Ray Peat on serotonin

January 29, 2026

Estrogen's influence on tryptophan metabolism

"Estrogen strongly influences tryptophan metabolism by promoting its conversion to serotonin – at the expense of niacinamide. This explains the symptoms of pellagra when tryptophan is deficient in the diet. When sufficient protein is present in the diet, the promotion of serotonin synthesis does not lead to a niacinamide deficiency, but conditions that increase the influence of estrogen will also exacerbate the dysfunctions associated with serotonin."

September 2019 - Ray Peat's Newsletter

Estrogen, serotonin and the water retention cycle

"Estrogen increases the production of serotonin, and both substances increase the production of prolactin, activate the renin-angiotensin system, and increase the release of the antidiuretic hormone vasopressin – all factors that work synergistically with estrogen and promote water retention. Serotonin, in turn, increases the production of estrogen, so a vicious cycle can easily develop under stress."

September 2019 - Ray Peat's Newsletter

Hyperventilation, CO₂ loss and serotonin release

"Hyperventilation tends to increase under various forms of stress, and the resulting loss of carbon dioxide increases blood alkalinity, causing platelets to release serotonin. Estrogen stimulation and hypothyroidism are common causes of chronic hyperventilation – with their effect on platelets releasing serotonin, with all its harmful consequences."

September 2019 - Ray Peat's Newsletter

ATP exit and serotonin's vicious cycle

"Any disruption of normal cell or tissue structure is recognized by the organism as a problem that needs to be corrected; the appearance of ATP outside the cells is a fundamental sign of damage and danger. Special enzymes break down extracellular ATP into ADP, AMP, adenosine, and other purines, and these contribute to alarm and stress signals. Increased serotonin synthesis is one of the most important responses to leaked ATP and adenosine, but serotonin can exacerbate disorder in the actin system and increase permeability—in a vicious cycle."

September 2019 - Ray Peat's Newsletter

Serotonin production and the body's defense mechanisms

"By far the largest proportion of serotonin in the body is produced in the gut, where the tissue is constantly exposed to foreign material such as endotoxins. But all cells in the body can produce serotonin and histamine under stress, and blood platelets are one of the body's defense mechanisms against serotonin: they can sequester it and transport it to the lungs for destruction. The lungs have a large capacity to oxidize it."

September 2019 - Ray Peat's Newsletter

Spread of damage through bystander effects

"Severe stress in one part of the body spreads its influence throughout the entire body – through a process now known as the bystander or off-target effect. Serotonin, nitric oxide, and ATP are among the substances known to propagate damage."

September 2019 - Ray Peat's Newsletter

SSRIs, serotonin myths, and the synthesis of allopregnanolone in the brain

"Since it was not possible to provide evidence for the idea that serotonin is a mood-enhancing 'happiness hormone,' the industry sought a way to explain the therapeutic benefits it claims. Most often, it settled on the notion that after several weeks of use, SSRIs increase the synthesis of the progesterone metabolite allopregnanolone in the brain. This does indeed happen, but the synthesis of these protective steroids is also increased by any brain injury."

September 2019 - Ray Peat's Newsletter

Aerobic glycolysis and lactic acid in cancer metabolism

“Aerobic glycolysis – the metabolism typical of cancer, in which lactic acid is formed from glucose despite the presence of oxygen – is promoted by serotonin.”

September 2019 - Ray Peat's Newsletter

Serotonin, estrogen, and the stimulation of pituitary hormones

"Serotonin, along with estrogen, is the most important promoter of prolactin release, and it also promotes TSH, ACTH, FSH, LH, GH, MSH, POMC, vasopressin and oxytocin – that is, all pituitary hormones."

September 2019 - Ray Peat's Newsletter

The costly adaptations through serotonin production

“Various types of stress increase the production of serotonin and various pituitary hormones, leading to adaptive responses in the body—but at the cost of inflammation and degeneration. Studies of several pituitary hormones have shown age-accelerating effects, leading to edema, inflammation, fibrosis, and a shortened lifespan. W.D. Denckla’s experiments, which demonstrated a strong life-extending effect of removing the pituitary gland—while simultaneously supplementing thyroid and glucocorticoid hormones—suggest the possibility of finding ways to prevent the overproduction of serotonin and its associated hormones and cytokines.”

September 2019 - Ray Peat's Newsletter

Biochemical similarities between lithium and progesterone and its effects

"Several of the known biochemical effects of lithium are similar to those of progesterone, including the antagonistic effect on aldosterone, the alteration of serotonin metabolism, the increase of nerve thresholds and the facilitated processing of ammonia."

Nutrition For Women

Psychoactive substances and their effects on chronic diseases

“During LSD research, it was observed that people with chronic headaches, asthma, or psoriasis sometimes fully recovered during treatment with frequent doses of LSD. Another alkaloid derived from ergot, bromocriptine, is now used to suppress lactation (such as that caused by a prolactin-secreting pituitary tumor that develops after the use of oral contraceptives) and is being used experimentally to treat Parkinson's disease. Both LSD and bromocriptine shift the ratio of two brain chemicals, DOPA and serotonin, toward DOPA dominance. One consequence of this is the inhibition of prolactin secretion. Excess prolactin is implicated in breast cancer and other cell proliferation, and probably also in the rapid cell division seen in psoriasis.”

Nutrition For Women

Reduction of excess prolactin with vitamin B6, thyroid function and progesterone

"All the effects of excess prolactin (including amenorrhea) that respond to an increase in the DOPA/serotonin ratio can also be achieved to some extent by other, more readily available means. Vitamin B6, thyroid function, and progesterone all have this effect."

Nutrition For Women

Relationship between tryptophan, serotonin, prolactin and acne

"Since tryptophan promotes the formation of serotonin, which stimulates the release of prolactin, and prolactin in turn activates the formation of sebum (skin oil) in the skin, large amounts of milk – in the case of a deficiency of B6, thyroid, progesterone, etc. – could promote a tendency towards acne."

Nutrition For Women

Anti-inflammatory treatments in response to the new coronavirus

"In response to the new coronavirus, some groups reacted quickly and successfully treated patients with anti-inflammatory drugs – losartan, cinanserin (a serotonin antagonist), aspirin, as well as azithromycin or erythromycin, which lower intracellular calcium. The effects of aspirin overlap with those of losartan, and it downregulates the angiotensin receptor ATR1."

May 2020 - Ray Peat's Newsletter

Serotonin: Beyond the myth of the "happiness hormone"

"The pharmaceutical myth of serotonin as a 'happiness hormone' has led most people – even researchers – to ignore the fact that it increases inflammation and activates the stress system, while reducing the efficiency of energy production."

May 2019 - Ray Peat's Newsletter

Estrogen, serotonin, and manipulation by pharmaceutical companies

"The manipulation of information about estrogen by pharmaceutical companies was even more extreme than their handling of serotonin. Activated by stress, it is—along with serotonin—one of the most important activators of corticotropin-releasing hormone (CRH), which activates the pituitary gland and adrenal glands, promotes inflammation, and is an important factor in PPD (Glynn and Sandman, 2014; HahnHolbrook, 2016)—as well as in other forms of depression, aging, and Alzheimer's disease."

May 2019 - Ray Peat's Newsletter

Estrogen increases serotonin synthesis in the brain.

"Estrogen increases the brain's ability to synthesize serotonin."

May 2019 - Ray Peat's Newsletter

Estrogen, serotonin, and diseases that more commonly affect women

"If it weren't for advertising culture, it would probably be generally accepted that both estrogen and serotonin play an important role in the development of depression, migraines, and Alzheimer's disease – all conditions that are much more common in women than in men."

May 2019 - Ray Peat's Newsletter

Postpartum progesterone and brain health

"With insufficient cholesterol, it is unlikely that the normally high progesterone concentration will be maintained after childbirth. Instead of brain regeneration, the various pro-inflammatory effects of serotonin and estrogen then predominate – with consequences such as depression, joint pain, anxiety and cerebral edema."

May 2019 - Ray Peat's Newsletter

Stress, metabolic energy and system integration

"In good health, the stimulation of CRH production by histamine, serotonin, endorphins, IL-1, nitric oxide, and/or estrogen leads to the activation of complex and appropriate anti-stress responses. However, if stress is very intense or prolonged, or if nutrition has been inadequate, all the activating signals—CRH itself and the anti-stress glucocorticoids—can produce effects that are not integrated into the organism's functions as it copes with its problems, causing symptoms and ultimately degenerative processes and aging. This failure of integration is almost always the result of insufficient metabolic energy."

May 2019 - Ray Peat's Newsletter

Effects of stress hormones on mitochondria

"The levels of aldosterone and parathyroid hormone are increased by stress, with serotonin acting on the adrenal cortex and parathyroid glands and increasing their secretion. All three of these hormones act on the mitochondria and lower oxidative energy production."

May 2019 - Ray Peat's Newsletter

Factors for healthier pregnancies and a better life after birth

"The most important factors that can be optimized with existing resources. Healthier pregnancies lead to a healthier and happier life after birth. These factors include sunlight, vitamin D, milk, cheese, eggs, fruits and well-cooked vegetables, high-fiber foods, and optimizing thyroid function and pregnenolone and progesterone (which support mitochondrial function and protect against aldosterone, parathyroid hormone, excess serotonin, CRK, and cortisol—in addition to increasing allopregnanolone), as well as using the safest anti-inflammatory and antiserotonergic medications, such as aspirin and cyproheptadine, when needed."

May 2019 - Ray Peat's Newsletter

Environmental factors that may contribute to autism

“Things in the environment—or substances that arise in response to environmental stress—that could cause autism include prenatal and neonatal radiation exposure, including isotopes from the energy sector, bomb tests, Chernobyl, and Fukushima; exposure to air pollution, including nitrogen oxides, ozone, carbon monoxide, sulfur dioxide, and particulate matter (Jung et al., 2013); aluminum (Mold et al., 2018), lead, mercury, manganese, arsenic, cadmium, chromium, manganese, and nickel (Windham et al., 2006); acetaminophen, infections, endotoxins, exogenous and endogenous estrogens, hypothyroidism, progesterone deficiency, agmatine deficiency, serotonin excess, endogenous nitric oxide (Sweeten et al., 2004), and vitamin D deficiency.”

May 2018 - Ray Peats Newsletter

The role of endotoxin in the activation of inflammatory processes

"Endotoxin, a lipopolysaccharide, has a generally excitatory effect that activates cellular inflammatory processes and impairs energy production – mediated by cell products such as nitric oxide, carbon monoxide, serotonin, histamine, prostaglandins, estrogens, and various cytokines (interleukins and tumor necrosis factor, TNF). Some of these substances enter the bloodstream from the intestine, others are produced elsewhere in the body, but some are also formed in the brain itself when endotoxin is taken up into the brain."

March 2017 - Ray Peat's Newsletter

Evaluation of L-DOPA and alternative treatments for Parkinson's disease

"Despite its toxicity, L-DOPA remains the primary medical treatment for Parkinson's disease, although the more suitable drugs bromocriptine, amantadine, and memantine are also widely used. Anticholinergics, similar to the hyoscyamine and belladonna used by Charcot, are sometimes employed to control excessive salivation. Amantadine and memantine incidentally protect against nitric oxide, serotonin, inflammation, and endotoxin, and also protect the mitochondria."

March 2017 - Ray Peat's Newsletter

Serotonin: more than just a “neurotransmitter”

"Serotonin is often described as a neurotransmitter and viewed as transmitting information via receptors, which is then processed – much like computers process digital information. I find it more helpful to think of it in terms of fields and formative processes that shape how the organism uses energy to adapt to stress and opportunities. It is involved in the energetic and structural changes that occur during stress and adaptation."