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

Mechanism.

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.

Values below describe how Melatonin has been administered in published trials and 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.

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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.

Grade B

Grade B. 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.

Study quality

2 indexed studies in our dataset. Designs vary — see Research log for per-study grades.

Regulatory clarity

FDA-approved for at least one indication.

Safety profile

Based on 4 documented contraindications, 5 interactions, 3 lab checkpoints.

Long-term data

Years of post-approval surveillance available.

Part 05 · Research log

Every study we cite.

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

2013

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 ↗

2017

Melatonin as an antioxidant

Melatonin and its metabolites form an antioxidant cascade that is particularly effective in mitochondria

Review of strong mechanistic evidence

PMID 28204908 ↗

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.

What is the optimal dose of melatonin for my specific sleep issue?

Should I use immediate-release or extended-release melatonin?

How does melatonin interact with my blood pressure or diabetes medications?

Is long-term melatonin use safe, and does it suppress natural production?

What does the published oncology literature say about high-dose melatonin used adjunctively, and what are the limitations of that evidence?

At what time should I take melatonin relative to my desired bedtime?