A comprehensive five-year review involving over 130,000 adults suffering from insomnia has uncovered concerning findings regarding the long-term use of melatonin supplements. The study indicates that prolonged melatonin consumption is associated with a heightened risk of heart failure and mortality rates, prompting researchers to advocate for more extensive investigations into the cardiovascular safety of this popular sleep aid. Individuals who consistently utilized melatonin for at least a year were found to have a significantly higher likelihood of being diagnosed with heart failure, requiring hospitalization for heart-related issues, or succumbing to any cause compared to their counterparts who did not use the supplement.
This pivotal finding will be presented at the American Heart Association’s Scientific Sessions 2025, scheduled for November 7–10 in New Orleans. Melatonin, a hormone naturally produced by the pineal gland in the brain, plays a crucial role in regulating the body’s internal clock and the sleep-wake cycle. Typically, melatonin levels rise in the evening and taper off during the day. Synthetic melatonin, which mirrors the natural hormone, is widely taken to alleviate insomnia and mitigate the effects of jet lag. In many countries, including the United States, melatonin is available without a prescription. However, it’s essential to note that over-the-counter products are not regulated, leading to significant variations in the potency and purity of melatonin across different brands.
For this significant study, scientists meticulously analyzed electronic health records, categorizing participants based on their melatonin usage. Those with documented melatonin use for one year or longer were classified as the “melatonin group,” while individuals with no record of melatonin use were categorized as the “non-melatonin group.” Dr. Ekenedilichukwu Nnadi, the lead author and chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn, New York, emphasized, “Melatonin supplements may not be as harmless as commonly assumed. If our study is confirmed, this could significantly influence how doctors advise patients about sleep aids.”
Melatonin has been extensively marketed as a safe and natural solution for improving sleep quality. However, the long-term effects of its use on heart health remain largely unexplored. This knowledge gap prompted researchers to delve into whether regular melatonin consumption could increase the risk of developing heart failure, particularly in individuals grappling with chronic insomnia. The American Heart Association defines heart failure as a condition where the heart struggles to pump sufficient oxygen-rich blood to fulfill the body’s needs, affecting approximately 6.7 million adults in the United States alone.
To investigate this potential link, researchers utilized data from the TriNetX Global Research Network, a substantial international database of electronic health records. They scrutinized five years of data from adults diagnosed with chronic insomnia who had a documented history of melatonin use for over a year, comparing them with insomnia patients who had no record of melatonin intake. Participants with a prior diagnosis of heart failure or those prescribed other sleep medications were excluded from the study.
The primary analysis revealed that among adults with insomnia, those whose electronic health records indicated long-term melatonin use (12 months or more) had nearly a 90% higher likelihood of being diagnosed with heart failure over the five-year period compared to matched non-users (4.6% vs. 2.7%, respectively). Additionally, a similar outcome was observed (an 82% increase) when analyzing individuals who had filled at least two melatonin prescriptions at least 90 days apart. (It’s noteworthy that melatonin is only available by prescription in the United Kingdom.)
A secondary analysis uncovered that participants taking melatonin were nearly 3.5 times more likely to be hospitalized for heart failure compared to those not using the supplement (19.0% vs. 6.6%, respectively). Moreover, individuals in the melatonin group were almost twice as likely to die from any cause as those in the non-melatonin group (7.8% vs. 4.3%) over the same five-year period. Dr. Nnadi expressed concern, stating, “Melatonin supplements are widely perceived as a safe and ‘natural’ option for enhancing sleep, making it surprising to witness such consistent and significant increases in severe health outcomes, even after accounting for various risk factors.”
Commenting on the findings, Dr. Marie-Pierre St-Onge, chair of the writing group for the American Heart Association’s 2025 scientific statement on sleep health, expressed her surprise at the prescribing practices surrounding melatonin for insomnia, particularly for durations exceeding 365 days. She noted that while melatonin can be obtained over the counter in the U.S., its chronic use should not occur without a valid medical reason. Dr. St-Onge, who did not participate in this study, is a professor of nutritional medicine at Columbia University Irving Medical Center in New York City.
The study does bear limitations. It draws from a database that encompasses countries with varying prescription requirements for melatonin, and the geographical locations of patients were not included in the anonymized data. Since the identification of melatonin use was based solely on medication entries within electronic health records, individuals purchasing melatonin over the counter in the U.S. or similar nations would not have been represented in the melatonin group, potentially skewing the results. Furthermore, the researchers lacked access to information regarding the severity of insomnia and the presence of other psychiatric conditions.
Dr. Nnadi highlighted the need for caution in interpreting the results, noting, “Worse insomnia, anxiety, or the concurrent use of other sleep medications might contribute to both melatonin use and heart health risks. While our findings raise safety concerns regarding this widely utilized supplement, the study does not establish a direct cause-and-effect relationship, necessitating further research to assess melatonin’s safety concerning heart health.”
The research encompassed 130,828 adults with an average age of 55.7 years, consisting of 61.4% women diagnosed with insomnia. The data was sourced from TriNetX, a growing global network providing access to de-identified patient data for research since its establishment in 2013. Among the participants, 65,414 individuals had received at least one melatonin prescription and reported using it for a year or longer. A control group was formed from individuals who had never been prescribed melatonin, matched across 40 variables, including demographics, health conditions, and medications.
The researchers meticulously analyzed electronic medical records from the five years following the matching date, searching for codes related to initial heart failure diagnoses. Secondary findings included hospitalization data related to heart failure and mortality. To validate their findings, the researchers conducted a sensitivity analysis, adjusting the criteria to include only participants in the melatonin group who filled at least two prescriptions spaced at least 90 days apart. This adjustment was aimed at assessing whether the duration of confirmed melatonin prescriptions influenced the outcomes.
The upcoming presentation titled “Effect of Long-term Melatonin Supplementation on Incidence of Heart Failure in Patients with Insomnia” at the American Heart Association Scientific Sessions 2025 promises to shed more light on these significant findings.
