Are There Health Benefits of Higher-Dose Melatonin?
Melatonin is best known as the hormone that helps regulate your sleep-wake cycle. But researchers have been studying melatonin for something much broader than sleep.
Clinical and laboratory research has investigated melatonin’s effects on oxidative stress, inflammation, mitochondrial function, blood sugar, cardiovascular health, cancer-related symptoms and age-related neurological changes.
Some of this research has also used doses considerably higher than the amounts normally taken for sleep.
That raises an important question:
Are there health benefits to taking higher doses of melatonin?
The answer is more complicated than simply saying that more melatonin is better.
There is good evidence that melatonin has biological effects extending beyond sleep. Researchers including Russel J. Reiter, PhD, one of the most extensively published scientists in the field of melatonin biology, have spent decades investigating its antioxidant and mitochondrial effects.
Some clinicians, including John Lieurance, ND, DC, have taken this research further and advocate substantially higher doses for their proposed cellular and mitochondrial effects rather than simply for sleep. Lieurance currently describes high-dose melatonin as approximately 20–200 mg or more. However, those protocols should not be confused with established dosing recommendations from randomized clinical trials.
The distinction between interesting biology, promising clinical research and proven long-term health benefits is important.
Key Takeaways
- Higher-dose melatonin is generally defined as 10 mg or more in clinical safety research. A major systematic review used ≥10 mg/day as its definition of high-dose melatonin.
- Higher doses do not appear necessary for sleep. A 2024 dose-response meta-analysis found sleep effects peaking at approximately 4 mg/day.
- Melatonin does considerably more than regulate sleep. Research led by Russel Reiter has documented antioxidant, free-radical-scavenging and mitochondrial effects.
- The rationale for higher doses is different from the rationale for sleep doses. Researchers are interested in pharmacological concentrations that may influence oxidative stress and mitochondrial function rather than simply stimulating melatonin receptors involved in circadian signaling.
- John Lieurance advocates 20–200 mg or more for these proposed cellular effects, but this represents his clinical interpretation of the literature rather than an established high-dose protocol validated in large randomized trials.
- There is now some human experience with substantially higher doses. A 2025 observational study examined 81 older patients receiving 40–200 mg/day, with an average dose of 72.7 mg. More than half had been treated for over four years.
- That study is interesting but does not prove that high-dose melatonin prevents disease, because it was retrospective and observational rather than a randomized placebo-controlled trial.
- Human trials suggest melatonin can influence inflammatory, oxidative and cardiometabolic markers, but this does not establish that very high doses are superior to conventional doses.
- There is no convincing human evidence that high-dose melatonin extends lifespan, prevents cancer or prevents Alzheimer’s disease.
- Short-term high-dose safety appears relatively reassuring, but long-term safety remains insufficiently established.
Table of Contents
- What Is Considered a High Dose of Melatonin?
- Why Are Researchers Studying Higher-Dose Melatonin?
- Why Might Higher Doses Act Differently?
- What Does Russel Reiter’s Research Show?
- What Does John Lieurance Say About High-Dose Melatonin?
- Melatonin, Oxidative Stress and Inflammation
- Melatonin and Cardiometabolic Health
- What Have Human Studies Using High Doses Found?
- Melatonin, Cancer and Supportive Care
- Does Higher-Dose Melatonin Have Anti-Aging Benefits?
- Is Higher-Dose Melatonin Safe?
- Frequently Asked Questions
- The Bottom Line
- Research References
1. What Is Considered a High Dose of Melatonin?
There is no universally agreed cutoff separating a normal dose from a high dose.
For sleep, supplemental doses commonly range from fractions of a milligram to several milligrams.
For clinical research purposes, however, there is a useful benchmark.
A 2022 systematic review specifically examining higher-dose melatonin defined high dose as 10 mg per day or more. The review identified 79 randomized controlled trials involving 3,861 participants.
A practical way to understand the research literature is:
| Daily Dose | General Research Context |
|---|---|
| Under 1 mg | Low-dose/circadian dosing |
| 1–5 mg | Common sleep and supplemental range |
| 5–10 mg | Pharmacological range used in many clinical studies |
| 10–20 mg | Higher-dose clinical research |
| 20–100 mg | High-dose experimental or condition-specific research |
| 100–200 mg+ | Very-high-dose research or clinician-directed protocols |
These categories describe how doses appear in the literature. They are not dosing recommendations.
1.1 Does More Melatonin Mean Better Sleep?
Not necessarily.
A 2024 systematic review and dose-response meta-analysis found that melatonin’s effects on sleep onset and total sleep time increased with dose up to approximately 4 mg/day, after which additional benefit appeared to level off.
So there are really two different questions:
How much melatonin is useful for sleep?
and
Could larger pharmacological doses produce biological effects unrelated to sleep?
The second question is where higher-dose melatonin research becomes particularly interesting.
2. Why Are Researchers Studying Higher-Dose Melatonin?
Melatonin is not simply a sedative.
Its nighttime secretion helps provide the body with a signal of biological darkness and plays an important role in circadian timing.
But scientists have also identified effects involving:
- oxidative stress
- free-radical scavenging
- mitochondrial function
- antioxidant enzymes
- inflammatory signaling
- glucose metabolism
- cardiovascular physiology
- cellular stress responses
Russel Reiter and colleagues have documented these functions extensively over several decades.
This leads to an important concept:
The concentration of melatonin needed to influence a cellular oxidative process may not necessarily be the same concentration needed to provide a circadian signal.
That is the biological rationale behind much of the interest in higher-dose melatonin.
But a major caution is necessary:
A biological effect does not automatically mean a demonstrated health benefit.
Changing an inflammatory or oxidative-stress marker is different from proving that taking melatonin will prevent heart disease, dementia or cancer.
3. Why Might Higher Doses Act Differently?
One of the most important concepts in the high-dose melatonin discussion is that melatonin appears to work through more than one biological mechanism.
3.1 Circadian Signaling
At relatively low concentrations, melatonin interacts with receptors including MT1 and MT2.
These receptors are involved in circadian regulation and help communicate the biological signal of nighttime.
You do not necessarily need a large amount of melatonin to activate these signaling systems.
That may help explain why increasing a sleep dose indefinitely does not continue improving sleep.
3.2 Antioxidant and Mitochondrial Activity
Melatonin also has actions that extend beyond classical melatonin-receptor signaling.
Reiter’s research has shown that melatonin can directly neutralize reactive oxygen and nitrogen species and can also influence antioxidant enzymes.
Later work increasingly focused on mitochondria.
Mitochondria are the structures inside cells responsible for producing much of the body’s usable cellular energy.
They are also major sites of free-radical generation.
Reiter and colleagues proposed that melatonin should be viewed as a mitochondria-targeted antioxidant, noting both its accumulation and activity within mitochondria.
This gives scientists a plausible reason to investigate doses beyond those required simply for circadian signaling.
But it still leaves one major question unanswered:
How much melatonin is actually required to produce clinically meaningful mitochondrial benefits in humans?
We do not yet have a definitive answer.
4. What Does Russel Reiter’s Research Show?
Russel J. Reiter, PhD, has studied melatonin for decades and has authored or coauthored a large body of research on its biological actions.
His work is particularly important to the high-dose discussion because it challenges the idea that melatonin should be viewed exclusively as a sleep hormone.
4.1 Melatonin as an Antioxidant
In a major review published in 2000, Reiter and colleagues described several antioxidant actions of melatonin.
Melatonin can directly interact with reactive species while also influencing the body’s antioxidant defense systems.
A later 2016 review developed this argument further, describing melatonin’s antioxidant effects across a broad range of experimental conditions and suggesting that mitochondrial protection is central to many of these effects.
4.2 Melatonin Inside the Mitochondria
In 2017, Reiter and colleagues published a major review titled “Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas.”
The authors described evidence that mitochondria can accumulate melatonin and may also synthesize it locally.
They proposed that the relatively high concentration of melatonin within mitochondria helps protect these organelles from the reactive molecules naturally generated during energy production.
This is a fundamentally different concept from taking melatonin simply to fall asleep faster.
4.3 More Recent Work on Aging and the Brain
In 2024, Reiter and colleagues published a review examining mitochondrial dysfunction in age-related neurodegeneration.
They described several proposed actions of melatonin, including:
- reducing electron leakage from the mitochondrial electron transport chain
- supporting ATP production
- detoxifying reactive oxygen and nitrogen species
- supporting antioxidant enzymes
- influencing neuronal glucose metabolism
The authors proposed melatonin as an interesting compound for further investigation in age-related neurological decline.
However, this is an important distinction:
Mechanistic evidence supporting mitochondrial protection is much stronger than human evidence showing that high-dose supplementation prevents Alzheimer’s disease, Parkinson’s disease or other neurodegenerative conditions.
4.4 Does Reiter’s Research Prove That Healthy People Should Take 100 mg?
No.
Reiter’s work provides an important scientific rationale for studying pharmacological melatonin concentrations.
It does not establish a universal dose such as 20, 50, 100 or 200 mg that healthy adults should take every night.
That question requires controlled human trials comparing different doses and following participants for meaningful clinical outcomes.
Those data remain limited.
5. What Does John Lieurance Say About High-Dose Melatonin?
John Lieurance, ND, DC, is one of the more visible advocates of using melatonin at doses considerably above conventional sleep doses.
His approach draws heavily on research into melatonin’s antioxidant and mitochondrial functions.
Lieurance currently describes high-dose melatonin as approximately 20–200 mg or more, used for proposed antioxidant and mitochondrial effects rather than simply for sedation.
5.1 His Central Argument
Lieurance makes a distinction between:
Melatonin for circadian signaling and sleep
and
Melatonin used pharmacologically for cellular and mitochondrial effects.
His argument is that relatively small amounts can activate the receptors associated with circadian timing, while much larger concentrations may be required when the objective is free-radical scavenging or mitochondrial protection.
This idea is not arbitrary.
Reiter’s research provides substantial biological support for melatonin’s antioxidant and mitochondrial actions.
Where the uncertainty begins is dose.
5.2 Does Research Prove Lieurance’s 20–200 mg Range Is Optimal?
No.
There are studies using doses within and even above this range, and emerging human data suggest that surprisingly large doses can sometimes be tolerated.
But we do not currently have large randomized dose-comparison trials demonstrating that:
100 mg works better than 10 mg
or that:
200 mg produces better long-term health outcomes than 20 mg.
This distinction is important.
Lieurance’s high-dose protocol should therefore be described as a clinical interpretation of existing melatonin research, rather than as a dosing protocol established through large randomized controlled trials.
His own current discussion of high-dose melatonin also acknowledges that long-term safety data above 100 mg remain limited.
6. Melatonin, Oxidative Stress and Inflammation
Oxidative stress is one of the strongest scientific rationales for studying melatonin outside sleep.
6.1 What Is Oxidative Stress?
Normal metabolism produces reactive oxygen species and other chemically reactive molecules.
The body also possesses antioxidant systems designed to control them.
Oxidative stress occurs when reactive activity exceeds the body’s ability to maintain normal redox balance.
Persistent oxidative stress has been associated with aging and many chronic diseases.
6.2 What Does Human Research Show?
Human clinical trials have investigated melatonin’s effects on markers including:
- C-reactive protein (CRP)
- interleukin-6 (IL-6)
- tumor necrosis factor alpha (TNF-α)
- malondialdehyde (MDA)
- total antioxidant capacity
A recent systematic review and dose-response meta-analysis encompassing 63 randomized controlled trials reported significant reductions in CRP, TNF-α, IL-6 and MDA, together with an increase in total antioxidant capacity.
This reinforces the argument that supplemental melatonin can influence oxidative and inflammatory biology in humans.
But two limitations matter.
First, many of these studies involved people with existing health conditions rather than healthy adults.
Second, the results do not demonstrate that extremely high doses work better than moderate doses.
So the current evidence supports the statement:
Melatonin can influence oxidative and inflammatory pathways in humans.
It does not yet support:
Everyone should take 100 mg of melatonin as an antioxidant.
7. Melatonin and Cardiometabolic Health
Melatonin has also been investigated in relation to blood glucose, blood pressure, cholesterol and inflammation.
A comprehensive systematic review and dose-response meta-analysis of 63 randomized controlled trials reported average reductions of approximately:
- 2.34 mmHg in systolic blood pressure
- 11.63 mg/dL in fasting blood glucose
- 6.28 mg/dL in LDL cholesterol
- 6.97 mg/dL in total cholesterol
- 0.59 mg/L in CRP
The analysis also reported improvements in several oxidative-stress and inflammatory markers.
However, significant overall effects were not seen for several other outcomes, including body weight, BMI, fasting insulin, HOMA-IR, HbA1c, triglycerides and diastolic blood pressure.
That tells us something important.
Melatonin appears biologically active in cardiometabolic pathways.
But the evidence does not establish that:
higher dose = greater metabolic benefit.
8. What Have Human Studies Using High Doses Found?
This is where the high-dose discussion becomes particularly interesting.
Until recently, much of the very-high-dose argument depended heavily on animal research, short clinical trials and mechanistic reasoning.
There is now some human experience with substantially larger doses.
8.1 40–200 mg Per Day in Older Adults
A 2025 study published in Brain Sciences examined 81 patients between 55 and 98 years old who had sleep disorders and accompanying medical conditions.
Patients were treated with:
40–200 mg of melatonin per day
with an average dose of:
72.7 mg/day.
More than half of the patients had used melatonin for over four years.
Researchers reported decreases in the documented prevalence of hypertension, ischemic heart disease and diabetes during treatment, while routine laboratory measures were generally similar to those of matched patients who were not taking melatonin.
That is certainly interesting.
It is also important not to overinterpret it.
The study used a retrospective mixed observational design, not a prospective randomized placebo-controlled design.
People weren’t randomly assigned to take 70 mg of melatonin or placebo for several years.
Therefore, the study cannot prove that melatonin caused the differences observed.
Factors such as medical care, lifestyle, medications and differences between groups could potentially influence the findings.
Still, this study is valuable because it provides something the high-dose literature has historically lacked:
real-world human experience with 40–200 mg doses used over several years.
It deserves additional controlled investigation.
8.2 60 mg Around Heart Surgery
A randomized placebo-controlled study published in 2025 investigated 60 mg/day of melatonin in patients undergoing coronary artery bypass graft surgery.
Researchers reported changes in inflammatory and cardiac-injury markers consistent with a potential protective effect against ischemia/reperfusion injury.
Again, context matters.
These patients were undergoing major heart surgery.
This was a specific short-term medical intervention—not evidence that healthy adults should take 60 mg indefinitely.
9. Melatonin, Cancer and Supportive Care
Cancer is another field in which pharmacological melatonin doses have attracted considerable interest.
Laboratory research has investigated melatonin’s relationships with:
- oxidative stress
- cellular signaling
- apoptosis
- inflammation
- tumor metabolism
- treatment-related symptoms
But human evidence remains much less certain.
9.1 What Did the 2025 Cochrane Review Find?
A 2025 Cochrane review examined 30 studies involving 5,093 cancer patients.
The reviewers concluded that evidence was insufficient to determine whether melatonin meaningfully improved overall quality of life or sleep quality during cancer treatment.
When used alongside standard cancer treatment, melatonin probably reduced fatigue and may have reduced nausea, but many outcomes remained uncertain because of study limitations and risk of bias.
9.2 Does High-Dose Melatonin Prevent Cancer?
There is currently no established human evidence that healthy people can prevent cancer by taking high-dose melatonin.
Research into melatonin and cancer provides important hypotheses and potential therapeutic applications, but cancer prevention is a much stronger claim requiring long-term human outcome data.
Those data do not currently exist.
10. Does Higher-Dose Melatonin Have Anti-Aging Benefits?
This is perhaps the most intriguing—and most easily exaggerated—area of melatonin research.
Aging is associated with:
- mitochondrial dysfunction
- increased oxidative stress
- changes in circadian organization
- chronic low-grade inflammation
- declining cellular energy efficiency
Melatonin interacts with several of these pathways.
Reiter’s recent research specifically focuses on the relationship between melatonin, mitochondrial deterioration and age-related neurodegeneration.
This creates a plausible argument for studying melatonin as a healthy-aging compound.
But there is an important difference between plausibility and proof.
What We Know
Melatonin is involved in biological pathways relevant to aging, including:
- mitochondrial function
- free-radical control
- antioxidant defenses
- inflammatory signaling
- circadian regulation
What We Don’t Know
We currently do not have convincing clinical evidence showing that taking 20, 50, 100 or 200 mg of melatonin:
- slows biological aging
- extends human lifespan
- prevents Alzheimer’s disease
- prevents Parkinson’s disease
- prevents cardiovascular disease
- prevents cancer
The correct conclusion is therefore:
Melatonin has several biological properties relevant to aging, but whether high-dose supplementation improves human healthspan or lifespan remains unknown.
11. Is Higher-Dose Melatonin Safe?
The safety evidence is relatively reassuring in the short term, although important uncertainties remain.
A 2022 systematic review examined randomized clinical trials using 10 mg or more of melatonin per day.
The review included 79 studies involving 3,861 participants.
High-dose melatonin did not produce a detectable increase in serious adverse events or withdrawals due to adverse events in the studies suitable for quantitative analysis.
However, minor adverse effects were more common.
These included:
- drowsiness
- headache
- dizziness
The relative risk of these adverse events was approximately 40% higher among people receiving high-dose melatonin.
11.1 What About 40–200 mg?
The 2025 observational study in older adults provides some additional reassurance because participants received 40–200 mg/day, and many were treated for several years.
But observational data cannot replace randomized safety trials.
11.2 What We Still Don’t Know
The NIH National Center for Complementary and Integrative Health states that short-term melatonin supplementation appears safe for most people, but information about long-term safety remains limited—particularly at exposures substantially higher than normal physiological levels.
That means there is a major difference between:
100 mg for several days or weeks in a research setting
and
100 mg every night for 20 years.
The second scenario has not been adequately studied.
Frequently Asked Questions
Is 10 mg of melatonin considered a high dose?
In the major systematic safety review of higher-dose melatonin, 10 mg/day or greater was classified as high dose.
Ten milligrams is also above what appears necessary for most sleep applications.
Is 20 mg of melatonin safe?
Twenty milligrams has been used in clinical research, and available short-term safety data are reasonably reassuring.
However, the long-term safety of taking 20 mg every night for many years is not well established.
Why would someone take 100 mg of melatonin?
The rationale is generally not to produce stronger sleep effects.
Researchers and clinicians interested in high-dose melatonin are attempting to produce pharmacological concentrations associated with melatonin’s antioxidant, mitochondrial and cytoprotective effects.
Reiter’s research provides important mechanistic support for these biological actions.
However, the optimal dose for producing meaningful health benefits in humans remains unknown.
Does Dr. Russel Reiter recommend high-dose melatonin?
Reiter’s published work strongly supports studying melatonin as an antioxidant and mitochondria-targeted molecule rather than viewing it exclusively as a sleep hormone.
His research provides much of the scientific rationale behind pharmacological-dose melatonin research.
However, his research should not be interpreted as establishing one universal high dose that all healthy people should take.
What dose does Dr. John Lieurance recommend?
Lieurance currently describes high-dose melatonin as approximately 20–200 mg or more, particularly when the objective is antioxidant and mitochondrial effects rather than sleep.
These doses reflect his clinical protocol and interpretation of the research.
They are not established general-health dosing recommendations supported by large randomized controlled trials.
Has anyone studied 40–200 mg in humans?
Yes.
A 2025 observational study evaluated 81 older adults receiving 40–200 mg/day, averaging 72.7 mg/day. More than half had been treated for more than four years.
The findings were encouraging enough to justify additional research, but the study design cannot establish that melatonin caused the reported health differences.
Is 100 mg better than 10 mg?
We do not know.
This is one of the most important unanswered questions in high-dose melatonin research.
There is a biological rationale for greater tissue exposure, but there are not adequate dose-comparison trials demonstrating that 100 mg produces superior long-term health outcomes compared with 10 mg.
Does high-dose melatonin improve mitochondrial function?
Laboratory and animal research strongly supports effects of melatonin on mitochondrial biology, and Reiter’s work has been central to this field.
Whether very-high-dose supplementation improves mitochondrial function enough to produce measurable long-term health benefits in healthy humans remains uncertain.
Is melatonin an antioxidant?
Yes, melatonin has well-documented antioxidant activity.
It can interact directly with reactive species and also influence antioxidant defense systems.
What remains uncertain is how much supplemental melatonin is necessary to maximize clinically meaningful antioxidant effects.
Does high-dose melatonin have anti-aging benefits?
There is a legitimate scientific rationale for investigating melatonin in aging because of its relationships with mitochondria, oxidative stress and cellular metabolism.
But there is currently no human evidence showing that high-dose melatonin extends lifespan or meaningfully slows biological aging.
Can high-dose melatonin prevent cancer?
There is no established evidence that high-dose melatonin prevents cancer in healthy people.
Clinical cancer research remains interesting but uncertain, and melatonin should not be considered a substitute for conventional cancer prevention, screening or treatment.
The Bottom Line
The most interesting thing about melatonin may be that sleep represents only one part of its biology.
Research led by Russel Reiter and others has established a strong biological case that melatonin participates in antioxidant defense and mitochondrial function.
That research helps explain why some investigators and clinicians are interested in doses considerably higher than those normally used for sleep.
John Lieurance takes this idea further and advocates doses in the 20–200 mg+ range for proposed antioxidant and mitochondrial effects rather than simply for sleep.
Importantly, there is now some human experience at these doses. A 2025 study followed older adults using 40–200 mg/day, including many people treated for several years.
But the evidence still has substantial gaps.
A useful way to summarize the science is:
For sleep: More is not necessarily better. Current dose-response research suggests sleep benefits peak at around a few milligrams.
For antioxidant and mitochondrial effects: There is substantial mechanistic evidence that melatonin has biological actions beyond sleep.
For 20–200 mg dosing: Human experience exists and the safety data are interesting, but high-quality randomized long-term trials remain limited.
For longevity and disease prevention: We currently do not have evidence showing that routinely taking very-high-dose melatonin prevents cancer, dementia, cardiovascular disease or aging.
So, are there health benefits of higher-dose melatonin?
Possibly. The biological rationale is stronger than many people realize, and emerging human evidence is intriguing. But we do not yet know the optimal dose, which people are most likely to benefit, or whether taking very high doses long term produces better health outcomes than substantially lower doses.
That is the question future clinical research still needs to answer.
Research References
- Schrire ZM, Phillips CL, Chapman JL, et al. Safety of higher doses of melatonin in adults: A systematic review and meta-analysis. Journal of Pineal Research. 2022;72(2):e12782. DOI: 10.1111/jpi.12782. This systematic review defined higher-dose melatonin as ≥10 mg/day and evaluated 79 randomized controlled trials.
- Cruz-Sanabria F, Bruno S, Crippa A, et al. Optimizing the Time and Dose of Melatonin as a Sleep-Promoting Drug: A Systematic Review of Randomized Controlled Trials and Dose-Response Meta-Analysis. Journal of Pineal Research. 2024;76(5):e12985. DOI: 10.1111/jpi.12985. Sleep effects in the dose-response analysis peaked at approximately 4 mg/day.
- Reiter RJ, Tan DX, Osuna C, Gitto E. Actions of melatonin in the reduction of oxidative stress: A review. Journal of Biomedical Science. 2000;7(6):444–458. DOI: 10.1007/BF02253360.
- Reiter RJ, Mayo JC, Tan DX, Sainz RM, Alatorre-Jimenez M, Qin L. Melatonin as an antioxidant: under promises but over delivers. Journal of Pineal Research. 2016;61(3):253–278. DOI: 10.1111/jpi.12360.
- Reiter RJ, Rosales-Corral S, Tan DX, Jou MJ, Galano A, Xu B. Melatonin as a mitochondria-targeted antioxidant: one of evolution’s best ideas. Cellular and Molecular Life Sciences. 2017;74(21):3863–3881. DOI: 10.1007/s00018-017-2609-7.
- Reiter RJ, Sharma RN, Manucha W, et al. Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment. Ageing Research Reviews. 2024;101:102480. DOI: 10.1016/j.arr.2024.102480.
- Mohammadi S, Ashtary-Larky D, Erfanian-Salim M, et al. Comprehensive Effects of Melatonin Supplementation on Cardiometabolic Risk Factors: A Systematic Review and Dose-Response Meta-Analysis. Nutrients. Published 2025/2026;18(1):134. This analysis included 63 randomized controlled trials examining cardiometabolic, inflammatory and oxidative-stress outcomes.
- Valiensi SM, Vera VA, Folgueira AL, et al. Rethinking Melatonin Dosing: Safety and Efficacy at Higher-than-Usual Levels in Aged Patients with Sleep Disturbances and Comorbidities. Brain Sciences. 2025;15(10):1040. DOI: 10.3390/brainsci15101040. The study evaluated 81 older patients receiving 40–200 mg/day, with a mean dose of 72.7 mg/day.
- Casper EA, El Wakeel L, Sabri NA, et al. Melatonin ameliorates inflammation and improves outcomes of ischemia/reperfusion injury in patients undergoing coronary artery bypass grafting surgery: a randomized placebo-controlled study. Apoptosis. 2025;30:267–281. The study investigated 60 mg/day around CABG surgery.
- Yu ZY, Peng RY, Cheng N, et al. Melatonin in cancer treatment. Cochrane Database of Systematic Reviews. 2025;Issue 4:CD010145. DOI: 10.1002/14651858.CD010145.pub2. The review included 30 studies involving 5,093 cancer patients and concluded that evidence for many proposed benefits remains uncertain.
- National Center for Complementary and Integrative Health. Melatonin: What You Need To Know. National Institutes of Health. NCCIH notes that short-term melatonin use appears safe for most people, while information about long-term safety—particularly at higher exposure—is limited.
- Lieurance J. The High-Dose Melatonin Protocol: Dosing, Evidence, and Safety. 2026. Lieurance describes clinical use of approximately 20–200 mg or more for proposed antioxidant and mitochondrial effects. This is included as a reference for Lieurance’s clinical position and protocol, not as peer-reviewed evidence establishing the efficacy of these doses.
Medical Disclaimer
This article is for educational purposes only and is not intended to diagnose, treat, cure or prevent disease. Discussion of doses used in research does not constitute a recommendation to take those doses. Higher-dose melatonin is pharmacologically active and should be discussed with a qualified healthcare professional, particularly for people taking prescription medications or managing medical conditions.
