For millions of people struggling with the restless nights of chronic insomnia, melatonin has long been viewed as the gold standard of "natural" sleep aids. It is the hormone our bodies produce to signal that it is time to wind down, and its synthetic counterpart is easily accessible in pharmacy aisles worldwide. However, a sobering new study presented at the American Heart Association’s Scientific Sessions 2025 suggests that the widespread reliance on this supplement may come with a hidden, high-stakes price tag for cardiovascular health.
Preliminary research indicates that long-term use of melatonin is linked to a significantly higher risk of heart failure, hospitalization, and mortality among patients suffering from chronic insomnia. While the study stops short of declaring a direct causal link, the findings have sent ripples through the medical community, prompting experts to call for a reassessment of how we view these popular supplements.
The Foundation of the Study: Investigating a "Natural" Myth
Melatonin is a hormone secreted by the pineal gland, acting as the body’s internal timekeeper. By regulating the circadian rhythm, it helps the body transition from wakefulness to sleep as darkness falls. Because it is chemically identical to the hormone the brain naturally produces, synthetic melatonin has garnered a reputation as a benign, non-addictive, and "harmless" intervention for jet lag and insomnia.
However, Dr. Ekenedilichukwu Nnadi, lead author of the study and chief resident in internal medicine at SUNY Downstate/Kings County Primary Care, notes that this reputation for safety is largely untested in the long term.
"Melatonin supplements may not be as harmless as commonly assumed," Dr. Nnadi said. "If our study is confirmed, this could affect how doctors counsel patients about sleep aids."
The research team set out to bridge this gap in clinical knowledge by analyzing data from the TriNetX Global Research Network, a massive, international database of de-identified electronic health records. The objective was to isolate the long-term impact of melatonin on the heart—a vital organ that relies on the very circadian rhythms that melatonin helps regulate.
Chronology of the Investigation
The study design was rigorous in its attempt to create a "clean" comparison group. Researchers examined five years of medical history for adults with chronic insomnia. Participants were split into two distinct cohorts:
- The Melatonin Group: Individuals who had at least one year of documented melatonin use in their electronic medical records.
- The Non-Melatonin Group: Individuals with no recorded history of melatonin use.
To ensure the results were not skewed by pre-existing conditions, the researchers excluded any participants who had been previously diagnosed with heart failure or who had been prescribed other conventional sleep medications. By matching these cohorts based on various health indicators, the team sought to isolate the potential impact of melatonin itself.
Supporting Data: A Statistical Alarm
The results of the analysis were, by the researchers’ own admission, "striking." When looking at the five-year trajectory of the participants, the difference between the two groups was stark.
Heart Failure Risk
The primary analysis revealed that adults with chronic insomnia who used melatonin for at least 12 months faced an approximately 90% higher risk of developing heart failure compared to their non-using counterparts. In concrete numbers, heart failure was identified in 4.6% of the melatonin group, compared to only 2.7% of the comparison group.
Robustness of Findings
To verify these numbers, the team performed a secondary analysis, restricting the cohort to only those who had filled at least two melatonin prescriptions at least 90 days apart. Even with this stricter criteria, the association remained statistically significant, with an 82% increased risk of heart failure.
Hospitalization and Mortality
The secondary outcomes were even more concerning. Participants in the melatonin group were nearly 3.5 times as likely to be hospitalized for heart failure (19.0% vs. 6.6%). Furthermore, the mortality rate from all causes was nearly twice as high in the melatonin group (7.8%) compared to the non-melatonin group (4.3%) over the five-year study period.
Expert Perspectives and Official Concerns
The findings have drawn sharp criticism and concern from leading figures in sleep medicine. Dr. Marie-Pierre St-Onge, a professor of nutritional medicine and director of the Center of Excellence for Sleep & Circadian Research at Columbia University Irving Medical Center, expressed profound surprise at the clinical patterns observed.
"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 stated. She emphasizes that in the United States, melatonin is regulated as a dietary supplement, not a pharmaceutical drug. This lack of strict regulation means that potency, purity, and dosage can vary wildly from brand to brand, a factor that complicates the interpretation of the study.
Dr. St-Onge, who chaired the writing group for the American Heart Association’s 2025 scientific statement on cardiovascular health, argues that the public must move away from the mindset that "natural" equals "safe."
The Limitations of the Research
Despite the alarming statistics, the research team remains cautious. They acknowledge that the study is observational and possesses several limitations that prevent it from establishing a definitive cause-and-effect relationship.
The "Documentation" Gap
Because the study relied on electronic medical records, it likely undercounted total melatonin use. In countries like the U.S., where melatonin is sold over the counter, many patients use the supplement without ever informing their doctor. Consequently, these "silent users" were likely categorized as non-users, potentially blurring the lines between the two groups.
Missing Clinical Context
The researchers lacked granular data on the severity of each patient’s insomnia. It is possible that patients with more severe, treatment-resistant insomnia—which may be linked to other health issues like depression or anxiety—are the ones most likely to reach for long-term melatonin.
"Worse insomnia, depression/anxiety, or the use of other sleep-enhancing medicines might be linked to both melatonin use and heart risk," Dr. Nnadi admitted. "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."
Diagnostic Ambiguity
Another complication lies in the way hospitals code patient visits. The study noted that hospitalizations for heart-failure-related issues were higher than new diagnoses. Because hospital records often contain multiple diagnostic codes, it is sometimes difficult to determine if a patient was admitted because of a primary heart failure event or if heart failure was simply a secondary finding during a visit for another condition.
Implications for Public Health and Future Practice
The implications of this study are twofold. First, it serves as a wake-up call for the public. The "natural" label on a supplement bottle should not be viewed as an invitation for indefinite use. Consumers should consult with healthcare providers before starting any long-term supplement regimen, especially if they have pre-existing cardiovascular concerns or risk factors.
Second, it challenges the medical establishment. If a widely used supplement is potentially linked to severe cardiovascular events, the standard of care for chronic insomnia must be re-evaluated. Physicians may need to prioritize evidence-based behavioral therapies—such as Cognitive Behavioral Therapy for Insomnia (CBT-I)—over pharmacological or hormonal interventions that lack long-term safety data.
As the scientific community digests these findings, the path forward is clear: more robust, prospective studies are required to determine if melatonin is truly a factor in cardiovascular decline or if it is merely a marker for other underlying health struggles. Until then, the message from the 2025 American Heart Association sessions is one of caution: sleep is essential for heart health, but the way we choose to achieve that sleep requires greater scrutiny and clinical oversight.
