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 lacking in the diet. When enough protein is present in the diet, promoting serotonin synthesis does not lead to niacinamide deficiency, but conditions that increase estrogen's influence will also exacerbate serotonin-related dysfunctions."

September 2019 - Ray Peat's Newsletter

Estrogen, serotonin, and the cycle of water retention

"Estrogen increases serotonin production, and both substances boost prolactin formation, activate the renin-angiotensin system, and increase the release of the antidiuretic hormone vasopressin – all factors that synergize with estrogen and promote water retention. Serotonin, in turn, increases estrogen production, 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 raises the alkalinity of the blood, 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 leakage and serotonin's vicious cycle

"Any disruption of normal cell or tissue structure is recognized by the organism as a problem that must be corrected; the presence 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, which contribute to alarm and stress signals. Increased serotonin synthesis is one of the most important responses to leaked ATP and adenosine, but serotonin can amplify the disorder in the actin system and increase permeability – creating a vicious cycle."

September 2019 - Ray Peat's Newsletter

Serotonin production and the body's defense mechanisms

"The vast majority of serotonin in the body is produced in the gut, where the tissue is constantly exposed to foreign material such as endotoxin. But all cells in the body can produce serotonin and histamine under stress, and 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 great 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 the 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 has sought a way to explain the therapeutic benefit it claims. Mostly, the focus has been on the notion that SSRIs increase the synthesis of the progesterone metabolite allopregnanolone in the brain after several weeks of use. 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 cancer-typical metabolism where lactic acid is produced from glucose despite the presence of oxygen – is promoted by serotonin."

September 2019 - Ray Peat's Newsletter

Serotonin, Estrogen, and the Promotion of Pituitary Hormones

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

September 2019 - Ray Peat's Newsletter

The Costly Adaptations Caused by Serotonin Production

"Various types of stress increase the production of serotonin and different pituitary hormones, leading to adaptive responses of the organism – but at the cost of inflammation and degeneration. Studies on several pituitary hormones have shown aging-accelerating effects that lead 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 possibilities for finding ways to prevent the overproduction of serotonin and the associated hormones and cytokines."

September 2019 - Ray Peat's Newsletter

Biochemical Similarities of Lithium with Progesterone and Its Effects

"Several of the known biochemical effects of lithium resemble those of progesterone, including the antagonistic effect to 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 LSD doses. Another ergot-derived alkaloid, bromocriptine, is now used to suppress lactation (as caused, for example, by a prolactin-secreting pituitary tumor that can develop after the use of oral contraceptives) and is experimentally used 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 release. Prolactin excess is involved in breast cancer and other cell proliferation, probably also in the rapid cell division in psoriasis."

Nutrition For Women

Reducing prolactin excess with B6, thyroid, and progesterone

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

Nutrition For Women

Connection 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 production 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 to 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 with anti-inflammatory agents – 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 the ‘happiness hormone’ has led most people – even researchers – to ignore the fact that it enhances 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 – together with serotonin – one of the most important activators of corticotropin-releasing hormone (CRH), which activates the pituitary and adrenal glands, promotes inflammation, and is a key factor in PPD (Glynn and Sandman, 2014; Hahn-Holbrook, 2016) – as well as in other forms of depression, aging, and Alzheimer’s.”

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 affect women more often

“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, migraine, and Alzheimer’s – all conditions that occur much more frequently 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 after birth will be maintained. Instead of brain regeneration, the various pro-inflammatory effects of serotonin and estrogen then predominate – with consequences such as depression, joint pain, anxiety, and brain edema.”

May 2019 - Ray Peat's Newsletter

Stress, metabolic energy, and system integration

“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 in good health. However, if stress is very intense or prolonged, or nutrition has been insufficient, all activating signals – CRH itself and the anti-stress glucocorticoids – can produce effects that are not integrated into the organism’s functions as it faces its problems, causing symptoms and eventually 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 the mitochondria

"Levels of aldosterone and parathyroid hormone are increased by stress, with serotonin acting on the adrenal cortex and parathyroid gland to increase their secretion. All three of these hormones affect the mitochondria and reduce oxidative energy production."

May 2019 - Ray Peat's Newsletter

Factors for Healthier Pregnancies and a Better Life After Birth

"The main factors that can be optimized with available 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, fiber-rich foods, as well as 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) and the use of 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

"Environmental factors – or substances produced in response to environmental stress – that could cause autism include prenatal and neonatal radiation exposure, including isotopes from the energy industry, bomb tests, Chernobyl, and Fukushima; air pollution exposure, including nitrogen oxides, ozone, carbon monoxide, sulfur dioxide, and particulates (Jung et al., 2013); aluminum (Mold et al., 2018), lead, mercury, manganese, arsenic, cadmium, chromium, manganese, and nickel (Windham et al., 2006); acetaminophen, infections, endotoxin, exogenous and endogenous estrogens, hypothyroidism, progesterone deficiency, agmatine deficiency, serotonin excess, endogenous nitric oxide (Sweeten et al., 2004), as well as vitamin D deficiency."

May 2018 - Ray Peat's Newsletter

The Role of Endotoxin in Activating Inflammatory Processes

"Endotoxin, lipopolysaccharide, has a general excitatory effect that activates cellular inflammatory processes and damages energy production – mediated by cellular 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 gut, 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

“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 hyoscyamine and belladonna, which Charcot used, are sometimes employed to control excessive saliva flow. 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 called a neurotransmitter and viewed as transmitting information via receptors that is then processed – similar to how computers process digital information. I find it more helpful to consider 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.”