Long-Term Melatonin Use Tied to Nearly Double the Death Risk and Higher Heart Failure Rates

A preliminary study set to be presented at the American Heart Association’s Scientific Sessions 2025 suggests that long-term use (one year or more) of melatonin supplements may be associated with a significantly higher risk of heart failure diagnosis, heart failure hospitalization, and death from any cause in adults with chronic insomnia.

Key Findings and Statistics

Researchers analyzed five years of electronic health records from the TriNetX Global Research Network for over 130,000 adults (average age 55.7 years; 61.4% women) with chronic insomnia.

• Heart Failure Diagnosis: Adults whose records indicated long-term melatonin use (12 months or more) had approximately a 90\% higher chance of incident heart failure over five years compared with matched non-users ($4.6%$ vs. $2.7%$).
• Heart Failure Hospitalization: Participants taking melatonin were nearly 3.5 times as likely to be hospitalized for heart failure ($19.0%$ vs. $6.6%$) compared to those not taking it.
• Death from Any Cause: The melatonin group was nearly twice as likely to die from any cause ($7.8%$ vs. $4.3%$) over the five-year period.

Study Design and Context

The study's lead author, Ekenedilichukwu Nnadi, M.D., noted that melatonin supplements are often perceived as harmless, but long-term cardiovascular safety data is lacking.

• Melatonin Group: Included 65,414 participants who had been prescribed melatonin and used it for at least a year, identified through their electronic health records.
• Non-Melatonin Group (Control): A matched group of participants with insomnia who never had melatonin recorded in their health records.
• Matching: The groups were matched on 40 factors, including age, sex, race/ethnicity, existing heart and nervous system diseases, and blood pressure/BMI.

Melatonin is a naturally occurring hormone regulating the sleep-wake cycle and is widely available as an over-the-counter supplement in countries like the U.S. and by prescription in others, such as the U.K. The study authors acknowledge that a limitation is the lack of over-the-counter use data, as those users would have been placed in the non-melatonin group, potentially underrepresenting melatonin's true usage.

The researchers emphasize that this is an association, not a cause-and-effect relationship, and more research is needed to confirm melatonin's safety for the heart.

Disclaimer: This information is for educational and informational purposes only and is not a substitute for professional medical advice. Always consult with a doctor/healthcare professional regarding your specific health concerns.