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

Adults with chronic insomnia who used melatonin supplements for a year or more showed significantly higher risks of heart failure diagnosis, heart failure hospitalization, and death from any cause compared to those who never used the supplement, according to research to be presented at the American Heart Association's Scientific Sessions 2025. The preliminary study analyzed five years of electronic health records for 130,828 adults with insomnia, finding that long-term melatonin users had approximately 90% higher incidence of heart failure compared to matched non-users.

The study, which used data from the TriNetX Global Research Network, revealed that 4.6% of melatonin users developed heart failure over five years compared to 2.7% of non-users. Even more concerning were the secondary findings: melatonin users were nearly 3.5 times more 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%) during the study period. These results remained consistent even when researchers conducted a sensitivity analysis requiring participants to have filled at least two melatonin prescriptions at least 90 days apart, which showed an 82% higher heart failure risk.

Lead author Ekenedilichukwu Nnadi, M.D., expressed surprise at the findings, noting that "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." The study raises important questions about the cardiovascular safety of melatonin, particularly given its widespread availability as an over-the-counter supplement in many countries including the United States, where supplements are not regulated for strength or purity.

The implications of these findings are significant for the millions of adults who use melatonin for sleep support. According to the American Heart Association's 2025 Heart Disease and Stroke Statistics, heart failure affects 6.7 million adults in the U.S. alone. Marie-Pierre St-Onge, Ph.D., who chairs the writing group for the American Heart Association's scientific statement on sleep health but was not involved in this study, emphasized that "melatonin, at least in the U.S., is not indicated for the treatment of insomnia" and cautioned against chronic use without proper medical indication.

Researchers note several limitations to the study, including the inability to prove cause-and-effect relationships and challenges in accurately capturing over-the-counter melatonin use in countries where prescriptions aren't required. The study also lacked information on insomnia severity and presence of other psychiatric disorders that might influence both melatonin use and heart risk. Despite these limitations, the consistent association between long-term melatonin use and adverse cardiovascular outcomes warrants further investigation into the supplement's safety profile, particularly for the growing number of consumers who rely on it for chronic sleep issues.