Protocol
Melatonin 0.3 to 0.5 mg (low dose), 30 to 60 minutes before bed
Low doses act mainly by shifting circadian timing, though the low-dose trials themselves attribute part of the benefit to a direct sleep-promoting effect.
Grade C: human trials exist, but they are small, mixed or not yet repeated. This is not a finding that it does not work. How to read a grade →
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How this letter has changedLatest: October 2026 · Corrected.
The protocol named 0.5 to 1 mg at 90 minutes before sleep and said a low dose was as effective as a high one. No trial tested that dose range at that lead time; the low-dose trials used 0.3 mg at 30 minutes (Zhdanova et al., 2001; PMID PubMed ID: the permanent number the US National Library of Medicine gives a published paper. Each one links to that paper's record on PubMed. 11600532) and 0.5 mg at one hour (Sletten et al., 2018; PMID 29912983), and the dose-response evidence runs the other way (Cruz-Sanabria et al., 2024; PMID 38888087; Herxheimer and Petrie, 2002; PMID 12076414). The name now states the studied dose and timing, in the pattern already applied to other protocols. The endpoint The outcome a trial measures to decide whether the treatment worked, such as heart attacks, blood pressure or a symptom score. type is corrected to measured function, since the trials used polysomnography and actigraphy. Added: the adult-only insomnia null (Choi et al., 2022; PMID 36179487) and the glucose-tolerance signal at 5 mg (Qian et al., 2026; PMID 42346809). C unchanged. Applied the written grade definition under the editor's standing instruction of October 2026 (Arnold Sandlow, D.C.).PMID 11600532 PMID 12076414 PMID 29912983 PMID 36179487 PMID 38888087 PMID 42346809
The melatonin 0.5 to 1 mg protocol held a B on a meta-analysis A study that pools the numbers from several trials into one combined estimate. that pooled all doses and found larger effects at higher doses (Ferracioli-Oda et al., PLoS One 2013; PMID 23691095), which does not test a low-dose protocol. Direct low-dose trials are small and population-specific (Zhdanova et al., J Clin Endocrinol Metab 2001; PMID 11600532; Sletten et al., PLoS Med 2018; PMID 29912983), and a jet lag trial with 0.5 mg arms was null (Spitzer et al., Am J Psychiatry 1999; PMID 10484950). C. Editor adjudication, October 2026.PMID 23691095 PMID 11600532 PMID 29912983 PMID 10484950
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This protocol is a low dose of melatonin, 0.3 to 0.5 mg, taken before bed. The main review mixed all doses and found bigger effects at higher doses, so it does not test the low dose. Another review found the effect kept rising up to about 4 mg. Studies of low doses alone are few and small.
Low doses act mainly by shifting circadian timing, though the low-dose trials themselves attribute part of the benefit to a direct sleep-promoting effect. Small trials found 0.3 mg taken 30 minutes before bed improved sleep efficiency in older adults with insomnia, and 0.5 mg taken one hour before desired bedtime, with behavioral scheduling, brought sleep onset forward in delayed sleep phase disorder. Pooled analyses find larger effects at higher doses, and the adult-only analysis of chronic insomnia is null, so the letter is C. The record formerly named 0.5 to 1 mg at 90 minutes before sleep, a dose and lead time no trial tested; it is renamed to what was studied.
Why this gradeGrade C, small or unreplicated trials. The reasoning, and what the grade does not cover.
Grade C on sleep at low dose. The main meta-analysis pooled all doses in primary sleep disorders and found larger effects at higher doses, so it does not test a low-dose protocol (Ferracioli-Oda et al., 2013; PMID 23691095), and a dose-response analysis found efficacy rising to about 4 mg (Cruz-Sanabria et al., 2024; PMID 38888087). Low-dose trials are small and in different groups: 0.3 mg in 15 adults over 50 with insomnia (Zhdanova et al., 2001; PMID 11600532), and 0.5 mg with behavioral scheduling in 116 people with delayed sleep phase disorder (Sletten et al., 2018; PMID 29912983). A jet lag trial with 0.5 mg arms was null (Spitzer et al., 1999; PMID 10484950), and the adult-only insomnia analysis is null at any dose (Choi et al., 2022; PMID 36179487). Small, inconsistent evidence in mixed populations is C.
WHAT THIS GRADE DOES NOT COVERdoses of 1 mg or a 90-minute lead time, which the record formerly named and no trial tested; insomnia secondary to another condition; and melatonin at standard doses, graded separately on the melatonin record.
A grade describes the human evidence for a named use. It is not advice, and it is not a judgment on any individual prescription. How the letters are decided →
The evidence, in fullSeven papers, each linked to its PubMed record.
Zhdanova et al. (J Clin Endocrinol Metab, 2001; PMID 11600532): 0.3 mg 30 minutes before bed in 15 adults over 50 with insomnia, sleep efficiency improved on polysomnography, the only polysomnography trial of a physiological dose. Sletten et al. (PLoS Med, 2018; PMID 29912983): 0.5 mg one hour before desired bedtime with behavioral scheduling in 116 people with delayed sleep phase disorder, actigraphic sleep onset 34 minutes earlier; the authors attribute part of the benefit to a direct sleep-promoting effect. Spitzer et al. (Am J Psychiatry, 1999; PMID 10484950): 257 travelers including two 0.5 mg arms, null for jet lag. Ferracioli-Oda et al. (PLoS One, 2013; PMID 23691095): pooled all doses in adults and children and found larger effects at higher doses, so it does not test a low-dose protocol. Cruz-Sanabria et al. (J Pineal Res, 2024; PMID 38888087): dose-response meta-analysis, efficacy rising to about 4 mg and larger with earlier administration. Choi et al. (Sleep Med Rev, 2022; PMID 36179487): in adults with chronic insomnia melatonin at any dose did not significantly improve sleep. Safety: a single 5 mg dose, higher than this protocol, impaired glucose tolerance in MTNR1B risk-allele carriers (Qian et al., Diabetes Care, 2026; PMID 42346809).
Sleep onset latency and sleep efficiency from a sleep diary or wearable at baseline and 2 weeks. The PSQI at baseline and 4 weeks for global sleep quality. Timing follows the trials: 30 to 60 minutes before the intended bedtime; a 2024 dose-response analysis found earlier evening timing predicted larger effects, so taking it later than that is the untested direction.
Evidence notes: meta-analysis, not independently replicated The same finding reproduced by a separate research group. A result seen once can be chance or bias; a replicated one is harder to explain away.
Endpoint graded: Sleep onset and sleep efficiency at low doses (0.3 to 0.5 mg) (functional)
Last reviewed: July 2026
Educational use only · Not medical advice · EBL grades published human evidence and does not recommend treatment. Stopping a prescription is a decision for your physician.
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melatonin[tiab] AND ("0.3 mg"[tiab] OR "0.5 mg"[tiab] OR "low dose"[tiab] OR "low-dose"[tiab]) AND sleep[tiab] AND randomized controlled trial[pt]Grades move when new trials publish. A free monthly email lists every grade EBL moved, with the reason and the trial behind it: the sign-up is on the Evidence Log →