Adults with chronic insomnia who used melatonin supplements for a year or more showed significantly higher risks of heart failure diagnosis, 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 study analyzed five years of health records for more than 130,000 adults with insomnia, finding that long-term melatonin users had approximately 90% higher incidence of heart failure and nearly double the risk of death compared to matched non-users.
The findings are particularly significant given melatonin's widespread availability and perception as a safe, natural sleep aid. Melatonin is a hormone naturally produced by the pineal gland that regulates sleep-wake cycles, with synthetic versions commonly used to treat insomnia and jet lag. In the United States and many other countries, melatonin is available over-the-counter without prescription, and supplements are not regulated for strength or purity.
Researchers used the TriNetX Global Research Network database to examine electronic health records of 65,414 adults with insomnia who had used melatonin for at least one year, comparing them to 65,414 matched controls who never used melatonin. The analysis excluded people with previous heart failure diagnoses or those taking other sleep medications. The results showed 4.6% of melatonin users developed heart failure over five years compared to 2.7% of non-users. Hospitalization rates for heart failure were even more striking, with melatonin users nearly 3.5 times more likely to be hospitalized (19.0% vs. 6.6%).
"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 association remained significant even when researchers required participants to have filled at least two melatonin prescriptions at least 90 days apart, with an 82% higher heart failure risk in this subgroup.
The study's implications are substantial given that heart failure affects approximately 6.7 million adults in the U.S. according to the American Heart Association's 2025 Heart Disease and Stroke Statistics. Melatonin's popularity as an unregulated supplement means millions of people may be using it without medical supervision, potentially unaware of possible cardiovascular risks. Dr. Marie-Pierre St-Onge, chair of the writing group for the American Heart Association's scientific statement on sleep health, noted surprise that physicians would prescribe melatonin for insomnia long-term since it's not indicated for chronic insomnia treatment in the U.S.
However, researchers caution that the study has limitations and cannot prove causation. The database included countries with different melatonin regulations, and over-the-counter users in the U.S. would have been classified as non-users since their use wouldn't appear in prescription records. The researchers also lacked information on insomnia severity and other psychiatric conditions that might influence both melatonin use and heart risk. The findings are considered preliminary until published in a peer-reviewed journal, as abstracts presented at American Heart Association scientific meetings are not peer-reviewed.
Despite these limitations, the consistent association across multiple outcomes suggests the need for more rigorous investigation into melatonin's cardiovascular safety. As Dr. 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 study highlights the importance of considering potential risks even for supplements generally regarded as safe, particularly when used long-term for chronic conditions like insomnia.
