Sleep and stressModerate evidence
Melatonin
Also called: N-acetyl-5-methoxytryptamine, sleep hormone, extended-release melatonin, sublingual melatonin.
A hormone sold over the counter in Canada, where the formats on store shelves exceed the doses used in trials and the tablet does not always contain what the label claims.
What it is
Melatonin is a hormone the brain secretes in response to darkness to set the sleep-wake cycle; as a supplement, it is generally synthetic. In Canada, it is sold as a natural health product, whereas in several other countries it is classified as a prescription drug. People buy it to fall asleep, for jet lag and for night shift work.
What the label does not say
- More is not better. Cochrane reports similar effectiveness from 0.5 to 5 mg for jet lag and no gain above 5 mg; for shift work, no dose-response effect between 1 and 10 mg. The 5 and 10 mg formats sit at the top of what the Canadian monograph allows (0.1 to 10 mg), not at the level of the trials.
- The tablet does not contain what the label says. Of 31 products bought in Guelph, Ontario, 71% deviated by more than 10% from the declared content, from 83% less to 478% more, with up to 465% variation from one lot to another; 26% contained undeclared serotonin (Erland and Saxena, 2017).
- The clearest evidence is for jet lag: 8 of 10 trials report fewer symptoms for flights across 5 or more time zones, provided it is taken close to bedtime at the destination; taken at the wrong time, it delays adaptation. For shift work, the evidence is of low quality: about 24 minutes more daytime sleep.
- For chronic insomnia, the American Academy of Sleep Medicine (2017) and the American College of Physicians (2016) judge the data insufficient; a meta-analysis of 19 trials (1,683 people) puts the effect at about 7 minutes faster to fall asleep and 8 minutes more sleep. The Canadian label asks you to consult if insomnia persists beyond 4 weeks.
The forms on the shelf
- Immediate release (tablets, sublinguals, gummies, liquids): the form used in the jet lag trials, where the Cochrane review found fast release superior to slow release.
- Extended release: the form of the 2 mg medication authorized in Europe for primary insomnia from age 55, taken 1 to 2 hours before bedtime, for at most 13 weeks.
- Gummies: the NCCIH reports that in 2023, 22 of 25 products were mislabelled, from 74 to 347% of the stated content, including one with no detectable melatonin.
Published reference values
- No recommended intake or upper limit: it is a hormone, not a nutrient. Health Canada allows 0.1 to 10 mg per day (0.5 to 10 mg for jet lag), 30 to 60 minutes before bedtime, with three statements: avoid alcohol, do not drive for 5 hours, stop in case of headache, confusion or nausea.
- Short-term effects: headaches, dizziness, nausea, drowsiness; long-term data are lacking, including on puberty, menstrual cycles and prolactin.
- In older adults, the blood peak from the 2 mg tablet reaches about 1,200 pg/mL versus 500 in young adults, hence possible daytime drowsiness; guidelines advise against it in dementia.
- Children: about 11,000 U.S. emergency department visits from 2019 to 2022 for unsupervised ingestion in children 5 and under.
When
Thirty to 60 minutes before bedtime according to the Canadian monograph. For jet lag, close to bedtime at the destination (10 p.m. to midnight in the trials), never earlier in the day.
Keep apart from
- Fluvoxamine: multiplies melatonin exposure by 17; a combination to avoid according to the European monograph.
- Estrogen-based contraceptives and hormone therapy, quinolones: raise melatonin levels (inhibition of CYP1A1 and CYP1A2). Carbamazepine, rifampicin and tobacco: lower them.
- Benzodiazepines, zolpidem, zopiclone and other sedatives: additive sedation.
- Warfarin and anticoagulants: case reports of harm, and Health Canada asks you to consult before use. A medical decision, not a matter of spacing doses by the hour.
To mention to a professional
- Epilepsy, anticoagulants, immunosuppressants, medications for blood pressure, diabetes or mood, steroids, autoimmune, liver or kidney disease, asthma, dementia, children: check with a health care professional. Pregnancy and breastfeeding: a contraindication according to the Canadian monograph.
Sources
- NCCIH, Melatonin: What You Need To Know
- Health Canada, natural health product monograph, Melatonin (oral)
- Cochrane, Herxheimer and Petrie, Melatonin for the prevention and treatment of jet lag
- Cochrane, Liira et al., Pharmacological interventions for sleepiness and sleep disturbances caused by shift work
- Ferracioli-Oda et al., Meta-analysis: melatonin for the treatment of primary sleep disorders, PLoS One, 2013
- Erland and Saxena, Melatonin natural health products and supplements: presence of serotonin and significant variability of melatonin content, Journal of Clinical Sleep Medicine, 2017 (AASM summary)
- European Medicines Agency, melatonin 2 mg prolonged-release, summary of product characteristics
- Examine.com, Melatonin
Educational information, drawn from the sources above. It does not replace the advice of a health professional, who remains the reference for your situation, your medications, pregnancy or breastfeeding.