Long-Term Melatonin Use Linked to Increased Heart Failure Risk in Insomnia Patients, Study Finds

A preliminary study to be presented at the American Heart Association's Scientific Sessions 2025 has found that long-term use of melatonin supplements was associated with a higher risk of heart failure diagnosis, heart failure hospitalization, and death from any cause in adults with chronic insomnia. The research, which analyzed five years of health records for more than 130,000 adults, raises significant safety concerns about melatonin, a hormone supplement widely promoted as a safe sleep aid. Researchers classified participants who had used melatonin for at least one year as the "melatonin group" and compared them to matched peers who had never used melatonin.

The main analysis revealed that adults with insomnia who used melatonin long-term had about a 90% higher chance of developing heart failure over five years compared to non-users (4.6% vs. 2.7%, respectively). A secondary analysis showed even more striking results: participants taking melatonin were nearly 3.5 times as likely to be hospitalized for heart failure (19.0% vs. 6.6%) and nearly twice as likely to die from any cause (7.8% vs. 4.3%) than those in the non-melatonin group. "Melatonin supplements may not be as harmless as commonly assumed," said Dr. Ekenedilichukwu Nnadi, lead author of the study and chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn, New York. "If our study is confirmed, this could affect how doctors counsel patients about sleep aids."

The findings are particularly concerning given that melatonin supplements are widely available over-the-counter in many countries, including the United States, where they are not regulated for strength or purity. The study used data from the TriNetX Global Research Network, examining electronic health records of 130,828 adults with an average age of 55.7 years, 61.4% of whom were women. Researchers matched the melatonin and control groups on 40 factors including demographic information, health conditions, and medications. All participants had been diagnosed with insomnia, and those with pre-existing heart failure or prescriptions for other sleep medications were excluded from the analysis.

Marie-Pierre St-Onge, Ph.D., chair of the writing group for the American Heart Association's 2025 scientific statement on sleep health, expressed surprise at the findings. "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 St-Onge, who was not involved in the study. She emphasized that people should be aware that melatonin "should not be taken chronically without a proper indication." The study has several limitations, including the fact that it cannot prove a cause-and-effect relationship between melatonin use and increased health risks.

The database included countries that require prescriptions for melatonin (such as the United Kingdom) and countries that don't (such as the United States), but patient locations were not available in the de-identified data. This means that people taking melatonin as an over-the-counter supplement in the U.S. would have been classified in the non-melatonin group, potentially affecting the accuracy of the results. Researchers also lacked information on insomnia severity and the presence of other psychiatric disorders, which could influence both melatonin use and heart risk. "Worse insomnia, depression/anxiety or the use of other sleep-enhancing medicines might be linked to both melatonin use and heart risk," Nnadi explained. The findings are considered preliminary until published as a full manuscript in a peer-reviewed scientific journal, and the researchers emphasize that more research is needed to definitively assess melatonin's cardiovascular safety.