You get whiplash from the contrasting headlines. One minute, the internet is ablaze from an alarming study linking melatonin to a sharp increase in the risk of heart failure [1]. The next, a new study tells a completely different story [2].
This is why clickbait sucks, and it confuses everyone. Luckily though, when you go through the data, it actually all points in the same direction and gives us a clear picture regarding whether to take melatonin supplements or not.
Table of Contents
- Why This Matters
- The Alarming Study
- The New Meta-Analysis
- How Melatonin Actually Works
- Practical Considerations
- References
Why This Matters
This is important because Americans now take melatonin at 5x the rate they did in 1999 [3]. And a 2023 survey found 64% of adults have taken it at some point [4]. That's tens of millions of people.
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's why the alarming 2025 study was so significant. It looked at 5 years of electronic health records to assess the effects of melatonin on a longer time horizon [1].
And 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's the sort of data journalists love. It makes for wonderful clickbait titles. But if we take a careful look at the study, there were some big issues with the methodology behind it.
The first has to do with the composition of the two groups the researchers compared. What they're trying to do is separate long-term melatonin users from those who didn't use it. This is obviously foundational when it comes to answering their central question, which is about the safety of longer-term melatonin use.
But when we look at the details of how the researchers established the two groups, we spot a key flaw. On one side were those whose electronic medical records indicated a prescription for melatonin. That's the melatonin group. The non-melatonin group was made up of those whose health records didn't mention melatonin.
Now here's the problem. The TriNetX Global Research Network database the study relies on 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 don't. But in this study, the melatonin group included just those whose records showed a prescription. So, and this is the key point, anyone who was taking melatonin over the counter would end up in the non-melatonin group [7].
And that's a huge problem. How can we draw any conclusions from this study if the non-melatonin group is consuming melatonin?
The second major issue is that this is an observational study, not a randomized controlled trial. So that means it just tells us about association, not causation. It's crucial to remember that we can find all sorts of associations when we look at data sets, but not all of them can be explained by an underlying connection. Consider, for instance, the relationship between ice cream sales and shark attacks. They both peak in the summer. If you think about that for a moment, it's obvious why. And it isn't because ice cream is causing the attacks.
But if we ignore these two issues and assume that this association between heart failure and melatonin use is real, why might that be? And how would that impact our decision to use melatonin supplements?
Here's a possibility. Maybe people with more severe insomnia are more likely to get a prescription for melatonin. If that were true, that would make sense of the pattern. Because we have plenty of data that shows sleep disruption leads to worse heart-related health outcomes. For instance, a 2024 meta-analysis concluded there's strong evidence of a causal connection between insomnia and the risk of heart disease [8].
This would make sense, since we know a lack of sleep ramps up inflammation. And inflammation is at the heart of many kinds of heart disease [9].
So it's not necessarily the melatonin that's causing the increase in heart failure; it might instead be due to the insomnia itself. To really figure out what's going on, we'd need randomized controlled trials where one group takes melatonin, and the other gets a placebo.
And, besides all this, what we're looking at is just an abstract for a paper presented at a conference. It hasn't yet gone through the gauntlet of the peer-review process. It's preliminary.
And this preliminary finding, with highly suspect methodology, got a lot of press — even though we have studies that point in the opposite direction.
For instance, a 2025 meta-analysis looked at melatonin use in those already diagnosed with heart failure. It combined 4 randomized controlled trials. Melatonin improved patient scores on a measure of heart failure and significantly boosted quality of life. It also increased an important metric of blood vessel health. There was even a trend toward an improvement in the heart's pumping ability, but this wasn't statistically significant [10].
This is consistent with an earlier analysis in 2022. It summarized study evidence finding that melatonin protected the heart in numerous human and animal studies [11].
The New Meta-Analysis
Still, scary studies that grab headlines can leave people confused and in doubt. So who's right? Is melatonin dangerous for heart health or not? A new study makes a decisive contribution to the discussion.
It's a meta-analysis including 63 randomized controlled trials and over 3,000 participants [2].
This is a much more compelling kind of evidence than the study that raised alarm bells last fall. Not only are we dealing with randomized controlled trials instead of an observational study, but it's a meta-analysis that combines data from a large number of individual trials. It includes the best evidence available through October of 2025 — just weeks before the heart failure study made headlines.
The focus of this study isn't heart failure, and it doesn't speak directly to that condition. But it gives us a wider-angle view of a set of factors that are highly relevant to heart health. They are also relevant to chronic conditions like type 2 diabetes and high blood pressure.
Here's what they found when they ran the analysis. Melatonin supplements significantly reduced waist circumference, blood pressure, fasting blood glucose, LDL cholesterol, and total cholesterol [2].
They also measured the effects of melatonin in another area: inflammation. They found significant drops in several key markers of inflammation and oxidative stress, including C-reactive protein, malondialdehyde, tumor necrosis factor-alpha, interleukin-6, and alanine aminotransferase [2].
And melatonin use boosted antioxidant capacity in the blood [2].
It's like melatonin acts as a systemic coolant, damping down inflammation and oxidative stress. This is hugely significant, since inflammation and oxidative stress have a big impact on heart disease and related conditions like obesity and insulin resistance [2].
The size of the effects here are generally modest, but meaningful. But the crucial thing to notice is that, cumulatively, they point decisively in the direction of an impact that supports heart health.
I want to add an important caution here, though. The trials included in the meta-analysis were mostly shorter-term, with many lasting just a few weeks. The longest was just over a year. So this doesn't settle the question about the long-term effects of melatonin use. We'll need longer-term randomized controlled trials for that. But there's no question the evidence trends in a direction that looks positive.
How Melatonin Actually Works
So the most up-to-date study data we have today is encouraging. We don't see anything here that supports the alarming headlines from the heart failure study. But there's another way to approach the issue, and that's to look at what melatonin actually does. Does it make sense that it would promote heart health — or get in the way?
The first thing to understand is that melatonin is way more than just a sleep hormone. It is produced by the pineal gland in the brain, but also throughout many of the body's organs, including the heart, gastrointestinal tract, skin, bone marrow, and lymphocytes [12].
It's a potent antioxidant and anti-inflammatory. It has been shown to exhibit strong antioxidant properties and is capable of protecting against oxidative stress. These antioxidant capabilities enable it to scavenge free oxygen radicals and prevent oxidative damage to cells and tissues [12].
It may also enhance the functioning of our blood vessels. Melatonin 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 inflammation are central to heart disease. So the cardioprotective signals in the meta-analysis data make mechanistic sense.
And sleep itself is linked to heart health, as I mentioned earlier. So melatonin's ability to improve sleep metrics likely has a multi-faceted beneficial effect.
Practical Considerations
So the benefits of melatonin supplements make sense in theory. And we have some compelling study evidence about their effectiveness for better sleep, along with suggestive evidence about heart health. But, as always, there are some things we need to watch out for when moving from studies to how we approach supplementation.
First, there's the matter of dosing. Melatonin supplements often contain very high doses — even over 5 mg/day. And as I mentioned earlier, we don't have data on the long-term safety of this.
Let me put this dose into perspective. The body produces between 10 to 80 micrograms of melatonin at night [13]. About 15% of the melatonin in a supplement is absorbed by the body [14].
So think of that 5 mg dose. That would be 5,000 micrograms. And if 15% gets absorbed, that's 750 micrograms. That's 10 times the amount our bodies naturally produce or more. Personally, I wouldn't take more than 1 mg per night.
In fact, I do take melatonin regularly as part of my Sleep supplement. But it includes just 0.3 mg (or 300 micrograms).
Given the typical bioavailability, that dose sits right in the middle of the range normally produced by the body. And it's a mile away from the doses seen in some supplements. But just because I take a supplement, that certainly doesn't mean you also need to.
Second, we want to be careful about product quality. A 2023 study of melatonin gummy products found the actual quantity of melatonin ranging from 74% to 347% of the amount specified on the label. Incredibly, one product didn't contain any detectable melatonin at all [15]. It's a bit like playing gummy roulette. So if you're shopping for a melatonin supplement, make sure you look for a reputable manufacturer.
Finally, timing is critical. And here it's important to remember how melatonin functions. It isn't like a sedative that knocks you out. Rather, it's a hormone that plays a central role in regulating the body's natural sleep-wake cycle. Our shift from a daytime mode of full alertness to a nighttime mode of sleep involves changes that play out slowly over hours, not minutes [16].
For optimal effect, we should take melatonin around 2-4 hours before we want to fall asleep.
When it comes to sleep supplements, melatonin gets all the attention. But the evidence for its cardiometabolic benefits 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, stick to low doses, choose reputable products, and time your supplementation wisely.
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
