Melatonin

Indoleamine synthesized from tryptophan in the pineal gland and present in foods including pistachios, tart cherries, and eggs. Circadian regulator and potent mitochondrial antioxidant. Food-sourced doses are orders of magnitude lower than supplement doses.

Melatonin is an indoleamine synthesized from the amino acid tryptophan in the pineal gland, and is also present in various foods including pistachios, tart cherries, and eggs. It is best known as a circadian rhythm regulator and potent mitochondrial antioxidant.

Mechanism of action

Melatonin acts as a free radical scavenger that protects mitochondria from oxidative damage, a process thought to be relevant to aging and age-related diseases. It also helps regulate circadian rhythms by binding to melatonin receptors, which synchronize the body's sleep-wake cycle and may support cellular repair processes that occur during sleep. Additionally, melatonin may activate antioxidant enzymes and indirectly reduce oxidative stress through receptor-independent mechanisms. The bioavailability and physiological effects differ substantially between food-sourced doses (typically micrograms) and supplement doses (milligrams).

Evidence overview

Published evidence on melatonin's longevity-relevant effects comes primarily from cell culture and animal model studies, which demonstrate its antioxidant and circadian-regulatory properties. Observational and prospective studies have associated better sleep quality and circadian alignment with longer healthspan and reduced age-related disease risk, suggesting potential indirect benefits of melatonin through circadian support. However, randomized controlled trials examining melatonin supplementation's effects on aging or longevity in humans remain limited, and long-term safety and optimal dosing for anti-aging purposes have not been definitively established. Food-sourced melatonin provides only trace amounts compared to supplement doses, which raises questions about whether dietary sources confer measurable longevity benefit. Note: Specific evidence from the Verisource evidence pipeline is not yet available for this compound; this summary is based on general scientific knowledge.

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