A preliminary analysis presented at the American Heart Association’s Scientific Sessions 2025 found that adults with chronic insomnia who used melatonin for a year or longer had higher rates of new heart failure, heart‑failure hospitalization and all‑cause death over five years than matched nonusers. The observational findings do not prove causation and are not yet peer‑reviewed.
Researchers led by Ekenedilichukwu Nnadi, M.D., chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn, New York, presented the results at the American Heart Association’s annual meeting in New Orleans, held Nov. 7–10, 2025.
Study design and cohort
- Data source: TriNetX Global Research Network, an international database of de‑identified electronic health records.
- Population: 130,828 adults with insomnia (average age 55.7; 61.4% women).
- Exposure groups: 65,414 with documented melatonin use for at least 12 months vs. a matched control group with no recorded melatonin use. Matching balanced 40 variables, including demographics, cardiovascular and neurologic conditions, relevant medications, blood pressure and body mass index.
- Key exclusions: prior heart failure and prescriptions for other sleep medicines such as benzodiazepines.
Key results over five years
- Incident heart failure: about 90% higher among long‑term melatonin users (4.6%) vs. nonusers (2.7%).
- Sensitivity analysis: among people with at least two melatonin prescriptions 90 days apart, the risk remained elevated (about 82% higher).
- Secondary outcomes: heart‑failure hospitalization was nearly 3.5 times more likely (19.0% vs. 6.6%), and all‑cause mortality was nearly twice as likely (7.8% vs. 4.3%) in long‑term users.
What researchers and experts say
- “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,” Nnadi said.
- Marie‑Pierre St‑Onge, Ph.D., a Columbia University sleep researcher who was not involved in the study, said she was surprised to see chronic prescribing. She noted that in the United States melatonin is an over‑the‑counter supplement and is not indicated as a treatment for insomnia, cautioning against chronic use without a proper indication.
Important caveats
- The analysis is observational and based on health‑record entries; it cannot determine causality.
- Because many countries sell melatonin over the counter, people who used non‑prescription products may have been misclassified as nonusers.
- Dose information and patient location were not consistently available, and the dataset lacked detail on insomnia severity and certain psychiatric conditions.
Context
Melatonin is a hormone that helps regulate the sleep‑wake cycle and is widely used for insomnia and jet lag. In the U.S., it is sold over the counter as a dietary supplement, and products may vary in strength and purity. The American Heart Association characterized these findings as preliminary until published in a peer‑reviewed journal.
