Benefits
Time to fall asleep and total sleep
In pooled trials of people with primary sleep disorders, melatonin shortened the time to fall asleep by about 7 minutes and added about 8 minutes of total sleep compared with placebo: real but modest. A dose-response meta-analysis found both effects peaked at about 4 mg a day. A separate review found no significant effect in adults with chronic insomnia alone.
Sleep in children and adolescents
A review of 24 placebo-controlled trials found melatonin shortened the time to fall asleep and lengthened total sleep in children and adolescents with chronic insomnia, but not significantly in adults. Effects were larger in children with autism, where pooled crossover trials found about 39 minutes faster sleep onset and 44 minutes more sleep than placebo. Pediatric use belongs under a clinician's guidance.
Jet lag
A Cochrane review of 10 trials found that melatonin taken close to the target bedtime at the destination reduced jet lag in 9 of them, for flights crossing five or more time zones. Doses of 0.5 to 5 mg worked similarly, and higher doses appeared no more effective. Benefit is likely larger with more time zones crossed and smaller on westward flights. Taken early in the day it can cause sleepiness. The review dates from 2002.
Daytime sleep after night shifts
A Cochrane review of shift-work trials found melatonin (1 to 10 mg) taken after a night shift lengthened daytime sleep by about 24 minutes and night sleep by about 17 minutes compared with placebo. It did not change how fast workers fell asleep or other sleep-quality measures, and the reviewers graded the evidence low quality.
Macular health in older adults
In a large US medical-records study of adults 50 and older, melatonin use was linked to a 58% lower risk of a new age-related macular degeneration (AMD) diagnosis and a 56% lower risk of progression to the wet form. This is an association, not a trial: users may differ in ways records cannot capture, and no controlled trial has tested melatonin for AMD.
Calm before surgery (hospital premedication)
A Cochrane review of 12 trials (774 patients) found melatonin at 3 to 14 mg, given 50 to 100 minutes before surgery, lowered preoperative anxiety by about 13 points on a 100 point scale compared with placebo (high quality evidence). Two small studies found no clear difference from midazolam (low quality). This is given by hospital teams; tell your anesthesia team what you take.
Fatigue in people with cancer
A pooled analysis of nine randomized trials found a small reduction in fatigue with melatonin in people with cancer, significant mainly in trials lasting 13 weeks or longer. A double-blind crossover trial of 20 mg nightly in advanced cancer found no benefit on fatigue or other symptoms. This is supportive-care research done under oncology supervision, not something to start on your own during cancer treatment.
Headache frequency in adults with migraine
One randomized double-blind trial in 196 adults with migraine compared melatonin 3 mg, amitriptyline 25 mg and placebo for 12 weeks. Migraine days fell by 2.7 a month on melatonin versus 1.1 on placebo, and melatonin was better tolerated than amitriptyline. The difference in migraine days between melatonin and amitriptyline was not significant, which does not show they are equal. It is a single trial.
Label accuracy of melatonin products
In 31 melatonin products bought in Canada, more than 71% were outside 10% of the labeled amount, ranging from 83% below to 478% above it, and 8 contained serotonin. Of 25 US melatonin gummies, 22 were inaccurately labeled; in those containing melatonin, the amount was 74% to 347% of the label. Choosing third-party tested products and starting at a low dose is a reasonable precaution.
Heartburn as an add-on to acid-reducing medicine
In a randomized double-blind trial of 78 adults with reflux symptoms, adding 3 mg of sublingual melatonin to omeprazole for 4 weeks eased heartburn, upper-stomach pain and a reflux symptom score more than omeprazole plus placebo. A smaller study of 3 mg at bedtime, not described as randomized, reported improvement, but omeprazole alone did better than melatonin alone. Both are small trials; melatonin has not been shown to replace that medicine.
Mechanism of action
Circadian rhythm regulation
Melatonin binds MT1 and MT2 receptors, including those in the suprachiasmatic nucleus (SCN) of the hypothalamus, the master circadian clock, signaling biological darkness and helping align the sleep-wake cycle with day and night. The body's own secretion is suppressed by light, especially blue wavelengths, and rises in darkness.
Damping the clock's evening wake signal
Acting on MT1 receptors in the SCN, melatonin damps the clock's evening wake-promoting signal, while MT2 activity helps shift the clock's timing. It works more as a timing signal than as a strong sedative, which is one reason the timing of a dose matters.
Direct and indirect antioxidant activity
Melatonin directly neutralizes reactive oxygen and nitrogen species and upregulates antioxidant enzymes such as superoxide dismutase, glutathione peroxidase and catalase. It crosses cell membranes and the blood-brain barrier easily. This antioxidant role, shown mainly in laboratory studies, may underlie some proposed non-sleep uses.
Anti-inflammatory effects
In laboratory studies melatonin inhibits pro-inflammatory cytokine production (TNF-alpha, IL-6, IL-1 beta) and modulates NF-kB signaling, a central inflammatory pathway. These effects have been described in brain, immune and peripheral tissues and are part of the rationale for proposed uses beyond sleep.
GABA and serotonin links
Laboratory studies suggest melatonin enhances GABA-A receptor signaling, which may contribute to its calming effect before surgery. In the body, melatonin is made from serotonin by the enzymes arylalkylamine N-acetyltransferase and hydroxyindole-O-methyltransferase, which ties it to serotonin pathways rather than raising serotonin itself.
Neuroprotective and retinal effects
By reducing oxidative stress and stabilizing neuronal membranes, melatonin protects brain cells in laboratory models of neurodegeneration. The retina makes its own melatonin, and levels decline with age; whether this matters for age-related macular degeneration is unproven.
Autonomic nervous system regulation
Melatonin is reported to reduce sympathetic nervous system activity and increase parasympathetic tone, part of the physiological wind-down that precedes sleep, including small drops in heart rate and blood pressure.
Immune system modulation
Melatonin influences immune cell function in laboratory studies, including T-cell activity, natural killer (NK) cell function and the balance of pro- and anti-inflammatory cytokines. Clinical evidence for immune effects in healthy adults is limited.
Clinical trials
Systematic review and dose-response meta-analysis of double-blind randomized placebo-controlled trials (Cruz-Sanabria et al. 2024, J Pineal Res).
26 trials published 1987 to 2020, 1,689 observations, in people with insomnia and healthy volunteers.
Melatonin gradually shortened sleep onset latency and increased total sleep time, with effects peaking at 4 mg a day. Insomnia status and the time between dosing and sleep predicted the effect on sleep onset. The authors suggest that taking it about 3 hours before the desired bedtime, rather than the common 2 mg 30 minutes before, might work better; this is a modelling result, not a head-to-head trial.
Systematic reviews and meta-analyses of placebo-controlled randomized trials, with subgroup analysis by age (Choi et al. 2022, Sleep Med Rev).
24 randomized trials in chronic insomnia, 4 of them in comorbid insomnia.
In insomnia without other conditions, melatonin significantly improved sleep onset latency and total sleep time only in children and adolescents; in adults it did not significantly improve sleep onset latency, total sleep time or sleep efficiency. In comorbid insomnia it improved sleep onset latency in all age groups, but only one study was in adults. The authors concluded it did not appear effective in adults but might be in children and adolescents.
Meta-analysis of randomized placebo-controlled trials (Ferracioli-Oda et al. 2013, PLoS One).
19 trials, 1,683 adults and children with primary sleep disorders.
Sleep latency fell by 7.06 minutes (95% CI 4.37 to 9.75, p<0.001) and total sleep time rose by 8.25 minutes (95% CI 1.74 to 14.75, p=0.013) compared with placebo, and overall sleep quality improved modestly (SMD 0.22). Longer trials and higher doses showed larger effects on latency and total sleep time, and the effects did not appear to fade with continued use.
Retrospective cohort study of US electronic health records (TriNetX) with propensity score matching (Jeong et al. 2024, JAMA Ophthalmol).
121,523 adults aged 50 or older without AMD (4,580 per matched group) and 66,253 with nonexudative AMD (4,064 per matched group).
Melatonin use was associated with a lower risk of a new AMD diagnosis (risk ratio 0.42, 95% CI 0.28 to 0.62) and of progression to exudative AMD (risk ratio 0.44, 95% CI 0.34 to 0.56). The authors note lifestyle factors may have influenced the association. This is observational data, not a controlled trial, so it cannot show that melatonin caused the difference.
Systematic review of 35 studies with a meta-analysis of five randomized double-blind placebo-controlled crossover trials (Rossignol et al. 2011, Dev Med Child Neurol).
Children with autism spectrum disorder; two of the five pooled trials also enrolled children with other developmental disorders, and only the autism data were used.
Compared with placebo, melatonin increased sleep duration by about 44 minutes and shortened sleep onset latency by about 39 minutes, with large effect sizes; night-time awakenings did not improve. Reported side effects were minimal to none. The authors note small samples and varied protocols.
Randomized double-blind placebo-controlled add-on trial, 4 weeks (Malekpour et al. 2023, Turk J Gastroenterol).
78 adults with mild to moderate gastroesophageal reflux disease and heartburn or regurgitation at least 2 days a week, given omeprazole 20 mg each morning plus sublingual melatonin 3 mg at night or omeprazole plus a matching placebo; 72 completed (35 vs 37).
Heartburn (P = .04), epigastric pain (P = .03) and the FSSG reflux symptom score (P = .0001) fell more with melatonin added than with omeprazole plus placebo, and quality of life scores were higher (P = .0001). Adverse events were similar between groups (P = .55), with no serious events. The trial tested melatonin on top of omeprazole, not as a replacement.
Controlled four-group clinical study, not described as randomized or blinded, 4 and 8 weeks (Kandil et al. 2010, BMC Gastroenterol).
27 patients with GERD (9 per group) given oral fast-release melatonin 3 mg at bedtime, omeprazole 20 mg twice daily, or both, plus 9 healthy controls.
The authors reported that melatonin alone and with omeprazole improved heartburn and epigastric pain over 4 and 8 weeks; in the melatonin-alone group, heartburn was present in 7 of 9 people at the start and in none at 8 weeks. Omeprazole alone did better than melatonin alone. With 9 people per group and no described randomization or blinding, this is weak evidence.