A preliminary study supported by the American Heart Association found that, compared to a population of non-melatonin-users, adults with insomnia who had been using melatonin for at least a year were more likely to be diagnosed with heart failure, hospitalized for heart failure, or to die from any cause.

The unpublished findings, which will be presented at AHA’s Scientific Sessions 2025 this month, were based on five years of health records from more than 130,000 adults who had used melatonin for at least a year. Melatonin use was monitored via prescriptions on electronic health records (melatonin is a prescription product in the U.K.).

“Melatonin supplements may not be as harmless as commonly assumed. If our study is confirmed, this could affect how doctors counsel patients about sleep aids,” said Ekenedilichukwu Nnadi, MD, lead author of the study and chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn, New York.

According to AHA, long-term cardiovascular safety data are lacking on melatonin, prompting researchers to investigate potential impacts on heart health. The organization also stated in its reporting that “over-the-counter supplements are not regulated,” and products can vary in strength, purity, and quality as a result.

The researchers used the TriNetX Global Research Network Database to review five years of health records for adults with chronic insomnia, to compare melatonin users and non-users. People were excluded from the study if they had previously been diagnosed with heart failure or were prescribed sleep medications.

Key Findings

Among over 130,000 adults with insomnia, those who had been prescribed melatonin for a year or more had a 90% higher chance of incident heart failure over 5 years, compared to matched non-users (4.6% vs. 2.7%, respectively). Similarly, they were 82% more likely to have heart failure when they had two melatonin prescriptions filled at least 90 days apart (melatonin is a prescription product in the United Kingdom).

Participants taking prescription melatonin were 3.5 times as likely to be hospitalized for heart failure compared to non-users (19% versus 6.6% respectively), and were twice as likely to die from any cause than those in the non-melatonin group (7.8% versus 4.3%).

The study had several limitations, the authors noted. For instance, the database includes participants from the U.S. and the U.K., and only monitored melatonin use in the form of prescription products. Therefore, subjects taking melatonin as an over-the-counter product were categorized as non-users of melatonin.

Additionally, the range of diagnostic codes used by hospitals may not always include the code for a new diagnosis of heart failure, the researchers noted. Lastly, information on the severity of insomnia or the presence of other psychiatric disorders was not acquired.

“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,” Nnadi said. “Worse, insomnia, depression/anxiety, or the use of other sleep enhancing medicines may 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.”

”I’m surprised that physicians would prescribe melatonin for insomnia and have patients use it for more than 365 days, since melatonin, at least in the U.S., is not indicated for the treatment of insomnia. In the U.S., melatonin can be taken as an over-the-counter supplement and people should be aware that it should not be taken chronically without a proper indication,” said Marie-Pierre St-Onge, PhD, chair of the writing group for the American Heart Association’s 2025 scientific statement, Multidimensional Sleep Health: Definitions and Implications for Cardiometabolic Health.

Early Findings Warrant ‘Caution and Context’

The Natural Products Association (NPA) responded to AHA’s report, noting that in the U.S., melatonin is a dietary supplement and, by law, is not intended to treat, cure, or prevent any disease, including chronic insomnia.

“We recommend that consumers with chronic sleeplessness and other chronic diseases always consult with their physicians to properly diagnose and treat their medical conditions,” said Daniel Fabricant, PhD, president and CEO of NPA. “The preliminary study examined whether melatonin use alters the risk of heart failure in chronic insomnia patients, which is not the supplement industry’s target population. Furthermore, the established literature demonstrates that short-term use of melatonin is safe. NPA agrees that consumers should not take melatonin supplements for chronic insomnia without a proper indication and in close consultation with a medical professional.”

NPA also noted that supplements are regulated, and subject to current good manufacturing practices (cGMPs) which confirm identity, purity, strength, composition, and absence of harmful adulterants, enforced via inspections from the U.S. Food and Drug Administration.  

The fact that non-prescription melatonin users fell into the non-melatonin arm of the observational study raised serious questions about the quality of the data, NPA noted. “The study did not focus on the occasional use of melatonin for sleeplessness or other conditions, or FDA-regulated supplements containing versions of the hormone.”

Fabricant noted that NPA supports research on long-term melatonin use, but that these findings can’t be extrapolated to healthy people. Supplements, per the Dietary Supplements Health and Education Act (DSHEA), are distinctly intended for use by healthy people, and not to treat, cure, or mitigate any disease. “We do not promote the use of melatonin supplements to treat chronic insomnia or any other disease,” he said. “NPA and its members take very seriously the industry’s responsibility to manufacture quality products on cGMP requirements that FDA enforces.”

The Council for Responsible Nutrition (CRN) also noted that early findings such as these should be interpreted with “caution and context,” and chronic insomnia itself may be a contributing factor to heart health outcomes. “Quality sleep is critical for cardiovascular health, and individuals who sleep poorly tend to have higher heart rates and blood pressure and experience more cardiovascular events. Therefore, these findings are unlikely to apply to healthy adults who use melatonin dietary supplements occasionally for sleep support.”

CRN also emphasized that melatonin has no indications for chronic insomnia or sleep disorders. The association’s voluntary labeling guidelines for melatonin adopted last year required upper dosage levels and include advisory statements such as “for occasional and/or intermittent use only” and “consult a healthcare professional if you are experiencing long-term sleep difficulties.”

CRN also noted that the study’s limitations may have “distorted” the apparent association. Further, decades of widespread short-term use and safety studies indicate low-dose, short-term supplementation is safe for healthy adults, the association said.

“CRN supports ongoing scientific research to better understand long-term use patterns of all dietary supplements and welcomes rigorous, peer-reviewed investigations that contribute to evidence-based guidance,” CRN stated. “However, no single study, especially a preliminary abstract, should serve as the basis for broad conclusions or alarmist headlines about dietary supplements.”