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

A preliminary study analyzing health records of more than 130,000 adults with insomnia revealed that long-term melatonin supplement use was associated with significantly increased risks of heart failure diagnosis, hospitalization, and death from any cause. The research, to be presented at the American Heart Association's Scientific Sessions 2025, found that adults who used melatonin for at least one year had approximately 90% higher chance of developing heart failure over five years compared to matched peers who never used the supplement.

Researchers examined electronic health records from the TriNetX Global Research Network, focusing on adults with chronic insomnia who had documented melatonin use for more than a year. The study population included 65,414 participants who had been prescribed melatonin at least once and reported taking it for at least a year, matched with a control group of similar individuals who had never been prescribed melatonin. The analysis excluded people with previous heart failure diagnoses or those prescribed other sleep medications.

The primary findings showed that 4.6% of melatonin users developed heart failure compared to 2.7% of non-users, representing a 90% increased risk. When researchers conducted a sensitivity analysis requiring at least two melatonin prescriptions filled at least 90 days apart, they found a similar 82% increased risk. Secondary analyses revealed even more striking results: 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%) over the five-year study period.

According to lead author Ekenedilichukwu Nnadi, M.D., chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn, New York, the findings challenge common assumptions about melatonin safety. Melatonin supplements are widely promoted as safe sleep aids, but data demonstrating their long-term cardiovascular safety have been lacking. The hormone, naturally produced by the pineal gland to regulate sleep-wake cycles, is available in chemically identical synthetic versions that are widely available over-the-counter in many countries including the United States.

The study has several important limitations that researchers acknowledge. The database included countries with different melatonin regulations—some requiring prescriptions like the United Kingdom and others allowing over-the-counter purchase like the United States. Since melatonin use was based only on medication entries in electronic health records, people taking over-the-counter supplements in countries without prescription requirements 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 heart risk.

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 that physicians would prescribe melatonin for insomnia long-term, noting that in the United States, melatonin is not indicated for insomnia treatment and should not be taken chronically without proper indication. The association found in this study cannot prove cause-and-effect, and researchers emphasize that more investigation is needed to properly assess melatonin's cardiovascular safety.

According to the American Heart Association's 2025 Heart Disease and Stroke Statistics, heart failure affects 6.7 million adults in the United States and occurs when the heart cannot pump enough oxygen-rich blood to properly supply the body's organs. The study findings raise important questions about the cardiovascular safety of long-term melatonin use, particularly given its widespread availability and perception as a natural and harmless sleep aid.