Long-Term Melatonin Use Tied to 90% Higher Heart Failure Risk in Insomnia Patients

Millions of Americans reach for melatonin every night without a second thought. A large preliminary study presented at the American Heart Association's 2025 Scientific Sessions is giving clinicians a reason to look more carefully at patients who've been doing that for years.

The study, whose abstract is published in Circulation, pulled five years of electronic health records from the TriNetX Global Research Network. Researchers focused on adults already diagnosed with chronic insomnia and compared two groups: those with documented melatonin use for at least 12 months, and a matched set of insomnia patients with no record of melatonin use. To keep the signal clean, the researchers excluded anyone who had a prior heart failure diagnosis or who was already taking other prescription sleep medications.

The numbers were stark. According to the abstract reviewed by the American Heart Association's newsroom, adults with chronic insomnia who used melatonin for 12 months or longer had roughly a 90 percent higher chance of developing heart failure over the following five years compared to those who didn't use the supplement. The hospitalization picture was worse: melatonin users were nearly 3.5 times as likely to be hospitalized for heart failure. All-cause mortality was also higher, with melatonin users roughly twice as likely to die during the study period.

That's a signal size that commands attention. But before patients clear out their medicine cabinets, the study's own design demands equal attention.

The most important limit is one that heart failure clinicians and sleep specialists have already flagged publicly: this is a retrospective, observational analysis. The data was collected, then reviewed. It can't establish that melatonin caused anything. Cardiologists at Hackensack University Medical Center, speaking to their institution's health blog, pointed out that the association could run the other way entirely. Difficulty sleeping is a known symptom of existing, undiagnosed heart failure, meaning some patients in the melatonin group may have already been on a cardiac trajectory before they ever opened a bottle of supplements.

There's also a classification problem baked into the data. According to a statement reviewed by the American Heart Association newsroom, melatonin use was identified only through prescription entries in electronic health records. In the United States and several other countries, melatonin is sold over the counter, so a substantial number of habitual melatonin users would have landed in the control group, which would compress the apparent difference between the two groups, not inflate it.

What the study does well is scale. Researchers matched participants on more than 40 baseline variables across a multinational cohort of more than 130,000 adults, according to the abstract in Circulation. The association held up in sensitivity analyses that required at least two melatonin prescription fills at least 90 days apart, suggesting it isn't an artifact of one-time use.

For clinicians, the practical takeaway isn't "tell every patient to stop melatonin." It's closer to: be deliberate. Melatonin's marketing has long leaned on a low-risk reputation, and until now there's been almost no long-term cardiovascular safety data to test that claim. This study doesn't answer the question definitively, but it's the first large-scale look at what happens in the five years after a patient commits to the supplement.

What's missing, as Northwestern Medicine physicians noted in a review of the findings, is any dose or duration curve. Nobody yet knows whether the risk climbs linearly with years of use, whether it kicks in only at high doses, or whether interactions with common cardiac medications are doing part of the work.

The researchers themselves called for prospective trials. Those don't exist yet. In the meantime, patients who've been on melatonin for more than a year, especially those with other cardiovascular risk factors, should bring it up with their primary care provider or cardiologist the same way they'd bring up any long-term supplement. "Safe" has always been a relative word in pharmacology. This study makes that point in a category most people assumed was exempt.

Sources cited:
- Circulation (AHA Journals), Abstract 4371606 (https://www.ahajournals.org/doi/10.1161/circ.152.suppl_3.4371606)
- American Heart Association Newsroom (https://newsroom.heart.org/news/long-term-use-of-melatonin-supplements-to-support-sleep-may-have-negative-health-effects)
- Hackensack Meridian Health (https://www.hackensackmeridianhealth.org/en/healthier-you/2026/01/26/long-term-use-of-melatonin-may-increase-risk-of-heart-failure)
- Northwestern Medicine HealthBeat (https://www.nm.org/healthbeat/healthy-tips/does-taking-melatonin-raise-your-risk-of-heart-failure)
- American College of Cardiology (https://www.acc.org/latest-in-cardiology/articles/2025/11/03/16/19/mon-melatonin-aha-2025)