Overview
Melatonin is an endogenous hormone produced primarily by the pineal gland in response to darkness.
It signals nighttime to the body's internal clock, promoting sleep onset and coordinating circadian rhythms. Secretion begins around dusk, peaks in the middle of the night (typically 2 to 4 AM), and declines toward morning as light exposure increases.
Exogenous melatonin supplementation mimics this natural pattern, though timing and dose substantially influence outcomes. Low doses taken at the appropriate circadian phase shift the sleep-wake cycle and facilitate sleep onset. The effect is not sedative in the classical sense but rather chronobiotic, working with the body's timing systems.
Melatonin is among the most commonly used sleep supplements in the United States.
Despite widespread use, understanding of optimal dosing and timing remains incomplete among users. Many take doses far exceeding the amounts that produce physiological effects, potentially reducing efficacy through receptor desensitization or disrupting natural melatonin rhythms.
Clinical applications extend beyond simple sleep onset. Shift work disorder, jet lag, delayed sleep phase syndrome, and sleep disturbances in various medical conditions show responses to appropriately timed melatonin administration.
What it means
Melatonin is a natural hormone your brain makes when it gets dark, signaling it's time to sleep. Supplementing it helps shift your internal clock and makes falling asleep easier. It's not a sedative like sleeping pills - it works by aligning your sleep timing. Most people use way more than they need. Clinical uses include jet lag, shift work, and circadian rhythm disorders.
Mechanisms of Action
Melatonin binds to MT1 and MT2 receptors in the suprachiasmatic nucleus (SCN), the brain's master circadian pacemaker.
MT1 activation promotes sleep through direct inhibition of SCN neuronal firing, reducing arousal signals. MT2 activation phase-shifts circadian rhythms, advancing or delaying the biological clock depending on administration timing relative to the endogenous melatonin rhythm.
The timing of supplementation determines whether circadian phase advances or delays. Taking melatonin in the late afternoon or early evening (before endogenous melatonin rises) advances the clock, promoting earlier sleep and wake times. Taking it in the late night or early morning delays the clock, though this application is less common clinically.
Sleep-promoting effects involve mechanisms beyond circadian shifting.
Melatonin reduces core body temperature slightly, which facilitates sleep onset (falling core temperature is a signal for sleep). It may also have mild anxioly tic effects through GABAergic pathways, though this mechanism is less well established than the chronobiotic and thermoregulatory actions.
Antioxidant properties are well demonstrated in cell culture and animal studies. Melatonin scavenges free radicals and upregulates antioxidant enzymes. Whether these effects occur at supplemental doses in humans and contribute meaningfully to health outcomes beyond sleep is uncertain.
What it means
Melatonin works by activating receptors in your brain's clock center (SCN). This both makes you feel sleepy and shifts your internal timing earlier or later depending on when you take it. Taking it before your natural melatonin rises (late afternoon/early evening) shifts you earlier; taking it late shifts you later. It also lowers your core body temperature slightly, another sleep signal. Antioxidant effects are real in labs but unclear in humans at supplement doses.
Effects and Benefits
Sleep Onset and Insomnia
Meta-analyses consistently find that melatonin reduces sleep latency (time to fall asleep) by an average of 7 to 12 minutes across multiple studies. The effect size is modest but clinically meaningful for those with prolonged sleep onset. A review by Ferracioli-Oda et al. (2013) analyzing 19 trials found sleep latency reduction of 7.2 minutes on average.
Total sleep time increases modestly, typically by 8 to 15 minutes. Sleep quality improvements are less consistent, with subjective reports showing mixed results.
The benefit is clearest in individuals with circadian misalignment (delayed sleep phase) or low endogenous melatonin production. In those with normal melatonin rhythms and non-circadian insomnia, benefits are smaller or absent.
Delayed Sleep Phase Syndrome
Delayed sleep phase syndrome (DSPS), where the natural sleep-wake cycle is significantly shifted later than desired, responds well to timed melatonin administration.
Taking melatonin 3 to 5 hours before the current sleep time gradually advances circadian phase over days to weeks. Combined with morning bright light exposure, this approach produces significant improvements in sleep timing in most DSPS patients.
Jet Lag
Melatonin effectively reduces jet lag symptoms across multiple trials. A Cochrane review by Herxheimer and Petrie (2002) found that melatonin taken at bedtime in the destination time zone reduced jet lag symptoms in 9 of 10 trials.
Efficacy increases with the number of time zones crossed. For trips crossing 5+ time zones, melatonin shows large effect sizes. For trips crossing 2 to 4 zones, benefits are smaller but still present.
Eastward travel (where you need to advance your clock) shows better response to melatonin than westward travel, consistent with its phase-advancing properties when taken in the evening.
Shift Work Disorder
Evidence for shift work is mixed. Some studies show improved sleep quality and duration in night shift workers taking melatonin before daytime sleep. Others find minimal benefit, possibly reflecting the difficulty of overriding strong circadian and environmental cues promoting wakefulness during the day.
Age-Related Sleep Changes
Endogenous melatonin production declines with age. Older adults often show flattened, delayed, or reduced melatonin rhythms. Supplementation may be particularly beneficial in this population.
Several studies in elderly adults with insomnia report sleep improvements with prolonged-release melatonin formulations. The effect size is modest but occurs without the cognitive impairment, falls, or dependence risks associated with benzodiazepines and z-drugs commonly used in this population.
What it means
Melatonin helps you fall asleep about 7 to 12 minutes faster on average - modest but real. It works best if your circadian rhythm is off (delayed sleep phase) or you're older with reduced natural melatonin. For jet lag, it's proven effective, especially going east across 5+ time zones. Shift work evidence is weaker. It's safer for older adults than prescription sleep meds, with no cognitive impairment or fall risk.
Dosing and Timing
The effective dose range is far lower than many commercial products provide. Physiological melatonin levels peak at 80 to 120 pg/mL (roughly 0.1 to 0.3 mg circulating in total). Doses of 0.3 to 1 mg raise blood melatonin to physiological nocturnal levels.
Higher doses (3 to 10 mg) produce supraphysiological blood levels, potentially desensitizing receptors or disrupting feedback mechanisms that regulate endogenous production.
Lower doses (0.3 to 1 mg) often work as well or better than higher doses for sleep onset and circadian shifting. A study by Zhdanova et al. (2001) found that 0.3 mg was as effective as 3 mg for sleep onset, with the lower dose showing better maintenance of effect with repeated use.
Timing is critical and depends on the goal.
For sleep onset in normally-timed individuals, take melatonin 30 to 60 minutes before desired bedtime. For circadian phase advancement (shifting sleep earlier), take it 3 to 5 hours before current sleep time. For jet lag, take it at the destination bedtime starting the night of arrival.
Prolonged-release formulations mimic natural overnight melatonin secretion patterns better than immediate-release. They may maintain sleep better by providing melatonin throughout the night. Immediate-release is cleared within hours, potentially allowing early morning awakening.
Sublingual forms show faster absorption, reaching peak levels in 15 to 30 minutes versus 60 to 90 minutes for oral tablets. This makes sublingual useful when timing is less predictable or when rapid onset is desired.
What it means
Start with 0.3 to 1 mg, not the 5 to 10 mg doses commonly sold. Higher doses aren't better and may reduce effectiveness over time. Timing matters hugely: for sleep, take it 30 to 60 minutes before bed. For shifting your clock earlier, take it 3 to 5 hours before your current sleep time. For jet lag, take it at bedtime in your destination time zone. Prolonged-release formulations maintain levels better overnight. Sublingual works faster (15 to 30 min).
Safety and Interactions
General Safety
Short-term use (weeks to months) shows excellent safety. Side effects at typical doses are minimal, most commonly next-day grogginess (particularly with higher doses taken late), vivid dreams or nightmares, and mild headache.
Long-term safety data (years of daily use) is limited. Concerns about suppressing endogenous production with chronic supplementation exist theoretically but lack strong clinical evidence.
Melatonin does not appear to cause dependence or withdrawal in the traditional sense, though psychological habituation to nightly use is common.
Next-day impairment is dose-dependent. Lower doses (0.3 to 1 mg) rarely cause daytime sedation. Higher doses (5 to 10 mg) increase risk of morning grogginess, potentially affecting driving or work performance.
Medication Interactions
Sedatives and sleep aids: Combining melatonin with benzodiazepines, z-drugs, or other CNS depressants may increase sedation. While the interaction is not dangerous, it may increase next-day impairment.
Blood thinners: Melatonin may increase bleeding risk when combined with warfarin or antiplatelet drugs, though clinical evidence is limited. Monitoring INR in warfarin users starting melatonin is prudent.
Immunosuppressants: Melatonin has immunomodulatory properties that could theoretically interact with immunosuppressive drugs used in transplant or autoimmune conditions. The clinical significance is uncertain.
Antidepressants: No major pharmacokinetic interactions are documented, but melatonin may enhance sedative side effects of antidepressants or interact with circadian effects of certain medications like agomelatine.
Seizure threshold: Case reports suggest melatonin might lower seizure threshold in susceptible individuals, though evidence is limited. Those with seizure disorders should use with caution and medical supervision.
Population Considerations
Pregnancy and breastfeeding: Melatonin safety in pregnancy is not established. While it's naturally produced during pregnancy, supplemental doses may not be safe. Avoid use unless specifically recommended by a physician.
Children: Melatonin is increasingly used in pediatric sleep disorders, particularly in children with ADHD or autism spectrum disorders. Short-term use appears safe, though long-term effects on development are unknown. Pediatric use should involve medical supervision and behavioral sleep interventions rather than supplements alone.
Autoimmune conditions: Theoretical concern exists that melatonin's immune-modulating effects could worsen autoimmune activity, though clinical evidence is sparse. Those with active autoimmune disease should consult their physician before use.
What it means
Melatonin is very safe short-term with minimal side effects. Higher doses increase next-day grogginess risk. Long-term safety (years) isn't well studied, though dependence doesn't appear to occur. Be cautious combining with sleep medications, blood thinners, or immunosuppressants. Avoid during pregnancy unless medically advised. Kids can use it short-term for sleep issues, but involve a doctor. If you have autoimmune disease or seizures, check with a physician first.
Stacking and Combinations
With Magnesium
Magnesium and melatonin work through complementary mechanisms for sleep support. Magnesium promotes muscular and nervous system relaxation while melatonin regulates circadian timing. Combining both is common and physiologically sound, with no documented negative interactions.
Typical combinations use 200 to 400 mg magnesium glycinate with 0.5 to 3 mg melatonin 30 to 60 minutes before bed.
With L-Theanine
L-theanine provides calming effects without sedation, potentially helping with racing thoughts that interfere with sleep initiation. Combined with melatonin's circadian effects, some users find the combination more effective than either alone for falling asleep when anxiety is a factor.
No clinical studies directly test this combination, but mechanisms don't overlap problematically.
With Glycine
Glycine (3 grams before bed) improves subjective sleep quality in some studies, possibly through temperature regulation and neurotransmitter effects. Combining with melatonin addresses both circadian misalignment and sleep quality through distinct pathways.
Stacking Cautions
Avoid stacking multiple sedating supplements (melatonin plus valerian plus GABA plus others) as this increases next-day impairment risk without necessarily improving sleep quality. Combining melatonin with one other well-tolerated sleep-support compound is reasonable, but complex multi-supplement sleep stacks often cause more problems than they solve.
What it means
Melatonin combines well with magnesium (complementary sleep mechanisms), L-theanine (calms racing thoughts), or glycine (improves sleep quality). These pairings are physiologically sound and commonly used. Avoid stacking many sedating supplements together - stick to melatonin plus one other compound max to reduce next-day grogginess risk.
Research Strength and Limitations
Melatonin has extensive research support for jet lag and delayed sleep phase, with multiple meta-analyses confirming efficacy. Primary insomnia evidence is weaker, showing modest benefits that don't consistently achieve clinical significance thresholds.
Dose-response relationships are poorly characterized in many studies.
Most research uses doses in the 3 to 10 mg range, higher than the 0.3 to 1 mg doses that match physiological levels. Whether lower doses would show equivalent or superior effects with repeated use remains inadequately tested in large trials.
Long-term studies are scarce. Most trials last weeks to a few months. Effects of years of daily use on endogenous melatonin production, receptor sensitivity, and other biological parameters are largely unknown.
Formulation variability is a significant concern. Studies of over-the-counter melatonin products find actual content ranging from 83 percent below to 478 percent above labeled amounts, with significant lot-to-lot variation. Some products contain serotonin, which is not declared on labels and carries distinct pharmacological effects and risks.
Publication bias likely exists. Negative trials may be underreported given the widespread belief in melatonin's effectiveness and commercial interests in positive findings.
What it means
Melatonin research is strong for jet lag and delayed sleep phase, weaker for regular insomnia. Most studies use higher doses (3 to 10 mg) than the physiological range (0.3 to 1 mg), so we don't know if lower is better long-term. Data on years of daily use doesn't really exist. Product quality is a massive problem - many supplements contain wildly different amounts than labeled, and some contain unlabeled serotonin. Evidence is decent but not bulletproof.
Practical Considerations
Melatonin works best for circadian timing issues (delayed sleep phase, jet lag) rather than as a general sleep aid. If your sleep timing is normal but you can't fall asleep due to racing thoughts, anxiety, or environmental factors, behavioral interventions or other supplements may be more appropriate.
Start with the lowest effective dose (0.3 to 1 mg).
You can always increase if needed, but starting high makes it difficult to find your optimal dose and increases side effect risk.
Product quality matters significantly. Choose USP Verified or NSF Certified products to reduce the risk of receiving wildly inaccurate doses or undeclared contaminants. The quality issues in melatonin supplements are more severe than in most other supplement categories.
Behavioral sleep hygiene remains foundational. Melatonin cannot compensate for late-night screen use, irregular sleep schedules, excessive caffeine, or poor sleep environment. Use it as part of a comprehensive sleep strategy, not a standalone fix.
If melatonin proves ineffective after 2 to 4 weeks of appropriately timed use, other factors likelydominate your sleep difficulties.
Sleep apnea, restless leg syndrome, medication side effects, psychiatric conditions, and other medical issues won't respond to melatonin and require professional evaluation.
Cycling off periodically may be wise given the absence of long-term safety data, though no specific cycling protocol is established. Some users take melatonin for several months, then discontinue for a month to assess whether it remains necessary and whether endogenous production recovers.
What it means
Use melatonin for circadian timing problems (jet lag, delayed sleep phase), not as a general sleep aid. Start with 0.3 to 1 mg - don't assume more is better. Buy USP or NSF certified products to avoid the rampant quality issues in this category. Melatonin can't fix poor sleep habits - use it alongside good sleep hygiene. If it doesn't work after a month of proper use, you probably need professional sleep evaluation, not more melatonin.
References
Ferracioli-Oda E, Qawasmi A, Bloch MH. Meta-analysis: melatonin for the treatment of primary sleep disorders. PLoS One. 2013;8(5):e63773.
Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev. 2002;(2):CD001520.
Lemoine P, Nir T, Laudon M, Zisapel N. Prolonged-release melatonin improves sleep quality and morning alertness in insomnia patients aged 55 years and older and has no withdrawal effects. J Sleep Res. 2007;16(4):372-380.
Erland LAE, Saxena PK. Melatonin Natural Health Products and Supplements: Presence of Serotonin and Significant Variability of Melatonin Content. J Clin Sleep Med. 2017;13(2):275-281.
Van Geijlswijk IM, Korzilius HP, Smits MG. The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep. 2010;33(12):1605-1614.
Zhdanova IV, Wurtman RJ, Regan MM, Taylor JA, Shi JP, Leclair OU. Melatonin treatment for age-related insomnia. J Clin Endocrinol Metab. 2001;86(10):4727-4730.