Melatonin is a hormone that regulates the sleep-wake cycle. It is widely available as an over-the-counter (OTC) medication for managing insomnia. But it remains unregulated in the U.S., leading to variations in purity and dosage. According to a recent study at the American Heart Association’s (AHA) Scientific Sessions 2025 in New Orleans, long-term usage of melatonin supplements may increase the risk of hospitalization, heart failure, and death.
Researchers compared patients with at least 12 months of melatonin use to those with no record of use in their EHRs. Dr. Ekenedilichukwu Nnadi, lead author, internal medicine, Kings County Primary Care/SUNY Downstate, New York, stated, “Melatonin may not be as harmless as commonly assumed.”
The current study utilized the five-year data from the TriNetX Global Research Network, an international database of electronic health records (EHRs). A total of 130,828 adults with chronic insomnia (female = 61.4%, average age = 55.7 years) were included in this study. Approximately 65,414 people had documented long-term use of melatonin, which was defined as at least one year, whereas the remaining people had never taken melatonin in their EHRs. Individuals with a prior heart failure or those taking other sleeping pills like benzodiazepines were excluded. The primary outcome was the incidence of new diagnoses of heart failure. The secondary outcomes were hospitalization codes for death or heart failure among participants.
The primary analysis demonstrated that chronic insomnia adults had nearly 90% higher chance of developing heart failure over 5 years compared to non-melatonin users (4.6% vs 2.7%). When researchers examined individuals who received at least two melatonin prescriptions filled 90 days apart, they showed a similar outcome (82% higher).
Secondary analysis revealed that melatonin users were 3.5 times more likely to be hospitalized for heart failure (19% vs 6.6%) and nearly twice as likely to die from any cause (7.8% vs 4.3%) compared to non-melatonin users.
Dr. Marie-Pierre St-Onge, chair of the AHA’s scientific statement on multidimensional sleep health and cardiometabolic health. She noted that melatonin is not FDA-approved in the U.S. market as a long-term insomnia therapy. She also said that “people should be aware that the overuse of melatonin without medical supervision could have unintended consequences.
The study had several limitations, including missing data on patient locations and unrecorded OTC melatonin usage, potentially misclassifying people in the non-melatonin group. Hospitalization records might include a lack of information on psychiatric disorders, depression, and insomnia severity, as well as varying diagnostic codes. This affects the generalizability and accuracy of the study results.
Dr. Nnadi emphasized that more evidence is needed to confirm whether melatonin directly raises the risk of heart failure or if other contributing factors are involved. The findings underscore the need for evaluating the long-term cardiovascular safety of commonly used sleep aids and promoting appropriate medical oversight in their use.
Reference: American Heart Association. Long-term use of melatonin supplements to support sleep may have negative health effects. Published November 03, 2025. Accessed November 4, 2025. Long-term use of melatonin supplements to support sleep may have negative health effects | American Heart Association
