Adults with chronic insomnia who took melatonin supplements for at least one year faced a 90% higher risk of developing heart failure over five years compared to non-users, according to a large retrospective analysis presented today at the American Heart Association’s Scientific Sessions 2025 (Abstract MP2306). The same group also showed 3.5 times higher odds of heart failure hospitalization and nearly double the risk of death from any cause. While the study cannot prove causation, it raises urgent safety questions about the world’s most popular over-the-counter sleep aid.
Melatonin—marketed as a “natural” hormone mimic—is widely used for insomnia and jet lag. In the U.S., it is unregulated and available in varying doses; in the U.K., it requires a prescription. “Many assume melatonin is harmless, but our data suggest prolonged use may carry serious cardiovascular consequences,” said lead author Ekenedilichukwu Nnadi, M.D., chief internal medicine resident at SUNY Downstate/Kings County in Brooklyn.
Study Design and Key Findings
Using the TriNetX Global Research Network, researchers analyzed 130,828 adults (average age 55.7; 61% women) diagnosed with insomnia.
- Melatonin group (n=65,414): At least one year of documented use.
- Control group: Matched on 40 factors (age, sex, race, BMI, comorbidities, medications) but no melatonin record.
Primary outcome (5-year incident heart failure):
- Melatonin users: 4.6%
- Non-users: 2.7%
? Adjusted hazard ratio: 1.90 (90% increased risk)
Secondary outcomes:
- Heart failure hospitalization: 19.0% vs. 6.6% (HR 3.48)
- All-cause mortality: 7.8% vs. 4.3% (HR 1.93)
A sensitivity analysis requiring ?2 prescriptions 90 days apart (mostly U.K. data) confirmed an 82% higher heart failure risk.
Expert Reaction
“Melatonin is not FDA-approved for chronic insomnia in the U.S., yet patients take it nightly for years,” said Marie-Pierre St-Onge, Ph.D., chair of the AHA’s 2025 sleep health statement and director of Columbia University’s Center of Excellence for Sleep & Circadian Research. “This study underscores that ‘natural’ does not equal ‘safe’ for long-term use.”
Limitations
- Observational: Cannot prove melatonin causes heart failure.
- OTC use underestimated: U.S. patients buying melatonin without prescription were counted as non-users.
- Missing data: Insomnia severity, depression, or other sleep aids not captured.
- Abstract stage: Not yet peer-reviewed; full manuscript pending.
Clinical Implications
“Physicians should reconsider routine melatonin prescriptions for insomnia,” Nnadi urged. “Cognitive behavioral therapy for insomnia (CBT-I) remains the gold standard.” The AHA recommends 7–9 hours of sleep nightly as part of Life’s Essential 8 for heart health.
