Melatonin

Melatonin is the pineal hormone whose secretion Ray Peat characterized as a primary endocrine signal of darkness and stress, fundamentally acting to induce a winter-like, sluggish metabolic state. 2 Peat argued that its production is triggered not simply by an absence of light, but by the adrenergic nervous stimulation that increases during the stress of darkness, driving the conversion of serotonin into melatonin within the pineal gland. 2 He consistently maintained that melatonin suppresses thyroid and progesterone production, shrinks the sex organs and the thymus gland, and increases estrogen, thereby damaging immunity and fertility. 3

Peat identified a crucial protective function for melatonin as an antidote to serotonin, a substance he viewed as a central mediator of inflammation and stress damage. 2 He explained that the adrenergic stress response activates enzymes that convert serotonin into melatonin, and that this same enzymatic activity appears in inflamed joint tissue and breast cancer, suggesting that melatonin production is a detoxifying response to pathological serotonin accumulation. 6 In a fatigued, de-energized brain state, Peat noted that melatonin can be effective at turning off a vicious cycle involving nitric oxide and acetylcholine, thereby protecting against excitatory damage. 2 He considered melatonin much safer than serotonin itself, but emphasized that its presence is evidence of an underlying stress response. 2

Regarding supplementation, Peat drew a sharp distinction between physiological and pharmacological doses. He cited research indicating that a true physiological dose is equivalent to roughly 5 micrograms for an average adult, and acknowledged that an amount much smaller than a milligram can induce sleep. 2 However, he expressed serious doubt about the safety of larger amounts, noting that animal studies showed melatonin could lower both progesterone and thyroid while increasing estrogen, and that its effects on the immune system and tumor growth are dose-dependent and sometimes contradictory. 3 He observed that while high-dose melatonin was used in experiments as an antioxidant protecting against gamma rays, the long-term consequences of such doses could include the involution of the thymus and reproductive systems, mirroring the effects of winter. 7

Peat extensively documented melatonin's role as a disease-promoting agent in chronic inflammatory conditions, particularly rheumatoid arthritis. 3 He cited studies showing that nocturnal plasma melatonin is higher in RA patients than in healthy controls, that melatonin is present in their synovial fluid, and that synovial macrophages express specific melatonin receptors, leading to enhanced inflammatory cytokine production. 1 He highlighted the circadian opposition between melatonin and cortisol, where the early morning peak of melatonin coincides with the lowest cortisol levels and the highest pro-inflammatory Th1-type cytokine activity, perpetuating the clinical symptoms of the disease. 8 This pro-inflammatory effect, observed at physiological amounts, reinforced his view that melatonin is fundamentally a hormone of the winter sickness, with reduced light exposure driving higher and more prolonged serum concentrations that disturb immune function. 2