DEEN
Knowledge · Natural Compounds

Melatonin

Melatonin is a hormone produced by the body that helps regulate the sleep-wake rhythm; human studies show benefits mainly for sleep problems and migraine.

Last updated:

We evaluated 273 human studies on Melatonin, including 146 randomised controlled trials and 91 meta-analyses or systematic reviews; the controlled studies include 11,675 participants in total. As of 7 October 2026.

This page as PDF · Summary

1. What Is Melatonin? Occurrence, Origin and Forms

Melatonin is a hormone produced by the body that helps govern the sleep-wake rhythm and is formed in the pineal gland of the brain. It occurs in many living organisms and, in small amounts, in some plants and foods. It is commonly used when the sleep-wake rhythm is shifted in time, for example after flights across several time zones, in shift work, or with a delayed sleep-wake rhythm.

In the body, melatonin is formed in the pineal gland, and its amount follows a daily rhythm with higher levels in darkness. As a preparation it is taken at different times of day, and it is studied in this form.

For preparations, melatonin is mainly produced synthetically, while foods contain only small amounts. Studies examine above all immediate-release and prolonged-release oral forms, along with sublingual preparations and sprays.

Forms and Preparations Studied

  • Immediate-release melatonin
  • Prolonged-release melatonin
  • Oral tablets and capsules
  • Sublingual preparations and sprays
  • Combination products with further ingredients, each of which has to be named individually

Not covered on this page:

  • Melatonin receptor agonists such as ramelteon, tasimelteon and agomelatine are separate drugs and not melatonin.
  • Tryptophan and 5-hydroxytryptophan are metabolic precursors and separate substances.
  • Herbal sleep aids such as valerian and hops are different substances.
  • Light therapy and sleep-hygiene programmes are separate procedures and not melatonin administration.

2. What Does Melatonin Do? Results by Area

AreaResult in controlled studiesStrength of evidenceStudiesParticipants
Sleep and falling asleepmixedhigh23 meta-analyses · 49 controlled · 12 other2,899
Children and adolescentsmostly improvedhigh4 meta-analyses · 5 controlled · 3 other359
Delirium and confusion in hospitalmostly no differencemoderate6 meta-analyses · 4 controlled · 4 other501
Migraine and headachemostly improvedmoderate3 meta-analyses · 1 controlled · 0 other60
Jet lag after flights across time zonesreviews onlylow1 meta-analyses · 0 controlled · 1 other0
Shift and night workmostly improvedlow0 meta-analyses · 1 controlled · 0 other27
Shifted sleep-wake rhythmmostly improvedlow0 meta-analyses · 1 controlled · 3 other51
Other investigationsmostly improvedhigh56 meta-analyses · 108 controlled · 27 other6,192

How to read the table: counted are human studies whose results concern the area. “High” means at least one meta-analysis and two controlled studies showing improvement, or at least three controlled studies of which three quarters show improvement, with at least 300 participants in total. “Moderate” means at least two controlled studies showing improvement, as a majority, or one meta-analysis alongside controlled studies. “Low” means one controlled study showing improvement. Where an area has no controlled study, the strength of evidence is at most “low” (result “reviews only” or “observational data only”). Everything else is “unclear”. A study counts as showing improvement when at least half of its outcomes in this area improved. Reviews of combination products do not count as meta-analyses; results that only describe side effects or shares of users do not count as an effect. The same study is counted only once.

3. What the Studies Show in Detail

Melatonin, Sleep and Falling Asleep: Human Studies

Meta-analyses found better sleep quality in the PSQI with melatonin compared with placebo, for example in hemodialysis, Parkinson's disease, and respiratory and metabolic diseases 314460. In the intensive care unit and in chronic musculoskeletal pain, the reported sleep quality also improved 714, but not after operations 142425. In healthy adults with poor sleep, prolonged-release melatonin improved sleep efficiency and sleep onset latency in the sleep laboratory compared with placebo 133. A network meta-analysis on insomnia found an improvement in difficulties falling asleep for melatonin 70. Randomized controlled trials found no difference from placebo in the PSQI in insomnia in middle age and in advanced glaucoma 96119. The body of studies is extensive, but the individual studies are mixed; different populations, forms and comparison groups as well as sometimes short observation periods limit the transferability.

StudyDesign · participantsPreparation · dose · duration · comparisonResult
3 Nissen et al. 2024meta-analysis · 6,528 participantsMelatonin (form not specified); vs. CBT-I and other interventionsinsomnia severity: improved
4 Yu et al. 2025systematic review · 5,093 participantsMelatonin alone or with standard anticancer treatment; outcomes within three months; vs. placebo or standard anticancer treatmentsleep score: unclear (MD 2.80, 95% CI 0.18 to 5.42)
7 Tang et al. 2025meta-analysis · 3,895 participantsExogenous melatonin; vs. Melatonin versus no melatoninReported sleep quality: improved (SMD 0.54; 95% CI, 0.01-1.07); Sleep awakenings: unclear
9 Natale et al. 2019systematic review · 3,427 participantsMelatonin (one of many interventions assessed); Follow-up 0.3 to 52.8 weeks (median 5 weeks); vs. various interventions including relaxation, exercise, acupressure, CBT, benzodiazepinesSleep quality (relaxation techniques): unclear; Sleep duration (relaxation techniques): unclear; Sleep quality (exercise): unclear (SMD -1.10, 95% CI -2.26 to 0.05)
13 Liu et al. 2025systematic review · 2,408 participantsMelatonin 6 mg/d versus placebo and other insomnia drugs; 6 mg/d; Follow-up 10 to 40 weeks; vs. Placebo, dimdazenil, lemborexant, daridorexant, zolpidem, doxepinWake after sleep onset (WASO): improved (SMD = -0.741, 95 % CI: -1.423 to -0.044); WASO after adjusting for follow-up period: no difference (SMD = -0.727, 95 % CI: -1.48 to 0.01); Time window of significant superiority over control: improved (from the 10th to 40th weeks)
14 Wu et al. 2026meta-analysis · 2,028 participantsMelatonin (form not reported); vs. Placebo or active controls (eg, analgesics)Sleep quality in chronic pain: improved; Sleep quality in postoperative pain: no difference
22 Abouelmagd et al. 2026meta-analysis · 788 participantsMelatonin (form, dose and timing not reported); vs. Placebo or amitriptylineSleep quality (PSQI): improved (MD -1.64; 95% CI -2.85 to -0.42; p = 0.008)
24 Tsukinaga et al. 2023meta-analysis · 516 participantsMelatonin or melatonin agonists; short, night before and day of surgery or day of surgery only; vs. placebo or no treatmentsleep quality (VAS): no difference (mean difference, -0.75 mm; 95% confidence interval, -4.86 to 3.35); postoperative adverse events

Further studies in this area: 25 31 34 38 44 47 48 49 56 60 61 62 70 77 80 85 86 91 94 96 99 101 103 106 107 108 110 113 114 116 117 119 123 124 125 127 128 130 131 133 134 135 140 141 149 150 151 153 157 163 164 171 176 181 183 185 189 192 195 196 197 201 203 206 214 216 218 219 226 229 230 233 238 239 241 242

Melatonin, Children and Adolescents: Human Studies

In children with cerebral palsy, melatonin shortened sleep onset latency and lengthened total sleep time compared with placebo in a randomised controlled trial 93. In children with chronic sleep-onset insomnia and late melatonin onset, melatonin shortened sleep onset latency and improved sleep efficiency in a randomised controlled trial, but lengthened nighttime wake time 104. In children with autism spectrum disorder, a network meta-analysis found an improvement in sleep disorders with melatonin; only exercise programmes had a stronger effect 11. In healthy children with sleep-onset problems, melatonin and light therapy shortened sleep onset latency more than psychological approaches in a network meta-analysis 57. In anxious children with insomnia, melatonin improved sleep habits compared with placebo, to a similar extent as clonidine 111. The findings apply to the forms and preparations studied; questions remain open about dose, timing of intake and duration, as well as transferability to other age groups and comorbidities.

StudyDesign · participantsPreparation · dose · duration · comparisonResult
11 Sirao et al. 2026meta-analysis · 2,700 participantsProlonged-release melatonin; vs. Physical activity, behavioral interventions, parent education, adjunctive therapiesSleep disturbances (SMD): improved (standardized mean difference = 0.57); Ranking (SUCRA): improved (surface under the cumulative ranking curve = 62.8%)
49 Paditz et al. 2025systematic reviewOral melatonin, rapid-release; one combination preparation with sustained-release and non-released components; low oral dose (no numeric value); vs. Placebo (randomised placebo-controlled trials)efficacy for non-organic sleep disorders: improved
57 Mombelli et al. 2023meta-analysisMelatonin (form, dose and timing not reported); vs. Evidence-based psychological interventions, light therapy, combinationsSleep onset latency (SOL): improved; Wake after sleep onset (WASO): unclear; Total sleep time (TST): unclear
72 Abramova et al. 2020systematic reviewExogenous melatonin supplement; vs. Randomized controlled trials, crossover studies, meta-analysesSleep improvement: improved
93 K et al. 2026randomised controlled · 120 participantsOral melatonin; 3 mg escalated to 10 mg once daily; 12 weeks; vs. Placebo, randomized double-blindTotal sleep time (hours): improved (MD 1.31; P < 0.001); Sleep onset latency (minutes): improved (MD 27.72; P < 0.001)
104 van et al. 2017randomised controlled · 84 participantsmelatonin pills (N = 26) versus light therapy (N = 30) versus placebo pills (N = 28); 3 to 4 weeks after a baseline week; vs. placebo pills and bright light therapysleep latency (sleep diary): improved; sleep onset advanced (sleep diary and actigraphy): improved; DLMO advanced: improved
111 Jalali et al. 2026randomised controlled · 72 participantsMelatonin (off-label), oral; 6 weeks; vs. Placebo and clonidineSleep habits (CSHQ) at 6 weeks: improved (P < 0.001)
122 Tse et al. 2024randomised controlled · 62 participantsmelatonin supplement, alone or with cycling exercise; vs. placebo control and exercise groupsleep efficiency: improved; sleep onset latency: improved; sleep duration: improved

Further studies in this area: 192 217 219 235

Melatonin, Delirium and Confusion in Hospital: Human Studies

In hospitalised adults, there is no consistent benefit for preventing delirium: several randomised controlled trials found no lower delirium incidence than with placebo 85949599. Several meta-analyses also reach mixed results: some found a lower delirium risk in intensive care patients 7 and a lower delirium incidence 865, while others saw no difference 210. One meta-analysis reported a lower delirium risk for melatonin and melatonin receptor agonists combined, but not for midazolam benzodiazepines 5. Delirium duration showed no difference in one meta-analysis 8. The robustness is moderate; the studies differ in form, dose, timing of intake and duration, and most examined intensive care or perioperative patients. It remains open whether certain subgroups or higher doses benefit; a randomised trial without a placebo group found less delirium with the higher of two doses 92.

StudyDesign · participantsPreparation · dose · duration · comparisonResult
2 de et al. 2026meta-analysis · 7,845 participantsMelatonin (other agents assessed: ramelteon, suvorexant, lemborexant); vs. Placebo or standard careDelirium incidence (RCTs, melatonin vs. control): no difference (RR 0.94; 95% CI 0.72-1.22)
7 Tang et al. 2025meta-analysis · 3,895 participantsExogenous melatonin; vs. Melatonin versus no melatoninDelirium risk: improved (RR 0.72; 95% CI, 0.58-0.89)
8 Wu et al. 2026meta-analysis · 3,706 participantsMelatonin or melatonin receptor agonists (incl. ramelteon); vs. Placebo or standard careIncidence of delirium: improved (RR 0.75, 95% CI 0.63 to 0.90, P = 0.001); Duration of delirium: no difference (MD 0.18 days, 95% CI -0.16 to 0.52, P = 0.56)
10 Lakbar et al. 2025meta-analysis · 2,830 participantsMelatonin; vs. PlaceboDelirium incidence (primary analysis, 6 RCTs, 2209 patients): no difference (RR 0.89, [95% confidence interval (CI) 0.73-1.09]); Delirium incidence (secondary analysis, 13 RCTs, 2830 patients): no difference (RR 0.86, [95% CI 0.70-1.04])
19 Barnes et al. 2023systematic review · 1,244 participantsMelatonin in variable doses; four studies used ramelteon; variable, not specified; vs. control group without melatoninincidence of postoperative delirium: improved (OR 0.41 (95% CI 0.21 to 0.80, p=0.01))
65 You et al. 2022meta-analysismelatonin (form not reported); 6 mo in included RCTs; vs. placebo or controlincidence of delirium: improved (RR = 0.69, 95%CI: 0.60-0.80); delirium incidence in medical patients: improved (RR = 0.60, 95%CI: 0.47-0.76), P < 0.001)
73 Asleson et al. 2020systematic reviewmelatonin (form not reported); varied between studies; varied between studies; vs. heterogeneous control groups across included studiesdelirium prevention: unclear (four studies that showed positive results and three that showed negative results)
85 Gandolfi et al. 2020randomised controlled · 203 participantsOral melatonin 10 mg versus placebo; 10 mg; up to seven consecutive nights; vs. placebo, double-blind randomizedoccurrence of delirium: no difference

Further studies in this area: 92 94 95 99 213 223

Melatonin, Migraine and Headache: Human Studies

Two meta-analyses found fewer headache days and a higher response rate with melatonin than with placebo in adults with migraine 622; in the network meta-analysis, immediate-release melatonin at bedtime performed best 6. In the meta-analysis with placebo and amitriptyline comparison, duration and severity of attacks, painkiller use and impairment also improved compared with placebo 22. As an add-on to propranolol, melatonin reduced the frequency and duration of attacks compared with placebo in a randomised controlled trial, but not their severity 127. Compared with amitriptyline, melatonin was mostly less effective for duration and severity of attacks, but caused drowsiness less often 22; a systematic review on migraine and sleep found no clear influence for melatonin 16. Form, dose and timing of intake are not reported in several of the pooled studies, and the robustness is moderate overall.

StudyDesign · participantsPreparation · dose · duration · comparisonResult
6 Tseng et al. 2020meta-analysis · 4,499 participantsOral melatonin, immediate-release; 3 mg/day; vs. Placebo and other approved migraine prophylaxis drugsChange in monthly migraine days: improved (mean difference = -1.71 days, 95% confidence interval (CI): -3.27 to -0.14 days compared to placebo); Response rate: improved (odds ratio = 4.19, 95% CI = 1.46 to 12.00 compared to placebo)
16 Sforza et al. 2026systematic review · 1,941 participantsMelatonin (form not specified); vs. other migraine and sleep interventionsmigraine frequency and pain intensity: no difference (no significant impact)
22 Abouelmagd et al. 2026meta-analysis · 788 participantsMelatonin (form, dose and timing not reported); vs. Placebo or amitriptylineAttack duration: improved (MD -4.98 h; 95% CI -9.30 to -0.67; p = 0.02); Headache days: improved (MD -1.54 days; 95% CI -2.50 to -0.58; p < 0.01); Headache severity: improved (MD -2.08; 95% CI -2.91 to -1.26; p < 0.01)
127 Mehramiri et al. 2024randomised controlled · 60 participantsoral melatonin 3 mg vs. placebo, plus propranolol 20 mg BID; 3 mg daily; 2 months treatment, follow-up up to 4 months; vs. placebo plus propranolol 20 mg BIDattack frequency: improved (P=0.032); attack duration: improved (P=0.001); attack severity (VAS): no difference (P=0.126)

Melatonin and Jet Lag After Flights Across Time Zones: Human Studies

A systematic review found that melatonin taken shortly before bedtime at the destination reduced jet lag after flights across multiple time zones 80. A prolonged-release preparation was comparatively less effective, and taken at the wrong time of day, melatonin can delay adaptation 80. The evidence is weak because the finding is based on reviews; dose, timing, and duration are not uniform there.

StudyDesign · participantsPreparation · dose · duration · comparisonResult
80 Herxheimer et al. 2001systematic reviewOral melatonin, including slow-release; one comparison with zolpidem; 0.5 to 5 mg daily; 2 mg slow-release; doses above 5 mg; short-term, close to target bedtime; vs. Placebo; one trial additionally zolpidemjet-lag symptoms: improved (NNT is 2)
230 Wani et al. 2026reviewExogenous melatoninCircadian phase-shifting: improved

Melatonin, Shift and Night Work: Human Studies

In overweight nurses on night duty who took melatonin on nights without night duty, a randomised controlled trial found a reduced shift of the internal rhythm compared with placebo 188. Weight, BMI and waist and hip circumference decreased only in early chronotypes with a strong rhythm shift 188. A second analysis of the same study found no difference in energy intake, nutrient distribution and meal times 187. The evidence is weak because both analyses are based on the same small study in overweight nurses on night duty 187188.

StudyDesign · participantsPreparation · dose · duration · comparisonResult
188 Marqueze et al. 2021randomised controlled · 27 participantsMelatonin 3 mg or placebo, double-blind, randomized, crossover; 3 mg; 12 weeks, only on non-night shift nights; vs. PlaceboCircadian misalignment (actigraphy-based Composite Phase Deviations): improved (approximately 20% reduction); Body weight: improved; BMI: improved

Melatonin and Shifted Sleep-Wake Rhythm: Human Studies

In adults with ADHD and delayed sleep-wake rhythm, low-dose melatonin in a randomized controlled trial advanced the evening melatonin onset (DLMO) compared with placebo 141. However, sleep times did not shift accordingly in an analysis of the same study 149. Reviews describe better alignment of the circadian rhythm through exogenous melatonin 230, while regulation in Alzheimer's dementia remains unclear 236. The evidence is weak because only one controlled trial is available; dose, timing, and duration can be found in the study card.

StudyDesign · participantsPreparation · dose · duration · comparisonResult
141 van et al. 2021randomised controlled · 51 participants0.5 mg/d oral melatonin, placebo, or melatonin plus bright light therapy; 0.5 mg/d, starting 3 h before individual DLMO, advanced weekly by 1 h; 3 weeks treatment, 2 weeks follow-up; vs. Placebo (double-blind) and melatonin plus 30 min 10,000 lux bright light therapyDLMO advance (saliva): improved (1h28 (p = .001)); DLMO advance (saliva): improved (1h58 (p < .001))
221 Tavartkiladze et al. 2026case series · 8 participantsAminoTriComplex, phytochemical-melatonin formulation, adjuvant to standard of care; vs. active arm of a double-blind, placebo-controlled trialrestoration of circadian rhythm: improved
230 Wani et al. 2026reviewExogenous melatoninCircadian rhythm alignment: improved
236 Zhang et al. 2025reviewmelatoninregulation of circadian rhythms: unclear

Melatonin: Further Outcomes in Studies

Melatonin improved quality of life compared with placebo in heart failure and in breast cancer under antihormone therapy 97126; a network meta-analysis also found this in Alzheimer's dementia 63. Anxiety and depression scores also improved under oral melatonin, including in Parkinson's patients, women with PCOS, and people on methadone maintenance 130134140. Several studies also found improvements in blood sugar and inflammation markers as well as oxidative stress under oral melatonin 213950. In contrast, randomized controlled trials found no difference from placebo for fatigue during breast cancer radiation, brain damage markers after brain injury, and vascular function in healthy individuals 108129186. It remains open how robust individual findings are, as many studies were small, examined different populations and doses, and sometimes provided no information on release type or timing.

StudyDesign · participantsPreparation · dose · duration · comparisonResult
1 An et al. 2022meta-analysis · 883,627 participantsMelatonin as micronutrient supplementation; vs. Control groups of the randomized trialsCardiovascular risk factors: improved (moderate- to high-quality evidence for reducing CVD risk factors)
4 Yu et al. 2025systematic review · 5,093 participantsMelatonin alone or with standard anticancer treatment; outcomes within three months; vs. placebo or standard anticancer treatmentquality of life score: unclear (MD 2.60, 95% CI -14.53 to 19.73); headache (RR 2.77, 95% CI 0.33 to 23.14); fatigue (RR 1.02, 95% CI 0.90 to 1.17)
7 Tang et al. 2025meta-analysis · 3,895 participantsExogenous melatonin; vs. Melatonin versus no melatoninICU length of stay: improved (MD -0.57 d; 95% CI, -0.95 to -0.18 d); Frequency of adverse events; Anxiety level: unclear
8 Wu et al. 2026meta-analysis · 3,706 participantsMelatonin or melatonin receptor agonists (incl. ramelteon); vs. Placebo or standard careLength of ICU stay: no difference (MD -0.45 days, 95% CI -1.10 to 0.20, P = 0.09); Overall mortality: no difference (RR 0.92, 95% CI 0.79 to 1.06, P = 0.25)
9 Natale et al. 2019systematic review · 3,427 participantsMelatonin (one of many interventions assessed); Follow-up 0.3 to 52.8 weeks (median 5 weeks); vs. various interventions including relaxation, exercise, acupressure, CBT, benzodiazepinesDepression (exercise): improved (MD -9.05, 95% CI -13.72 to -4.39); Fatigue (exercise): improved (SMD -0.68, 95% CI -1.07 to -0.29); Fatigue (acupressure): improved (MD -1.07, 95% CI -1.67 to -0.48)
10 Lakbar et al. 2025meta-analysis · 2,830 participantsMelatonin; vs. PlaceboMortality (primary analysis, 7 RCTs, 2165 patients): no difference (RR 0.87, [95% CI 0.73-1.02]); Mortality (secondary analysis, 8 RCTs, 2396 patients): no difference (RR 0.92, [95% CI 0.79-1.06])
12 Zeng et al. 2025meta-analysis · 2,481 participantsmelatonin (MLT) as nutritional supplement; vs. other supplements (TCM products, calcitriol) and controlsmodified Medical Research Council (mMRC) dyspnea score: improved (MD=-0.9, 95% CI (-1.6, -0.21))
13 Liu et al. 2025systematic review · 2,408 participantsMelatonin 6 mg/d versus placebo and other insomnia drugs; 6 mg/d; Follow-up 10 to 40 weeks; vs. Placebo, dimdazenil, lemborexant, daridorexant, zolpidem, doxepinDyspnoea constituent ratio versus suvorexant: worsened (OR = 1.568, 95 % CI = 1.192 to 2.061, p = 0.001)

Further studies in this area: 14 15 17 18 20 21 23 26 27 28 29 30 32 33 35 36 37 38 39 40 41 42 43 44 45 46 47 50 51 52 53 54 55 56 58 59 62 63 64 66 67 68 69 71 74 75 76 78 79 80 83 84 85 86 87 90 92 94 95 97 98 99 100 101 102 103 105 106 107 108 109 110 111 112 113 114 115 116 117 118 119 120 121 124 126 128 129 130 131 132 133 134 135 136 137 138 139 140 142 143 144 145 146 147 148 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166 167 168 169 170 171 172 173 174 175 176 177 178 179 180 182 183 184 185 186 189 190 191 193 194 195 198 199 200 201 202 203 204 205 207 208 209 210 211 212 214 215 218 219 220 221 222 224 225 227 228 229 231 232 233 234 236 237 239 240 241 242

4. How Is Melatonin Dosed? Preparation, Dose and Duration in Studies

The studies mostly used oral tablets or capsules, sometimes prolonged-release or sublingual preparations; many do not state the release type. Some studies tested melatonin together with other substances, such as zinc and multivitamins; such results apply to the mixture, not to melatonin alone. Form, dose, timing of intake and duration differ between the studies and can be found in the study cards.

Preparation or formDoseDurationStudy
5 mg melatonin alone or with 15 mg CBD and 15 mg CBN5 mg melatonin4 weeks of use, 5 weeks assessed81
Capsules with 5 mg melatonin, alone or with CBD/CBN/CBC5 mg melatonin4 weeks82
3 mg pure melatonin, alone or with 80 mg soy isoflavones3 mg melatonin daily3 months84
Oral melatonin 10 mg versus placebo10 mgup to seven consecutive nights85
Melatonin 3 mg/day alone or with ashwagandha root extract 600 mg/dayMelatonin 3 mg/day; combination: melatonin 3 mg + ARE 600 mg/day8 weeks86
Melatonin 10 mg versus placebo, plus cervical ripening as required10 mg every 6 h, maximum four dosesduring induction of labor until birth87
Integrative perioperative program including controlled-release melatonin—6 months (outcomes), 12-month follow-up88
Melatonin plus zinc and multivitaminsdaily doses (amount not stated)follow-up to day 1589
bedtime melatonin, with or without bright light—3.5 years90
Oral melatonin 5 mg, nightly5 mg nightly14 days postoperatively91
Oral melatonin3 mg escalated to 10 mg once daily12 weeks93
Oral melatonin 5 mg or 8 mg versus placebo5 mg or 8 mgNightly for up to 5 days or until discharge94
Melatonin6 mg twice daily for 3 days3 days of treatment, follow-up to day 795
3 mg fast-release melatonin vs. placebo3 mg daily, 1 h before bedtimefour weeks96
Melatonin tablets or placebo10 mg every night24 weeks97

5. Is Melatonin Safe? Side Effects in Studies

One meta-analysis and one randomised controlled trial described adverse events as mild and temporary 14133. In intensive care patients, no more adverse events occurred with melatonin 7, and in children with autism, morning drowsiness was reported 11. In one meta-analysis, drowsiness with melatonin was less common than with amitriptyline 22. A review of high doses mentions reduced insulin release, suppression of ovulation and reduced attention 58. Case reports point to possible risks in epilepsy and with warfarin 80.

StudyReported side effects
4 Yu et al. 2025headache, fatigue, nausea; no data on dizziness
6 Tseng et al. 2020Dropout rate and any adverse event rates included in ranking
7 Tang et al. 2025Slight reduction in adverse event frequency (low certainty)
11 Sirao et al. 2026Morning drowsiness
13 Liu et al. 2025Higher dyspnoea proportion than suvorexant (OR 1.568)
14 Wu et al. 2026Adverse events were mild and transient
15 Etesamnia et al. 2026not reported
18 Wu et al. 2025favorable safety profile, no details reported
20 Ang et al. 2026Adverse events were a prespecified outcome but not reported
22 Abouelmagd et al. 2026Sleepiness less frequent than with amitriptyline (RR 0.49)
23 Leung et al. 2025described as relatively safe
24 Tsukinaga et al. 2023postoperative adverse events comparable between melatonin and control

6. What Remains Open: Limits of the Evidence

  • The studies differ greatly in population, melatonin form, dose, timing of intake and observation period, which limits transferability.
  • Prolonged-release and sublingual forms were tested less often, and many studies do not state the release type.
  • For shift work and jet lag, the evidence is weak; larger controlled trials are still pending.
  • For children, older and hospitalised people, and for people with concomitant conditions, dose, timing of intake and duration have not yet been sufficiently clarified.

7. Bottom Line: What Is Established About Melatonin

Melatonin is a hormone produced by the body in the pineal gland that helps regulate the circadian rhythm. For sleep, meta-analyses found better sleep quality than with placebo in various conditions 314460, and in children melatonin shortened sleep onset latency 93104. In episodic migraine, two meta-analyses found fewer headache days and a higher response rate 622.

The findings in hospitalised adults for delirium prevention are less consistent: several controlled trials found no difference from placebo 85949599, while individual meta-analyses reported a lower risk 7865. Above all, the best dose and timing of intake remain open, as do larger studies on shift work, jet lag and shifted sleep-wake rhythm.

Frequently Asked Questions

How well has Melatonin been studied in humans?

We evaluated 273 human studies on Melatonin, including 146 randomised controlled trials and 91 meta-analyses or systematic reviews; the controlled studies include 11,675 participants in total. As of 7 October 2026.

Does Melatonin help with sleep and falling asleep? What the studies show

We evaluated 23 meta-analyses or systematic reviews, 49 controlled studies and 12 further studies; the controlled studies include 2,899 participants in total. Result of the controlled studies: mixed. Strength of evidence under our published rules: high. Sources: 3479

Does Melatonin help with children and adolescents? What the studies show

We evaluated 4 meta-analyses or systematic reviews, 5 controlled studies and 3 further studies; the controlled studies include 359 participants in total. Result of the controlled studies: mostly improved. Strength of evidence under our published rules: high. Sources: 11495772

Does Melatonin help with delirium and confusion in hospital? What the studies show

We evaluated 6 meta-analyses or systematic reviews, 4 controlled studies and 4 further studies; the controlled studies include 501 participants in total. Result of the controlled studies: mostly no difference. Strength of evidence under our published rules: moderate. Sources: 27810

Does Melatonin help with migraine and headache? What the studies show

We evaluated 3 meta-analyses or systematic reviews and one controlled study; the controlled studies include 60 participants in total. Result of the controlled studies: mostly improved. Strength of evidence under our published rules: moderate. Sources: 61622127

Does Melatonin help with jet lag after flights across time zones? What the studies show

We evaluated one meta-analysis or systematic review and one further study. There are no controlled studies yet, only reviews; the strength of evidence is therefore low at most. Sources: 80230

Does Melatonin help with shift and night work? What the studies show

We evaluated one controlled study; the controlled studies include 27 participants in total. Result of the controlled studies: mostly improved. Strength of evidence under our published rules: low. Sources: 188

Which melatonin forms were used in the studies?

Mostly oral tablets or capsules were tested, sometimes prolonged-release or sublingual preparations; many studies do not state the release type.

How well tolerated is melatonin in the studies?

The studies mostly described adverse events as mild and temporary 14133; a review of high doses mentions, among other things, reduced insulin release and suppression of ovulation 58.

Does melatonin help with jet lag and shift work?

In night-shift nurses who took melatonin on nights without night duty, a randomised controlled trial found a reduced shift of the internal rhythm compared with placebo 188. For jet lag, a Cochrane review found fewer symptoms when melatonin was taken shortly before bedtime at the destination 80. The evidence is weak in both areas because only one small study is available for shift work and mainly review data for jet lag.

What should be considered with combination products containing melatonin?

With combination products, the results refer to the mixture and not to melatonin alone. The other ingredients may also influence the findings, so these results cannot readily be transferred to pure melatonin.

Sources

  1. 1
    Micronutrient Supplementation to Reduce Cardiovascular Risk
    An P, Wan S, Luo Y, Luo J, Zhang X, Zhou S et al. · 2022
  2. 2
    Pharmacologic Modulation of Circadian Rhythms for Delirium Prevention: An Age-Stratified Systematic Review and Meta-Analysis
    de Oliveira HM, Gallo Ruelas M, Parker T, Diaz CAV, Oliveira de Paula G, Zamora FV et al. · 2026
  3. 3
    Interventions for insomnia in cancer patients and survivors-a comprehensive systematic review and meta-analysis
    Nissen ER, Neumann H, Knutzen SM, Henriksen EN, Amidi A, Johansen C et al. · 2024
  4. 4
    Melatonin in cancer treatment
    Yu ZY, Peng RY, Cheng N, Wang RT, Nan MD, Milazzo S et al. · 2025
  5. 5
  6. 6
  7. 7
    Melatonin Use in the ICU: A Systematic Review and Meta-Analysis
    Tang BHY, Manalo J, Chowdhury SR, Aldrich JM, Weinhouse GL, Cordoza M et al. · 2025
  8. 8
  9. 9
    Interventions for improving sleep quality in people with chronic kidney disease
    Natale P, Ruospo M, Saglimbene VM, Palmer SC, Strippoli GF · 2019
  10. 10
  11. 11
  12. 12
  13. 13
  14. 14
  15. 15
    Exploring the impact of melatonin on cancer-related fatigue: a dose-response meta-analysis with GRADE evidence evaluation
    Etesamnia S, Nasiraie-Moghadam M, Mostafazadeh P, Jowshan MR, Roudini K, Miri SR et al. · 2026
  16. 16
    Interventions for Migraine and Sleep: A Systematic Review Exploring Their Bidirectional Association
    Sforza M, Mariani I, Fazzini F, Genovese F, Salibba A, Filippi M et al. · 2026
  17. 17
  18. 18
  19. 19
    Does melatonin administration reduce the incidence of postoperative delirium in adults? Systematic review and meta-analysis
    Barnes J, Sewart E, Armstrong RA, Pufulete M, Hinchliffe R, Gibbison B et al. · 2023
  20. 20
  21. 21
  22. 22
    Efficacy and Safety of Melatonin in Migraine Prophylaxis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
    Abouelmagd ME, Aldemerdash MA, Khatatbeh AA, Osman ASA, Abbas A, Allam S et al. · 2026
  23. 23
  24. 24
  25. 25
  26. 26
  27. 27
  28. 28
  29. 29
  30. 30
  31. 31
  32. 32
  33. 33
  34. 34
  35. 35
  36. 36
  37. 37
  38. 38
  39. 39
  40. 40
  41. 41
  42. 42
  43. 43
  44. 44
  45. 45
  46. 46
    Impact of Melatonin Supplementation on Glycemic Parameters in Patients with Type 2 Diabetes: A Systematic Review and Meta-analysis
    Abadi RNS, Jazinaki MS, Bahari H, Rashidmayvan M, Amini MR, Aliakbarian M et al. · 2025
  47. 47
  48. 48
  49. 49
  50. 50
    Comprehensive Effects of Melatonin Supplementation on Cardiometabolic Risk Factors: A Systematic Review and Dose-Response Meta-Analysis
    Mohammadi S, Ashtary-Larky D, Erfanian-Salim M, Alaghemand N, Yousefi M, Sanjari Pirayvatlou P et al. · 2025
  51. 51
  52. 52
  53. 53
    Impact of Melatonin Supplementation on Sports Performance and Circulating Biomarkers in Highly Trained Athletes: A Systematic Review of Randomized Controlled Trials
    Celorrio San Miguel AM, Roche E, Herranz-López M, Celorrio San Miguel M, Mielgo-Ayuso J, Fernández-Lázaro D · 2024
  54. 54
  55. 55
    Mood Disorders in Youth: Complementary and Integrative Medicine
    Saxena K, Kurian S, Kumar R, Arnold LE, Simkin DR · 2023
  56. 56
    Clinical efficacy and safety of melatonin supplementation in multiple sclerosis: a systematic review
    Morsali S, Sabahi Z, Kakaei J, Hakimzadeh Z, Hamidi S, Gholipour-Khalili E et al. · 2023
  57. 57
  58. 58
    Melatonin &amp; the High Dose Mystery: The Yin-Yang
    Siddiqui A, Aaqil SI, Haider R, Adnan A, Ochani S, Vaid R et al. · 2023
  59. 59
  60. 60
  61. 61
  62. 62
  63. 63
  64. 64
  65. 65
  66. 66
  67. 67
  68. 68
  69. 69
    Effect of melatonin supplementation on oxidative stress parameters: A systematic review and meta-analysis
    Morvaridzadeh M, Sadeghi E, Agah S, Nachvak SM, Fazelian S, Moradi F et al. · 2020
  70. 70
  71. 71
  72. 72
  73. 73
  74. 74
    Effects of melatonin supplementation on oxidative stress: a systematic review and meta-analysis of randomized controlled trials
    Ghorbaninejad P, Sheikhhossein F, Djafari F, Tijani AJ, Mohammadpour S, Shab-Bidar S · 2020
  75. 75
  76. 76
  77. 77
  78. 78
  79. 79
    The Effects of Melatonin Supplementation on Glycemic Control: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
    Doosti-Irani A, Ostadmohammadi V, Mirhosseini N, Mansournia MA, Reiter RJ, Kashanian M et al. · 2018
  80. 80
    Melatonin for preventing and treating jet lag
    Herxheimer A, Petrie KJ · 2001
  81. 81
  82. 82
  83. 83
  84. 84
    Soy isoflavones and melatonin for the relief of climacteric symptoms: a multicenter, double-blind, randomized study
    Secreto G, Chiechi LM, Amadori A, Miceli R, Venturelli E, Valerio T et al. · 2004
  85. 85
  86. 86
  87. 87
  88. 88
  89. 89
  90. 90
  91. 91
    Does Melatonin Improve Sleep Following Primary Total Hip Arthroplasty? A Randomized, Double-Blind, Placebo-Controlled Trial
    Haider MA, Lawrence KW, Christensen T, Schwarzkopf R, Macaulay W, Rozell JC · 2025
  92. 92
  93. 93
  94. 94
  95. 95
  96. 96
  97. 97
  98. 98
  99. 99
  100. 100
  101. 101
  102. 102
  103. 103
  104. 104
  105. 105
    The Effect of Melatonin as an Adjuvant Therapy on COVID-19: A Randomized Clinical Trial
    Davoodian N, Sharifimood F, Salarbashi D, Elyasi S, Baniasad A, Bejestani FS · 2021
  106. 106
    Melatonin Supplementation in Adult Patients With Atopic Dermatitis: A Randomized Clinical Trial
    Heidari Z, Gharibi G, Alaeen H, Ghadrdan E, Shahrestanaki E, Sadeghi-Ghadi Z et al. · 2026
  107. 107
  108. 108
  109. 109
  110. 110
  111. 111
    Efficacy of clonidine and melatonin for treating insomnia in anxious children: a randomized comparison
    Jalali Firouzkohi A, Behmanesh H, Doostizadeh M, Soltanian A, Etesamifard T · 2026
  112. 112
  113. 113
  114. 114
  115. 115
    The effects of melatonin on follicular oxidative stress and art outcomes in women with diminished ovarian reserve: a randomized controlled trial
    Sadeghpour S, Ghasemnejad-Berenji M, Maleki F, Behroozi-Lak T, Bahadori R, Ghasemnejad-Berenji H · 2025
  116. 116
    Sleep disturbance in patients with cancer: a feasibility study of multimodal therapy
    Yennurajalingam S, Carmack C, Balachandran D, Eng C, Lim B, Delgado M et al. · 2021
  117. 117
  118. 118
    Melatonin in the prevention of cisplatin-induced acute nephrotoxicity: a randomized, controlled clinical trial
    Karvan S, Sadeghi A, Farrokhi P, Nekouee A, Sharifi M, Moghaddas A · 2022
  119. 119
  120. 120
  121. 121
    Melatonin Pharmacological Blood Levels Increase Total Antioxidant Capacity in Critically Ill Patients
    Mistraletti G, Paroni R, Umbrello M, D'Amato L, Sabbatini G, Taverna M et al. · 2017
  122. 122
  123. 123
  124. 124
    The role of melatonin timing on short-term memory retention during sleep restriction
    Alemán-Villa KM, Sosa-Arámbula HJ, Armienta-Rojas DA, Camberos-Barraza J, Rábago-Monzón ÁR, Camacho-Zamora A et al. · 2026
  125. 125
  126. 126
  127. 127
  128. 128
  129. 129
  130. 130
  131. 131
  132. 132
    The effect of long-term melatonin supplementation on psychosomatic disorders in postmenopausal women
    Chojnacki C, Kaczka A, Gasiorowska A, Fichna J, Chojnacki J, Brzozowski T · 2018
  133. 133
  134. 134
  135. 135
  136. 136
  137. 137
  138. 138
  139. 139
  140. 140
  141. 141
  142. 142
  143. 143
  144. 144
  145. 145
  146. 146
  147. 147
  148. 148
  149. 149
  150. 150
  151. 151
  152. 152
  153. 153
    Low-Dose Melatonin, Climacteric Symptoms and Sleep in Female Shift Workers: A Randomized Controlled Trial
    Saraiva SP, D'Aurea CVR, Luz CSS, Amaral FG, Cipolla-Neto J, Marqueze EC et al. · 2026
  154. 154
  155. 155
  156. 156
  157. 157
  158. 158
  159. 159
    Randomised controlled trial of melatonin for paediatric functional abdominal pain disorders
    Dipasquale V, Palermo L, Barbalace A, Tumminello G, Romano C · 2023
  160. 160
  161. 161
    Melatonin Supplementation Alleviates Bone Mineral Density Decline and Circulating Oxidative Stress in Iron-Overloaded Thalassemia Patients
    Piriyakhuntorn P, Tantiworawit A, Phimphilai M, Kaewchur T, Niprapan P, Srivichit B et al. · 2025
  162. 162
  163. 163
  164. 164
  165. 165
    Melatonin-Attenuated Oxidative Stress in High-Risk Pregnant Women Receiving Enoxaparin and Aspirin
    Azarmehr N, Porhemat R, Roustaei N, Radmanesh E, Moslemi Z, Vanda R et al. · 2023
  166. 166
    P075 Feasibility of 12 weeks melatonin supplementation in Mild Cognitive Impairment
    · 2022
  167. 167
  168. 168
  169. 169
    Melatonin supplementation enhances pulmonary rehabilitation outcomes in COPD: a randomized, double-blind, placebo-controlled study
    Viana SMDNR, de Bruin VMS, Vasconcelos RS, Nogueira ANC, Mesquita R, de Bruin PFC · 2023
  170. 170
    Melatonin Supplementation and Anthropometric Indices: A Randomized Double-Blind Controlled Clinical Trial
    Mohammadi S, Rastmanesh R, Jahangir F, Amiri Z, Djafarian K, Mohsenpour MA et al. · 2021
  171. 171
  172. 172
  173. 173
  174. 174
  175. 175
  176. 176
    Efficacy of melatonin for sleep disturbance following traumatic brain injury: a randomised controlled trial
    Grima NA, Rajaratnam SMW, Mansfield D, Sletten TL, Spitz G, Ponsford JL · 2018
  177. 177
  178. 178
  179. 179
  180. 180
    Safety and efficacy of topical melatonin add-on in healing of diabetic foot ulcer: a double blind, randomized clinical trial
    Ahmadvash F, Gharabagh LH, Emami S, Ghafari MR, Ghaderi F, Akhavan S et al. · 2025
  181. 181
  182. 182
  183. 183
  184. 184
  185. 185
  186. 186
    Melatonin supplementation does not alter vascular function or oxidative stress in healthy normotensive adults on a high sodium diet
    Ramos Gonzalez M, Axler MR, Kaseman KE, Lobene AJ, Farquhar WB, Witman MA et al. · 2023
  187. 187
    The Effect of Exogenous Melatonin on Eating Habits of Female Night Workers with Excessive Weight
    Nogueira LFR, Crispim CA, Cipolla-Neto J, de Castro Moreno CR, Marqueze EC · 2022
  188. 188
    Exogenous melatonin decreases circadian misalignment and body weight among early types
    Marqueze EC, Nogueira LFR, Vetter C, Skene DJ, Cipolla-Neto J, Moreno CRC · 2021
  189. 189
  190. 190
    Melatonin in Newborn Infants Undergoing Surgery: A Pilot Study on Its Effects on Postoperative Oxidative Stress
    Perrone S, Romeo C, Marseglia L, Manti S, Rizzo C, Carloni S et al. · 2023
  191. 191
  192. 192
    Sleep Management and Recovery After TBI in Kids (SMART-Kids): Pilot Trial Using Melatonin
    Williams CN, Hall TA, Alberts H, Heierle J, Lim MM, Shea SA et al. · 2026
  193. 193
  194. 194
  195. 195
  196. 196
    The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome
    Wirojanan J, Jacquemont S, Diaz R, Bacalman S, Anders TF, Hagerman RJ et al. · 2009
  197. 197
  198. 198
  199. 199
  200. 200
    Effect of Melatonin Supplementation on Glycemic and Lipid Profiles in Kidney Transplant Recipients: A Clinical Trial
    Pourrezagholi F, Amini H, Omid Moradi, Mahdavi B, Nadiri Niri A, Taherpour N et al. · 2026
  201. 201
    Melatonin supplementation for quality of life in older patients with advanced cancer: a randomized controlled trial
    Ginzac A, Bourbouloux E, Rivoirard R, Jouannaud C, Hager MO, Dubois S et al. · 2025
  202. 202
  203. 203
  204. 204
  205. 205
    Exogenous melatonin boosts vaccine-induced immunity in individuals with high pre-existing influenza immunity
    Oda K, Danko J, Villasante E, Bergmann-Leitner E, Lee R, Wijayalath W · 2025
  206. 206
  207. 207
  208. 208
    Impact of Melatonin Supplementation in Women with Unexplained Infertility Undergoing Fertility Treatment
    Espino J, Macedo M, Lozano G, Ortiz Á, Rodríguez C, Rodríguez AB et al. · 2019
  209. 209
  210. 210
  211. 211
  212. 212
  213. 213
    Effects of Melatonin Administration on Post-Stroke Delirium in Patients with Intracerebral Hemorrhage
    Siokas V, Roesch S, Stefanou MI, Buesink R, Wilke V, Sartor-Pfeiffer J et al. · 2023
  214. 214
    Patients' attitudes toward melatonin for musculoskeletal pain: Insights for rehabilitation practice
    Wu K, Puterflam J, Beckenkamp PR, Hall M, Gordon C, Ferreira ML et al. · 2026
  215. 215
    The Neuroprotective Role of Melatonin in Intracerebral Hemorrhage: Lessons from an Observational Study
    Stefanou MI, Feil K, Zinsser S, Siokas V, Roesch S, Sartor-Pfeiffer J et al. · 2025
  216. 216
  217. 217
  218. 218
    Circadian function in patients with advanced non-small-cell lung cancer
    Levin RD, Daehler MA, Grutsch JF, Quiton J, Lis CG, Peterson C et al. · 2005
  219. 219
    [Clinical experience with melatonin and memantine combination (Miladean) in children with cognitive and behavioral impairments]
    Goryunov AV, Morozova MA, Koval-Zaytsev AA, Britova VS, Beniashvili AG, Shushpanova OV et al. · 2026
  220. 220
  221. 221
    Exceptional and typical biomarker responses to AminoTriComplex in metastatic prostate cancer: a case series
    Tavartkiladze A, Simonia G, Reiter RJ, Lou R, Okrostsvaridze N, Kasradze D et al. · 2026
  222. 222
  223. 223
    Delirium REduction after administration of melatonin in acute ischemic stroke (DREAMS): A propensity score-matched analysis
    Mengel A, Zurloh J, Boßelmann C, Brendel B, Stadler V, Sartor-Pfeiffer J et al. · 2021
  224. 224
    Glioblastoma and Melatonin's Effects: A Narrative Review
    Favero G, Sulas F, Labanca M, Scilla F, Punzi CF, Lonati C et al. · 2026
  225. 225
  226. 226
  227. 227
    Therapeutic Potential of Melatonin in Osteoarticular Diseases and Musculoskeletal Medicine: A Narrative Review
    Bisaccia M, Bifarini B, Ripani U, Lucchetta L, Bonanno E, Siragusano M et al. · 2026
  228. 228
    Dietary and nutraceutical interventions for functional dyspepsia: A narrative review
    Pasta A, Formisano E, Calabrese F, Navazzotti G, Giannini EG, Savarino V et al. · 2026
  229. 229
  230. 230
  231. 231
  232. 232
  233. 233
  234. 234
  235. 235
    Sleep in Children with Neurodevelopmental Disorders: From Diagnostic Labels to Phenotype-directed Care
    Bruni O, Breda M, Mammarella V, Polese D, Mogavero MP, Lanza G et al. · 2026
  236. 236
    Melatonin: A potential nighttime guardian against Alzheimer's
    Zhang Z, Xue P, Bendlin BB, Zetterberg H, De Felice F, Tan X et al. · 2025
  237. 237
    Melatonin, Zinc, and Vitamin C: Potential Adjuvant Treatment for COVID-19 Patients
    Borges L, Gennari-Felipe M, Dias BB, Hatanaka E · 2021
  238. 238
    Current Treatment Options for REM Sleep Behaviour Disorder
    Jiménez-Jiménez FJ, Alonso-Navarro H, García-Martín E, Agúndez JAG · 2021
  239. 239
  240. 240
  241. 241
    Advances in the research of melatonin in autism spectrum disorders: literature review and new perspectives
    Tordjman S, Najjar I, Bellissant E, Anderson GM, Barburoth M, Cohen D et al. · 2013
  242. 242
    Therapeutic potential of melatonin and its analogs in Parkinson's disease: focus on sleep and neuroprotection
    Srinivasan V, Cardinali DP, Srinivasan US, Kaur C, Brown GM, Spence DW et al. · 2011

Every statement on this page carries its evidence tier — proven, plausible or hypothesis — and leads to the original work. The decision in the individual case rests with the practitioner; we provide the connections.

International Health Research · https://ih-research.com/en/knowledge/melatonin/ · Last updated: 2026-10-15