For millions of people struggling with the restless nights of chronic insomnia, melatonin has long been viewed as the "natural" solution—a gentle, hormone-based remedy that offers a path to sleep without the heavy sedative effects of prescription hypnotics. However, a jarring new study presented at the American Heart Association’s (AHA) Scientific Sessions 2025 suggests that the widespread reliance on this supplement may come with a hidden, high-stakes cost.
Preliminary research indicates that long-term use of melatonin is linked to a significantly higher risk of heart failure, increased hospitalizations, and even a higher rate of mortality. While the findings do not establish a definitive cause-and-effect relationship, they have sent a ripple of concern through the medical community, forcing a re-evaluation of how sleep aids are recommended and consumed.
The Core Findings: A Significant Statistical Link
The study, which analyzed five years of longitudinal health data, compared patients with chronic insomnia who were documented users of melatonin against a matched group of non-users. The results were stark.
Among those who used melatonin for at least one year, the risk of developing heart failure was approximately 90% higher than in the comparison group. Specifically, 4.6% of the melatonin-using cohort developed heart failure over the five-year study period, compared to only 2.7% of those who did not take the supplement.
The data became even more concerning when researchers narrowed the scope to individuals who had confirmed, repeated use of the hormone. When looking at patients who had filled at least two prescriptions at least 90 days apart, the risk of heart failure remained elevated at 82%.
"Melatonin supplements may not be as harmless as commonly assumed," said Dr. Ekenedilichukwu Nnadi, lead author of the study and chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn. "If our study is confirmed, this could affect how doctors counsel patients about sleep aids."
Chronology of a Widespread Habit
To understand why these findings are so significant, one must look at the ubiquity of melatonin. A hormone naturally secreted by the pineal gland in the brain, melatonin acts as the body’s internal timekeeper, signaling the onset of the circadian rhythm as daylight fades.
In the late 20th and early 21st centuries, synthetic melatonin became a global phenomenon. In the United States, it is classified as a dietary supplement, meaning it bypasses the rigorous FDA approval process required for prescription drugs. This regulatory "blind spot" allows for immense variability in the strength, purity, and quality of products available on pharmacy shelves.
The Research Timeline
- Initial Investigation: Driven by a lack of long-term cardiovascular safety data, researchers turned to the TriNetX Global Research Network, a massive, international database of de-identified electronic health records.
- Data Matching: The team isolated adults with chronic insomnia who had documented melatonin use for more than 12 months. These individuals were matched with a control group of insomnia patients who had no record of using the supplement.
- Exclusion Criteria: To maintain the integrity of the data, the researchers systematically excluded anyone who had a pre-existing diagnosis of heart failure or had been prescribed other sleep-related medications, ensuring that the observed effects were not merely a byproduct of pre-existing heart conditions.
- The 5-Year Window: The study tracked these cohorts for half a decade, documenting new diagnoses of heart failure, occurrences of hospitalization for heart failure, and death from any cause.
Supporting Data: Beyond Heart Failure
The implications of the study extend beyond a simple heart failure diagnosis. The researchers conducted a secondary analysis that revealed alarming trends in hospitalizations and overall survival rates.
According to the data, participants in the melatonin group were nearly 3.5 times more likely to be hospitalized for heart failure compared to those who did not use the supplement. The hospitalization rates were 19.0% for the melatonin group versus 6.6% for the non-melatonin group.
Perhaps most sobering was the finding regarding all-cause mortality. Over the five-year study duration, 7.8% of the participants who had used melatonin for at least a year died, compared to 4.3% of the control group. This represents a nearly two-fold increase in the risk of death, a statistic that has prompted calls for immediate, more rigorous clinical trials.
"Melatonin supplements are widely thought of as a safe and ‘natural’ option to support better sleep," Dr. Nnadi noted. "So it was striking to see such consistent and significant increases in serious health outcomes, even after balancing for many other risk factors."
Expert Perspectives: A Call for Clinical Caution
The medical community has reacted to these findings with a mix of surprise and caution. 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 deep concern regarding the current state of clinical practice.
"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 emphasized that while melatonin is often treated as a benign health aid, the public perception of the supplement is dangerously misaligned with the reality of its long-term physiological impact. As the chair of the writing group for the AHA’s 2025 scientific statement on sleep health, Dr. St-Onge advocates for a paradigm shift: patients should be warned that chronic use of any supplement, even one perceived as "natural," should only occur under the direct supervision of a medical professional.
Critical Limitations and the Need for Nuance
While the statistics are compelling, the research team is the first to acknowledge the limitations inherent in their study. Because the data was derived from a large, international database of electronic medical records, there are gaps that must be addressed before definitive conclusions can be drawn.
1. The "Over-the-Counter" Variable
In countries like the United States, melatonin is sold over the counter. Because these purchases are rarely logged in a patient’s formal medical history, there is a high probability that many people in the "non-melatonin" control group were actually taking the supplement regularly. This "misclassification bias" could potentially skew the results, though it would typically lead to an underestimation of the risk, rather than an overestimation.
2. Lack of Contextual Data
The study did not have access to the severity of the participants’ insomnia, nor did it track their mental health history—such as the presence of depression or anxiety. It is possible that patients with more severe underlying health issues are more likely to seek out melatonin, creating a "confounding factor" where the health risks are caused by the severity of their condition, not the supplement itself.
3. Diagnostic Coding Ambiguity
The researchers noted that hospital records for heart failure can be inconsistent. Hospitals often use a variety of diagnostic codes, and not all of these accurately reflect a new diagnosis of heart failure. Consequently, the high hospitalization rates must be interpreted with a degree of caution.
The Path Forward: Implications for Patients
The most immediate implication of this study is the need for a more critical approach to sleep hygiene. For patients suffering from chronic insomnia, the "quick fix" of a daily supplement may be masking underlying issues that require a more comprehensive, evidence-based treatment plan.
Dr. Nnadi and his colleagues emphasize that this study is a starting point, not an end. It serves as a loud wake-up call for both the public and the medical establishment.
Recommendations for Current Users:
- Consult Your Physician: If you are using melatonin daily for an extended period, speak with your healthcare provider about the risks and benefits.
- Address the Root Cause: Insomnia is often a symptom of other physiological or psychological issues. Seeking a formal diagnosis from a sleep specialist may be more effective than long-term self-medication.
- Monitor Symptoms: Anyone with a history of cardiovascular risk should be particularly vigilant when adding any supplement to their daily regimen.
As research continues, the scientific community will look to isolate the variables that link melatonin to cardiovascular strain. Until more definitive, prospective clinical trials are conducted, the message is clear: the "natural" label does not equate to "risk-free." The long-term safety of melatonin remains an open question, and until it is answered, patients should approach the supplement with the same caution they would afford any other medical intervention.
