Melatonin
A hormone naturally produced by the pineal gland to regulate the sleep-wake cycle. The most widely used sleep supplement globally, with strong evidence for circadian rhythm disorders.
What is Melatonin?
Melatonin is an endogenous indoleamine hormone synthesized from serotonin in the pineal gland during darkness. It serves as the body's primary chronobiotic signal, synchronizing circadian rhythms with the light-dark cycle and functioning as a potent direct free radical scavenger.
Known Health Benefits
How It Works
Melatonin synthesis begins when darkness signals the suprachiasmatic nucleus (SCN) to activate the sympathetic innervation of the pineal gland, triggering the enzymatic conversion of serotonin to N-acetylserotonin (by AANAT) and then to melatonin (by ASMT). Melatonin acts on two G-protein-coupled receptors: MT1 and MT2. MT1 receptors in the SCN inhibit neuronal firing, promoting sleepiness. MT2 receptors phase-shift circadian rhythms, which explains melatonin's efficacy for jet lag and delayed sleep phase. Beyond receptor-mediated effects, melatonin is a powerful direct antioxidant that scavenges hydroxyl radicals, singlet oxygen, and peroxynitrite — without requiring enzymatic cycling, each melatonin molecule can neutralize up to 10 reactive oxygen species through a cascading scavenging pathway. Melatonin also enhances the activity of glutathione peroxidase, superoxide dismutase, and catalase. It modulates immune function by enhancing T-helper cell production and natural killer cell activity. Melatonin stabilizes mitochondrial membrane potential and inhibits the mitochondrial permeability transition pore, protecting against apoptosis.
What Research Says
A meta-analysis by Ferracioli-Oda et al. (PLoS ONE, 2013) of 19 RCTs with 1683 participants found melatonin significantly reduced sleep onset latency by 7.06 minutes, increased total sleep time by 8.25 minutes, and improved overall sleep quality. For jet lag, a Cochrane review by Herxheimer & Petrie (2002) found melatonin remarkably effective for preventing or reducing jet lag when crossing five or more time zones. Brzezinski et al. (Sleep Medicine Reviews, 2005) confirmed melatonin's efficacy across multiple sleep parameters with no significant adverse effects. For shift work, a systematic review by Liira et al. (Cochrane, 2014) found limited but suggestive evidence for melatonin improving daytime sleep quality. Extended-release melatonin (Circadin 2 mg) is approved in Europe for insomnia in adults over 55, with the NEU-120 trial showing improved sleep quality and morning alertness without rebound or withdrawal. Melatonin's antioxidant capacity has been demonstrated in numerous studies to be several-fold greater than vitamin E or glutathione.
Active Compounds
N-acetyl-5-methoxytryptamine
Forms & Bioavailability
Oral melatonin has 15–33% bioavailability due to significant first-pass hepatic metabolism by CYP1A2. Sublingual delivery bypasses first-pass metabolism, achieving higher and faster peak levels. Half-life is 40–60 minutes for immediate-release, explaining why some people wake mid-sleep.
Dosage Guidance
| Use Case | Dosage |
|---|---|
| Sleep onset support | 0.5–3 mg, 30–60 min before bed |
| Jet lag (eastward travel) | 0.5–5 mg at destination bedtime |
| Delayed sleep phase syndrome | 0.5–1 mg, 3–5 hours before desired sleep |
| Shift work | 1–3 mg before daytime sleep |
Always consult a healthcare provider for personalized dosing.
Potential Side Effects
Drowsiness, vivid dreams, headache; may affect hormonal systems with long-term high doses
Who Should Avoid It
- Autoimmune conditions (melatonin stimulates immune activity)
- Seizure disorders (may lower seizure threshold in some)
- Depression (may worsen in susceptible individuals)
- Children under 3 without physician guidance
- Operating machinery within 4–5 hours of ingestion
Pregnancy & Lactation
Melatonin crosses the placenta and is present in breast milk, playing a role in fetal circadian rhythm development. However, exogenous melatonin supplementation during pregnancy is not well studied in humans. Some animal studies suggest protective effects, but clinical use during pregnancy should only occur under physician supervision.
Known Drug Interactions
May interact with blood thinners, diabetes medications, immunosuppressants, and sedatives
Evidence Classification
Supported by randomized controlled trials (RCTs), systematic reviews, or meta-analyses published in peer-reviewed journals.
Frequently Asked Questions
Is lower-dose melatonin really more effective?
Yes. Physiological melatonin production is 0.1–0.3 mg nightly. Doses of 0.5–1 mg often work as well as 5–10 mg for sleep onset, with fewer side effects like morning grogginess. Supraphysiological doses may actually desensitize MT1/MT2 receptors over time.
Is melatonin safe for long-term use?
Short-term use (weeks to months) is well established as safe. Long-term data is more limited but generally reassuring. European approval of extended-release melatonin for up to 13 weeks in adults over 55 provides regulatory confidence. Unlike benzodiazepines, melatonin does not cause dependence or withdrawal.
Can children take melatonin?
Melatonin is commonly used in children with ADHD, autism, and delayed sleep phase syndrome, with studies supporting 1–3 mg doses. However, long-term effects on pubertal development are unknown, and expert guidance recommends behavioral sleep interventions first.
Why do I have vivid dreams on melatonin?
Melatonin increases REM sleep duration and REM rebound, particularly in people with previously suppressed REM sleep. This often leads to more vivid, emotionally charged dreams. This effect is generally harmless but may be disturbing for some people.
Does melatonin affect hormones?
At physiological doses (0.5–3 mg), melatonin's hormonal effects are minimal. At very high doses (>10 mg), it may suppress GnRH and affect reproductive hormones. Melatonin naturally has mild anti-gonadotropic effects, which is why darkness (high melatonin) suppresses fertility in photoperiod-sensitive species.
What time should I take melatonin?
For sleep onset, take melatonin 30–60 minutes before desired bedtime. For circadian rhythm shifting (jet lag, delayed sleep phase), the timing relative to your current circadian phase is more important than the dose. For eastward travel, take at the destination's bedtime.
References
- Meta-analysis: melatonin for the treatment of primary sleep disorders. Ferracioli-Oda E, Qawasmi A, Bloch MH. PLoS ONE (2013)View study
- Melatonin for the prevention and treatment of jet lag. Herxheimer A, Petrie KJ. Cochrane Database of Systematic Reviews (2002)View study
- Effects of exogenous melatonin on sleep: a meta-analysis. Brzezinski A, Vangel MG, Wurtman RJ, et al.. Sleep Medicine Reviews (2005)View study
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This entry is for educational purposes only. It is not medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement regimen, especially if you take medications or have health conditions.