Immune system

The immune system defends against infection and clears damaged tissue. It needs energy, thyroid support, protein, and controlled inflammation to work properly; chronic stress and endotoxin keep it in a noisy, dysregulated state.

Hormones that normalize immune function

The steroids (e.g., progesterone) and thyroid hormones normalize the immune system when they are present in normal amounts.

— Ray Peat

Both testosterone and progesterone normalize the immune system, suppressing auto-immune problems.

— Ray Peat

The thymus gland is extremely sensitive to stress, and atrophies quickly under the influence of cortisone or the sex steroids, but it can also regenerate under the influence of thyroid and progesterone.

— Ray Peat

Ray Peat, "Generative Energy", p. 127

Progesterone is the only steroid hormone I know of which will cause the thymus to regenerate.

— Ray Peat

Vitamin A contributes to synthesis of pregnenolone and progesterone (which moderate cortisol's effects) and also acts hormone-like directly on immune cells. With aging, pregnenolone, progesterone, and DHEA decline sharply; the brain has multiple systems for adapting to that decline, but the immune system is probably less able to compensate.

Estrogen and immune suppression

Vitamin A, thyroid hormone, progesterone, and DHEA oppose estrogen's immunosuppressive effects, which include thymic atrophy, reduced T-cell activity, and lower production of gamma-interferon and interleukin-2, meaning chronically high estrogen relative to these opposing hormones tends to weaken immune defense even as it can also promote autoimmune-type inflammation elsewhere. Thyroid disease's roughly five-fold higher incidence in women is a sign of this same connection: estrogen sensitizes the immune system, and the resulting shift away from glucose oxidation toward fat oxidation and lactic acid production promotes the inflammation that drives autoimmune thyroid disease.

Thyroid, infection, and inflammation

Experimental hypothyroidism involutes the thymus (thymocyte cell death and depopulation; remodeling of epithelium, mast cells, and collagen).

Suppressed thyroid function leaves the immune system exposed to chronic infection; people with recurring infections such as acne, bladder or kidney infections, periodontitis, and sinusitis often show combined thyroid and vitamin A deficiency. A Cochrane review of 47 trials in over a million children found routine vitamin A supplementation cut all-cause mortality by 12% and diarrhea-related mortality by 12%. Vitamin A has a direct role in immune defense. Because cellular energy production is controlled largely by thyroid hormone, low thyroid function is a major driver of chronic inflammation itself: in the low-thyroid state the body loses the structure and control that normally restrain degenerative and inflammatory processes.

Forest exposure and natural killer cells

A series of Japanese studies on "forest bathing" (short leisurely visits to a forest) beginning in 2005 found trips of this kind significantly raised natural killer (NK) cell activity, NK cell count, and intracellular anti-cancer proteins in adult participants, with the increase persisting for over a month after a single trip; the effect is proposed to run partly through inhaled phytoncides, antimicrobial compounds released by trees. A 2023 randomized controlled trial in gynecological cancer survivors found phytoncide exposure raised immune cell counts and lowered psychological stress markers in the same direction.

Practice

Support metabolic rate and gut-barrier integrity rather than treating "boosting immunity" as a single supplement problem. See Endotoxin, Thyroid, Fever, Inflammation, Iron, Vitamin A, Progesterone, Estrogen.

Autoimmunity

Autoimmune disease means immune attack on self tissues. Examples include Hashimoto thyroiditis, celiac disease, and type 1 diabetes.

Thymus, estrogen, and thyroid

The thymus regulates the immune system, and its age-related shrinkage tracks rising "autoimmune" disease incidence. Radiation, PUFA, estrogen, and heavy metals damage the thymus and can produce immunodeficiency while also stimulating autoimmune antibodies. Estrogen shrinks the thymus and blocks NK cells; thyroid stimulates its regeneration even after age-related atrophy; progesterone protects against the thymic atrophy produced by stress and cortisol.

Animals fed diets completely lacking polyunsaturated fatty acids appear free of autoimmune disease; their tissues can even be transplanted into other animals with less antigenicity than normal. Systemic lupus, rheumatoid arthritis, and other autoimmune diseases are usually corrected by the combined use of progesterone and thyroid, both of which help restore the thymus gland.

A prospective nationwide study of 84 rheumatoid arthritis patients tracked this directly across pregnancy: disease activity fell significantly by the third trimester (when progesterone and estrogen are highest), with at least 48% of patients starting with moderate-to-high disease activity showing a moderate treatment response by EULAR criteria, less medication needed overall, and 39% of patients flaring again postpartum once those hormones dropped.

Medical diagnosis and disease-specific care still apply. Do not replace immunosuppressants with internet protocols alone.

Bacterial antigens

Cross-reacting antibodies to bacteria that flourish during the fertile years are one proposed route to the female excess in lupus and rheumatoid arthritis:

For example, the lactobacilli that thrive in women during their fertile years have some antigens that resemble human connective tissues, and it’s possible that they are a factor in diseases such as lupus and rheumatoid arthritis that are prevalent in women especially during those years. Any infection or vaccination, especially when there’s an excess of estrogen or a deficiency of antiinflammatory factors, can permanently damage your health.

— Ray Peat

For the thyroid, laboratory work has found components of Bifidobacterium and Lactobacillus strains that bind human anti-TPO and anti-Tg antibodies, with no animal or clinical confirmation yet. See Hashimoto#Lactobacilli and antigen overlap.

Psychiatric disorders

Autoimmune disease precedes higher rates of psychiatric diagnosis in national registers. In Denmark, a prior autoimmune disease raised schizophrenia risk by 45% in a register-linkage study of 7,704 patients and by 29% in a later 30-year register cohort. In a Swedish national register cohort, patients hospitalized with rheumatoid arthritis, systemic lupus, or ankylosing spondylitis had standardized incidence ratios for later psychiatric hospitalization of 1.45, 2.38, and 1.69 in men and 1.36, 2.16, and 1.95 in women. UK adults reporting an autoimmune condition had 1.49 times the adjusted odds of lifetime depression, anxiety, or bipolar disorder in a cross-sectional analysis. These are observational associations; shared genes, infections, and closer medical follow-up remain possible explanations. See Schizophrenia#Autoimmune disease and Bipolar disorder#Autoimmune disease.

COVID

COVID-19 is disease from SARS-CoV-2. Acute care and vaccination policy are medical and public-health domains outside this wiki's scope. Support food, sleep, and thyroid context during recovery; follow current medical guidance for acute illness.

Naringenin inhibited endosomal two-pore channel activity and blocked pan-coronavirus replication in vitro while dampening TNF-alpha and IL-6, positioning citrus flavonoids as broad antiviral and anti-inflammatory candidates.

Lower COVID-19 mortality in pregnancy and higher severity after delivery align with falling progesterone and allopregnanolone and rising estrogen, supporting progestogens as endogenous anti-inflammatory buffers.

Hospitalized COVID-19 patients with very high serum cortisol deteriorated and died faster, raising concern that additional glucocorticoid therapy may worsen outcomes in already hypercortisolemic patients.

Observational data associated prophylactic low-dose aspirin with reduced SARS-CoV-2 acquisition and faster recovery.

Population data linked low mean 25(OH)D to higher COVID-19 case mortality, with authors arguing vitamin D deficiency may explain most lethal outcomes.

Nasal and throat saline rinses reduced SARS-CoV-2 viral load and symptom duration in a randomized trial, with hypotonic saline showing antiviral activity in vitro.

Low admission testosterone and high estradiol-to-testosterone ratio independently predicted COVID-19 death in hospitalized men with hyperinflammatory markers.

Fever

Fever symptoms

Fever is a controlled rise in core body temperature during infection or inflammation. Mainstream medicine treats fever as a symptom to reduce when uncomfortable or dangerous. Ray Peat's view: fever is often a protective metabolic response, raising heat production, opposing infection, and overlapping with Thyroid-like effects. Routine antipyretic suppression can be counterproductive in mild illness.

This is framework commentary, not advice to avoid medical care in high fever, infants, or vulnerable patients.

Peat on fever and aspirin

Early in the 20th century, people were told that fevers were very bad, and that aspirin should be used whenever there is a fever.

— Ray Peat

Pharmaceutical marketing later shifted toward acetaminophen (e.g. Tylenol) after Reye-syndrome warnings around aspirin in children. Orlowski et al. (1987) found acetaminophen exposure was also common in Reye cases. In the original case series (26 Reye syndrome cases, Australia, 1973-1982), aspirin/salicylate ingestion had occurred in only 5% of confirmed cases, while paracetamol had been given in 30%, despite aspirin usage in Australian children already being under 1% of total dosage units sold at the time.

Mechanism: prostaglandins and metabolism

Prostaglandins mediate fever in standard physiology; Aspirin inhibits COX and prostaglandin synthesis, which is why it lowers temperature. Blocking prostaglandins and fever may interrupt a coordinated defensive chemistry. Aspirin also has many non-antipyretic protective actions: mitochondrial support, anti-estrogenic effects, and lowered free fatty acids.

By activating T3, aspirin can sometimes increase the temperature and pulse rate.

— Ray Peat

Fever and stress hormones interact. Caffeine and fever can lower TSH apart from thyroid hormone feedback, one reason isolated lab tests misread thyroid status during illness.

In mammals, temperature is regulated by hormones and nerves, partly through constriction or widening of blood vessels. Combined with small doses of caffeine or adrenaline-promoting substances, aspirin acts as a thermogenic substance, despite its anti-fever reputation. Because aspirin lowers temperature, opposes inflammation and acts as an antioxidant, it may slow degenerative diseases such as multiple sclerosis.

Practical framing

• Mild fever in otherwise healthy adults: Peat-adjacent writers often favor rest, adequate Glucose, salt, and Thyroid support over aggressive antipyretics, not a universal rule.
• High or prolonged fever, dehydration, infants, elderly, pregnancy: seek medical care. See Harm reduction.

In a small randomized pilot trial in adults with a common cold, rinsing the nose and gargling with home-made hypertonic salt water shortened the illness by about two days and cut spread to people in the same household by about a third.

Herpes

Herpes simplex virus type 1 (HSV-1) causes oral cold sores (herpes labialis). After primary infection the virus remains latent in sensory neurons and can reactivate as visible lesions.

Thyroid hormone

T3 suppresses herpesvirus replication in clinical observations and in vivo experiments; neuron-like cells resist HSV-1 replication when T3 is added.

Thyroid hormone and thyroid nuclear receptor inhibit HSV-1 key gene expression and block viral replication, favoring neuronal latency.

Transient or chronic hypothyroidism lowers thyroid hormone, relieves that block, and yields viral replication, gene expression, release of infectious viruses, and viral reactivation.

Removal of thyroid hormone reverses prior inhibition and restarts replication previously blocked by hormone.

Stress, sugar, and hormones

Low blood sugar precipitates cold-sore eruptions after stress, prolonged sun, or going too long without eating. Premenstrual herpes outbreaks are controlled with progesterone or thyroid.Ray Peat, "Nutrition for Women", p. 54

Canker sores, herpes infections, and bleeding gums with mental symptoms point to thyroid and/or progesterone deficiency.Ray Peat, "Nutrition for Women", p. 35

Lymphatic system

The lymphatic system clears interstitial fluid and macromolecules, carries absorbed fats as chylomicrons, and forms part of the extracellular field between blood and cells. The cited framework treats that field, extracellular matrix plus lymphatics, as the real milieu intérieur: the medium through which cells communicate with some independence from outside stress.

Drainage and vessel contractility

Lymphatic vessels have smooth muscle. Their contractions reduce edema. Swelling and inflammation impair that contractile ability; anti-inflammatory agents such as aspirin (or other prostaglandin-synthesis inhibitors) and antihistamines can restore it. The same logic applies to bowel smooth muscle and peristalsis.

Peat cited experimental work showing altered lymphatic contractile activity in intestinal inflammation (Wu et al., 2005, 2006).

In large artery walls, removal of interstitial macromolecules via lymphatic drainage is poor. The Glycemia article quotes that point from vascular research on diabetic vessels (albumin leaking into the aortic interstitial compartment).

Fat and hormone absorption

Dietary fats form chylomicrons in the small intestine and enter the general circulation by the lymphatic route rather than going straight to the liver in the portal vein. Oral progesterone dissolved in vitamin E follows that path: it is incorporated into chylomicrons, absorbed via the lymphatics, and largely avoids hepatic first-pass conjugation.

The same chylomicron route is why oil-dissolved oral progesterone can reach tissues efficiently compared with forms that hit intestinal and hepatic enzymes immediately.

Gut barrier and lymphatics

The microscopic integrity of intestinal cells regulates passage of materials into blood and lymphatic vessels. Poisons, malnutrition, and stress-related low circulation weaken that barrier; estrogen (including oral contraceptives or Premarin) can shut off intestinal blood supply and produce colitis.

Particles and poorly digested polymers can also cross into lymphatic vessels, a theme Peat developed around carrageenan and other food-junk exposures.

Interstitium and the extracellular field

Between blood and tissue cells, the extracellular matrix and the lymphatic system form the permissive medium for cellular communication. A 2021 KMUD interview connects that extravascular system to older "third circulatory" descriptions and to exosome / microvesicle traffic outside blood vessels, channels in extracellular material that can carry stress signals and repair factors.

Structural integrity of that field tracks energy metabolism: low energy activates pro-inflammatory peptides; adequate calcium (against excess phosphate) supports anti-inflammatory, pro-energy conditions that keep interstitial structure intact.

Iron and lymphatic tissue

Excess stored iron is linked to leukemia and cancers of lymphatic tissues, and abnormal iron handling in lymph nodes and macrophages in Hodgkin's disease and related conditions.

Cerebral lymphatics and the glymphatic path

Brain interstitial waste (including amyloid and tau in Alzheimer's models) drains in part through meningeal / cervical lymphatic routes related to the glymphatic clearance story. A 2024 Chinese case report described "Cervical Shunting to Unclog cerebral Lymphatic Systems" (CSULS): decompression plus bilateral cervical lymphatic-venous anastomosis so high-pressure lymph can empty into veins. At five weeks the authors reported lower tau-PET signal and higher FDG-PET metabolism, especially in the left temporal lobe, in one patient (trial registration ChiCTR2400084617).

That report is a single-patient case, not a controlled trial. Related deep cervical lymphovenous anastomosis (dcLVA) later saw rapid clinical uptake in China and was subsequently restricted to research settings amid efficacy and safety disputes; treat it as an experimental drainage hypothesis, not established therapy.

Social posts sometimes frame the surgery as "draining seed oils" from the brain. The Li et al. paper discusses glymphatic waste clearance and tau / amyloid pathways, not seed-oil drainage as the measured endpoint.

Implications

• Keep lymphatic vessel muscle workable: lower systemic inflammation (aspirin where appropriate, less PUFA drive, clear endotoxin). See Inflammation, Aspirin.
• Support the extracellular / interstitial field with cellular energy (thyroid, sugar when tolerated, CO2), and dietary calcium against phosphate load.
• For oral progesterone, the vitamin E / chylomicron / lymphatic route is the absorption design Peat used; dose from small amounts. See Progesterone.
• Swollen lymph nodes need medical evaluation; imaging such as CT has its own risks Peat warned about on KMUD.

This page summarizes Peat's framing and cited physiology; it is not medical advice.

Multiple sclerosis

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, more common in women and often worsening premenstrually. Neurology treats it with immunosuppressants and anti-inflammatory drugs.

In *Multiple sclerosis, protein, fats, and progesterone*, Ray Peat read MS as destructive inflammation driven by Estrogen relative to Progesterone, stored PUFA, distorted protein metabolism from chronic cortisol, and hypothyroid stress chemistry, not a primary genetic mystery.

In MS, it is clear that the inflammatory process itself is destructive, and that estrogen is a major predisposing factor.

— Ray Peat

SIBO-associated gut bacteria

Twin and germ-free mouse transfer studies implicate ileal Eisenbergiella tayi and Lachnoclostridium (Lachnospiraceae) overgrowth in MS-like paralysis; ileal bacteria from affected twins colonized transgenic mice and produced spinal lesions in most animals within 12 weeks.

Reversible myelin lipid mobilization

Marathon running transiently lowers brain myelin water fraction in motor and sensory white matter, recovering within two months, an acute, reversible myelin-content reduction under extreme metabolic demand.

Estrogen, mediators, and the inflammation trap

Women with higher estrogen-to-progesterone ratios show more active brain lesions in studies Peat cited. Mediators he listed include mast cells, nitric oxide, Serotonin, prolactin, Lipid peroxidation, free fatty acids, prostaglandins, isoprostanes, and cytokines, all tied to estrogen actions.

Nitric oxide and serotonin are both neurotoxic... NO plays a major role in lipid peroxidation and demyelination.

— Ray Peat

The idea that estrogen protects MS because women are affected more often fails the same way as calling a hot stove safe because it caused a burn. Immunosuppressive "essential fatty acid" therapies may relieve symptoms temporarily while worsening underlying pathology.

The number of brain lesions in MS tracks the ratio of estrogen to progesterone; estrogen activates mast cells to release histamine and serotonin, and activated mast cells can cause brain edema and demyelination. Progesterone counters estrogen's effects on both mast cells and platelets.

The first five or six people with an MS diagnosis whom Peat saw recovered quickly on thyroid; low thyroid can enlarge the pituitary into a prolactin-secreting tumor that presses on the optic nerve, a vision loss often misread as brain disease, so checking prolactin and thyroid is useful.

Cortisol, protein, and amino acid imbalance

People with MS have chronically increased cortisol production, distorting protein assimilation toward a nutritional protein deficiency pattern. Excess serotonin and estrogen drive relatively uncontrolled cortisol output; inflammatory mediators and amino acid imbalance can form a vicious circle.

High quality protein, thyroid, pregnenolone and progesterone tend to correct the underlying pathology. These are antiinflammatory, but they are not immunosuppressive or catabolic.

— Ray Peat

Depression, lupus, migraine, menopause, diabetes, and aging share several metabolic features with MS.

Vitamin D and progressive cortical demyelination

Vitamin D repletion from weaning attenuated cortical demyelination, microglial activation, and neurofilament light chain elevation in a rat model of progressive MS-like pathology. During interferon beta treatment in 88 relapsing-remitting MS patients from the OFAMS trial (12 MRI scans and nine serum alpha-tocopherol measures over two years), each 10 umol/L increase in serum alpha-tocopherol reduced odds of simultaneous new T2 lesions by 36.8% and combined unique activity by 35.4%; the same increment predicted 65.4% lower odds of new T1 gadolinium-enhancing lesions and 61.0% lower odds of new T2 lesions two months later. Associations were not significant before interferon beta.

Mitochondrial oxygen consumption

ALS motor neurons with impaired glucose handling survived longer when supplied extra glucose, converting it to usable energy despite mitochondrial stress, supporting high-carbohydrate dietary trials in metabolically compromised ALS patients. The thyroid-hormone mimetic sobetirome promoted oligodendrocyte differentiation and remyelination in mouse models of demyelination with CNS penetration and fewer systemic thyroid side effects than native T3. In relapsing-remitting MS, cerebral metabolic rate of oxygen consumption (CMRO₂) is lower than in healthy controls even before measurable atrophy, which points to faulty cellular respiration as a possible driver of the disease. In a placebo-controlled trial in progressive MS, high-dose biotin (MD1003) reversed disability in a subset of patients.

Glucose, altitude, and supportive therapy

Progressive MS cerebrospinal fluid elevated ceramides, impaired neuronal mitochondrial respiration, and drove compensatory glucose uptake, creating "virtual hypoglycosis" rescuable by exogenous glucose or lactate in culture. Blood glucose and Sodium concentration strongly modulate inflammatory reactivity in animal work: adequate glucose blunts antigen reactions; hypoglycemia amplifies them. MS incidence falls at high altitude and in sunny dry climates in epidemiology he cited.

High-quality protein, Thyroid, Pregnenolone, and Progesterone correct underlying pathology without being catabolic immunosuppressants. Pork and horse meat associate with higher incidence in dietary studies. See Altitude, Harm reduction.

Thymus

The thymus is a primary lymphoid organ in the chest where T cells mature. It shrinks with age and under stress, and thyroid status strongly shapes its structure.

Hypothyroidism

In rats made hypothyroid with carbimazole or methimazole, progressive thymic involution appeared from about week 4 through week 7: more thymocyte cell death and macrophage phagocytosis, thymocyte depopulation, more interdigitating cells, altered subcapsular and medullary epithelium, more mast cells and collagen in capsule and septa, and more B cells and plasma cells.

Broda Barnes removed thyroid glands from baby rabbits and reported continuous sniffles, repeated acute infections, and early death from pneumonia among the consequences of thyroid loss; see Broda Barnes.

Atrophy drivers

Cortisol and other glucocorticoids, estrogen, prostaglandins, PUFA, lipid peroxidation, nitric oxide, endotoxin, hypoglycemia, and ionizing radiation shrink the thymus; progesterone and thyroid hormone support restoration by opposing those agents, and more dietary sugar can correct some aging metabolic changes.Ray Peat, "Arthritis, Autoimmunity, and Aging", p. 4

In young mice, cortisol injection emptied lymphocytes from the thymus within two days and raised the macrophage and fibroblast share, a pattern like old thymus except for greater lymphocyte loss and no collagen increase.

In rats, a PUFA-rich diet changed key enzyme activities in the thymus, spleen and lymph nodes more than a saturated-fat diet. The weight of the thymus is reduced by PUFA in the diet.

Sex steroids act on the thymic epithelial cells that train T cells, not only on lymphocytes. Age-related rises in androgens and estrogens and pregnancy-related rises in progestins all cause dramatic thymic atrophy, and much of that atrophy is driven by steroid signaling in thymic epithelial cells, which shapes the T cell receptor repertoire.

In a small imaging study of young women, those on the pill had smaller thymus glands than women with natural cycles. In naturally cycling women the thymus usually shrank between menses and the early luteal phase; a bigger estradiol rise went with more shrinkage, and a bigger progesterone rise went with thymus growth. The study compared women at one point in their lives and has not been peer reviewed, so it cannot show that the pill shrank the thymus. See Birth control.

Zinc and aromatase

Mild oral zinc supplementation in aging mice restores zinc status toward young levels and partially rebuilds thymus structure, lymphoid mass, and thymic hormone output.

Aromatase inhibitors regenerate the thymus in intact aging male rats without surgical or chemical castration.

Melatonin and winter

In hamsters kept under winter-like conditions, the thymus practically disappeared while fertility fell. Increased pineal activity (and likely melatonin) under winter adrenaline drive was the proposed fertility-suppressing signal. The high-estrogen, low-progesterone, low-thyroid pattern melatonin favors predisposes the organism to seizures and causes the thymus to atrophy.

Tuberculosis

Chest X-ray showing advanced tuberculosis

Tuberculosis is infection with *Mycobacterium tuberculosis*. Historical links between low thyroid, low metabolic rate, and TB susceptibility appear in Broda Barnes and Peat writing. Modern treatment is antibiotics under public health rules.

Peat's view

Early in the 20th century, light therapy was recognized as effective for tuberculosis, alongside a broader tradition including Coley's toxins, W.F. Koch's free-radical work, Szent-Gyorgyi, Warburg, Gerson, and Broda Barnes. That tradition treated respiration and general resistance, not just the pathogen, as central to recovery. A modern echo of that light-linked mechanism: a meta-analysis of trials adding vitamin D to standard anti-TB drug therapy found it significantly raised the rate of sputum smear conversion (relative risk 1.12) and cut adverse events during treatment (relative risk 0.54), with the most consistent benefit in trials running 12 weeks or longer, though it did not significantly affect sputum culture conversion, a stricter outcome measure.

Practice (Tuberculosis)

Medical and public-health care. See Broda Barnes, Thyroid, Hypothyroidism, Harm reduction.