Life-Extending Properties of Melatonin
I've read this study and I will explain 15 reason's why this study is simply wrong :
This study got a lot of headlines and has been discussed multiple times on this forum so I am posting my rebuttal to it so that people can get a better idea of the weaknesses and shortcomings of this study. I am also making this post so that I can link to it in the future when other people post this study again. Here is a link to an article about it if you want to read it :
https://www.sciencedaily.com/releases/2026/08/260829035228.htm
1. To start with :
The researchers stated that their study cannot prove a cause-and-effect relationship between melatonin use and heart problems, then they said this
Long-term melatonin use linked to 90% higher heart failure risk.
That was a major clue about the veracity of this study. The title seems aimed more at sensationalism than truth and accuracy.
2. They failed to mention that people with insomnia are at far greater risk for heart failure and their 5 year follow up seemed to confirm this finding yet they placed the blame on melatonin with zero blame placed on the underlying disease. Here is what AI says about people who have had insomnia for 5 years or more :
Having chronic insomnia with multiple symptoms can increase your relative risk of heart failure by 80% to threefold compared to people without sleep issues.
3. Although they mentioned that some of the patients also had sleep apnea and it is well established that sleep apnea significantly increases your chances for heart failure, they still placed the blame on melatonin. Here is what AI says about people who have had sleep apnea for 5 years or more :
Untreated sleep apnea can increase the risk of developing heart failure by roughly 140%, though specific cumulative percentages tied strictly to a 5-year duration depend heavily on the severity of the condition and individual health factors.
4. Having both sleep apnea and insomnia together (known as COMISA) significantly multiplies your overall cardiovascular risk, raising the likelihood of major heart disease events by nearly 3.8 times compared to having neither condition. Again, no mention of this fact in the study as they placed the blame for heart failure on melatonin.
5. They chose to use melatonin prescriptions as the determining factor for who was taking melatonin and they stated that the patient had to have at least two filled prescriptions of melatonin to qualify as long term melatonin users and be included in the study, but this does not prove they actually took the melatonin since there was zero monitoring of patients, only going by what was written in their files. Since this was an international study, this criteria creates another major problem for this study because they also included patients medical records from the US and the US does not require a prescription for melatonin and many people don't bother mentioning to their doctor's that they are taking melatonin even if their doctor asks if they are taking supplements. This means that many of the people that the study listed as non melatonin users, may have actually been taking melatonin. To me this one point alone should have been a disqualifying point against the study.
6. Try asking AI this question :
Going back decades, is there one other available study that would confirm that melatonin causes or contributes to heart failure?
What you will find is that AI can not find one other study that suggests that melatonin causes heart failure, let alone in people with insomnia, but AI can find plenty of studies suggesting that melatonin may be cardiovascular protective because of the antioxidant, anti inflammatory, powerful antiapoptotic effects and mitochondrial protective effects of melatonin and its over 10 metabolites. Their study goes against hundreds if not thousands of valid studies for melatonin.
7. They did not tell you what dosages of melatonin people were using, but prescription dosing is generally low in the 2 or 3 mg area. While this dose may help some people sleep it is highly likely not to be high enough to take advantage of melatonin's heart protective effects.
8. There was no mention or screening of insomnia severity and this point would have been crucial because heart failure risk significantly increases with insomnia symptoms and severity. How can you even perform such a study without screening for such an important factor that significantly increases heart failure risk on its own?
9. They report approximately:
7.8% vs. 4.3% mortality.
That's a very large difference.
But mortality is affected by virtually everything:
- underlying disease
- frailty
- sleep disorder severity
- psychiatric illness
- socioeconomic factors
- healthcare access
- medication adherence
- lifestyle
- undiagnosed disease
So an observational HR around 2 for mortality is not something I would casually attribute to melatonin, particularly when the exposure and insomnia severity aren't well characterized.
10. A 2026 peer-reviewed NHANES analysis that provides an interesting counterpoint. It examined U.S. adults from 1999–2018 and, after adjustment, found no statistically significant association between melatonin use and heart failure: adjusted OR 0.88 (95% CI 0.43–1.80) in the core model and 0.67 (95% CI 0.33–1.38) after additionally accounting for depression and sleep disturbance.
11. Their study was not peer reviewed. Why is that important?
It validates Methods: Other experts in the same field check if the study design, data collection, and statistics are correct.
Catches Errors: Reviewers spot hidden mistakes, weak arguments, or rushed conclusions that the original authors missed.
Builds Trust: Published papers that pass this strict test give scientists and the public a dependable foundation of knowledge to build upon.
Filters Out Poor Work: It stops flawed, biased, or low-quality papers from being accepted as proven science.
Improves Clarity: Reviewers give helpful advice on how to rewrite and present the data so it is clear and easy for others to understand.
To me, if you felt your study was of good quality, you would have it peer reviewed to add to the significance and importance of it, but they haven't done that .
12. A 2026 Open Heart analysis using nationally representative NHANES data found no statistically significant association between melatonin use and heart failure. The authors explicitly describe their findings as a "contextual counterpoint" to the recent alarm signal—not proof that melatonin is beneficial, but also not evidence of cardiovascular harm.
13. A randomized clinical trial in patients with HFrEF found that melatonin supplementation reduced NT-proBNP and improved quality of life, with the investigators concluding that it might be a useful adjunct in HFrEF.
14. The study population of 130, 828 adults had a mean age of 55.7 years, and 61.4% were women. This means that a significant portion of the patients were in an age range where the risk of heart failure is increasing. So another potential cause for increased heart failure that the study did not address, but still pointed at melatonin as the cause.
15. Though the study matched for age, it did not take into account the effect on the cardiovascular system that comes with aging and that is a significant factor relevant to the veracity of the study.
There were more issues with this study, but I felt 15 issues was enough to show that this study is lacking in many areas.
Imo, the study has too many weaknesses and insufficient data points to prove the point they claimed to be making and the researchers involved, plainly stated that that their study cannot prove a cause-and-effect relationship between melatonin use and heart problems.
So you can believe one inherently bad study or believe hundreds if not thousands of other studies that prove that melatonin is healthful for humans, animals and plants. It is your choice!
Art
Cancer
★★★★★
This new review article (July 2025) goes into detail of why Melatonin is an important molecule to help fight cancer through multiple methods of action. It details much of what is known about how melatonin fights cancer and interacts well with standard of care :
https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1617508/full
Here is a relevant quote from the article :
' Melatonin (MLT), a naturally occurring hormone produced by the pineal gland, exhibits significant anticancer effects. It has superior antioxidant, inhibit tumor cell proliferation, migration, angiogenesis-inhibiting, and tumor cell apoptosis-inducing functions. Mechanistically, melatonin inhibits tumor development through epigenetic regulation, metabolic reprogramming, immune micro-environment, and regulation of important signaling pathways (PI3K/AKT). In addition, MLT significantly enhances anticancer efficacy in combination with other anticancer drugs, such as cisplatin, 5-fluorouracil, and paclitaxel. However, the shortcomings of melatonin, such as its low bioavailability, rapid metabolism, and significant individual variation in secretion, have limited its clinical application in anticancer therapy. This limitation has been mitigated by targeted delivery and individualized therapy. Therefore, MLT may be a promising candidate for natural hormone therapy in the future. '
I would like to add that melatonin lotion and melatonin gel may also offer a way to help overcome the poor bioavailability of oral melatonin as well as the rapid metabolism of the molecule.
Art
Melatonin and Daytime Use
★★★★★
When we had covid back in January we all used high dose Melatonin (thanks to Art who kept us informed about the protocol! ) I used it on everyone in the house - ages 9 to 83, based on weight, as Dr. Neel recommends. We took it 4 times a day.
My 83 year old mother in law with dementia did not know what the pills I gave her were, I just added them with her other meds and supplements. She was not symptomatic of covid, but we were using it to try and prevent covid since others in the home had it. (I think it worked, or at least helped! She never got sick, but did lose her sense of smell.) Anyway, her sleep/wake patterns were no different than when she wasn't taking round the clock melatonin. (She always takes it at night.)
It was hard to tell how it affected those of us who were actually sick. Sick people sleep more.
I take 15-20 mg of melatonin every night to help me with sleep (and it definitely improves my quality of sleep! )
Last summer, an hour after taking my melatonin dose, my daughter-in-law went into labor. I had an hour of sleep but woke up easily and drove an hour and 20 minutes to the birth center where she had the baby. I had no trouble driving and no trouble staying awake all night.
I had the opportunity to repeat the experiment last week. I had taken my 20 mg of melatonin and fallen asleep when my daughter went into labor. I woke up and stayed up the rest of the night with her and was able to see another grandchild born. (What a privilege! )
I cannot know how it affects others. But I can say that melatonin does not make it impossible for at least some people to stay awake after taking a significant dose. Certainly it would be wise to know how such a dose would affect you before driving a long way or using heavy equipment.
~Mama to Many~
Multiple Conditions
★★★★★
In the above chart, you can see that by age 50, melatonin levels have declined to the level of a newborn which is quite low when compared to the peak seen in childhood. In the following link, there is a chart that you have to scroll down to page 10 to see and it shows how the incidence of Parkinson's Disease (PD) increases with age. Interestingly, the incidence of PD starts to increase noticeably from age 50.
Seems like an interesting coincidence.
Look at the following chart and notice how Deaths from Covid-19 start to notably increase from age 50 and up.
https://www.statista.com/statistics/1191568/reported-deaths-from-covid-by-age-us/
Seems like an interesting coincidence.
Men age 45 or older and women age 55 or older are more likely to have a heart attack than are younger men and women.
https://www.mayoclinic.org/diseases-conditions/heart-attack/symptoms-causes/syc-20373106
Seems like an interesting coincidence.
Middle age is when diabetes diagnoses really start to spike. An estimated 14% of Americans ages 45 to 64, or 11 million people, are diagnosed with type 2. That's almost five times the rate for those 18 to 44.
https://www.webmd.com/diabetes/diabetes-link-age
Seems like an interesting coincidence.
Risk increases significantly after age 50, and half of all cancers occur at age 66 and above. According to the National Cancer Institute, one quarter of new cancer diagnoses are in people aged 65 to 74. Refer to the attached chart to see where melatonin levels are at this age range.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544764/
Seems like an interesting coincidence.
Osteoporosis also starts to become a bigger issue around age 50 when bone stability starts to head south.
Seems like an interesting coincidence.
From this link, you can see that stroke starts to noticeably increase from age 50.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3006180/
Seems like an interesting coincidence.
Another interesting coincidence is that melatonin has been shown in studies to help all of these diseases.
Art
Induce Dreaming
★★★★★
