Melatonin may be one of the most popular sleep supplements in the United States, but new research suggests it might not be as harmless as many assume.
A review of electronic health records for more than 130,000 adults with insomnia found that long-term melatonin use, defined as taking it for a year or more, was associated with higher rates of heart failure, hospitalization and death from any cause. The findings, presented at the American Heart Association’s Scientific Sessions 2025, are considered preliminary until published in a peer-reviewed journal.
“Melatonin supplements may not be as harmless as commonly assumed. If our study is confirmed, this could affect how doctors counsel patients about sleep aids,” said Ekenedilichukwu Nnadi, M.D., chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn, New York, and the study’s lead author.
Researchers analyzed data from the TriNetX Global Research Network, an international database of electronic health records. They compared people who had used melatonin for at least a year to those with insomnia who had never been prescribed melatonin. Participants with previous heart failure or prescriptions for other sleep medications were excluded.
Among adults with insomnia, long-term melatonin users had about a 90% higher chance of developing heart failure over five years than those who did not take melatonin (4.6% vs. 2.7%). They were also nearly 3.5 times as likely to be hospitalized for heart failure and nearly twice as likely to die from any cause (7.8% vs. 4.3%).
“Melatonin supplements are widely thought of as a safe and ‘natural’ option to support better sleep, so it was striking to see such consistent and significant increases in serious health outcomes, even after balancing for many other risk factors,” Nnadi said.
Melatonin is a hormone naturally produced by the body to regulate the sleep-wake cycle. Synthetic versions are widely sold over the counter in the U.S., but product strength and purity can vary because supplements are not regulated like prescription drugs.
“I’m surprised that physicians would prescribe melatonin for insomnia and have patients use it for more than 365 days, since melatonin, at least in the U.S., is not indicated for the treatment of insomnia,” said Marie-Pierre St-Onge, Ph.D., C.C.S.H., FAHA, chair of the American Heart Association’s writing group on sleep and cardiometabolic health, who was not involved in the study. “In the U.S., melatonin can be taken as an over-the-counter supplement and people should be aware that it should not be taken chronically without a proper indication.”
The researchers noted several limitations. Because melatonin is available without a prescription in the U.S., many users would not have been captured in medical records. They also lacked information on insomnia severity, psychiatric conditions and other medications that could influence results.
“Worse insomnia, depression or the use of other sleep-enhancing medicines might be linked to both melatonin use and heart risk,” Nnadi said. “Also, while the association we found raises safety concerns about the widely used supplement, our study cannot prove a direct cause-and-effect relationship. This means more research is needed to test melatonin’s safety for the heart.”
Sleep and nutrition are closely connected. The body’s own melatonin production depends on nutrients found in foods such as dairy, nuts, seeds, eggs and some fruits. Eating patterns that support steady blood sugar and avoiding heavy meals close to bedtime may help maintain the body’s natural sleep-wake rhythm without long-term reliance on supplements. Experts emphasize that improving sleep habits and overall diet quality remains the safest first step before turning to pills or over-the-counter aids.
While the findings are not definitive, experts say they highlight the need for caution with long-term supplement use. For people struggling with chronic sleep issues, improving sleep hygiene, such as limiting screens before bed, keeping a regular bedtime, managing stress and supporting the body’s natural rhythm through balanced eating, remains the first-line approach.
This research was presented at the American Heart Association’s Scientific Sessions 2025. St-Onge, who provided independent commentary on the findings, reported no outside research funding or conflicts of interest in her most recent American Heart Association scientific statement on sleep and cardiometabolic health.