Compound Profile
Melatonin
Dose response meta analysis indicates melatonin effects depend heavily on timing and dose; adult chronic insomnia evidence is nuanced and not uniformly positive.
Last reviewed: •6 sources citedReport a correctionProfile-wide ·A Strong
Use extra caution — Safety evidence: higher dose adult trials found more drowsiness, headache, and dizziness without a detected serious adverse event increase, but reporting and long term evidence were limited. Details
- Evidence
- Strong evidence
- Typical onset
- Varies by prep
- Safety rating
- Use extra caution: Use caution
- Best for
- Melatonin Receptors MT1/MT2, Suprachiasmatic Nucleus, MT1 MT2
Verdict: MelatoninSituation-dependent
Bottom line
A timing signal, not a sedative. Excellent for jet lag and shifted clocks at low doses; underwhelming for ordinary insomnia, where lower doses often beat higher ones.
- Evidence confidence
- Strong for timing (jet lag, delayed sleep phase); weak for general insomnia
- Expected onset
- 30–60 minutes (timing-dependent)
- Give it
- A few nights for circadian use
Safety: Most people overshoot the dose; more is not better and can cause next-day grogginess. Use the lowest effective amount and involve a clinician for children or ongoing use.
On the evidence: Robust for circadian rhythm timing; effect on general insomnia is small.
Best for
- Jet lag
- Delayed sleep phase / shifted clock
- Resetting a disrupted schedule
Not ideal for
- Staying asleep through the night
- Everyday "can't switch off" insomnia
- A relaxation aid
Consider instead: Magnesium — for relaxation-type sleep trouble
How strong is the evidence?Moderate — split by use case
Why not higher
- For ordinary insomnia the benefit is small (often minutes)
- Over-the-counter doses are frequently far higher than needed
- Long-term and pediatric data are limited
Why not lower
- Strong, consistent evidence for circadian uses (jet lag, delayed sleep phase)
- The mechanism (circadian signaling) is well understood
- Short-term use is well tolerated in healthy adults
Practical takeaway: Best matched to a timing problem, at the lowest effective dose. If the issue is "can't switch off," a relaxation-first option often fits better. Involve a clinician for children or ongoing use.
Safety
Safety & Cautions
High caution
Caution level: High. Multiple caution categories apply, or the record uses avoid/contraindication language.
- Interaction-AwareMedication or interaction context is explicitly noted.
- Hormonal Activity ContextHormone-adjacent wording is present and should be interpreted carefully.
- Stimulant-Like ProfileStimulant-like or activating caution language is present.
- Anticoagulant CautionBleeding or anticoagulant-adjacent caution language is present.
- Safety evidence
- higher-dose adult trials found more drowsiness, headache, and dizziness without a detected serious-adverse-event increase, but reporting and long-term evidence were limited
- Who should avoid this?
- No specific evidence-backed contraindication is documented for this profile. This is not the same as established safety.
- Talk to a professional if
- you are pregnant or breastfeeding.
Driving, concurrent sedatives, pregnancy, breastfeeding, pediatric use, and chronic use require individualized review.
Evidence-based safety
Caution when combined
Severity and certainty are shown separately. A high-priority caution can still be theoretical: these pairings are screened from shared contraindication mechanisms and are not automatically documented clinical interactions. Provenance identifies the source fields that produced each flag; it does not upgrade the certainty of the pairwise claim.
High-Priority Caution
147 flagged pairingsBleeding / anticoagulant risk
High-Priority Caution
147 flagged pairingsBleeding / anticoagulant risk
Representative pairings are shown below. Large mechanism groups are intentionally summarized to keep profiles focused and crawl-efficient.
Bleeding / anticoagulant riskCertainty: Theoretical
Data provenance recorded for 147 of 147 pairings in this mechanism group.
- aescin — Theoretical interaction certainty
- Aged Garlic Extract — Theoretical interaction certainty
- ajoene — Theoretical interaction certainty
- Ajwain — Theoretical interaction certainty
- Allicin — Theoretical interaction certainty
- Garlic — Theoretical interaction certainty
- American Ginseng Extract — Theoretical interaction certainty
- Andrographis — Theoretical interaction certainty
- Angelica Archangelica — Theoretical interaction certainty
- Angelica Dahurica — Theoretical interaction certainty
- Angelica Pubescens — Theoretical interaction certainty
- Angelica Root — Theoretical interaction certainty
+135 more pairings share this mechanism. Use the Safety Checker to review a specific combination.
Moderate Caution
68 flagged pairingsSedation / CNS depression
Moderate Caution
68 flagged pairingsSedation / CNS depression
Representative pairings are shown below. Large mechanism groups are intentionally summarized to keep profiles focused and crawl-efficient.
Sedation / CNS depressionCertainty: Theoretical
Data provenance recorded for 68 of 68 pairings in this mechanism group.
- American Yellow Lotus — Theoretical interaction certainty
- Artemisia Absinthium — Theoretical interaction certainty
- Ashwagandha (Withania somnifera) — Theoretical interaction certainty
- Bacopa — Theoretical interaction certainty
- Black Seed — Theoretical interaction certainty
- Black Tea — Theoretical interaction certainty
- Blue Lotus — Theoretical interaction certainty
- Calamus — Theoretical interaction certainty
- Catuba — Theoretical interaction certainty
- Celastrus Paniculatus — Theoretical interaction certainty
- Chamomile — Theoretical interaction certainty
- Chinese Skullcap — Theoretical interaction certainty
+56 more pairings share this mechanism. Use the Safety Checker to review a specific combination.
Evidence Summary
Profile-wide ·A StrongEvidence lens
Most useful for practical interpretation when safety context also fits.
StrongStrong evidence
Human clinical evidence: Present in source signals
Mechanistic / preclinical: Mechanism mapped — Immune Signaling Modulation · Hormonal Signaling Context · Circadian Rhythm Modulation
Research maturity: Established research — main contexts: Melatonin Receptors MT1/MT2 · Suprachiasmatic Nucleus · MT1 MT2
Safety boundary: Safety note available — Safety evidence: higher dose adult trials found more drowsiness, headache, and dizziness without a detected serious adverse event increase, but reporting and long term evidence were limited.
This profile cites 6 human studies.
Evidence Strength
Confidence estimate based on the design quality and consistency of published clinical trials.
Melatonin has a strong evidence rating.
Sleep SupportSleep
Citation density
4.7
Sources
14
Effects
3
Research recency
Mixed recency
Evidence Grade
Grade A: Strong Evidence
Evaluation of methodological rigor, population reach, and evidence alignment.
- Design Match
- Meta analysis
- Risk of Bias
- Low
- Consistency
- Consistent
Strongest recorded design is a meta analysis, drawn from 18 recorded studies, 16 in people. No disagreement is recorded across them.
How evidence grades work
Each grade reflects the strength and consistency of published human evidence — not marketing claims. Grades are based on study count, design quality, effect size, consistency, and recency.
- Strong
- Multiple RCTs, consistent direction, adequate effect size
- Moderate
- Some RCTs or consistent observational data in humans
- Preliminary / Mixed
- Animal or in-vitro only, or conflicting human data
- Traditional / Theoretical
- Traditional use only; no controlled human trials
Clinical Study Summaries (14)8 human evidence sources · 0 human trials · ~5,544 participants across 2 human evidence sources with reported N · Consistency not yet classifiable
Filter by study class
Showing 14 of 14 studies.
What the evidence actually shows
This table contains 14 structured sources, including 8 human evidence sources; 0 are human trials. Across 2 human evidence sources with a reported sample size, the approximate participant total is 5,544; overlapping publications may include some of the same people.
| Study | Design | N | Dose | Duration | Population | Outcome | Result & magnitude | Source |
|---|---|---|---|---|---|---|---|---|
Meta-analysis: melatonin for the treatment of primary sleep disorders PubMed · PLoS One · 2013 Background | Meta-analysis Statistically combines results from multiple eligible studies; confidence still depends on the quality, consistency, and directness of those studies. | n=1683 | — | — | — | — | — | PubMed → |
F. Cruz-Sanabria; S. Bruno; A. Crippa; P. Frumento; M. Scarselli; Debra J. Skene; U. Faraguna · Journal of Pineal Research · 2024 Background | Meta-analysis Statistically combines results from multiple eligible studies; confidence still depends on the quality, consistency, and directness of those studies. | — | — | — | — | — | — | PubMed → |
Safety of higher doses of melatonin in adults: A systematic review and meta-analysis Zoe M Schrire; C. Phillips; J. Chapman; S. Duffy; G. Wong; A. D’Rozario; M. Comas; I. Raisin; B. Saini; C. Gordon; A. McKinnon; S. Naismith; N. Marshall; R. Grunstein; C. Hoyos · Journal of Pineal Research · 2021 Background | Meta-analysis Statistically combines results from multiple eligible studies; confidence still depends on the quality, consistency, and directness of those studies. | n=3861 | — | — | — | — | — | PubMed → |
Background | Meta-analysis Statistically combines results from multiple eligible studies; confidence still depends on the quality, consistency, and directness of those studies. | — | — | — | — | — | Melatonin modestly reduced excessive daytime sleepiness (ESS MD -0.97, 95% CI -1.81 to -0.14). | PubMed → |
Background | Meta-analysis Statistically combines results from multiple eligible studies; confidence still depends on the quality, consistency, and directness of those studies. | — | — | — | — | — | Prolonged-release melatonin produced modest improvements in subjective and objective sleep-onset latency and objective sleep efficiency. | PubMed → |
Background | Meta-analysis Statistically combines results from multiple eligible studies; confidence still depends on the quality, consistency, and directness of those studies. | — | — | — | — | — | A 2026 meta-analysis of 31 randomized trials found no significant reduction in fasting glucose with melatonin, while HbA1c, fasting insulin, and HOMA-IR showed pooled improvements. | PubMed → |
Show 8 more studies
Background | Meta-analysis Statistically combines results from multiple eligible studies; confidence still depends on the quality, consistency, and directness of those studies. | — | — | — | — | — | A 2026 cancer-specific review found no statistically significant overall pooled improvement in sleep outcomes with melatonin, despite selected subgroup and short-term signals. | PubMed → |
Efficacy of melatonin for chronic insomnia: Systematic reviews and meta-analyses Background | Systematic review Uses a predefined method to find and evaluate relevant studies, but may or may not pool their results statistically. | — | — | — | — | — | In adults with non-comorbid chronic insomnia, melatonin did not clearly improve sleep latency, total sleep time, or sleep efficiency. | PubMed → |
PubMed · Int J Oral Maxillofac Surg · 2015 Background | Narrative review Summarizes selected literature without the full prespecified search and selection methods of a systematic review. | — | — | — | — | — | — | PubMed → |
Exogenous Melatonin and Sleep Quality: A Scoping Review of Systematic Reviews Background | Narrative review Summarizes selected literature without the full prespecified search and selection methods of a systematic review. | — | — | — | — | — | Most meta-analyses versus inactive comparators favored melatonin, but only a small fraction of reviews met all predefined rigor criteria. | Among 215 meta-analyses comparing melatonin with an inactive comparator, 80.9% favored melatonin, 7.9% favored the comparator, and 11.2% were unclear. | PubMed → |
Biopsychosocial determinants of physical and mental fatigue in patients with spondyloarthropathy PubMed · Rheumatol Int · 2011 Background | Other / unclear The study design is not yet classified clearly enough to infer its place in the evidence hierarchy. | — | — | — | — | — | — | PubMed → |
A putative novel nuclear-encoded subunit of the cytochrome c oxidase complex in trypanosomatids PubMed · Mol Biochem Parasitol · 2002 Background | Other / unclear The study design is not yet classified clearly enough to infer its place in the evidence hierarchy. | — | — | — | — | — | — | PubMed → |
Pediatric Melatonin Ingestions — United States, 2012–2021 Lelak K et al. · MMWR Morb Mortal Wkly Rep · 2022 Background | Other / unclear The study design is not yet classified clearly enough to infer its place in the evidence hierarchy. | — | — | — | — | — | — | PubMed → |
Freeman DI et al. · MMWR Morb Mortal Wkly Rep · 2024 Background | Other / unclear The study design is not yet classified clearly enough to infer its place in the evidence hierarchy. | — | — | — | — | — | — | PubMed → |
How Melatonin Works
Simplified mechanism pathway based on preclinical and pharmacological evidence. Does not confirm clinical efficacy.
Mechanism Pathway — How Melatonin Works
CompoundTarget / ReceptorMechanismEffect / Outcome
Dosing
- Dose guidance
- Dose response meta analysis suggested sleep effects peaking around 4 mg/day and timing about 3 hours before desired bedtime in that analysis; common practice varies. | Oral melatonin; immediate vs prolonged release and timing should be separated.
Mechanisms & biological pathways
Preclinical mechanism details from scientific profiles; these represent plausible pathways but do not guarantee clinical efficacy in humans.
- Immune Signaling Modulation
- Hormonal Signaling Context
- Circadian Rhythm Modulation
- Melatonin Receptor Agonism
Compare & Sourcing
Compare side-by-side tradeoffs or verify active marker guidelines.
Sourcing options
Melatonin product picks
Recommendation status
Product recommendations are not shown for this profile because the current site safety and monetization policy does not permit them.
Product form & quality guidelines
When sourcing Melatonin, verify the label for:
- Standardized Extract: Confirm active content percentages on the supplement facts panel (e.g. standardized to specific marker compounds) rather than simple raw herb weights.
- Third-Party Testing: Look for independent purity labels (USP, NSF, ConsumerLab, or Eurofins) to ensure the product is free from heavy metals, solvents, and contaminants.
- Form Bioavailability: Ensure the form matches evidence-supported configurations (e.g. chelated bisglycinate/glycinate for magnesium, micronized monohydrate for creatine) for optimal onset and digestion tolerance.
Safety first · Harm reduction
This information is educational and not medical advice. Start low, avoid risky combinations, and consult a licensed clinician before making health decisions—especially if you use medications, have diagnosed conditions, or are pregnant/breastfeeding.
Learn how we evaluate confidence, safety, and intensity on the methodology page.
Founder & Head Researcher · Oak Ridge, TN · Last reviewed August 2026
Editorial Review
Checked against primary sources, cited evidence, and contraindication language before publication. Evidence claims, safety language, and affiliate modules are reviewed independently. Not personal medical advice.
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