Study Finds Long-Term Melatonin Use Links to Increased Heart Failure Risk

A new study has found a potential association between long-term use of melatonin supplements and a heightened risk of heart failure, heart failure-related hospitalizations, and death in adults with chronic insomnia. The findings will be presented at the American Heart Association's Scientific Sessions 2025, held from November 7-10 in New Orleans. This annual gathering aims to showcase the latest advancements in cardiovascular science and clinical research.

Melatonin, a hormone naturally produced by the pineal gland to regulate the sleep-wake cycle, is commonly used as an over-the-counter sleep aid for insomnia and jet lag. Synthetic versions of the hormone are widely available in the U.S., where they are unregulated, leading to variability in dosage and purity between brands. However, despite its popularity, experts say there is limited data on the long-term cardiovascular safety of melatonin supplements, prompting this investigation.

Research Methods and Findings

The study used the TriNetX Global Research Network to analyze five years of electronic health data for over 130,000 adults (average age 55.7 years, 61.4% women) diagnosed with insomnia. Participants were divided into two groups: those who had used melatonin for at least a year (referred to as the "melatonin group") and those who had no record of melatonin usage ("non-melatonin group"). The groups were matched on 40 factors, including demographics, health conditions, and medications, to ensure balanced comparisons. Individuals with prior diagnoses of heart failure or prescriptions for other sleep medications were excluded from the analysis.

Key findings include:

• Adults in the melatonin group were 90% more likely to develop heart failure over a five-year period compared to the non-melatonin group (4.6% vs. 2.7%).
• In a secondary analysis requiring participants to have filled at least two melatonin prescriptions more than 90 days apart, the risk of heart failure was similarly elevated, increasing by 82%.
• Melatonin users were nearly 3.5 times more likely to be hospitalized for heart failure (19.0% vs. 6.6%) and had nearly double the risk of death from any cause (7.8% vs. 4.3%) compared to non-users.

"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", 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.

Expert Perspectives

The study's findings have raised questions about the widespread use of melatonin supplements, especially over long periods. "Melatonin supplements may not be as harmless as commonly assumed. If our study is confirmed, this could affect how doctors counsel patients about sleep aids", said Dr. Nnadi.

Marie-Pierre St-Onge, Ph.D., chair of the writing group for the American Heart Association's 2025 scientific statement on sleep health, emphasized the importance of caution when using melatonin. "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. In the U.S., melatonin can be taken as an over-the-counter supplement and people should be aware that it should not be taken chronically without a proper indication", said St-Onge, who is also a professor of nutritional medicine at Columbia University Irving Medical Center.

Study Limitations

The researchers acknowledged several limitations. Because melatonin use in the study was identified through electronic health records, individuals in the U.S. or other countries where melatonin is available without a prescription may have been misclassified in the non-melatonin group. Additionally, the study could not account for the severity of insomnia or the presence of other psychiatric conditions, which may also contribute to cardiovascular risks.

"Worse insomnia, depression/anxiety or the use of other sleep-enhancing medicines might be linked to both melatonin use and heart risk", Dr. Nnadi noted. He further clarified that while the study suggests a concerning association, it does not prove a direct cause-and-effect relationship between melatonin use and adverse health outcomes. "This means more research is needed to test melatonin's safety for the heart", he added.

Conclusion

As the use of melatonin supplements continues to grow, these findings highlight the need for further investigation into their long-term safety and potential cardiovascular impacts. Although melatonin is often marketed as a harmless sleep aid, this study underscores the importance of consulting healthcare professionals before starting or continuing its use for extended periods, particularly for individuals with chronic insomnia or other underlying health conditions. The research serves as a call for increased awareness and caution regarding prolonged reliance on over-the-counter sleep aids.

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