⚠ Restricted by at least one regulator (MHLW) — see Regulatory alerts by country below.
⚠ Product quality varies dramatically: actual content ranged from 83% below to 478% above label claim across commercial products [5].
⚠ Prescription-only in the EU, Australia, and Japan. OTC only in the US and Canada [2].
⚠ Beta-blockers suppress endogenous melatonin secretion. Melatonin supplementation may help restore sleep in beta-blocker users [1].
ℹ️ Not obtained from food. Not tracked as a daily dietary target — the body makes melatonin itself; only trace amounts occur in food.
☑ Risk checker
Aging (pineal calcification reduces melatonin production by 10–15% per decade after age 20) [6]
Evening blue light exposure (screens, LED lighting suppress melatonin onset) [6]
Shift work (disrupted light-dark cycle) [6]
Total blindness (no photic input to SCN for circadian entrainment) [6]
Beta-blocker use (propranolol inhibits pineal melatonin synthesis via β1-adrenergic blockade) [9]
Chronic alcohol use (suppresses nocturnal melatonin peak) [6]
Caffeine consumption in evening (suppresses melatonin via adenosine receptor antagonism) [9]
Select factors
🔬 Lab interpreter
Recommended test
Salivary melatonin (dim light melatonin onset — DLMO)
Salivary melatonin (dim light melatonin onset — DLMO)
Reference range / target
DLMO typically occurs 2–3 hours before habitual sleep onset. Measured in dim light (<30 lux) with serial samples every 30 minutes [6]
DLMO typically occurs 2–3 hours before habitual sleep onset. Measured in dim light (<30 lux) with serial samples every 30 minutes [6]
When to test
Circadian rhythm disorder assessment; delayed sleep-wake phase disorder diagnosis
Full lab monitoring ↓Circadian rhythm disorder assessment; delayed sleep-wake phase disorder diagnosis
⚕ For professionals — confirm ranges against your local laboratory.
Clinical verdict
Start with 0.5–1 mg, not 5–10 mg. Most commercial products are 10–50 fold above physiologic doses [1]. Effective for jet lag (0.5–5 mg at destination bedtime) [3] and delayed sleep-wake phase disorder [1]. Reduces sleep onset latency by approximately 7 minutes versus placebo [4]. Not a sedative — it shifts circadian phase, not depth of sleep.
1 How much do I need?
👤 Adults: Specific dosage data under clinical review
👴 Elderly: Specific dosage data under clinical review
🤰 Pregnancy: See guidance
Insufficient safety data. American Academy of Sleep Medicine advises against use during pregnancy.
👦 Pediatric: Specific dosage data under clinical review
🏃 Athletes: Standard dose
⚖️ Obesity: Standard dose
Fat-soluble compounds may require dose adjustment in obesity.
🩺 Renal: Consult specialist
Dose adjustment may be needed in renal impairment.
🌱 Vegan: Standard dose
How to take
🍽 Timing: 30–60 minutes before desired sleep time for sleep onset. For circadian rhythm disorders, timing is critical — administer at the same time nightly to entrain the clock [6].
💊 With food: Can be taken with or without food. High-fat meals may delay absorption of immediate-release forms [6].
2 Which form?
| Form | Bioavailability | Vegan | Cost |
|---|---|---|---|
| ['Immediate-release tablets/capsules', 'common', 'Standard form. Peak plasma in 20–60 minutes. Best for sleep onset difficulty. Duration 4–5 hours. Most studied form [6].'] | Standard | Check label | |
| ['Extended-release (Circadin)', 'preferred', 'Prescription in EU (2 mg). Mimics physiological secretion pattern. Better for sleep maintenance than immediate-release. FDA-approved for insomnia in adults >55 in some countries [7].'] | Standard | Check label | |
| ['Sublingual tablets', '', 'Absorbed directly through oral mucosa. Faster onset (10–20 minutes). Bypasses first-pass metabolism. Higher bioavailability than swallowed tablets [6].'] | Standard | Check label | |
| ['Liquid/drops', '', 'Allows precise low-dose titration (0.1–0.5 mg). Useful for children and patients needing micro-dosing. Absorbed sublingually if held in mouth [6].'] | Standard | Check label | |
| ['Gummies', 'common', 'Popular consumer form. Often contain 1–10 mg per gummy. May contain added sugar and flavoring. Dose accuracy varies between brands [6].'] | Standard | Check label |
3 Common questions
What is the correct dose of melatonin? ▼
Start with the lowest effective dose: 0.5–1 mg for sleep onset, taken 30–60 minutes before bedtime. Most commercial products are significantly overdosed (5–10 mg), which exceeds physiologic levels by 10–50 fold. Higher doses do not improve sleep quality and may cause grogginess, vivid dreams, and next-day drowsiness [1]. For jet lag, 0.5–5 mg at destination bedtime.
Is melatonin safe for daily long-term use? ▼
Short-term use (up to 3 months) is well-established as safe [4]. Long-term daily use lacks robust safety data. Concerns include potential suppression of endogenous melatonin production (though evidence is limited), hormonal effects (melatonin inhibits GnRH), and interaction with glucose metabolism. Periodic breaks are advisable for chronic users.
Why is melatonin prescription-only in Europe but OTC in the United States? ▼
Regulatory philosophy differs: the EU classifies melatonin as a medicinal product requiring physician oversight, particularly the prolonged-release 2 mg formulation (Circadin) approved for primary insomnia in adults over 55 [2]. The US classifies it as a dietary supplement with no dose regulation. This regulatory gap means US products have highly variable quality and potency [5].
Does melatonin interact with blood pressure medications? ▼
Melatonin may reduce the efficacy of some antihypertensive drugs (calcium channel blockers in particular) and potentiate the effect of others. Beta-blockers (propranolol, atenolol) suppress endogenous melatonin secretion, which may contribute to insomnia in patients on these drugs. Melatonin supplementation may help restore sleep quality in beta-blocker users [1].
4 Clinical evidence
Strong
Jet lag: 0.5–5 mg at destination bedtime for eastward travel reduces jet lag severity and sleep onset latency (Cochrane review of 10 trials) [3]. Delayed sleep-wake phase disorder: 0.3–5 mg taken 2–4 hours before desired bedtime advances circadian phase [1]. Sleep onset latency reduction: meta-analysis of 19 trials (n = 1,683) found melatonin reduces time to fall asleep by approximately 7 minutes versus placebo [4]. HIGH
Moderate
Shift work sleep disorder: 1–3 mg before daytime sleep improves total sleep duration [1]. Preoperative anxiety: 3–5 mg given 60–90 minutes before surgery reduces preoperative anxiety comparably to midazolam in some trials [1]. Pediatric sleep disorders in children with neurodevelopmental conditions (autism spectrum disorder, ADHD): 1–5 mg reduces sleep onset latency by 20–40 minutes [1]. MODERATE
Insufficient
Anti-aging effects: despite theoretical mechanisms involving antioxidant and mitochondrial protection, human longevity data does not exist [1]. Cancer treatment adjunct: some preclinical promise but insufficient clinical trial evidence [1]. COVID-19 treatment: observational associations reported but no randomized trial confirmation [1]. LOW
5 Safety, toxicity & adverse events
Relative
⚠ Autoimmune diseases — melatonin is immunostimulatory (enhances Th1 response)
⚠ Concurrent anticoagulants — melatonin may increase bleeding risk
⚠ Concurrent antihypertensives — additive blood pressure reduction
⚠ Concurrent fluvoxamine — CYP1A2 inhibition increases melatonin levels 17-fold
⚠ Seizure disorders — mixed evidence; may lower seizure threshold in some individuals
⚠ Depression — may worsen in some individuals
🚩 Red flags
● Excessive daytime sleepiness in patient taking >5 mg melatonin — likely supraphysiological; reduce to 0.3–1 mg [8]
● Patient on fluvoxamine + melatonin — 12×–17× increase in melatonin levels; dramatically reduce melatonin dose [9]
● Supplement quality: 71% of melatonin products deviate >10% from label claim; 26% contain serotonin as contaminant — recommend third-party tested products only [8]
● Child receiving adult melatonin dose (5–10 mg) — pediatric dose is 0.5–3 mg [6]
● Melatonin used as sole treatment for obstructive sleep apnea — it is not a treatment for OSA; polysomnography needed [6]
● Patient on immunosuppressants using melatonin — potential immunostimulatory conflict [6]
6 Interactions
Drug interactions
Fluvoxamine Major
Mechanism: Fluvoxamine is the most potent CYP1A2 inhibitor among SSRIs. Increases melatonin AUC by 12–17× and peak plasma concentration by ~12× [9].
Benzodiazepines and Z-drugs (zolpidem, zopiclone) Moderate
Mechanism: Additive GABAergic sedation. Melatonin may allow dose tapering of benzodiazepines in chronic users [6].
Warfarin Moderate
Mechanism: Mechanism unclear. Case reports of INR elevation with melatonin co-administration [9].
Nifedipine Minor
Mechanism: Melatonin may reduce the antihypertensive efficacy of nifedipine via competitive GABA receptor effects. Clinical data limited [6].
Caffeine Minor
Mechanism: Both metabolized by CYP1A2. Caffeine may increase melatonin levels modestly by competitive inhibition. Evening caffeine also suppresses endogenous melatonin secretion [9].
7 Regulatory
United States (FDA): Classified as a dietary supplement (OTC). No dose restriction. Product quality varies widely; not subject to pharmaceutical-grade manufacturing requirements.
European Union (EMA): Prescription medication. Circadin (prolonged-release melatonin 2 mg) approved for primary insomnia in patients aged 55 and older. Not available OTC.
Japan (PMDA): Prescription only. Ramelteon (melatonin receptor agonist) is available instead.
Australia (TGA): Schedule 4 (prescription only) for tablets above 2 mg. Recently reclassified to allow low-dose (up to 2 mg) OTC sales for adults over 55.
8 Regulatory alerts by country
3 regulatory actions on record — 2 with a verified source link, 1 with the official reference being verified.
Restricted · 3
🇯🇵
MHLW — Not approved as food supplement. Classified as pharmaceutical.
Japan MHLW classification — pharmaceutical/restricted status or mandatory safety labelling for this substance.
2024-01-01 · official reference being verified
🇦🇺
TGA — Schedule 4 (Rx only) for >2mg. Schedule 3 (pharmacist only) for ≤2mg since 2021.
Listed in the Poisons Standard (SUSMP), Therapeutic Goods (Poisons Standard—February 2026) Instrument 2026.
Source ↗ · 2026-02-01
🇪🇺
Various — Rx-only in many EU states (UK, Germany, Australia). OTC at low doses in some.
EFSA opinion underpins EU melatonin use; several EU states restrict melatonin >1–2 mg to medicinal status.
Source ↗ · 2010-01-01
9 US supplement products
250
on-market products containing Melatonin (NIH DSLD)
Brands carrying Melatonin (139)
Click a brand to see its Melatonin products.
10 Frequently paired with
11 References (5)
[1]National Institutes of Health, Office of Dietary Supplements. Melatonin: What You Need to Know. Updated 2024. www.nccih.nih.gov REVIEW Accessed: 2026-05-29
[2]European Medicines Agency. Circadin: EPAR summary for the public. www.ema.europa.eu REVIEW Accessed: 2026-05-29
[3]Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev. 2002;(2):CD001520. doi:10.1002/14651858.CD001520 REVIEW Accessed: 2026-05-29
[4]Ferracioli-Oda E, et al. Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS One. 2013;8(5):e63773. doi:10.1371/journal.pone.0063773 META-ANALYSIS Accessed: 2026-05-29
[5]Erland LA, Bhawsar PF. Melatonin natural health products and supplements: presence of serotonin and significant variability of melatonin content. J Clin Sleep Med. 2017;13(2):275-281. doi:10.5664/jcsm.6462 REVIEW Accessed: 2026-05-29
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13 Cite this page
Vancouver: Pkhakadze G. Melatonin — safety profile [Internet]. Tbilisi: PHIG; 2026 [cited 2026 Jun 02]. Available from: https://www.efsa.europa.eu/en/efsajournal/pub/1467
APA 7th: Pkhakadze, G. (2026). Melatonin — Safety profile. Public Health Institute of Georgia. https://www.efsa.europa.eu/en/efsajournal/pub/1467
📋 Editorial information
Author: Prof. G. Pkhakadze, MD, MPH, PhD
Institution: Public Health Institute of Georgia (PHIG)
Affiliation: David Tvildiani Medical University (DTMU)
First published: January 2026
Last reviewed: 2026-05-29
Next review: December 2026
References: 5 cited sources
COI: SupplementIndex receives no funding from supplement manufacturers. All content independently authored by PHIG.
Process: Systematic literature review
📄 License & reuse
Published under Creative Commons Attribution 4.0 International (CC BY 4.0). You may share and adapt for any purpose with attribution.
Pkhakadze G. "Melatonin — Safety Profile." SupplementIndex, PHIG, 2026. https://www.efsa.europa.eu/en/efsajournal/pub/1467 CC BY 4.0.
GP
Educational and public health purposes. CC BY 4.0. Consult your healthcare provider before starting any supplement. Corrections: info@accreditation.ge. Publisher: PHIG