Melatonin
Last reviewed 2026-09-22. How this works.
Sleep Grade C
Human evidence exists and does not settle it.
Two small trials in women having breast cancer treatment found that melatonin helped them sleep.
Two small randomised trials in breast cancer, both favourable for sleep.
The claim
The claim is that melatonin helps people with cancer sleep. It is the most modest claim made for this compound and the most likely to be true.
What it does
Melatonin is the hormone that signals darkness to the body, so using it for sleep is using it for the thing it does.
The evidence
Two randomised, double-blind, placebo-controlled trials in women with breast cancer have measured sleep. One ran alongside adjuvant chemotherapy and found better sleep latency, better sleep efficiency and a better total score on a standard sleep questionnaire than placebo.1
The other ran alongside hormonal therapy and found better sleep quality, latency and duration, and less use of medication prescribed for sleep.2
Neither trial found an effect on mood or on depression. Both were small, both were in breast cancer, and both measured what people reported about themselves rather than anything that happened to their cancer. That is why this sits where it does on the ladder rather than higher: the finding is real and the base it rests on is narrow.12
There is also a structured programme for persistent insomnia in this register, graded higher than anything here, and it is worth reading beside this entry.
The studies this rests on
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Melatonin and sleep quality during adjuvant chemotherapy for breast cancer1
A randomised trial, double blind, measured what patients reported, 40 participants.
better sleep latency, sleep efficiency and total sleep-questionnaire score against placebo across the three phases of chemotherapy; no effect on anxiety or depression.
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Melatonin for sleep and mood problems during hormonal therapy for breast cancer2
A randomised trial, double blind, measured what patients reported, 60 participants.
better sleep quality, latency and duration and less use of sleep-promoting medication; no significant improvement in depression severity or mood.
What is absent
Both trials measured mood alongside sleep, and neither found an effect on it. Melatonin helping someone sleep is not the same finding as melatonin helping how they feel.
Scope: mood and depression during cancer treatment.
Established by trial scope, checked 2026-09-22. Result: neither trial reported a significant improvement in depression severity or mood.12
Both trials were in breast cancer and both measured what people reported about their own sleep. Nothing here was measured in any other cancer, and nothing here measured what happened to anyone’s cancer.
Scope: cancers other than breast, and any outcome other than reported sleep.
Established by trial scope, checked 2026-09-22. Result: both recorded trials are in breast cancer with patient-reported sleep as the endpoint.12
What to ask
Is my sleep something we should treat properly, rather than something I should manage myself?
Treating cancer Grade D
No human evidence of benefit, or none that survived testing.
The trials report a big effect on survival, but nearly all came from one group and none was blinded.
Very large effects, from one unblinded source, never replicated elsewhere.
The claim
The claim is that melatonin extends survival in advanced cancer. The pooled numbers behind it are larger than most licensed cancer drugs produce, which is the first thing that should give a reader pause rather than hope.
What it does
Several mechanisms have been proposed. None of them is what this entry turns on. What it turns on is who ran the trials.
The evidence
A systematic review of ten randomised trials across 643 people with solid tumours reported a reduced risk of death at one year, with no measurable variation between trials. The same review records that every trial was conducted at the same hospital network and that none was blinded.3
A later review of twenty-one trials found much the same. Its authors state as a limitation that the majority were conducted by the same group of investigators in Italy and Poland, and that while this is not in itself grounds to infer bias, it is grounds for further investigation. That wording is theirs and the book follows it.4
A Cochrane review in 2025 found the included-studies list still dominated by the same investigator group, a substantial number of studies awaiting classification, and repeatedly described the evidence as very uncertain. Twenty years on, the confirmation those earlier reviewers asked for has not arrived.5
The studies this rests on
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Pooled randomised trials of melatonin in solid tumours3
A meta-analysis, summarising randomised trials, measured survival, 643 participants.
reduced risk of death at one year; all trials conducted at the same hospital network and none blinded.
relative risk 0.66, interval 0.59 to 0.73. death at one year
What is absent
Nobody outside the original investigator group has reproduced this result. That is the reason for the grade, not the size of the effect.
Scope: survival in solid tumours.
Established by published review, Cochrane Database of Systematic Reviews 2025, CD010145.pub2, checked 2026-09-16. Result: the included-studies list remains dominated by one investigator group and the evidence is repeatedly assessed as very uncertain.54
No blinded trial of melatonin for survival in cancer is recorded. In an unblinded trial of a supportive treatment, everyone involved knows who is getting what.
Scope: blinded comparison.
Established by trial scope, checked 2026-09-16. Result: the pooled reviews record that the trials were unblinded.3
What to ask
Is there a reason nobody outside one research group has repeated these melatonin trials?
The dish-to-person gap
The register records no human pharmacokinetic measurement for melatonin against any laboratory concentration.
When to call your team — no warning signs are recorded
Whatever you are taking or thinking of taking, the people treating you can only weigh it if they know about it. That is true when nothing has been written down here, and it is most true then.
The register records no warning signs for this entry.
Interactions
No interaction between melatonin and a cancer treatment class is recorded in this register.
Nobody having looked is not the same as nothing being there. That is what this line says and all it says.
The whole interaction list, and how to turn it into a pharmacy review request.
Find a trial instead
The unanswered question here is what happens when someone outside the original investigator group runs the trial.
Search ClinicalTrials.gov for recruiting studies of melatonin
A trial is the same decision with monitoring, a known preparation and a doctor who knows what else you are taking.
References
The effect of melatonin on sleep quality, anxiety, and depression in patients with primary breast cancer undergoing adjuvant chemotherapy: a randomized, double-blind, placebo-controlled trial. Cancer Investigation.
doi:10.1080/07357907.2025.2563202 · PubMed 42533530
How this was reached: transcribed from chapter note, via docs/CHAPTER-NOTES.json, chapter 20 note 1.
Vaziri N, Shakourifar M, Sattari P, Sadeghi A, Sharifi M, et al. Melatonin aids in treating mood and sleep problems resulting from hormonal therapy in breast cancer patients: a randomized, double-blinded, placebo-controlled trial. Iranian Journal of Pharmaceutical Research 2024;23(1):e156581.
doi:10.5812/ijpr-156581 · PubMed 40066115
How this was reached: transcribed from chapter note, via docs/CHAPTER-NOTES.json, chapter 20 note 1. The author string is abbreviated in the source that was read and has not been expanded.
Mills E and colleagues. Melatonin in the treatment of cancer: a systematic review of randomized controlled trials and meta-analysis. Journal of Pineal Research, 2005.
doi:10.1111/j.1600-079X.2005.00258.x · PubMed 16207291
How this was reached: transcribed from chapter note, via docs/CHAPTER-NOTES.json, chapter 20 note 2. The author string is abbreviated in the source that was read and has not been expanded.
Seely D, Wu P, Fritz H, Kennedy DA, Tsui T, Seely AJE, Mills E. Melatonin as adjuvant cancer care with and without chemotherapy: a systematic review and meta-analysis of randomized trials. Integrative Cancer Therapies 2012;11:293-303.
No persistent identifier recorded.
How this was reached: transcribed from chapter note, via docs/CHAPTER-NOTES.json, chapter 20 note 3.
Yu ZY and colleagues. Melatonin in cancer treatment. Cochrane Database of Systematic Reviews 2025, CD010145.pub2.
No persistent identifier recorded.
How this was reached: transcribed from chapter note, via docs/CHAPTER-NOTES.json, chapter 20 note 4. The author string is abbreviated in the source that was read and has not been expanded.