Long-Term Melatonin Use Linked to 90% Higher
A large preliminary study found adults with chronic insomnia who used melatonin long-term had a roughly 90% higher risk of developing heart failure over
Adults with chronic insomnia who used melatonin long-term had a roughly 90% higher risk of developing heart failure over five years, according to preliminary research presented at the American Heart Association's Scientific Sessions 2025. The findings, which do not prove causation, challenge common assumptions about the safety of the widely used sleep aid.
Lead author Dr. Ekenedilichukwu Nnadi, chief resident in internal medicine at SUNY Downstate/Kings County Primary Care, stated the results could affect how doctors counsel patients. "Melatonin supplements may not be as harmless as commonly assumed," Nnadi said.
Study Design and Limitations
Researchers used data from the TriNetX Global Research Network, examining five years of de-identified electronic health records for 130,828 adults with insomnia. The average age was 55.7 years, and 61.4% were women. Participants were divided into two groups: 65,414 people with at least one year of documented melatonin use, and a matched control group with no record of melatonin use.
The study had significant limitations. Melatonin use was identified only from medical records, meaning over-the-counter users in countries like the U.S. could have been misclassified. Researchers also lacked data on insomnia severity and other psychiatric conditions, which could influence both melatonin use and cardiovascular risk independently.
Key Findings on Heart Failure and Mortality
The analysis revealed substantial differences in health outcomes between the groups over the five-year period.
| Outcome | Melatonin Group | Non-Melatonin Group | Increased Risk |
|---|---|---|---|
| Heart Failure Diagnosis | 4.6% | 2.7% | ~90% higher |
| Hospitalization for Heart Failure | 19.0% | 6.6% | Nearly 3.5 times as likely |
| Death from Any Cause | 7.8% | 4.3% | Nearly twice as high |
When researchers performed a stricter analysis limited to people who had filled at least two melatonin prescriptions at least 90 days apart, the association with heart failure remained, showing an 82% higher risk.
Expert Reaction and Regulatory Context
The results drew concern from sleep researcher Dr. Marie-Pierre St-Onge of Columbia University Irving Medical Center, who was not involved in the study. St-Onge noted she was surprised physicians would prescribe melatonin for insomnia for over a year, as it is not indicated for that treatment in the U.S. "People should be aware that it should not be taken chronically without a proper indication," she said.
Regulatory differences complicate the findings. In the United Kingdom, melatonin requires a prescription, while in the United States it is an unregulated over-the-counter supplement. The study's de-identified data meant researchers could not account for these geographic variations.
Dr. Nnadi emphasized the need for more research. "Our study cannot prove a direct cause-and-effect relationship," he said. The final data point from the source was that control group participants were matched to the melatonin group using 40 factors, including demographic characteristics and existing health conditions.
