Long-term melatonin use is tied to a sharply higher risk of heart failure, a big analysis finds

A large review of health records is raising new questions about one of the most popular sleep aids on pharmacy shelves. Researchers who tracked more than a hundred thousand adults with chronic insomnia found that those who took melatonin for a year or longer were substantially more likely to develop heart failure over the following five years than those who did not. The finding does not prove melatonin causes heart problems, but its scale, and the fact that a widely used over-the-counter supplement is at the center of it, has drawn attention from cardiologists who say the pattern deserves a closer look.

The analysis looked specifically at people already dealing with insomnia, comparing those who relied on melatonin long term against those who managed their sleep problems another way.

What the Insomnia Cohort Showed

The research drew on health records from more than 130,000 adults diagnosed with insomnia, according to a summary released in August 2026. Within that group, people documented as taking melatonin for a year or more had roughly a 90% higher rate of newly diagnosed heart failure compared with insomnia patients who did not use the supplement long term. The same group also showed higher rates of hospitalization for heart failure once diagnosed, and a doubling of all-cause mortality over the five-year follow-up window, meaning the difference in outcomes went beyond heart failure alone.

How Researchers Built the Comparison Groups

The analysis, led by Ekenedilichukwu Nnadi, MD, and presented at the AHA’s Scientific Sessions in November 2025, drew its data from the TriNetX Global Research Network, an aggregator of real-world health records used widely in large observational studies like this one. Researchers identified 130,828 adults with an insomnia diagnosis, then split them into 65,414 who had been prescribed melatonin at least once and used it for a year or longer and 65,414 who had not, excluding anyone with a prior heart failure diagnosis or other prescription sleep drugs so the comparison would isolate melatonin’s association rather than pre-existing heart disease. The two groups were matched on age, sex, 15 separate health conditions, other cardiovascular medications, lab values, and health care use, a technique called propensity score matching meant to make the groups as similar as possible before comparing outcomes.

Over the five-year follow-up, heart failure hospitalization occurred in 19% of the melatonin group versus 7% of the matched group, and death from any cause occurred in 8% versus 4%. Researchers also reran the comparison using a stricter definition, requiring at least two melatonin fills 90 days apart, and found a similar heart failure risk, suggesting the pattern held regardless of exactly how “long-term use” was defined.

The American Heart Association’s Own Caveats

The findings were highlighted by the American Heart Association, which has been tracking this line of research since it was first presented at one of its scientific meetings. The organization has been explicit that the study is observational: researchers compared outcomes between groups of people who made their own choices about melatonin use, rather than randomly assigning some patients to take it and others not to. That design can reveal a strong statistical association, but it cannot by itself rule out the possibility that something else about long-term melatonin users, such as more severe underlying insomnia or other health conditions driving them to seek out the supplement, is actually responsible for the higher heart failure rates.

Why Chronic Insomnia Itself Is a Confounding Factor

Sleep researchers have long known that untreated or severe insomnia is associated with worse cardiovascular outcomes on its own, independent of any supplement a patient takes for it. That creates a specific challenge for interpreting this analysis: the people most likely to use melatonin for a year or longer may also be the people whose insomnia has proven hardest to treat with other methods, and it is that persistent, severe sleep disruption, not the melatonin itself, that could be driving some of the excess heart failure risk. Researchers who presented the original data acknowledged this limitation directly, and a summary from the American College of Cardiology noted that the results should be treated as preliminary until they appear in a full peer-reviewed manuscript rather than as a settled verdict on the supplement’s safety.

How Melatonin Differs From a Prescription Sleep Drug

Part of what makes this finding notable is how differently melatonin is regulated compared with prescription insomnia medications. In the United States, melatonin is sold as a dietary supplement, which means it does not go through the same premarket safety and efficacy testing the Food and Drug Administration requires for prescription drugs, and dosages on store shelves can vary widely from one product to the next, sometimes containing more or less melatonin than the label states. That regulatory gap means large-scale, real-world safety signals like this one carry more weight than they might for a heavily studied prescription drug, simply because there has been less rigorous, controlled research on melatonin’s long-term cardiovascular effects to compare against.

What Long-Term Users Are Being Told to Do

Cardiologists reacting to the analysis have generally stopped short of telling patients to abandon melatonin outright, instead framing the findings as a reason to treat long-term, nightly use the way any other long-term medication would be treated: as something worth discussing with a doctor rather than continuing indefinitely without a checkup. That advice lines up with existing sleep-medicine guidance, which has generally recommended melatonin for short-term or occasional use, such as adjusting to jet lag or a temporary disruption in sleep schedule, rather than as a permanent nightly habit. For people with chronic insomnia who have relied on melatonin for months or years, the analysis is likely to prompt more conversations about whether an underlying heart or sleep condition needs its own evaluation, separate from whatever benefit the supplement has provided for falling asleep.

This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.

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