For millions of people struggling to find a restful night’s sleep, the solution often seems simple: a quick trip to the pharmacy for a bottle of melatonin. Long marketed as a "natural," harmless, and non-habit-forming sleep aid, this hormone has become a staple of the modern medicine cabinet. However, a jarring new study presented at the American Heart Association’s (AHA) Scientific Sessions 2025 suggests that the pervasive use of this supplement may come with a hidden, high-stakes cost.
According to preliminary research, individuals with chronic insomnia who utilized melatonin for at least one year exhibited significantly higher risks of heart failure, hospitalizations related to cardiac issues, and even all-cause mortality compared to those who did not use the supplement. While the study stops short of declaring melatonin a direct cause of these health failures, the statistical findings are robust enough to rattle the foundation of how the medical community and the general public perceive "natural" sleep aids.
The Core Findings: A Significant Statistical Correlation
The study, which analyzed data from the expansive TriNetX Global Research Network, focused on adults suffering from chronic insomnia. Researchers categorized participants into two groups: those with documented, long-term melatonin use (defined as at least one year) and those with no record of melatonin consumption.
The results were stark. Among the long-term users, the risk of developing heart failure over the subsequent five-year period was approximately 90% higher than in the control group. Specifically, 4.6% of those in the melatonin group experienced heart failure, compared to only 2.7% of the non-melatonin users.
The alarm bells rang even louder regarding secondary health outcomes. The study found that long-term melatonin users were nearly 3.5 times more likely to be hospitalized for heart failure. Perhaps most concerning was the disparity in mortality rates: 7.8% of the participants in the melatonin group died during the five-year study period, nearly doubling the 4.3% mortality rate observed in the non-melatonin group.
"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," said Ekenedilichukwu Nnadi, M.D., the study’s lead author and chief resident in internal medicine at SUNY Downstate/Kings County Primary Care.
Understanding the "Natural" Hormone: Why We Use It
To understand why these findings are so provocative, one must first look at what melatonin is. Melatonin is a hormone produced by the pineal gland, a pea-sized structure located deep in the center of the brain. It is the body’s internal timekeeper, regulated by light and darkness; as dusk falls, the pineal gland releases melatonin, signaling to the body that it is time to prepare for sleep.
Synthetic melatonin, which is chemically identical to the endogenous hormone, has become the go-to remedy for jet lag, shift-work disorder, and the general malaise of insomnia. Because it is viewed as a replacement for something the body already makes, consumers often categorize it in the same "safe" bucket as vitamins or herbal teas.
However, the regulatory landscape for melatonin varies wildly. In the United Kingdom and many other nations, it is a prescription-only medication. In the United States, it is sold as a dietary supplement. This classification means it largely escapes the stringent oversight of the Food and Drug Administration (FDA). Consequently, consumers often have no way of knowing if the dosage listed on the bottle matches the actual contents, or if the purity of the supplement meets clinical standards.
Chronology of the Investigation
The impetus for this research was a growing concern among cardiovascular experts that, while melatonin is widely used, there is a paucity of clinical evidence regarding its safety when taken for months or years at a time. The research team sought to fill this knowledge gap by conducting a longitudinal analysis.
Phase 1: Data Acquisition
The researchers utilized the TriNetX platform, which provides access to de-identified electronic health records from a diverse, international pool of patients. This allowed for a robust, multi-year observation period.
Phase 2: Patient Matching
To ensure a fair comparison, the team matched patients who used melatonin for at least 12 months with peers who had chronic insomnia but no documented history of melatonin usage. Patients who had already been diagnosed with heart failure at the start of the study, or those who were already prescribed other sleep-enhancing medications, were systematically excluded to prevent data contamination.
Phase 3: The Sensitivity Analysis
To confirm the reliability of the initial data, the researchers performed a secondary, more rigorous analysis. They isolated participants who had filled at least two prescriptions for melatonin at least 90 days apart. Even within this tighter cohort, the risk of heart failure remained elevated at 82%, reinforcing the consistency of the association.
Expert Commentary and Professional Skepticism
The study has sent ripples through the sleep medicine community. Marie-Pierre St-Onge, Ph.D., C.C.S.H., FAHA, a prominent researcher in nutritional medicine and director of the Center of Excellence for Sleep & Circadian Research at Columbia University, expressed profound surprise at the duration of the use documented in the study.
"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," St-Onge noted. She emphasized that the casual, long-term consumption of the supplement—without a clear medical indication or clinical oversight—is a behavior that patients and providers must urgently re-evaluate.
As chair of the writing group for the AHA’s 2025 scientific statement on sleep health, St-Onge’s perspective carries significant weight. Her work highlights that while sleep is vital to cardiometabolic health, the tools we use to achieve it must be scrutinized with the same rigor as any other pharmaceutical intervention.
Limitations: Navigating the Data Fog
While the statistics are alarming, the researchers were quick to acknowledge the limitations of their study. Because the data was pulled from electronic health records, it contains inherent blind spots:
- The "Hidden" User Problem: In countries like the U.S., where melatonin is over-the-counter, the study could only track usage documented by a physician. If a patient purchased melatonin at a pharmacy and never reported it to their doctor, they would have been categorized as a "non-user." This potential misclassification suggests the groups may not have been perfectly divided.
- Diagnostic Coding: Heart failure-related hospitalizations are tracked via billing codes. These codes are sometimes broad and may not always distinguish between a new, acute heart failure diagnosis and a chronic flare-up, potentially inflating the hospitalization numbers.
- Comorbidity Confounding: The study could not fully account for the severity of a patient’s insomnia or the presence of underlying psychiatric conditions like anxiety or depression. It is possible that patients with more severe health profiles were more likely to seek out long-term sleep aids, meaning the melatonin might be a marker for other health issues rather than the cause of the heart failure itself.
Implications: The Need for Clinical Caution
The most important takeaway from this research is not an immediate ban on melatonin, but rather a shift toward informed caution. Dr. Nnadi emphasized that while they have found a significant association, they have not yet proven a causal link.
"Worse insomnia, depression/anxiety, or the use of other sleep-enhancing medicines might be linked to both melatonin use and heart risk," Nnadi explained. "This means more research is needed to test melatonin’s safety for the heart."
For the average patient, the implication is clear: melatonin should be treated as a drug, not a vitamin. Chronic insomnia is often a symptom of underlying physical or mental health conditions. Simply "masking" the symptoms with a nightly supplement for years at a time may prevent patients from seeking more effective, safer, and evidence-based treatments—such as Cognitive Behavioral Therapy for Insomnia (CBT-I)—which address the root cause of sleep disturbances without the potential cardiovascular risks.
As the scientific community prepares for further studies, the message to the public is one of prudence. If you are taking melatonin on a nightly basis, it is time to have a conversation with your primary care provider. The goal should be to move toward a sleep regimen that is not only effective for your rest but also protective of your heart.
