A year or more of melatonin use is tied to a 90% higher risk of heart failure

Adults with insomnia who had used melatonin for a year or longer developed heart failure at nearly twice the rate of those who had not, according to preliminary research the American Heart Association presented at its Scientific Sessions 2025 in New Orleans. Over five years of follow-up, 4.6% of long-term melatonin users developed heart failure compared with 2.7% of matched non-users, a gap the study’s authors describe as roughly a 90% higher relative risk.

The finding comes from 130,828 adults with a chronic insomnia diagnosis, drawn from the TriNetX Global Research Network’s de-identified electronic health records, with 65,414 of them showing at least a year of documented melatonin use matched against an equal-sized comparison group without it.

A Brooklyn chief resident’s read of 130,828 patient records

The American Heart Association’s own newsroom writeup names the lead author as Ekenedilichukwu Nnadi, M.D., a chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn. Nnadi’s team did not run a clinical trial or give anyone melatonin under controlled conditions; the study instead mined existing insurance and hospital records for a pattern, comparing outcomes between insomnia patients who already had a year or more of melatonin use documented and those who did not. “Melatonin supplements may not be as harmless as commonly assumed,” Nnadi said, adding that if the pattern holds up under further, more rigorous study, it could change how doctors counsel insomnia patients about sleep aids.

That framing matters because melatonin sits in a regulatory gray zone unlike prescription sleep medications. It is sold over the counter in the United States as a dietary supplement, not a drug, which means it never went through the kind of large randomized trial that would have caught a cardiovascular signal like this one before millions of people started taking it nightly. Columbia University sleep researcher Marie-Pierre St-Onge, reacting to the findings in Healio’s cardiology coverage, said she was surprised any physician would have patients use melatonin for more than a year at all, since the supplement is not actually indicated for treating insomnia in the country in the first place.

The study’s demographics help explain why the finding drew such a wide audience rather than being dismissed as a niche result. Participants averaged 56 years old, and 61% were women, a profile close to the broader population of adults who report chronic insomnia to a doctor rather than a narrow or unusual subgroup.

The numbers behind the 90%, and where they get shakier

Beyond heart failure diagnoses themselves, the gap widened further on harder outcomes, ScienceDaily’s account of the presentation shows. Hospitalization specifically for heart failure hit 19.0% of long-term melatonin users versus 6.6% of the comparison group, a rate the researchers put at roughly three and a half times higher. All-cause mortality followed the same pattern: 7.8% among melatonin users against 4.3% among non-users, or close to double.

Nnadi’s team also ran a stricter version of the analysis to guard against including patients who took melatonin only occasionally. Limiting the melatonin group to people with at least two separate prescriptions filled 90 or more days apart, a bar meant to isolate genuinely sustained use, still produced an 82% higher heart failure risk, according to figures the American College of Cardiology’s meeting coverage reported alongside the primary 90% figure. That the number moved from 90% to 82% under a tighter definition, rather than collapsing toward zero, is part of why the finding drew attention despite being unpublished, preliminary data.

What a TriNetX study can and cannot prove

Every caveat that applies to observational research applies here without exception. The study cannot establish that melatonin caused the additional heart failure cases, only that the two are statistically associated in this dataset; people who reach for a year of nightly melatonin may differ from people who do not in ways the records cannot capture, including how severe their underlying insomnia already was, what other sleep aids or psychiatric conditions they were managing, and how much unreported over-the-counter melatonin use went undocumented in the comparison group. TriNetX also does not capture where patients lived, so no regional pattern can be drawn from the result.

The supplement industry’s own trade group has pushed back specifically on how the finding traveled once headlines picked it up. The Council for Responsible Nutrition said in response that the research was an unpublished, non-peer-reviewed abstract that cannot establish causation and should not be treated as a reason for melatonin users to panic or stop a supplement their physician recommended without first discussing it. That response does not dispute the raw numbers Nnadi’s team reported; it disputes what those numbers are strong enough to support.

Nnadi’s own paper trail into that debate is direct: the association reported at the American Heart Association’s meeting is one preliminary result from one records database, not a settled finding, and the researchers built the sensitivity check for that exact reason. Whether the pattern survives peer review, a published paper, and replication in a second dataset is now the open question hanging over a supplement sold without a prescription in nearly every U.S. pharmacy and grocery store.

This article was produced with the assistance of AI and reviewed by Morning Overview editors prior to publication.

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