For millions of people struggling to find rest, the local pharmacy aisle offers a beacon of hope in a small, often unassuming bottle: melatonin. Widely marketed as a “natural” and harmless sleep aid, this hormone supplement has become a staple in medicine cabinets worldwide. However, a jarring new study presented at the American Heart Association’s (AHA) Scientific Sessions 2025 suggests that the long-term use of melatonin may carry significant, previously underestimated risks to cardiovascular health.
The research, which examined five years of electronic medical records, revealed a concerning correlation between chronic melatonin use and a higher incidence of heart failure, hospitalizations, and all-cause mortality. As the medical community digests these findings, the conversation surrounding sleep hygiene and the over-reliance on supplements is undergoing a rigorous, and perhaps overdue, re-evaluation.
The Foundation of the Study: Investigating a “Harmless” Supplement
Melatonin is fundamentally a hormone, synthesized naturally by the pineal gland in the brain. Its primary function is the regulation of the circadian rhythm—the body’s internal clock that dictates the sleep-wake cycle. Under normal physiological conditions, levels of melatonin rise as daylight fades, signaling to the body that it is time for restorative rest, and decline as dawn breaks.
Synthetic melatonin, which mimics this endogenous hormone, has become the go-to solution for jet lag, shift work disorders, and the pervasive challenge of insomnia. However, the regulatory environment for these supplements is far from uniform. In the United States, for instance, melatonin is classified as a dietary supplement, meaning it is not subject to the stringent FDA oversight applied to pharmaceuticals. This lack of standardization means that consumers often have no guarantee regarding the purity, concentration, or consistency of the doses they ingest.
It was this widespread, largely unchecked consumption that prompted a research team led by Ekenedilichukwu Nnadi, M.D., a chief resident in internal medicine at SUNY Downstate/Kings County Primary Care, to investigate the cardiovascular implications of long-term use.
“Melatonin supplements may not be as harmless as commonly assumed,” Dr. Nnadi stated. “If our study is confirmed, this could affect how doctors counsel patients about sleep aids.”
Chronology and Methodology: Tracking Five Years of Health Data
To determine whether the long-term consumption of melatonin was linked to heart failure, the research team utilized the TriNetX Global Research Network. This massive, international database contains de-identified electronic health records, providing a granular view of patient outcomes over extended periods.
The researchers conducted a longitudinal study by identifying adults with documented chronic insomnia. Participants were categorized into two groups:
- The Melatonin Group: Individuals with at least one year of documented melatonin use in their medical records.
- The Non-Melatonin Group: Individuals with no recorded use of melatonin throughout their medical history.
To ensure the integrity of the data, the researchers implemented strict exclusion criteria. Anyone with a pre-existing diagnosis of heart failure or those already prescribed other pharmaceutical sleep aids was removed from the study. This allowed the team to isolate the variable of melatonin use as cleanly as possible. The resulting comparison spanned five years, tracking how these two groups fared in terms of heart health and overall survival.
Supporting Data: A Stark Increase in Cardiovascular Risk
The findings, when presented at the AHA Scientific Sessions 2025, were sobering. The statistical analysis revealed a marked divergence between those who used melatonin regularly and those who did not.
Heart Failure Incidence
The primary analysis indicated that adults who used melatonin for 12 months or more had an approximately 90% higher risk of developing heart failure over the subsequent five-year period. Specifically, 4.6% of the melatonin group experienced a heart failure diagnosis, compared to only 2.7% in the control group.
To bolster these findings, the researchers performed a secondary analysis focusing on individuals who had filled at least two melatonin prescriptions at least 90 days apart. Even within this subset of “confirmed” chronic users, the association remained robust, showing an 82% higher risk of heart failure.
Hospitalization and Mortality
The secondary outcomes were perhaps even more alarming. The study found that individuals in the melatonin group were nearly 3.5 times more likely to be hospitalized for heart failure compared to their non-using counterparts (19.0% vs. 6.6%). Furthermore, mortality from all causes was significantly higher in the melatonin group, with a 7.8% death rate compared to 4.3% in the comparison group—nearly a two-fold increase in risk.
“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,” Dr. Nnadi noted.
Official Responses and Expert Perspective
The study has sent ripples through the cardiology and sleep medicine communities. Marie-Pierre St-Onge, Ph.D., a professor of nutritional medicine at Columbia University Irving Medical Center and chair of the writing group for the AHA’s 2025 scientific statement on sleep health, expressed surprise at the frequency with which melatonin is being used as a chronic treatment.
“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,” Dr. St-Onge explained. She emphasized that the public perception of melatonin as a benign supplement is a dangerous misconception. Her stance highlights a growing consensus among experts: that melatonin should not be treated as a long-term cure-all for sleep disturbances without professional medical indication and monitoring.
Implications and Limitations: The Need for Nuance
While the data presents a compelling argument for caution, the researchers themselves are the first to acknowledge the limitations of their work. Because the study relied on electronic medical records, it could not capture the use of over-the-counter melatonin that was never disclosed to a physician. This “hidden” use may have led to a misclassification of some participants in the non-melatonin group, potentially masking an even stronger association.
Furthermore, the study could not account for the severity of a patient’s underlying insomnia, nor could it identify other psychiatric comorbidities, such as depression or anxiety, which are often co-morbid with sleep disorders. As Dr. Nnadi pointed out, it is possible that the underlying conditions—rather than the supplement itself—could be contributing to the cardiovascular risks observed.
“Worse insomnia, depression/anxiety, or the use of other sleep-enhancing medicines might be linked to both melatonin use and heart risk,” Nnadi conceded. “Also, while the association we found raises safety concerns, our study cannot prove a direct cause-and-effect relationship. This means more research is needed to test melatonin’s safety for the heart.”
The Future of Sleep Medicine
The implications of this research are profound. In an era where sleep deprivation is an epidemic, millions of people are searching for a quick fix. If this study’s findings are corroborated by prospective clinical trials, it could necessitate a complete overhaul of how sleep aids are prescribed and sold.
For the average consumer, the message is clear: proceed with caution. Supplements, even those labeled “natural,” are biologically active substances that influence complex hormonal pathways. Before incorporating any supplement into a daily routine for a prolonged period, patients should consult with a healthcare professional to ensure that they are addressing the root cause of their insomnia rather than masking it with a substance that may carry hidden, long-term consequences for the heart.
As the medical community continues to investigate these links, the case of melatonin serves as a vital reminder that in the world of medicine, the line between “natural” and “safe” is not always as clear as the label on a bottle might suggest.
