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02Research · Supplement

Melatonin

Measured against the 58-marker panel. Human studies found an effect on 31, no change in 6 and conflicting results on 0; 21 have no result yet.

Most studied for

Primary insomnia / sleep onset latency reduction

  • Supported 31
  • No effect 6
  • Conflicting 0
  • No result yet 21
BOverall evidence grade
925Studies tracked
304Meta-analyses
400Randomized trials

01Read first

Who should be careful

From the dossier's safety review: 15 cautions and 15 interactions, 8 rated serious. They summarize research and labels; they are not advice for you.

Cautions15

  • SeriousUnsupervised OTC use in children <6 yearsGrade B

    NEISS-CADES surveillance documented ~10,930 ED visits for unsupervised pediatric ingestion. Gummy formulations and adult-size products are primary risk drivers.

  • SeriousPregnancyGrade C

    Melatonin crosses the placenta; endogenous melatonin plays critical roles in fetal circadian entrainment and organ maturation.

  • SeriousSevere hepatic impairment (Child-Pugh C)Grade C

    CYP1A2 is hepatically expressed; severe hepatic insufficiency dramatically reduces first-pass clearance, leading to supraphysiological accumulation.

  • SeriousSolid organ or bone marrow transplant recipients on immunosuppressionGrade C

    Immunostimulatory effects directly antagonize calcineurin/mTOR inhibitors, risking graft rejection or GVHD.

Show 11 more

  • SeriousInfants and children under 2 yearsGrade C

    Neonatal melatonin rhythm not established until 3-4 months; CYP1A2 activity <10% of adult in neonates.

  • ModerateConcurrent strong CYP1A2 inhibitor therapy (fluvoxamine, ciprofloxacin)Grade A

    CYP1A2 inhibition increases melatonin AUC 2-17 fold depending on inhibitor potency.

  • ModerateLactation / breastfeedingGrade C

    Melatonin is excreted into breast milk; neonatal CYP1A2 is immature (5-10% of adult activity), causing unpredictable melatonin accumulation in breastfed infants.

  • ModerateModerate hepatic impairment (Child-Pugh B)Grade C

    Reduced but not absent CYP1A2 activity leads to elevated melatonin exposure.

  • ModerateOrthostatic hypotension / clinically significant hypotensionGrade C

    Peripheral vasodilation via MT receptor-mediated vascular smooth muscle relaxation; nighttime BP reduction may be exaggerated, increasing fall risk.

  • ModerateActive autoimmune disease (MS, RA, lupus, T1DM, IBD)Grade C

    Melatonin stimulates NK cell cytotoxicity, Th1 polarization, and haemopoiesis. May exacerbate Th1-dominant autoimmune diseases and undermine anti-inflammatory biologics.

  • ModeratePre-surgical period (within 7-14 days of planned surgery)Grade C

  • ModerateSevere renal impairment (eGFR <30) / end-stage renal diseaseGrade D

    6-sulfatoxymelatonin (80% renal excretion) may accumulate; clinical consequences not well-characterized.

  • ModerateCongenital or acquired long QT syndrome / significant cardiac arrhythmiaGrade D

    additive QTc prolongation risk with concomitant QT-prolonging agents not excluded.

  • ModerateBiliary obstruction / cholestasisGrade D

    Impaired hepatic function reduces CYP1A2 activity, leading to accumulation.

  • ModerateSeizure disorders / epilepsyGrade D

    Human data are limited and conflicting. May alter seizure threshold or interact with antiepileptic drug metabolism.

Interactions15

  • SeriousFluvoxamineGrade A

    Potent CYP1A2 inhibition dramatically reduces melatonin first-pass clearance; AUC increases 12-17 fold

  • SeriousCyclosporineGrade C

    Dual mechanism: (1) Pharmacodynamic antagonism — melatonin's immunostimulatory effects (NK cell activation, Th1 polarization, haemopoiesis enhancement) directly oppose cyclosporine's immunosuppressive intent; (2) Possible PK interaction via shared P-gp and CYP3A4 pathways…

  • SeriousTacrolimusGrade C

    Pharmacodynamic antagonism — melatonin's Th1 polarization and NK cell activation oppose tacrolimus immunosuppression.

  • ModerateCiprofloxacinGrade B

    Moderate CYP1A2 inhibition reduces melatonin clearance during antibiotic course

Show 11 more

  • ModerateRifampicinGrade B

    Strong CYP1A2 induction markedly increases melatonin clearance, reducing systemic exposure; melatonin may be ineffective

  • ModerateMidazolamGrade B

    Pharmacodynamic additive CNS depression; melatonin potentiates sedative-hypnotic effect.

  • ModerateMetforminGrade B

    MTNR1B rs10830963 G-allele increases β-cell MTNR1B expression; Secondary: MATE transporter competition hypothesized for metformin renal clearance.

  • ModerateOral contraceptives (combined estrogen-progestin)Grade B

    Estrogen component inhibits CYP1A2, reducing melatonin clearance and increasing endogenous and exogenous melatonin levels in OCP users vs non-users

  • ModerateAlcohol (ethanol)Grade B

    Additive CNS sedation; acute ethanol transiently elevates then suppresses melatonin secretion, disrupting circadian phase.

  • ModerateWarfarinGrade C

    Melatonin may inhibit CYP2C9 at pharmacological concentrations (in vitro data), potentially increasing S-warfarin exposure and anticoagulant effect. FAERS contains hemorrhage reports with melatonin-warfarin combination.

  • ModerateQT-prolonging agents (antipsychotics, macrolides, antiarrhythmics, antihistamines)Grade D

    mechanism unclear but possibly via MT receptor effects on cardiac ion channels. Additive QT prolongation risk with concomitant QT-prolonging agents is theoretical but not excluded.

  • MinorAtorvastatinGrade C

    Limited PK interaction via shared CYP3A4 metabolism. Pharmacodynamic interaction: melatonin reduces oxidative stress and may produce additive lipid-modifying effects.

  • MinorCYP2D6 substrates (tramadol, codeine, metoprolol, venlafaxine, haloperidol, risperidone)Grade C

    Melatonin is NOT a CYP2D6 substrate; CYP1A2 (~85%) and CYP2C9 (~10%) account for virtually all hepatic melatonin clearance at therapeutic concentrations.

  • MinorCYP3A4 substrates (simvastatin, lovastatin, buspirone, triazolam, alprazolam, felodipine)Grade C

    PK interaction with CYP3A4 substrates is clinically negligible. Pharmacodynamic distinctions apply by substrate class: (1) benzodiazepines and buspirone — additive CNS sedation independent of CYP interaction.

  • MinorSSRIs — non-fluvoxamine (fluoxetine, paroxetine, sertraline, citalopram, escitalopram)Grade C

    Fluoxetine and paroxetine are potent CYP2D6 inhibitors — no direct PK effect on melatonin (not a CYP2D6 substrate). Fluvoxamine is a separate major interaction (CYP1A2, see dedicated entry).

02What it moves

37 markers studied

One row per marker on the panel that human studies measured. Open a row for the direction, who was studied, and the papers.

Read with this in mind

Pooled MAs suggest modest fasting glucose and HOMA-IR improvement in metabolic syndrome populations.

The majority of MAs contributing to inflammatory biomarker (CRP, IL-6, TNF-alpha) and metabolic (glucose, lipid) data originate from Iran, China, and Turkey.

Multiple MAs report significant reduction in ICU delirium incidence (RR ~0.78).

Blood sugar4 of 4 studied

HbA1cLowersGrade A

Melatonin lowers HbA1c.

Meta-analysis or review · Small effect · 14 studies linked

Studied in: Adults, T2DM

Marginal HbA1c reduction; do not present as clinically meaningful without context

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Fasting glucoseLowersGrade B

Melatonin lowers fasting glucose.

Small effect · 2 studies linked

Studied in: Adults, T2DM, Metabolic syndrome

Pooled MA shows modest fasting glucose reduction; contested — see contested_note; do not present as established benefit without genotype qualification

  • Chen (2022) · not matched to a paper yet
  • Lauritzen ES et al. (2022)
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Fasting insulinLowersGrade B

Melatonin lowers fasting insulin.

Small effect · 2 studies linked

Studied in: Adults, T2DM, PCOS, Metabolic syndrome

CONTESTED — shares genotype-dependent mechanism with HOMA-IR; 10 studies in MA vs single genotyped RCT for opposing signal

  • Mohammadi-Sartang M et al. (2021)
  • study mel shabani2019 · not matched to a paper yet
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HOMA-IRLowersGrade A

Melatonin lowers HOMA-IR.

Meta-analysis or review · Small effect · 15 studies linked

Studied in: Adults, T2DM, PCOS, Metabolic syndrome

Pooled decrease conflicts with individual RCT; genotype stratification essential

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Lipids4 of 6 studied

LDL-CLowersGrade A

Melatonin lowers LDL-C.

Meta-analysis or review · Small effect · 11 studies linked

Studied in: Adults, Metabolic syndrome, Dyslipidemia

Modest; below clinical action thresholds

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HDL-CNo changeGrade A

Studies of Melatonin found no change in HDL-C.

Meta-analysis or review · Negligible effect · 9 studies linked

Studied in: Adults, Metabolic syndrome

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TriglyceridesLowersGrade A

Melatonin lowers triglycerides.

Meta-analysis or review · Small effect · 15 studies linked

Studied in: Adults, Metabolic syndrome, NASH

High heterogeneity; may be secondary to hepatic lipid handling improvement

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Total cholesterolLowersGrade A

Melatonin lowers total cholesterol.

Meta-analysis or review · Small effect · 8 studies linked

Studied in: Adults, Metabolic syndrome

Total cholesterol modestly reduced; below clinical significance thresholds for cardiovascular risk reduction

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Inflammation4 of 5 studied

hs-CRPLowersGrade A

Melatonin lowers hs-CRP.

Moderate effect · 2 studies linked

Studied in: Adults, Metabolic syndrome, T2DM, NAFLD

Consistent reduction across 14-18 RCTs in two independent MAs; effect strongest at baseline CRP >3 mg/L; formulation-independent; minimal heterogeneity (I²≈38%)

  • Cho M et al. (2021)
  • Hallaji Z et al. (2023)
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IL-6LowersGrade A

Melatonin lowers IL-6.

Moderate effect · 3 studies linked

Studied in: Adults, Metabolic syndrome, T2DM, NAFLD

Replicated across two independent MAs; moderate heterogeneity (I²≈55%); ICU/critical illness subgroup contributes outsized effect; effect present but attenuated in metabolic-only subgroups

  • Cho M et al. (2021)
  • Zarezadeh M et al. (2022)
  • Hallaji Z et al. (2023)
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TNF-αLowersGrade A

Melatonin lowers TNF-α.

Small effect · 2 studies linked

Studied in: Adults, Metabolic syndrome, T2DM, NAFLD

Smaller effect than CRP/IL-6; consistent direction across 9 studies; less data from healthy populations; NF-κB suppression is primary mechanism

  • Cho M et al. (2021)
  • Zarezadeh M et al. (2022)
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ESRNo changeGrade B

Studies of Melatonin found no change in ESR.

Human trials · 1 study linked

9 studies reference ESR. No MA-level data for melatonin-specific effects.

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Liver5 of 6 studied

ALTLowersGrade A

Melatonin lowers ALT.

Meta-analysis or review · Moderate effect · 31 studies linked

Studied in: Adults, NASH, NAFLD, Metabolic syndrome

ALT reduction in NASH/NAFLD patients; Akhavan Rezayat 2021 and Mansoori 2020 both show significant hepatoprotective effects; effect size varies with baseline severity

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ASTLowersGrade A

Melatonin lowers AST.

Meta-analysis or review · Small to moderate effect · 73 studies linked

Studied in: Adults, NASH, NAFLD

AST reduction parallels ALT; AST/ALT ratio improvement suggests hepatocellular rather than cholestatic pattern

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GGTLowersGrade A

Melatonin lowers GGT.

Meta-analysis or review · Small effect · 4 studies linked

Studied in: Adults, NASH, NAFLD

GGT reduction in NASH context; less studied than ALT/AST but directionally consistent; may reflect biliary/hepatic oxidative stress improvement

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ALPLowersGrade A

Melatonin lowers ALP.

Meta-analysis or review · 9 studies linked

121 studies reference ALP in corpus but no MA-level data extracted for melatonin's direct effect on ALP. Insufficient evidence to characterize direction.

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AlbuminImprovesGrade C

Melatonin improves albumin.

Human trials · 2 studies linked

79 studies reference albumin. No MA-level data for melatonin-specific effects.

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Kidney3 of 4 studied

CreatinineLowersGrade A

Melatonin lowers creatinine.

Meta-analysis or review · Small effect · 11 studies linked

Studied in: Adults, CKD, Hemodialysis, Perioperative renal protection

Zhang 2021 MA; 7 studies; renal protective effect in CKD and perioperative settings. No data from healthy populations.

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eGFRRaisesGrade A

Melatonin raises eGFR.

Meta-analysis or review · Small effect · 4 studies linked

Studied in: Adults, CKD, Hemodialysis, Diabetic nephropathy

5 studies in MA; clinically modest. Requires replication.

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BUNLowersGrade A

Melatonin lowers BUN.

Meta-analysis or review · 6 studies linked

26 studies reference BUN. No MA-level data.

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Blood and iron3 of 7 studied

HemoglobinNo changeGrade A

Studies of Melatonin found no change in hemoglobin.

Meta-analysis or review · 1 study linked

43 studies reference hemoglobin. No MA-level data for direct melatonin effect.

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PlateletsRaisesGrade C

Melatonin raises platelets.

Small effect · 0 studies linked

This result is graded, but no study is linked to it yet. Treat it as unconfirmed.

Studied in: Adults, Cancer patients, Chemotherapy

Thrombocytopenia attenuation in chemotherapy patients; grade C — limited trials, heterogeneous populations; mechanistic basis involves platelet precursor protection from oxidative damage

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FerritinLowersGrade B

Melatonin lowers ferritin.

Human trials · 1 study linked

18 studies reference ferritin. NRF2-mediated ferritin upregulation theoretically possible but no clinical data.

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Hormones3 of 5 studied

TestosteroneRaisesGrade A

Melatonin raises testosterone.

Meta-analysis or review · 15 studies linked

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EstradiolRaisesGrade A

Melatonin raises estradiol.

Meta-analysis or review · 5 studies linked

189 studies reference estradiol. Aromatase modulation mechanism (mech_mel_008) is theoretical. ART context shows possible modulation but no systematic MA for serum estradiol.

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CortisolLowersGrade B

Melatonin lowers cortisol.

Small effect · 2 studies linked

Studied in: Adults, Preoperative anxiety, ICU, Stress

Evening and peri-operative cortisol reduction consistent; morning cortisol unchanged or slightly elevated; high heterogeneity across contexts; most robust effect in preoperative melatonin administration (3-10 mg); anxiolytic mechanism contributes independently of HPA axis suppression

  • study mel naguib2003 · not matched to a paper yet
  • study mel nordlund2000 · not matched to a paper yet
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Thyroid1 of 4 studied

TSHNo changeGrade C

Studies of Melatonin found no change in TSH.

Negligible effect · 1 study linked

Studied in: Adults, Euthyroid, Hypothyroid

Preclinical evidence for MT receptor expression on thyroid tissue; human RCT data insufficient to detect meaningful TSH change in euthyroid subjects; no robust MA-level data; grade C reflects mechanistic plausibility without human clinical confirmation

  • study mel luboshitzky2002 · not matched to a paper yet
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Heart2 of 2 studied

NT-proBNPImprovesGrade B

Melatonin improves NT-proBNP.

Human trials · 1 study linked

6 studies reference NT-proBNP. No MA-level data. Heart failure adjunct MA exists (Qin 2025) but NT-proBNP as endpoint not extracted.

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TroponinLowersGrade A

Melatonin lowers troponin.

Meta-analysis or review · Small effect · 4 studies linked

Studied in: Adults, CABG, Cardiac surgery

CABG perioperative MA suggests troponin reduction; limited studies. Grade C.

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Oxidative stress4 of 4 studied

MDALowersGrade A

Melatonin lowers MDA.

Moderate to large effect · 39 studies linked

Studied in: Adults, Metabolic syndrome, NASH, Oxidative stress conditions

MDA (lipid peroxidation marker) reduction is one of the most robust biomarker effects of melatonin; Zarezadeh 2022 and Morvaridzadeh 2020 both report large effects

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F2-isoprostanesLowersGrade B

Melatonin lowers F2-isoprostanes.

Human trials · Small effect · 3 studies linked

Studied in: Adults, Oxidative stress conditions

19 studies reference F2-isoprostanes. Lipid peroxidation marker similar to MDA. Directionally consistent but less studied than MDA.

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8-OHdGLowersGrade B

Melatonin lowers 8-OHdG.

Small to moderate effect · 0 studies linked

This result is graded, but no study is linked to it yet. Treat it as unconfirmed.

Studied in: Adults, Metabolic syndrome, Oxidative stress conditions

DNA oxidative damage marker; 29 studies in corpus. Reduction consistent with ROS scavenging mechanism. Limited MA-level data but directionally consistent with MDA reduction.

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GlutathioneRaisesGrade A

Melatonin raises glutathione.

Moderate effect · 1 study linked

Studied in: Adults, Metabolic syndrome, T2DM, NAFLD

Melatonin upregulates γ-GCS and GSH-Px enzymatically; effect size larger in populations with depleted baseline GSH; independent of direct radical scavenging — indirect antioxidant mechanism dominant at physiological concentrations

  • Zarezadeh M et al. (2022)
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Minerals2 of 5 studied

CalciumImprovesGrade B

Melatonin improves calcium.

Human trials · 1 study linked

236 studies reference calcium. Bone metabolism data suggests possible osteoprotective effects but no serum calcium MA.

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MagnesiumNo changeGrade C

Studies of Melatonin found no change in magnesium.

Meta-analysis or review · 1 study linked

36 studies reference magnesium. No MA-level data.

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Body2 of 2 studied

Blood pressureLowersGrade A

Melatonin lowers blood pressure.

Meta-analysis or review · 23 studies linked

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Weight and BMINo changeGrade A

Studies of Melatonin found no change in weight and BMI.

Meta-analysis or review · Negligible effect · 13 studies linked

Studied in: Adults, Metabolic syndrome

BMI non-significant across metabolic MAs; consistent with weight finding above

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Also measured20 outcomes

Outcomes these studies measured that are not on the shared panel, so they are not on the map.

Sleep onset latencyLowersGrade A

Melatonin lowers sleep onset latency.

Moderate effect · 3 studies linked

Studied in: Adults, Older adults, Insomnia, Circadian disorders

Consistent across multiple MAs; effect size modest but clinically meaningful for delayed sleep phase; Fatemeh 2022 and Cruz-Sanabria 2024 both grade A

  • Brzezinski (2005) · not matched to a paper yet
  • Fatemeh G et al. (2022)
  • Cruz-Sanabria F et al. (2024)
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SOD superoxide dismutaseRaisesGrade A

Melatonin raises SOD superoxide dismutase.

Moderate effect · 2 studies linked

Studied in: Adults, Metabolic syndrome, NASH, Oxidative stress conditions

SOD upregulation consistent with melatonin's antioxidant enzyme induction mechanism; complements direct ROS scavenging

  • Zarezadeh M et al. (2022)
  • Morvaridzadeh (2020) · not matched to a paper yet
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Total sleep timeRaisesGrade A

Melatonin raises total sleep time.

Small effect · 2 studies linked

Studied in: Adults, Older adults, Insomnia

Statistically significant but modest absolute increase; clinical significance debated

  • Fatemeh G et al. (2022)
  • Cruz-Sanabria F et al. (2024)
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Cat catalaseRaisesGrade A

Melatonin raises cat catalase.

Small to moderate effect · 1 study linked

Studied in: Adults, Metabolic syndrome, NASH

Catalase increase less consistent than SOD but significant in pooled analysis; hepatic expression likely dominant target given NASH populations studied

  • Zarezadeh M et al. (2022)
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TacRaisesGrade A

Melatonin raises tac.

Moderate effect · 1 study linked

Studied in: Adults, Metabolic syndrome, Chronic inflammatory conditions

Total antioxidant capacity increase; composite marker reflecting multiple antioxidant pathways

  • Zarezadeh M et al. (2022)
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Nocturnal sbpLowersGrade B

Melatonin lowers nocturnal sbp.

Small to moderate effect · 3 studies linked

Studied in: Adults, Hypertension, Metabolic syndrome

Effect specific to nocturnal blood pressure; daytime BP reduction is smaller and less consistent; Grossman 2011 and Akbari 2019 show significant nocturnal reduction; controlled-release formulation effect larger (Lee 2022: -6.1 mmHg nocturnal)

  • Grossman E et al. (2011)
  • Akbari (2019) · not matched to a paper yet
  • Lee (2022) · not matched to a paper yet
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Sleep efficiencyRaisesGrade B

Melatonin raises sleep efficiency.

Moderate effect · 3 studies linked

Studied in: Adults, Older adults, Insomnia, Perioperative

Improvement in sleep efficiency across MAs; effect smaller than pharmacological hypnotics but favorable safety profile

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Bm GGTLowersGrade B

Melatonin lowers bm GGT.

Small effect · 2 studies linked

Studied in: Adults, NAFLD, NASH, Metabolic syndrome

GGT reduction accompanies ALT/AST reduction in NAFLD RCTs; GGT is marker of hepatic oxidative stress and biliary microinflammation; consistent with melatonin's antioxidant mechanism; 12-month RCT data available (Gonciarz 2013)

  • Gonciarz M et al. (2013)
  • study mel hosseinzadeh2016 nafld · not matched to a paper yet
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Show 12 more
Delirium incidence icuLowersGrade B

Melatonin lowers delirium incidence icu.

Small effect · 2 studies linked

Studied in: Adults, Older adults, ICU, Critically ill

ICU delirium prevention: MAs show marginal benefit; high-quality RCTs null; clinical adoption remains controversial

  • Gu (2016) · not matched to a paper yet
  • Chen (2021) · not matched to a paper yet
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Nocturnal dbpLowersGrade B

Melatonin lowers nocturnal dbp.

Small effect · 2 studies linked

Studied in: Adults, Hypertension

Diastolic nocturnal reduction smaller than systolic; controlled-release shows larger effect

  • Grossman E et al. (2011)
  • Akbari (2019) · not matched to a paper yet
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WasoLowersGrade B

Melatonin lowers waso.

Moderate effect · 1 study linked

Studied in: Perioperative, Breast cancer surgery, Female, Adult

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Anxiety preoperativeLowersGrade B

Melatonin lowers anxiety preoperative.

Moderate effect · 0 studies linked

This result is graded, but no study is linked to it yet. Treat it as unconfirmed.

Studied in: Adults, Perioperative, Surgical patients

Preoperative anxiety reduction; comparable to low-dose midazolam in some RCTs; without addiction liability; non-significant sedation-level difference from placebo in most studies

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Cortisol eveningLowersGrade B

Melatonin lowers cortisol evening.

Small effect · 0 studies linked

This result is graded, but no study is linked to it yet. Treat it as unconfirmed.

Studied in: Adults, Stress anxiety, Insomnia

Evening/nocturnal cortisol reduction reported in perioperative and anxiety contexts; daytime cortisol less affected; likely HPA dampening via MT1/MT2 hypothalamic signaling

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Delirium incidence postoperativeLowersGrade B

Melatonin lowers delirium incidence postoperative.

Small to moderate effect · 0 studies linked

This result is graded, but no study is linked to it yet. Treat it as unconfirmed.

Studied in: Older adults, Postoperative, Orthopedic surgery

Postoperative delirium prevention shows more consistent signal than ICU context; older adults undergoing orthopedic procedures are the most studied subgroup

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Migraine frequencyLowersGrade B

Melatonin lowers migraine frequency.

Moderate effect · 0 studies linked

This result is graded, but no study is linked to it yet. Treat it as unconfirmed.

Studied in: Adults, Migraine

Melatonin as migraine prophylaxis: significant reduction in attack frequency; 3mg dose studied most; mechanism may involve CGRP modulation and vascular antioxidant effects

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Nausea chemotherapyLowersGrade B

Melatonin lowers nausea chemotherapy.

Moderate effect · 0 studies linked

This result is graded, but no study is linked to it yet. Treat it as unconfirmed.

Studied in: Adults, Cancer patients, Chemotherapy

Chemotherapy-induced nausea/emesis reduction as adjunct; multiple small RCTs meta-analyzed; antiemetic mechanism may involve 5-HT3 receptor modulation and HPA dampening

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Pain vrs perioperativeLowersGrade B

Melatonin lowers pain vrs perioperative.

Moderate effect · 0 studies linked

This result is graded, but no study is linked to it yet. Treat it as unconfirmed.

Studied in: Adults, Perioperative, Surgical patients

Perioperative pain reduction in surgical MAs; analgesic-sparing effect also reported; mechanism may involve endogenous opioid modulation and anti-inflammatory pathway

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Intraocular pressureLowersGrade C

Melatonin lowers intraocular pressure.

Small effect · 0 studies linked

This result is graded, but no study is linked to it yet. Treat it as unconfirmed.

Studied in: Adults, Glaucoma, Ocular hypertension

IOP reduction reported in glaucoma studies; circadian IOP rhythm involves melatonin receptor signaling in ciliary body; limited MA-level evidence; grade C

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Waist CircumferenceNo changeGrade A

Studies of Melatonin found no change in waist Circumference.

Meta-analysis or review · 9 studies linked

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Systolic blood pressureNo changeGrade B

Studies of Melatonin found no change in systolic blood pressure.

Negligible effect · 0 studies linked

This result is graded, but no study is linked to it yet. Treat it as unconfirmed.

Studied in: Adults, Hypertension

Daytime systolic BP non-significant; BP effect is timing-specific to nocturnal measurements; immediate-release formulations show less BP benefit than controlled-release

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How it might work4

Proposed mechanisms. Most rest on lab and animal work, so read them as explanations, not proof of an effect.

  • MT1/MT2 receptor agonism → Gi protein coupling → cAMP suppression → SCN circadian phase shift
  • NF-kB pathway suppression → reduced transcription of IL-6, TNF-alpha, IL-1beta
  • Direct ROS scavenging (hydroxyl radical, peroxynitrite) + upregulation of SOD, CAT, GPx gene expression via NRF2-ARE activation
  • Mitochondrial membrane stabilization → reduced cytochrome c release → anti-apoptotic effect in hepatocytes and neurons

03No result yet

21 markers

21 markers on the panel have no result for Melatonin yet. A gap is not a negative result.

Not yet reviewed21

No study in this dossier reported these, and they haven't been searched for one by one yet.

Lipids
ApoBLp(a)
Inflammation
Fibrinogen
Liver
Bilirubin
Kidney
Cystatin C
Blood and iron
HematocritRed cellsMCVWhite cells
Hormones
SHBGDHEA-S
Thyroid
Free T3Free T4Reverse T3
B vitamins
HomocysteineFolateVitamin B12MMA
Minerals
SodiumPotassiumPhosphate

Open questions4

  • Does melatonin's immunostimulatory profile (Th1 polarization, NK cell activation) differ at physiological replacement doses (0.3-0.5 mg) vs pharmacological doses (3-10 mg)?
  • Does chronic melatonin supplementation cause MT1/MT2 receptor downregulation or desensitization in humans, and does this attenuate clinical efficacy over time?
  • Does melatonin supplementation affect pubertal onset, gonadotropin pulsatility, or reproductive development in chronically supplemented pre-pubertal children?
  • Does long-term melatonin supplementation (>12 months) suppress endogenous pineal melatonin production through feedback mechanisms?
See these gaps on the map →Commission research on a gap →

04The studies and genetics

Go deeper

The three acts above are free. The paper-by-paper list and the genetics findings are part of the Research plan.
Research planResearch access

Every study and gene finding

Open the strongest papers with their populations and findings, and the gene differences human studies measured.

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Compare with

On the evidence map →

Each marker shows the strongest record in the dossier. Records are extracted from published studies by a model pipeline and graded A to D; records whose own notes say no usable human data exists count as no result yet. Research summaries for education, not medical advice. How this page is sourced