Melatonin
The pineal hormone that signals darkness to the body and entrains circadian rhythm. Most over-the-counter melatonin products are dosed at 3–10 mg, which is 10–20 times higher than a typical physiological nighttime level (roughly 0.1–0.3 mg equivalent). Low-dose use (0.3–1 mg) is generally preferred by sleep researchers for circadian re-entrainment, while higher doses are used more for their sedative effect. Melatonin also has direct antioxidant and mitochondrial-protective activity in preclinical models, which drives separate longevity-research interest distinct from its sleep use — an area where human evidence remains limited.
Mechanism of Action
Melatonin is synthesized from serotonin via AANAT and ASMT enzymes in the pineal gland and released in response to darkness. It binds MT1 and MT2 receptors in the suprachiasmatic nucleus (the body's master clock) to entrain circadian rhythm and promote sleep-associated drops in core body temperature. Independently of its receptor-mediated circadian role, melatonin has direct free-radical-scavenging and mitochondrial-protective activity in cell and animal models, which is the mechanistic basis for longevity-related interest, though this has not been shown to extend human healthspan or lifespan.
Dosing Protocol
0.5–3mg
Standard starting dose based on research
Therapeutic Range
0.3
Minimum
5
Maximum
30–60 minutes before intended sleep time; for circadian re-entrainment (jet lag, shift work), timing relative to the target time zone matters more than the absolute dose
Cycling Protocol
Best used short-term or intermittently (jet lag, shift transitions, temporary sleep disruption); avoid indefinite nightly use above 1–3 mg without periodic reassessment, given limited long-term safety data at supraphysiologic doses
Dosages are general guidelines. Individual requirements vary based on body weight, health status, and specific goals. Start with lower doses and adjust based on response.
Benefits
Primary Benefits
- Modestly reduces sleep onset latency and helps re-entrain circadian rhythm for jet lag, shift work, and delayed sleep phase
- Low doses (0.3–1 mg) approximate physiological nighttime levels and are generally preferred over high-dose sedative use for circadian applications
- Direct antioxidant and mitochondrial-protective activity in preclinical models supports ongoing longevity research, though human evidence for anti-aging benefit is currently lacking
Secondary Benefits
Safety Information
Contraindications
Do not use if any of the following apply:
- •Autoimmune disease — melatonin can stimulate immune activity
- •Pregnancy and breastfeeding — insufficient safety data at supplemental doses
- •Children — use only under pediatric medical guidance
- •A large 2025 retrospective analysis (130,828 adults with chronic insomnia, presented as a preliminary abstract at the American Heart Association Scientific Sessions 2025, not yet peer-reviewed) found higher rates of heart failure diagnosis, heart-failure hospitalization, and all-cause mortality in adults using melatonin for one year or more versus non-users. Causality is unconfirmed — it is observational, and chronic insomnia itself is an independent cardiovascular risk factor — but it supports using the lowest effective dose for the shortest necessary duration rather than indefinite high-dose use
Drug/Supplement Interactions
May interact with the following. Consult a healthcare provider before combining:
Potential Side Effects
Some users may experience:
This is not a complete list of interactions or side effects. Individual responses vary. Always start with the lowest effective dose and monitor your response. Report any adverse effects to your healthcare provider.
Quality Markers
Look for these specific quality indicators when sourcing this compound:
- U.S. over-the-counter melatonin is regulated as a supplement, not a drug; independent testing matters — prior product-testing surveys have found actual content ranging from well below to nearly 5x the labeled dose in some products
- Prefer products independently verified for label-claim accuracy (e.g., USP-verified or comparable third-party testing)
- Immediate-release formulations suit sleep onset; extended or controlled-release formulations are sometimes preferred for sleep maintenance or in older adults
Trusted Certifications
Note: Supplement quality varies dramatically between brands. Cheap supplements often contain fillers, incorrect doses, or contaminants. Investing in quality products from reputable manufacturers is essential for safety and efficacy.
Evidence Profile
Evidence Score
5/10
Moderate Evidence
Some clinical trials with positive results, emerging research
Evidence Scale
8-10
Strong
5-7
Moderate
1-4
Emerging
Sample member
Longevity Operator
One number for your longevity journey.
FICO for credit. PHS for longevity. Eight biological domains collapsed into one provable score — intuitive at a glance, rigorous underneath.
- Metabolic
- Hormonal
- Cardiovascular
- Brain / Cognitive
- Sleep
- Musculoskeletal
- Gut
- Immunity / Inflammation