National Animal Shelter & Rescue Appreciation Week Support A Shelter Today!
Long-Term Melatonin Use May Increase Heart Failure and Death Risk
Guest Contributor
Melatonin supplements are often treated as a gentle, “natural” shortcut to better sleep. Many people reach for them when they are tired of tossing and turning, assuming that because melatonin is a hormone the body already makes, long-term use must be safe. New preliminary research presented at the American Heart Association’s Scientific Sessions 2025 suggests that long-term melatonin use may not be as harmless as many believe and could be linked to a higher risk of heart failure and death among adults with chronic insomnia.
Melatonin is produced in the pineal gland and plays a central role in regulating the sleep-wake cycle. Levels normally rise at night and fall during daylight, guiding the body’s internal clock. Chemically identical synthetic melatonin is widely available as an over-the-counter supplement in many countries, including the United States, and is often used to help with insomnia or jet lag. That accessibility, combined with its “natural” label, has helped melatonin become a go-to sleep aid for millions.
Yet the new analysis of real-world data raises important safety questions, especially about long-term melatonin use. Researchers examined five years of electronic health records from more than 130,000 adults diagnosed with chronic insomnia. They focused on people who had melatonin documented in their health records for at least a year and compared them to similar patients with insomnia who had no melatonin recorded anywhere in their records.
In this study, adults with long-term melatonin recorded in their health records had about a 90% higher chance of developing heart failure over five years compared with matched adults who did not have melatonin listed. The rate of new heart failure diagnosis was 4.6% in long-term melatonin users compared with 2.7% in non-users. When the researchers tightened the criteria and looked only at people who had filled at least two melatonin prescriptions at least 90 days apart, the increased risk was still substantial at 82% higher.
The findings did not stop there. In a secondary analysis, participants taking melatonin were nearly 3.5 times as likely to be hospitalized for heart failure compared with those not taking melatonin, with hospitalization rates of 19.0% in the melatonin group versus 6.6% among non-users. Over the same five-year period, people in the melatonin group were also nearly twice as likely to die from any cause, 7.8% compared with 4.3% in the non-melatonin group.
The lead author, Ekenedilichukwu Nnadi, M.D., described the pattern as both consistent and striking. Nnadi noted that melatonin supplements are widely thought to be safe and natural sleep aids, yet the data showed significant increases in serious health outcomes even after the researchers attempted to balance for many other health factors. I found this detail striking because it challenges a very common assumption that “natural” automatically equals “safe,” especially over the long term.
These results came from a large international database known as the TriNetX Global Research Network, which aggregates de-identified electronic health records from health systems around the world. The study included 130,828 adults with an average age of 55.7 years, and women made up about 61% of the group. About half of these adults had melatonin noted in their records and reported using it for at least a year. The remaining adults with insomnia had no melatonin recorded and served as a comparison group.
To limit obvious confounding factors, the researchers matched people in the melatonin group and the control group on 40 different characteristics. These included demographic factors such as age, sex, and race or ethnicity, as well as health conditions like cardiovascular and nervous system diseases, medications for those conditions, blood pressure, and body mass index. They also excluded anyone who already had heart failure or had been prescribed other sleeping pills such as benzodiazepines. The goal was to create two groups that were as similar as possible, apart from recorded melatonin use.
It is important to highlight what this melatonin and heart failure research does not prove. The analysis is observational and based on health records, which means it can identify associations but cannot show that melatonin itself causes heart failure or death. The study authors themselves emphasized that more research is needed to determine whether melatonin directly affects cardiovascular health or whether melatonin use is simply a marker for something else that increases risk.
The study has several clear limitations. Melatonin is available only by prescription in some countries, such as the United Kingdom, yet is sold over the counter in the United States and other places. Because the researchers only captured melatonin that appeared in prescription or medication lists in electronic records, many people who bought melatonin on their own would have been misclassified as non-users. That could blur the true differences between groups. The database also did not include information about where patients lived, the severity of their insomnia, or the presence of psychiatric conditions such as depression and anxiety that might influence both sleep and heart health.
As Nnadi pointed out, more severe insomnia, mental health concerns, or the use of other sleep-related medicines could be tied to both melatonin use and higher cardiovascular risk. Without detailed information about these factors, it remains difficult to untangle cause and effect. Hospitalization rates were higher than new heart failure diagnoses in part because hospital stays can be coded with a variety of related diagnoses, and not every hospitalization will include a new heart failure code.
Another perspective came from Marie-Pierre St-Onge, Ph.D., who was not involved in the study but has led an American Heart Association scientific statement on multidimensional sleep health and cardiometabolic outcomes. St-Onge expressed surprise that some patients were using melatonin for more than a year, noting that in the United States it is not formally indicated for treating insomnia. St-Onge suggested that people should be cautious about using melatonin chronically without a clear and appropriate reason.
The bigger message here is not panic but perspective. Melatonin may be helpful in specific, short-term situations such as adjusting to a new time zone or when guided by a health professional for carefully chosen cases of sleep-wake rhythm problems. This preliminary study, however, suggests that long-term melatonin use in adults with chronic insomnia deserves closer scrutiny. It raises the possibility that long-term reliance on melatonin could be linked to serious heart-related outcomes, and it underscores the importance of treating any supplement, even one labeled “natural,” as a real drug with potential risks.
People who are currently using melatonin, especially for long stretches of time, may want to discuss their sleep health with a clinician. Alternatives such as improving sleep routines, addressing underlying health conditions, or exploring behavioral sleep therapies could provide safer, long-term strategies. Because this research is still in abstract form and has not yet been peer-reviewed or published as a full journal article, it should be viewed as an early signal rather than a final verdict. Even so, it contributes to a growing recognition that heart health and sleep health are closely connected, and that what seems like a simple sleep fix may carry more complexity than the label suggests.