Adults who took melatonin supplements for chronic insomnia over the long term had a substantially higher rate of heart failure and death over five years than matched insomnia patients who did not take the supplement, according to a large observational study presented at the American Heart Association's Scientific Sessions and newly detailed in a peer-review-pending research report.
The analysis, led by Ekenedilichukwu Nnadi, a chief medicine resident at SUNY Downstate/Kings County in Brooklyn, drew on de-identified health records from the TriNetX Global Research Network, covering 130,828 adults diagnosed with chronic insomnia. Of those, 65,414 had documented melatonin use for a year or more; researchers matched them against non-users on more than 40 baseline factors, including age, existing heart and metabolic conditions, and other medications, then tracked outcomes over five years.
The numbers
Melatonin users developed heart failure at nearly twice the rate of matched non-users — 4.6% versus 2.7%, an increase researchers characterized as roughly 90% higher risk. They were also 3.5 times more likely to be hospitalized for heart failure (19.0% versus 6.6% among those who did develop it) and had a substantially higher five-year death rate, 7.8% versus 4.3%. A sensitivity analysis restricted to patients with at least two separate melatonin prescriptions 90 or more days apart still found an 82% higher heart failure risk, suggesting the association wasn't driven by one-off or misclassified use.
"Melatonin supplements may not be as harmless as commonly assumed," Nnadi said. "If our study is confirmed, this could affect how doctors counsel patients about sleep aids."
"Melatonin is not indicated for the treatment of insomnia in the U.S. and should not be taken chronically without a proper indication."
Marie-Pierre St-Onge, Columbia University Irving Medical Center
Melatonin is sold over the counter in the United States as a dietary supplement rather than a regulated sleep medication, and its long-term cardiovascular effects have received little rigorous study despite widespread use — Americans' melatonin consumption has risen sharply over the past two decades. St-Onge, an AHA volunteer expert who was not involved in the research, noted the hormone is approved as a prescription insomnia treatment in parts of Europe but carries no such indication domestically, which may contribute to unsupervised long-term use at doses well above what the body naturally produces.
The study's authors and outside reviewers were emphatic that the findings show an association, not proof that melatonin causes heart failure. The research remains a conference abstract that has not completed peer review, and the retrospective design could not account for insomnia severity, undiagnosed psychiatric conditions, or over-the-counter melatonin purchases that never appeared in a patient's medical record — all of which could independently affect cardiovascular risk in ways the matching process didn't capture.
Nnadi's team said the next step is publishing the full analysis in a peer-reviewed journal and pursuing prospective studies that could establish whether the relationship is causal. In the meantime, the researchers and the AHA are urging people who use melatonin nightly for extended periods to discuss it with a physician rather than treating it as a risk-free habit.
