Long-Term Melatonin Use Associated with Increased Heart Failure Risk in Insomnia Patients

A preliminary study examining health records of more than 130,000 adults with chronic insomnia revealed that long-term use of melatonin supplements was associated with substantially increased risks of heart failure diagnosis, heart failure hospitalization, and death from any cause. The research, to be presented at the American Heart Association's Scientific Sessions 2025, raises important safety concerns about the widely available sleep aid that many consumers assume is completely harmless.

Researchers analyzed five years of electronic health records from the TriNetX Global Research Network, comparing 65,414 adults who had used melatonin for at least one year with a matched control group of insomnia patients who had never used melatonin. The study excluded individuals with pre-existing heart failure or those using other sleep medications. The findings showed that participants in the melatonin group had approximately 90% higher likelihood of developing heart failure compared to non-users (4.6% versus 2.7%, respectively).

Secondary analyses revealed even more striking results. Melatonin users were nearly 3.5 times more likely to be hospitalized for heart failure (19.0% versus 6.6%) and nearly twice as likely to die from any cause during the five-year study period (7.8% versus 4.3%). These associations remained consistent even when researchers conducted sensitivity analyses requiring participants to have filled at least two melatonin prescriptions at least 90 days apart, which showed an 82% increased risk of heart failure.

Lead author Ekenedilichukwu Nnadi, M.D., chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn, New York, expressed surprise at the findings. "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 stated.

The study's implications are particularly significant given melatonin's widespread availability and perception as a benign supplement. In the United States, melatonin is available over-the-counter without prescription and is not regulated by the Food and Drug Administration, meaning supplement strength and purity can vary considerably between brands. According to the American Heart Association's 2025 Heart Disease and Stroke Statistics, heart failure affects 6.7 million adults in the U.S. and occurs when the heart cannot pump enough oxygen-rich blood to meet the body's needs.

Marie-Pierre St-Onge, Ph.D., chair of the writing group for the American Heart Association's 2025 scientific statement on sleep health, who was not involved in the study, noted concerns about chronic melatonin use. "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. "People should be aware that it should not be taken chronically without a proper indication."

The study has several limitations that researchers acknowledge. The database included countries with different melatonin regulations, and patient locations were not available in the de-identified data. This means that individuals taking over-the-counter melatonin in countries like the U.S. would have been classified in the non-melatonin group, potentially skewing results. Researchers also lacked information on insomnia severity and presence of other psychiatric disorders that might influence both melatonin use and cardiovascular risk.

Importantly, the study cannot prove causation, only association. As Nnadi explained, "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." The findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal, as abstracts presented at American Heart Association scientific meetings are not peer-reviewed.

For the millions of Americans who use melatonin supplements regularly, these findings suggest the need for greater caution and medical consultation regarding long-term use. The research highlights the importance of understanding that "natural" supplements are not necessarily risk-free and that proper medical guidance should be sought for chronic sleep issues rather than relying on self-medication with over-the-counter products.