Melatonin for Insomnia Linked to Cardiovascular Harm
Key Clinical Summary
- Long-term melatonin use for insomnia was associated with higher risks of heart failure, hospitalization, and death over 5 years.
- Adults taking melatonin had an 89% higher risk of heart failure and a 3-fold higher rate of heart failure–related hospitalization.
- Findings from the American Heart Association’s 2025 Scientific Sessions highlight the need for further study on melatonin’s cardiovascular safety.
A new analysis presented at the American Heart Association’s (AHA) Scientific Sessions 2025 suggests that chronic melatonin use may not be as benign as widely believed. The large multinational study, drawn from the TriNetX Global Research Network, found that adults using melatonin for insomnia faced nearly double the risk of developing heart failure and higher all-cause mortality compared with non-users.
“Melatonin supplements may not be as harmless as commonly assumed,” said Ekenedilichukwu Nnadi, MD, study lead author and chief resident in internal medicine at SUNY Downstate/Kings County Primary Care, Brooklyn, New York. “If our study is confirmed, this could affect how doctors counsel patients about sleep aids.”
Study Findings
In this real-world cohort study of 130,828 adults with chronic insomnia, researchers compared 65,414 melatonin users with an equal number of matched controls who never used melatonin. Participants were adults aged 18 years and older (mean age 55.7 years; 61.4% women). Those with prior heart failure or prescriptions for other sleep medications were excluded.
Over a 5-year follow-up, incident heart failure occurred in 4.6% of melatonin users versus 2.7% of non-users (hazard ratio [HR] 1.89; 95% CI, 1.78–2.00). Heart failure–related hospitalizations were more than tripled among melatonin users (19.0% vs. 6.6%; HR 3.44; 95% CI, 3.32–3.56). All-cause mortality was also significantly higher (7.8% vs. 4.3%; HR 2.09; 95% CI, 1.99–2.18).
Sensitivity analyses—requiring at least 2 melatonin prescriptions 90 days apart—produced consistent results (HR for heart failure, 1.82). Investigators emphasized that the study’s observational design precludes causal inference but reveals a clear association warranting further research.
Clinical Implications
Melatonin is widely used to promote sleep and regulate circadian rhythm. However, this study challenges the long-held assumption that melatonin is a “cardiometabolic-friendly” sleep aid, especially with long-term use. Given that melatonin supplements in the United States are unregulated and vary in dosage and purity, clinicians should discuss the potential cardiovascular implications with patients using it chronically.
The findings underscore the importance of comprehensive medication and supplement reviews during clinical encounters. Physicians should advise patients that melatonin has not been approved for long-term insomnia management and that its cardiovascular effects remain uncertain. Randomized controlled trials are needed to determine whether melatonin contributes directly to adverse cardiac outcomes or reflects underlying health differences among chronic users.
Marie-Pierre St-Onge, PhD, CCSH, FAHA, professor of nutritional medicine and director of the Center of Excellence for Sleep & Circadian Research at Columbia University Irving Medical Center (New York City), said in a news release: “Melatonin should not be taken chronically without proper indication, especially since it is not approved for the treatment of insomnia in the U.S.”
Conclusion
Preliminary findings from this multinational study presented at AHA 2025 suggest that long-term melatonin use in adults with insomnia may increase risks of heart failure and death. Until peer-reviewed data confirm these results, healthcare professionals should counsel patients on responsible melatonin use and consider alternative, evidence-based treatments for chronic insomnia.
References
Nnadi E, Masara M, Offor R, et al. Effect of long-term melatonin supplementation on incidence of heart failure in patients with insomnia. Abstract presented at: American Heart Association’s Scientific Sessions 2025; November 10, 2025; New Orleans. Presentation ID MP2306
