Long-term melatonin use has been linked to a 90% higher risk of heart failure over five years among adults with chronic insomnia, according to preliminary research presented at the American Heart Association’s Scientific Sessions. Investigators analyzed health records for nearly 131,000 adults, noting associations with increased hospitalizations and mortality.
The finding challenges the widespread public assumption that over-the-counter sleep supplements are entirely benign when consumed over extended periods. While the observational data establishes an association rather than direct causation, clinicians are urging a re-evaluation of how chronic insomnia is managed.
In Plain English: The Clinical Takeaway
- Association, Not Proof: The study highlights a strong statistical link between long-term melatonin use and heart failure, but it does not prove that melatonin directly causes cardiac damage.
- Duration Matters: The elevated risk was observed in individuals tracking consistent melatonin supplement use for a year or longer, distinguishing routine short-term use for jet lag.
- Underlying Factors: Severe baseline insomnia, undiagnosed cardiovascular strain, or co-occurring mental health conditions may heavily influence these statistical correlations.
Unpacking the Clinical Data: What the Research Shows
Insomnia affects roughly 16% of the global population, prompting millions to seek interventions ranging from behavioral therapies to over-the-counter hormone supplements. Melatonin is a hormone naturally synthesized by the pineal gland to regulate circadian rhythms in response to darkness. However, synthetic formulations are readily accessible without a prescription in countries like the United States, where over-the-counter supplements do not require government approval to ensure quality and consistency.
To investigate the longitudinal impacts of these compounds, researchers evaluated electronic health records via the TriNetX Global Research Network. The cohort comprised approximately 131,000 adults with an average age of 56, all diagnosed with chronic insomnia. About 65,000 participants had documented prescriptions or records indicating melatonin use for at least one year, while the control group had no history of melatonin use.
The statistical signals emerging from the data are stark. Participants who utilized melatonin for more than 12 months experienced a 90% increase in their five-year heart failure risk compared to non-users. Individuals who filled at least two distinct melatonin prescriptions spaced 90 days apart faced an 82% greater chance of developing the condition. Furthermore, the melatonin cohort exhibited roughly 3.5 times the likelihood of hospitalization for heart failure and double the all-cause mortality rate over the five-year follow-up period.
| Exposure Metric | Participant Cohort Size | Observed Risk Delta vs. Non-Users |
|---|---|---|
| Melatonin Use > 1 Year | ~65,000 | 90% higher 5-year heart failure risk |
| Filled ≥ 2 Prescriptions (>90 days apart) | Subset of users | 82% greater chance of developing heart failure |
| Hospitalization Rates | ~65,000 | 3.5x higher likelihood of heart failure hospitalization |
| All-Cause Mortality | ~65,000 | 2x higher risk of death from any cause |
Mechanistic Hypotheses and Expert Perspectives
Because the investigation is an observational study utilizing retrospective health records, establishing a definitive biological mechanism remains an active challenge for cardiologists and pharmacologists. During a press release statement, the study’s lead author, Ekenedilichukwu Nnadi, MD—who serves as chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in New York—highlighted the clinical significance by stating: “Melatonin supplements are widely thought of as a safe and ‘natural’ option to support better sleep, so it was striking to see such consistent and significant increases in serious health outcomes, even after balancing for many other risk factors.”
Pointing out crucial confounding factors, Nnadi explained, “Worse insomnia, depression/anxiety or the use of other sleep-enhancing medicines might be linked to both melatonin use and heart risk. Also, while the association we found raises safety concerns about the widely used supplement, our study cannot prove a direct cause-and-effect relationship. This means more research is needed to test melatonin’s safety for the heart.”
Offering an independent perspective, Kanika P Mody, MD, a cardiologist based at the Advanced Heart Failure & Pulmonary Hypertension Center at Hackensack University Medical Center in New Jersey who did not participate in the research, immediately voiced worries about public perception.
“Melatonin is widely regarded by both the public and many in the medical community as a safe, ‘natural’ sleep aid, so it was striking to see a potential link to serious health issues like heart failure,” Mody stated. Expanding on her thoughts, Mody remarked, “While this study shows an association and not a direct cause-and-effect relationship, the consistency and significance of the increased risks are noteworthy. It’s particularly unexpected given that some previous research has suggested potential cardiovascular benefits of melatonin, such as its antioxidant properties.” Pointing out how the data challenges standard practices, she noted: “This new research challenges the common practice of long-term melatonin use for chronic insomnia, for which it is not an indicated treatment in the United States. These findings prompt a re-evaluation of how we counsel patients about sleep aids and underscore the importance of discussing long-term supplement use.”
Another prominent hypothesis raised by specialists is that severe chronic insomnia itself acts as a masked driver of cardiovascular pathology. In these scenarios, long-term supplement reliance may serve as a proxy indicator for severe, uncontrolled sleep pathology rather than serving as the isolated toxic agent.
Contraindications & When to Consult a Doctor
Future Outlook and Research Trajectory
As these findings are currently confined to preliminary research abstracts presented at scientific congresses, the medical community awaits full peer-reviewed manuscript publication to scrutinize adjustments for potential confounders. Until prospective clinical trials validate or refute these cardiovascular safety signals, regulatory bodies and practicing physicians face the task of realigning public health messaging around dietary supplements. The prevailing medical consensus emphasizes that while short-term supplementation remains a viable tool for acute circadian disruption like jet lag, chronic insomnia demands a diagnostic approach that looks far beyond over-the-counter fixes.
References
- American Heart Association. (2025). Scientific Sessions 2025 Abstract Releases: Long-term use of melatonin supplements to support sleep. AHA Newsroom.
- TriNetX Global Research Network. Electronic Health Records Database Analysis on Insomnia and Melatonin Outcomes.
Disclaimer: This article is intended for informational and educational purposes only and does not constitute medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider regarding any questions about prescription medications, dietary supplements, or medical conditions.
