruction:

After the thymus is consumed and turned to sugar, then the cortisol starts breaking down your muscles and then the skin. The brain, lungs and heart are spared from stress partly because they are very saturated in a healthy person with androgens, testosterone and DHEA especially, which block the breakdown function of cortisol.

It only takes about three hours typically for the thymus gland to disappear during profound stress.

Brain damage:

It is now clear that both stress and an excess of the glucocorticoid hormones cause brain damage (as well as damage to all other organs). Nerve cells are replaced by connective tissue cells.

There are actually imaging studies of people who have been under tremendous stress and they show drastic shrinkage of the volume of the brain, so you are literally eventually running on empty.

Gut barrier compromise:

Cortisol compromises the gut barrier and increases the expression of the TLR4 receptors, meaning you're going to flood the blood with endotoxin and increase the reactivity of the body to the toxin.

An unopposed excess causes destruction of detoxification enzymes, eliminating much of the intestine's barrier function, and leading to allergies. Endotoxin is known to destabilize and inactivate the bowel's detoxifying enzymes, just as an overdose of cortisol does.

Adrenal suppression:

High cortisol or glucocorticoid use can cause your adrenals to shrink to the point that if you suddenly stop the supplement, you might die from the absence of adrenal production. But the adrenals will gradually over about a month recover if you are well nourished after you've totally suppressed them with too much cortisol.

Psychological effects:

Since cortisol has a destabilizing, pro-convulsant effect on the nervous system, there are likely to be psychological symptoms, from compulsive behavior to depression or seizures, associated with the other chronic conditions.

Mifepristone and terminal cancer

Mifepristone (RU-486), originally developed as a glucocorticoid receptor antagonist before being repurposed as a progesterone-receptor antagonist for abortion, has been used off-label in a small compassionate-use case series for terminal cancers (lung, thymic, colon, brain, pancreatic) with no remaining treatment options, at a dose of around 200mg daily. Case reports describe stabilization or regression of tumors and survival well beyond expected prognosis in several patients, consistent with cortisol's role in promoting fatty acid synthase/oxidation and suppressing pyruvate dehydrogenase, the metabolic profile common to cancer generally.[39]

Mifepristone and type 2 diabetes

In a randomized, double-blind, placebo-controlled crossover trial, glucocorticoid-receptor blockade with mifepristone in men with type 2 diabetes lowered fasting glucose and insulin and improved insulin sensitivity of free fatty acid, glycerol, and hepatic glucose output.[40] These are real trials showing improved glycemic control and insulin sensitivity, a meaningfully weaker result than "completely reversed" diabetes; no published trial has reported a cure or full remission with mifepristone alone.

Vascular calcification via the mineralocorticoid receptor

Chronic exercise raises baseline cortisol, and over time cortisol acting through the mineralocorticoid receptor (not the glucocorticoid receptor) drives vascular smooth muscle cell calcification; the mineralocorticoid antagonist eplerenone blocks it while the glucocorticoid antagonist mifepristone does not.[41]

Obesity as a subclinical Cushing's syndrome

The "obesity of middle age" pattern (central fat, moon face, buffalo hump, protein wasting) resembles Cushing's syndrome closely enough that a chronic, mild increase in ACTH and beta-endorphin activity has been proposed as a normal part of aging, rather than a separate pathology.[42]

Chronic stress doubles diet-induced weight gain

Mice on the same high-fat diet, same caloric intake, and same physical activity gained twice as much weight when chronically stressed compared to unstressed controls. Chronic stress silenced the lateral habenula, a brain region that normally shuts off reward signaling once satiety is reached, keeping food-reward signaling active regardless of energy need.[43]

Sugar intake blunts the cortisol stress response

Glucocorticoids are released when psychological or physical stressors activate the hypothalamic-pituitary-adrenal stress axis. In rats given a human-equivalent dose of roughly 4 g/kg sucrose daily for three days (comparable to about 350-400g sugar per day in a person), the typical stress-induced rise in plasma corticosterone (the rodent analog of cortisol) was blunted, along with other HPA-axis stress measures, relative to unsupplemented controls.[44]

Forest walking and cortisol reduction

A series of field experiments across 24 forests in Japan, involving 280 male subjects walking roughly 14 minutes through a forest versus a city environment, found significantly lower salivary cortisol, lower pulse rate, lower blood pressure, and greater parasympathetic (relative to sympathetic) nervous activity after the forest walks.[45] Japan's forestry agency built a national Shinrin-yoku (forest bathing) program on this and related research starting in 1982.

See also

References

  1. ↑ Josephs RA, et al. "Testosterone and cortisol predict PTSD risk," Psychoneuroendocrinology. 2017. doi:10.1016/j.psyneuen.2017.03.014.
  2. ↑ Murakami M, et al. "GR and AR in triple-negative breast cancer," Breast Cancer. 2020. PMID 31989378.
  3. ↑ Clarke G, Cryan JF, Keane J, et al. "Chronic stress and liver cancer via tryptophan," Nat Metab. 2025. doi:10.1038/s42255-025-01446-z.
  4. ↑ Zhang B, He X, et al. "Chronic stress promotes metastasis via glucocorticoids," Cancer Cell. 2024. doi:10.1016/j.ccell.2024.01.013.
  5. ↑ Moda NB, Liston C, et al. "Ketamine restores corticosterone-damaged synapses," Science. 2019. doi:10.1126/science.aat8078.
  6. ↑ Tomiyama AJ, et al. "Low calorie dieting increases cortisol," Psychosom Med. 2010. PMID 20368473.
  7. ↑ Albrengues J, et al. "Stress hormones reawaken dormant cancer cells," Sci Transl Med. 2020. doi:10.1126/scitranslmed.abb5817.
  8. ↑ Mendelson GL, et al. "Hormonal status after myocardial infarction," J Clin Endocrinol Metab. 1974. PMID 4270621.
  9. ↑ Joseph JJ, et al. "Cortisol dysregulation and glycemia in type 2 diabetes," Psychoneuroendocrinology. 2021. doi:10.1016/j.psyneuen.2020.11.003.
  10. ↑ Barch DM, et al. "Early poverty, testosterone, and hippocampal development," Proc Natl Acad Sci U S A. 2021. doi:10.1073/pnas.2018303117.
  11. ↑ Dhillo W, et al. "Cortisol as a marker of COVID-19 severity," Lancet Diabetes Endocrinol. 2020. doi:10.1016/S2213-8587(20)30216-3.
  12. ↑ Graziano A, et al. "Glucocorticoids increase 5-lipoxygenase in brain," J Neurochem. 1999. PMID 10428066.
  13. ↑ Pujols L, et al. "Glucocorticoids enhance COX-2 in nasal polyps," Eur Respir J. 2009. doi:10.1183/09031936.00084808.
  14. ↑ Guzeloglu-Kayisli O, et al. "FKBP51, progesterone receptor, and preterm birth," Proc Natl Acad Sci U S A. 2021. doi:10.1073/pnas.2010282118.
  15. ↑ Lemke U, et al. "Glucocorticoid receptor controls hepatic dyslipidemia through Hes1," Cell Metab. 2008. doi:10.1016/j.cmet.2008.08.001.
  16. ↑ Busada JT, et al. "Glucocorticoids and androgens protect from gastric metaplasia," Gastroenterology. 2021. doi:10.1053/j.gastro.2021.04.075.
  17. ↑ Schulreich S, et al. "Altruism under stress: cortisol negatively predicts charitable giving and neural signatures of social decision making," J Neurosci. 2022. doi:10.1523/JNEUROSCI.1870-21.2022.
  18. ↑ Xue Y, et al. "Nicotinamide and D-ribose increase NAD+ metabolome," Nutrients. 2022. doi:10.3390/nu14112219.
  19. ↑ Winterdahl M, et al. "Birth control and stress hormone recovery," Behav Brain Res. 2023. doi:10.1016/j.bbr.2023.114550.
  20. ↑ Graziano A, et al. "Glucocorticoids, 5-LO, and amyloid beta," PLoS One. 2011. doi:10.1371/journal.pone.0015163. PMID 21253592.
  21. ↑ Landis GN, et al. "Mifepristone and rapamycin lifespan in Drosophila," Fly (Austin). 2024. doi:10.1080/19336934.2024.2419151.
  22. ↑ Gonzalez Deniselle MC, et al. "Steroid profiling in Wobbler mice," Endocrinology. 2016. doi:10.1210/en.2016-1244.
  23. ↑ Schmidt TJ, et al. "Beta-lapachone, a specific competitive inhibitor of ligand binding to the glucocorticoid receptor," J Biol Chem. 1984;259(6):3917-3923. PMID 6746659.
  24. ↑ Jensen PK, et al. "Effect of adrenal cortical hormones on DPNH oxidase systems," J Biol Chem. 1963;238:3749-3753.
  25. ↑ Hsu YC, et al. "Corticosterone inhibits GAS6 to govern hair follicle stem-cell quiescence," Nature. 2021;592(7854):428-432. doi:10.1038/s41586-021-03417-2.
  26. ↑ Stimson RH, et al. "Dietary macronutrients alter cortisol metabolism," J Clin Endocrinol Metab. 2007. PMID 17785367.
  27. ↑ Lane AR, Duke JW, Hackney AC. "Influence of dietary carbohydrate intake on the free testosterone: cortisol ratio responses to short-term intensive exercise training," Eur J Appl Physiol. 2010;108(6):1125-1131. doi:10.1007/s00421-009-1220-5. PMID 20091182.
  28. ↑ Whittaker J, Harris M. "Low-carbohydrate diets and men's cortisol and testosterone: Systematic review and meta-analysis," Ann Clin Biochem. 2022;59(3):161-171. doi:10.1177/02601060221083079. PMID 35254136.
  29. ↑ Bergmann N, et al. "Effects of short-term fasting on female steroid metabolism," J Clin Endocrinol Metab. 2022. PMID 35809683.
  30. ↑ Du B, et al. "Exercise increases pulmonary 11β-HSD1," J Appl Physiol. 2017. doi:10.1152/japplphysiol.00652.2016.
  31. ↑ Ayari H, et al. "Mutual amplification of corticosteroids and angiotensin systems in human vascular smooth muscle cells and carotid atheroma," J Mol Med (Berl). 2014;92(11):1175-1185. PMID 25088215.
  32. ↑ Masuzaki H, et al. "Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice," Diabetes. 2004;53(1):32-36. PMID 12840062.
  33. ↑ Dandona P, Ghanim H, Green K, et al. "Insulin infusion suppresses while glucose infusion induces Toll-like receptors and high-mobility group-B1 protein expression in mononuclear cells of type 1 diabetes patients," Am J Physiol Endocrinol Metab. 2013. doi:10.1152/ajpendo.00566.2012.
  34. ↑ Hsu YC, et al. "Stress and hair graying," Nature. 2020. doi:10.1038/s41586-020-1935-3.
  35. ↑ Herane-Vives A, et al. "Earwax cortisol as a chronic stress biomarker," Heliyon. 2020. doi:10.1016/j.heliyon.2020.e05373.
  36. ↑ Zych M, et al. "Vitamin D3 against glucocorticoid hepatotoxicity," J Physiol Pharmacol. 2020. PMID 33276664.
  37. ↑ Ray Peat, "Jefferies and cortisol supplementation," raypeatemails.com.
  38. ↑ Ray Peat, "Aspects of Wholeness," Ray Peat Newsletter.
  39. ↑ Jerome Check's compassionate-use mifepristone trial for terminal cancer, "Can the abortion pill treat advanced lung cancer?", The Philadelphia Inquirer, 2018. Case-report/small-series evidence, not a completed controlled trial.
  40. ↑ Willenberg HS, et al., "Effects of acute glucocorticoid blockade on metabolic dysfunction in patients with type 2 diabetes." A separate double-blind, placebo-controlled trial specifically in men, "Efficacy of Mifepristone in Males With Type 2 Diabetes Mellitus," NCT03052400, tested 600mg/day.
  41. ↑ Zhu D, Rashdan NA, Chapman KE, Hadoke PWF, MacRae VE. "A novel role for the mineralocorticoid receptor in glucocorticoid driven vascular calcification," Vascular Pharmacology. 2016;86:87-93.
  42. ↑ Margules DL, "The obesity of middle age: a common variety of Cushing's syndrome due to a chronic increase in adrenocorticotrophin (ACTH) and beta-endorphin activity," Neurosci Biobehav Rev. 1979;3(3):169-73.
  43. ↑ Ip CK, et al., Garvan Institute, reported in "How chronic stress drives the brain to crave comfort food", 2023. Published in Neuron.
  44. ↑ Ulrich-Lai YM, Ostrander MM, Thomas IM, Packard BA, Furay AR, Herman JP. "Daily Limited Access to Sweetened Drink Attenuates Hypothalamic-Pituitary-Adrenocortical Axis Stress Responses," Endocrinology. 2007;148(4):1823-1834. PMID 17204558.
  45. ↑ Park BJ, Tsunetsugu Y, Kasetani T, Kagawa T, Miyazaki Y. "The physiological effects of Shinrin-yoku (taking in the forest atmosphere or forest bathing): evidence from field experiments in 24 forests across Japan," Environ Health Prev Med. 2010;15(1):18-26. PMID 19568835.