Library / Peptides / Longevity & Anti-Aging / Melatonin
Strong evidence · Grade A

Melatonin

Melatonin (N-acetyl-5-methoxytryptamine)
Evidence
Strong Evidence
Route
Oral
Frequency
Once daily, 30-60 minutes before bed
Category
Longevity & Anti-Aging
TL;DR
Melatonin is an endogenous hormone produced primarily by the pineal gland in response to darkness, serving as the body's master circadian rhythm regulator. It is one of the most widely studied and used supplements globally, with strong evidence for treating circadian rhythm disorders, insomnia, and jet lag.
Part 01 · How it works

Mechanism.

Melatonin is an endogenous hormone produced primarily by the pineal gland in response to darkness, serving as the body's master circadian rhythm regulator. It is one of the most widely studied and used supplements globally, with strong evidence for treating circadian rhythm disorders, insomnia, and jet lag. Beyond sleep, melatonin is a potent antioxidant and has emerging roles in immune modulation, neuroprotection, and oncology support.

Melatonin is your body's internal sunset signal — when darkness falls, the pineal gland releases it to tell every cell in your body that it's nighttime. Taking melatonin is like manually dimming the lights in your body's control room when the automatic dimmer isn't working properly.

Mechanism · technical
Melatonin acts through two G-protein coupled receptors, MT1 and MT2, located in the suprachiasmatic nucleus (SCN) of the hypothalamus and throughout peripheral tissues. MT1 activation promotes sleep onset by inhibiting SCN neuronal firing, while MT2 helps phase-shift circadian rhythms. Beyond receptor-mediated actions, melatonin is a direct free radical scavenger, neutralizing hydroxyl radicals and stimulating antioxidant enzymes (SOD, glutathione peroxidase, catalase). It also modulates immune function by enhancing T-helper cell activity and has inflammation-modulating effects through NF-kB inhibition.
Part 02 · Dosing & administration

How it's taken.

Clinical · trial-validated

Values below describe how Melatonin has been administered in human clinical trials and/or approved labeling. Provided for educational purposes only — this is not medical advice and not instructions for self-administration. Consult your healthcare provider before making any health decision.

Standard dose
0.5-5 mg (sleep); up to 10-20 mg (antioxidant/oncology research)
Oral · Once daily, 30-60 minutes before bed
Duration
Ongoing as needed

OTC supplement. Start with lowest effective dose (0.5-1 mg often sufficient). Extended-release forms may help with sleep maintenance. Higher doses used in research for antioxidant and oncology applications.

Need help with reconstitution?

Use the free peptide calculator for dilution, unit conversion, and injection volume.

Open calculator
Part 03 · Safety

Side effects, rare serious events, who shouldn't.

Reported side effects
Melatonin is generally very well tolerated. Common side effects include daytime drowsiness, headache, dizziness, and vivid dreams. Less common effects include short-term depressive symptoms, mild anxiety, abdominal cramps, and irritability. Melatonin can lower blood pressure and may interact with anticoagulants, antihypertensives, diabetes medications, and immunosuppressants. It does not appear to cause dependence or withdrawal.
Absolute · do not use
×
Known hypersensitivity to melatonin or any component
×
Autoimmune conditions (melatonin stimulates immune function; use with caution)
×
Seizure disorders (mixed evidence; consult neurologist)
×
Pregnancy or breastfeeding (exogenous melatonin may affect reproductive hormones)
Interactions
Benzodiazepines and sedatives
Additive sedation; may cause excessive drowsiness
Moderate
Anticoagulants (warfarin)
Melatonin may affect platelet aggregation and enhance anticoagulant effect
Moderate
Immunosuppressants
Melatonin stimulates immune function and may oppose immunosuppressive therapy
Moderate
Antihypertensives
Melatonin can lower blood pressure; additive hypotensive effect possible
Minor
Fluvoxamine
Fluvoxamine inhibits CYP1A2, dramatically increasing melatonin levels
Moderate
Labs to monitor
Melatonin Level (optional, saliva or serum)
Baseline (optional)
Assess baseline endogenous production
TSH
Baseline and annually
Melatonin can modestly affect thyroid function
CMP (Comprehensive Metabolic Panel)
Annually for chronic use
General metabolic safety for higher doses
Part 04 · Evidence

How strong is the evidence?

Scores derived from rating, indexed studies, regulatory status, and catalogued safety data for this peptide. Curated per-peptide scoring replaces this when available.

86
Grade A
Grade A. Evidence is strongest where indications match regulatory approval — pair with a clinician when applying beyond label.
Clinical efficacy
Rating reflects consistent peer-reviewed evidence in its indication.
86
Study quality
6 indexed studies in our dataset. Designs vary — see Research log for per-study grades.
90
Regulatory clarity
FDA-approved for at least one indication.
90
Safety profile
Based on 4 documented contraindications, 5 interactions, 3 lab checkpoints.
88
Long-term data
Years of post-approval surveillance available.
74
Part 05 · Research log

Every study we cite.

Each study with its published finding and a plain-language note on limitations or funding.

01
2013
0
Meta-analysis of melatonin for sleep disorders
Melatonin reduced sleep onset latency by ~7 min and increased total sleep time by ~8 min
Large meta-analysis of 19 RCTs; statistically significant but modest effect sizes
PMID 23691095 ↗
02
2016
0
Melatonin as an antioxidant
Melatonin and its metabolites form an antioxidant cascade that is particularly effective in mitochondria
Review of strong mechanistic evidence
PMID 27500468 ↗
03
2026
0
Melatonin receptor signaling in disease (review)
A review summarized melatonin receptor (MTNR1A) signaling and associated single-nucleotide polymorphisms, linking receptor dysfunction to osteoporosis, diabetes, cancer and neurodegenerative disease.
04
2026
0
Melatonin in circadian rhythm and brain health (review)
A review synthesized evidence for melatonin's circadian, antioxidant and neuroprotective effects in brain aging and neurodegenerative disease, emphasizing that evidence strength varies and many findings derive from small trials or animal models.
05
2026
0
Structure of melatonin-related receptor GPR50 (cryo-EM)
A cryo-EM study determined the structure of the melatonin-related orphan receptor GPR50, providing a platform for identifying its ligands and clarifying its signaling.
06
2026
0
Melatonin agonists in insomnia management (review)
A clinical review listed melatonin receptor agonists among evidence-based options for short-term pharmacologic management of insomnia, with cognitive behavioral therapy as first-line.
Part 06 · Cost & access

Where you can get it.

Regulatory status
In the United States, melatonin is classified as a dietary supplement and available without a prescription. In the EU, Australia, and some other countries, it is a prescription medication (e.g., Circadin is approved in the EU for insomnia in patients over 55). Tasimelteon (Hetlioz), a melatonin receptor agonist, is FDA-approved for non-24-hour sleep-wake disorder.
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Part 07 · Your appointment

Questions to bring.

01
What is the optimal dose of melatonin for my specific sleep issue?
02
Should I use immediate-release or extended-release melatonin?
03
How does melatonin interact with my blood pressure or diabetes medications?
04
Is long-term melatonin use safe, and does it suppress natural production?
05
What does the published oncology literature say about high-dose melatonin used adjunctively, and what are the limitations of that evidence?
06
At what time should I take melatonin relative to my desired bedtime?
References

Every citation, numbered.

Citation list. For our editorial read of each study — including bias flags and quality grades — see the Research log above.

  1. 01.
    Meta-analysis of melatonin for sleep disorders · 2013 · PMID 23691095 ↗
  2. 02.
    Melatonin as an antioxidant · 2016 · PMID 27500468 ↗
  3. 03.
    Melatonin receptor signaling in disease (review) · 2026
  4. 04.
    Melatonin in circadian rhythm and brain health (review) · 2026
  5. 05.
    Structure of melatonin-related receptor GPR50 (cryo-EM) · 2026
  6. 06.
    Melatonin agonists in insomnia management (review) · 2026