Contrasting headlines have left melatonin users confused. One alarming 2025 study linked melatonin use to a sharp increase in heart failure risk [1]. Then a separate study told a completely different story [2].
This kind of whiplash is exactly why clickbait is so damaging when it comes to health topics. Individual alarming studies make for attention-grabbing headlines, but they rarely represent the full picture. Luckily, when all the available data is examined carefully, the evidence actually points in one consistent direction — and gives a clear picture of what the science says about melatonin supplementation and heart health.
Table of Contents
- Why This Matters
- The Alarming Study
- The New Meta-Analysis
- How Melatonin Actually Works
- Practical Considerations
- References
Why This Matters
Melatonin has become one of the most widely used supplements in the world. Americans now take it at 5x the rate they did in 1999 [3]. A 2023 survey found that 64% of adults have taken it at some point [4]. That is tens of millions of people making decisions about a supplement based on headlines that often contradict each other.
Plenty of short-term studies have shown benefits for sleep. An umbrella review of twelve papers evaluating melatonin found statistically significant improvement in sleep latency [5].
And while melatonin supplementation appears safe, long-term data has been lacking. As the authors of the new meta-analysis note, "although melatonin is generally considered safe based on short-term and early-phase clinical data, robust long-term safety evidence, particularly for higher doses and in individuals with chronic diseases, remains limited" [2].
The Alarming Study
That is why the alarming 2025 study drew so much attention. It looked at 5 years of electronic health records to assess the effects of melatonin on a longer time horizon [1].
It found long-term users had an 89% higher risk of heart failure, were about 3.5x more likely to be hospitalized for it, and over twice as likely to die from any cause [1].
It is the sort of data journalists love. But a careful examination of the study reveals significant methodological problems.
The first issue concerns how the researchers defined the two comparison groups. The goal was to separate long-term melatonin users from non-users — foundational to answering their central question about longer-term safety.
But the details reveal a key flaw. The melatonin group consisted of those whose electronic medical records showed a prescription for melatonin. The non-melatonin group was everyone whose records did not mention melatonin.
Here is the problem. The TriNetX Global Research Network database used in the study includes data from numerous countries [6]. In some countries, like the U.K., patients require a prescription for melatonin. In others, like the U.S., they do not. Because the melatonin group included only those with a recorded prescription, anyone taking melatonin over the counter would have ended up in the non-melatonin group [7].
That is a fundamental flaw. No meaningful conclusions about melatonin's effects can be drawn when the control group itself contains melatonin users.
The second major issue is that this is an observational study, not a randomized controlled trial. So it tells us about association, not causation. It is crucial to remember that associations in datasets do not automatically reflect an underlying causal connection. Consider, for instance, the relationship between ice cream sales and shark attacks. They both peak in the summer. But that is obviously not because ice cream is triggering shark attacks — both are driven by warm weather.
But if we set aside these methodological problems and consider whether the observed association between heart failure and melatonin use could have an alternative explanation, one emerges quickly.
People with more severe insomnia may be more likely to receive a prescription for melatonin. And there is substantial evidence that poor sleep worsens cardiovascular outcomes. A 2024 meta-analysis concluded there is strong evidence of a causal connection between insomnia and the risk of heart disease [8].
This connection is well-established mechanistically: poor sleep elevates inflammation, and inflammation is central to many forms of heart disease [9].
In other words, the insomnia itself — not the melatonin used to treat it — may be driving the elevated heart failure risk observed in the study. Randomized controlled trials, where one group receives melatonin and another receives a placebo, are needed to separate these effects.
There is one more important caveat. The concerning findings came from an abstract presented at a conference — not a peer-reviewed publication. The study had not yet gone through the scrutiny of the full peer-review process at the time it made headlines. It is preliminary research.
And this preliminary finding, with suspect methodology, generated widespread coverage — even though other studies point in the opposite direction.
For instance, a 2025 meta-analysis examined melatonin use specifically in people already diagnosed with heart failure. It combined data from 4 randomized controlled trials. Melatonin improved patient scores on a standard measure of heart failure and significantly boosted quality of life. It also improved an important metric of blood vessel health. There was a trend toward improvement in the heart's pumping ability, though this did not reach statistical significance [10].
This is consistent with a 2022 review that summarized findings from multiple human and animal studies, concluding that melatonin exerted cardioprotective effects across a range of conditions [11].
The New Meta-Analysis
Conflicting headlines leave people uncertain. So who is right? Is melatonin dangerous for heart health or not? A new study makes a decisive contribution to the discussion.
It is a meta-analysis including 63 randomized controlled trials and over 3,000 participants [2].
This is far more compelling evidence than the observational study that generated alarming headlines. It is not just that randomized controlled trials are the gold standard — it is that this meta-analysis synthesizes data across 63 of them, incorporating the best evidence available through October 2025, just weeks before the heart failure study made news.
The focus of this meta-analysis is not heart failure specifically. But it examines a set of cardiometabolic factors that are directly relevant to heart health, type 2 diabetes, and high blood pressure.
Melatonin supplements significantly reduced waist circumference, blood pressure, fasting blood glucose, LDL cholesterol, and total cholesterol [2].
The analysis also measured inflammatory and oxidative stress markers. It found significant reductions in C-reactive protein, malondialdehyde, tumor necrosis factor-alpha, interleukin-6, and alanine aminotransferase [2].
Melatonin use also boosted antioxidant capacity in the blood [2].
Melatonin appears to function as a systemic coolant — dampening inflammation and oxidative stress across multiple pathways. This is highly significant, given that inflammation and oxidative stress are major drivers of heart disease and related conditions such as obesity and insulin resistance [2].
The size of the individual effects is generally modest, but meaningful. Cumulatively, they point in a consistent direction: one that supports cardiometabolic health.
An important limitation applies here. The trials included in the meta-analysis were mostly shorter-term, with many lasting just a few weeks. The longest trial ran just over a year. So this does not settle the question about the long-term effects of melatonin use. Longer randomized controlled trials are still needed to fully characterize its safety profile over years, particularly at higher doses and in people with chronic conditions. But there is no question that the evidence trends in a direction that looks positive.
How Melatonin Actually Works
The most current study data is encouraging. Nothing in it supports the alarming headlines about heart failure. But there is another way to approach the question — and that is to look at what melatonin actually does at a biological level. Does its mechanism of action suggest it would promote heart health, or undermine it?
Melatonin is far more than a sleep hormone. It is produced by the pineal gland in the brain, but also by many of the body's organs, including the heart, gastrointestinal tract, skin, bone marrow, and lymphocytes [12].
It is a potent antioxidant and anti-inflammatory. Research has demonstrated strong antioxidant properties and the ability to protect against oxidative stress. These antioxidant capabilities allow melatonin to scavenge free oxygen radicals and prevent oxidative damage to cells and tissues [12].
Melatonin may also enhance blood vessel function. It regulates blood pressure through both central and peripheral mechanisms, enhancing endothelial function and promoting vasodilation, partly through pathways involving nitric oxide production [2].
Blood vessel dysfunction and chronic inflammation are central to the development of heart disease. The cardioprotective signals observed in the meta-analysis data align directly with these known mechanisms — which is why the RCT evidence looks encouraging and why the heart failure alarm appears increasingly at odds with the broader picture.
Sleep quality itself is closely linked to heart health, as discussed earlier in the context of insomnia. So melatonin's ability to improve sleep metrics likely has a multi-faceted beneficial effect on the cardiovascular system — through both direct antioxidant and anti-inflammatory pathways and indirectly via better sleep quality.
Practical Considerations
The cardiometabolic effects of melatonin make theoretical sense, and the study evidence is encouraging. But, as always, there are important things to consider when moving from research findings to how supplementation is actually approached in practice.
Dosing. Melatonin supplements are often formulated at very high doses — sometimes exceeding 5 mg per day — and long-term safety data at these levels is lacking.
To put this in perspective: the body naturally produces between 10 and 80 micrograms of melatonin at night [13]. Approximately 15% of supplemental melatonin is absorbed by the body [14]. Consider a 5 mg dose — that is 5,000 micrograms. With 15% absorption, around 750 micrograms would reach the bloodstream. That is ten times or more the amount the body produces naturally, and we simply do not have data on what long-term exposure to such doses does to the body's own melatonin regulation. The evidence base for low-dose melatonin — in the range of 0.3 to 1 mg — is more robust, and doses within that range sit much closer to what the body is designed to handle.
From the MicroVitamin range
Sleep by Dr Brad uses 300 mcg of melatonin — a dose that, given typical 15% bioavailability, sits within the range the body produces naturally — paired with magnesium bisglycinate and glycine 2400 mg to support the natural sleep-wake cycle. Sleep by Dr Brad.
At a 300 mcg dose with roughly 15% absorption, the amount actually reaching the bloodstream is approximately 45 mcg — well within the 10–80 mcg the body produces naturally. That is a very different picture from the supraphysiological exposure seen with 5 mg doses. Whether melatonin supplementation is right for any individual is a personal decision, and not everyone will need it. But for those who do supplement, dose selection matters considerably.
Product quality. A 2023 study of melatonin gummy products found the actual melatonin content ranging from 74% to 347% of the amount specified on the label [15]. Incredibly, one product in that study did not contain any detectable melatonin at all. It is a bit like playing gummy roulette. This kind of variability makes it especially important to choose products from manufacturers who use third-party testing and can demonstrate that what is on the label is what is in the product.
Timing. Finally, timing matters. Melatonin does not function as a sedative that induces sleep on demand. It is a hormone that plays a central role in regulating the body's natural sleep-wake cycle. The shift from full daytime alertness to nighttime sleep readiness involves a cascade of physiological changes that play out slowly over hours, not minutes [16]. Supplementing too close to the intended sleep time misses this window. For optimal effect, melatonin is generally taken around 2–4 hours before the intended sleep time.
Melatonin has long been associated with sleep. But the evidence for its broader cardiometabolic effects is growing. The key takeaway from the latest research is reassuring: the best available data — from randomized controlled trials, not clickbait-friendly observational studies — suggests melatonin may actually support heart health, not harm it. As always, the principles are consistent: stick to low doses, choose reputable products with verified third-party testing, and time supplementation appropriately to work with the body's natural rhythms.
References
1. https://www.ahajournals.org/doi/10.1161/circ.152.suppl_3.4371606
2. https://pmc.ncbi.nlm.nih.gov/articles/PMC12787795/
3. https://pmc.ncbi.nlm.nih.gov/articles/PMC8808329/
4. https://aasm.org/wp-content/uploads/2023/06/sleep-prioritization-survey-2023-melatonin.pdf
5. https://www.sciencedirect.com/science/article/abs/pii/S0022395619309872
6. https://trinetx.com/data-sets-analytics/
8. https://jcsm.aasm.org/doi/10.5664/jcsm.11326
9. https://link.springer.com/article/10.1007/s11818-025-00495-6
10. https://pmc.ncbi.nlm.nih.gov/articles/PMC11873767/
11. https://pmc.ncbi.nlm.nih.gov/articles/PMC9251346/
12. https://pmc.ncbi.nlm.nih.gov/articles/PMC10825492/
13. https://pmc.ncbi.nlm.nih.gov/articles/PMC4138917
14. https://pubmed.ncbi.nlm.nih.gov/10883420/
15. https://jamanetwork.com/journals/jama/fullarticle/2804077
