When Sleep Aids Backfire: Melatonin Tied to Heart Risks in Major Study

For millions of people, melatonin has become a nightly ritual, a small pill promising rest in an overstimulated world. But new research presented at the American Heart Association’s Scientific Sessions 2025 suggests that long-term use of this popular supplement may come with serious cardiovascular risks.

Analyzing five years of health records from more than 130,000 adults with chronic insomnia, researchers found that those who used melatonin for a year or more were significantly more likely to develop heart failure, be hospitalized for the condition, or die from any cause than those who did not use it. The findings were unveiled Monday, November 3, in advance of the annual AHA meeting in New Orleans.

Melatonin is a hormone produced naturally by the pineal gland to regulate the body’s sleep-wake cycle. In synthetic form, it is sold over the counter in the United States and widely perceived as a harmless, natural sleep aid. Yet the study’s authors say that perception may not match the data.

“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.

Risks Increase With Long-Term Use

The researchers used the TriNetX Global Research Network, a large international database of de-identified patient records, to identify adults with documented insomnia who had taken melatonin for at least a year. These individuals were matched with a control group of patients who also had insomnia but no record of melatonin use. None had been previously diagnosed with heart failure or prescribed other sleep medications such as benzodiazepines.

Over a five-year follow-up, the differences were striking. About 4.6 percent of long-term melatonin users developed new heart failure, compared to 2.7 percent of non-users, representing roughly a 90 percent higher risk. People who filled at least two melatonin prescriptions 90 days apart—an indication of consistent use—had an 82 percent higher risk.

Hospitalization and mortality rates told a similar story. Melatonin users were 3.5 times more likely to be hospitalized for heart failure and nearly twice as likely to die from any cause during the study period.

These findings remained consistent after accounting for 40 matching factors, including age, sex, body mass index, and other cardiovascular conditions. Still, the authors emphasized that the study could not prove that melatonin directly caused heart problems.

“Worse insomnia, depression or anxiety, 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.”

Experts Urge Caution

Melatonin is not approved by the U.S. Food and Drug Administration for the treatment of chronic insomnia, but its use has surged in recent years. Between 1999 and 2018, U.S. adults’ self-reported melatonin intake quintupled, according to prior research. Some formulations on the market contain vastly inconsistent doses, making it difficult for users to know exactly how much they are taking.

Marie-Pierre St-Onge, Ph.D., chair of the American Heart Association’s 2025 scientific statement on sleep health and a professor of nutritional medicine at Columbia University, said the findings highlight a potential gap in clinical guidance. “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,” St-Onge said. She was not involved in the study.

The authors note several limitations. Because melatonin is available over the counter in the United States but requires a prescription in the United Kingdom, some users may have been misclassified in the data. The database also lacked information about insomnia severity, psychiatric comorbidities, and over-the-counter supplement use. Even so, the association between melatonin and adverse heart outcomes remained robust across analyses.

As millions turn to supplements to manage sleep, the study underscores the need for more rigorous research on their long-term safety. For now, experts advise using non-drug interventions first, such as maintaining regular sleep schedules, reducing light exposure before bedtime, and addressing stress or anxiety that may underlie sleeplessness.

Further studies will be needed to confirm these findings once the research is published in a peer-reviewed journal. But for those who see melatonin as risk-free, the data offer a sobering reminder: sometimes the cure for sleepless nights can come at an unexpected cost.

American Heart Association Scientific Sessions 2025: Abstract MP2306