Long-Term Melatonin Use Linked to a 90% Higher Risk of Heart Failure

The findings do not prove that melatonin causes heart problems. However, they raise new questions about the long-term safety of a supplement that many people consider a harmless or “natural” way to improve sleep.

Why melatonin is widely used

Melatonin is a hormone produced naturally by the pineal gland in the brain. It helps regulate the body’s sleep-wake cycle, also known as the circadian rhythm. Melatonin levels typically rise in the evening as it gets dark and decline during daylight hours.

Synthetic melatonin is chemically similar to the hormone produced by the body. It is commonly used to help with jet lag and sleep problems, including difficulty falling asleep or staying asleep.

In many countries, including the United States, melatonin is available over the counter. Because dietary supplements are not regulated in the same way as prescription medicines in the U.S., products can vary in strength, purity, and ingredients.

For the study, researchers classified participants based on melatonin use documented in their electronic medical records. People with at least one year of recorded melatonin use were placed in the “melatonin group.” Those with no documented melatonin use were assigned to the “no-melatonin group.”

“Melatonin supplements may not be as harmless as commonly thought. If confirmed, our study could affect how physicians counsel patients about sleep aids,” said lead study author Ekenedrichukwu-Nnadi, M.D., chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn, New York.

Researchers examined long-term heart health risks

Melatonin is often promoted as a safe sleep aid, but researchers say limited evidence exists regarding its cardiovascular safety when used over long periods.

To address this uncertainty, the research team examined whether long-term melatonin use was associated with heart failure among adults with chronic insomnia.

Heart failure does not mean the heart has stopped beating. Instead, it occurs when the heart cannot pump enough oxygen-rich blood to meet the body’s needs. Approximately 6.7 million adults in the United States have heart failure, according to the American Heart Association’s 2025 Heart Disease and Stroke Statistics.

The researchers analyzed information from the TriNetX Global Research Network, a large international database of de-identified electronic health records.

They reviewed five years of medical data from adults with chronic insomnia who had documentation of melatonin use for more than one year. These participants were matched with people who also had insomnia but no record of melatonin use.

Individuals with a previous heart failure diagnosis or a prescription for other sleep medications were excluded from the analysis.

Long-term melatonin use was linked to a higher heart failure risk

The primary analysis found notable differences between the two groups.

Among adults with insomnia, those with documented melatonin use for at least 12 months were approximately 90% more likely to develop heart failure during the following five years than comparable non-users. Heart failure occurred in 4.6% of the melatonin group, compared with 2.7% of the comparison group.

The researchers conducted an additional analysis to strengthen the evidence that participants had used melatonin over an extended period.

The association remained when the analysis was limited to people who filled at least two melatonin prescriptions at least 90 days apart. In that group, the risk of heart failure was 82% higher. Melatonin is available by prescription in the United Kingdom.

Heart failure hospitalizations and deaths were also more common

Secondary analyses found even larger differences for some outcomes.

People in the melatonin group were nearly three times more likely to be hospitalized for heart failure than those in the comparison group. Hospitalization rates were 19.0% and 6.6%, respectively.

Death from any cause was also more common among participants with documented melatonin use. Over five years, the mortality rate was 7.8% in the melatonin group, compared with 4.3% in the non-melatonin group.

“Melatonin supplements are widely considered a safe, ‘natural’ option for supporting better sleep, so it was surprising to see such a consistent and substantial increase in serious health outcomes, even after balancing many other risk factors,” Nnadi said.

The findings also prompted concern from Marie-Pierre St-Onge, Ph.D., FAHA, CCSH, a sleep researcher who was not involved in the study.

“I’m surprised that doctors would prescribe melatonin for insomnia and have patients use it for more than 365 days, because melatonin is not indicated for the treatment of insomnia, at least in the United States,” St-Onge said. “Although melatonin is available over the counter in the United States, people should be aware that it should not be taken chronically without an appropriate indication and medical guidance.”

St-Onge is a professor of nutritional medicine in the Department of Medicine at Columbia University Irving Medical Center in New York City and director of the institution’s Center of Excellence for Sleep and Circadian Research. She also chairs the writing group for the American Heart Association’s 2025 scientific statement, “Multidimensional Sleep Health: Definition and Impact on Cardiometabolic Health.”

Study limitations make the findings difficult to interpret

The study has several important limitations, particularly because melatonin is regulated differently from one country to another.

Some countries, including the United Kingdom, require a prescription for melatonin, while others, including the United States, allow consumers to purchase it over the counter. Because the medical data was anonymized, researchers did not have access to participants’ specific locations.

Melatonin use was counted only when it appeared in an electronic medical record. As a result, people in the United States and other countries who purchased melatonin over the counter without reporting it to a health care provider may have been incorrectly classified as non-users.

This means the melatonin and comparison groups may not accurately represent who actually took the supplement.

The researchers also noted that the number of heart failure-related hospitalizations was higher than the number of newly diagnosed heart failure cases. Hospitals may use several related diagnosis codes, and the available records did not always include a code specifically identifying a new heart failure diagnosis.

In addition, the researchers did not have information about the severity of participants’ insomnia or whether they had conditions such as depression or anxiety.

These factors are important because people with more severe insomnia, depression, anxiety, or other health conditions may be more likely to use melatonin and may also have an independently higher risk of cardiovascular problems.

“Worsening insomnia, depression or anxiety, and the use of other sleep-promoting medications may be associated with both melatonin use and heart risks,” Nnadi said. “Although our findings raise safety concerns about this widely used supplement, the study cannot prove a direct cause-and-effect relationship. Additional research is needed to determine whether long-term melatonin use affects cardiovascular health and, if so, why.”

Research details

• The analysis included 130,828 adults diagnosed with insomnia. Their mean age was 55.7 years, and 61.4% were female.
• The data came from TriNetX, a growing global network of anonymized, real-world patient information used for medical research.
• Among the participants, 65,414 had documentation of receiving melatonin and using it for at least one year.
• The researchers created a comparison group of people with insomnia who had no documented melatonin prescriptions. Participants were matched using 40 factors, including demographic characteristics, existing health conditions, and medications.
• People with a previous heart failure diagnosis or prescriptions for other sleep medications, including benzodiazepines, were excluded.
• The groups were matched for age, sex, race and ethnicity, heart and nervous system conditions, cardiovascular and nervous system medications, blood pressure, and body mass index.
• The researchers examined electronic health records covering five years after the groups were matched.
• The primary analysis looked for medical codes indicating an initial heart failure diagnosis. Secondary outcomes included heart failure hospitalization and death from any cause.
• The researchers also conducted a sensitivity analysis to determine whether the findings remained similar when the study criteria were changed.
• For this additional analysis, participants in the melatonin group had to fill at least two prescriptions at least 90 days apart. The association with a higher heart failure risk remained.
• The researchers emphasized that this was an observational study. It identified an association between documented long-term melatonin use and serious health outcomes but cannot prove that melatonin directly caused heart failure, hospitalization, or death. Further research is needed to evaluate the long-term cardiovascular safety of melatonin.