A preliminary study that was presented at the American Heart Association’s Scientific Sessions 2025 has raised alarming questions between heart failure and melatonin use. Researchers discovered a notable association between long-term melatonin use and increased heart failure risk. The review examined medical records spanning 5 years for more than 130,000 adults with chronic insomnia. Those who used melatonin supplements continuously for at least 1 year showed approximately 90% higher likelihood of developing heart failure compared to non-users.
This finding has sparked considerable concern given that melatonin supplements remain widely available over-the-counter and are commonly perceived as entirely safe. However, the study remains preliminary and not peer-reviewed. The association between melatonin and increased risk of heart failure cannot prove a cause-and-effect relationship. As full manuscripts are peer-reviewed and then published, the study will remain preliminary.
What This Study Examined
Researchers analysed datasets sourced through the TriNetX Global Research Network to conduct the study. This database contains de-identified patient information from multiple countries, including the United States and the United Kingdom. The study team compared adults with chronic insomnia who had used melatonin for at least 12 months with carefully matched peers who had never used melatonin.
Researchers excluded participants who had already received heart failure diagnoses before the study began. They also excluded those who had been prescribed other types of sleep medications like benzodiazepines. The analysis examined what happened to participants over a 5-year follow-up period after the initial matching date.
Identifying Melatonin and Its Purpose
Melatonin occurs naturally in the human body as a hormone produced by the pineal gland. This small gland sits deep within the brain and works with the body’s internal clock. Natural melatonin levels rise during evening darkness and decline during daytime light. This hormone helps regulate the body’s sleep-wake cycle, also called the circadian rhythm. Many people experience disrupted sleep-wake cycles due to modern life demands including shift work and more recently excessive screen use. Pharmaceutical companies have created synthetic versions of this hormone to assist those with insomnia or suffering from jet lag. These manufactured copies are chemically identical to the body’s naturally produced melatonin. Supplements deliver supplemental melatonin to help people experiencing insomnia. Insomnia involves difficulty falling asleep, difficulty maintaining sleep, or both.
The Growing Popularity of Melatonin Supplements
Research and surveys have demonstrated a dramatic increase in melatonin supplement usage across America over recent decades. Between 1999 and 2000, only 0.4% of surveyed American adults reported using melatonin. By 2017 and 2018, this percentage had grown to 2.1% of surveyed adults. This is a 5 times increase of melatonin usage over approximately 2 decades. The growth trend remained consistent across both genders and different age groups and researchers noticed a pattern emerging regarding dosage level trends.
Higher-dose melatonin exceeding 5 milligrams daily became more common over time. These high-dose users represented 0.08% of respondents in 2005-2006. By 2017-2018, high-dose melatonin usage had increased to 0.28% of respondents. Some adults now take melatonin approximately 211 days annually. Among melatonin users, 38.6% report taking it everyday.
The Heart Failure Connection Explored
The preliminary research presented significant findings regarding heart failure risk among melatonin users. Among adults with insomnia, those using melatonin long-term demonstrated substantially elevated heart failure risk. Those with documented melatonin use for 12 months or longer showed 4.6% incident heart failure compared with 2.7% among non-users. This represented approximately a 90% higher relative risk over five years.
Researchers also examined people who had filled prescriptions twice within 90-day intervals. This subgroup analysis revealed similar results with an 82% higher heart failure risk compared to non-users. The findings proved consistent even after researchers balanced for numerous other risk factors.
Hospitalization and Mortality Outcomes
Beyond initial heart failure diagnosis, the study examined more severe outcomes requiring hospitalization. Participants taking melatonin were nearly 3.5 times as likely to require hospitalization for heart failure compared with non-users. Specifically, 19.0% of melatonin users experienced heart failure-related hospitalization. This compares with 6.6% of those who never used melatonin.
Researchers analyzing the mortality data findings proved particularly concerning. Participants in the melatonin group demonstrated nearly double the likelihood of dying from any cause during the 5-year study period. Approximately 7.8% of melatonin users died from any cause, compared with 4.3% among non-users. These substantial increases occurred despite researchers’ attempts to account for major risk factors including age, sex, race, heart disease history, and blood pressure.
Important Limitations of This Research
The study team, however, acknowledges several crucial limitations that could affect the resulting interpretations. The database includes countries requiring melatonin prescriptions, like the United Kingdom, and countries where it remains over-the-counter, like America. Patient locations were not part of the de-identified data that researchers could access. This means researchers only identified melatonin use through medication record entries in electronic health records. Every American taking melatonin as an over-the-counter supplement without prescription documentation would have been classified as a non-user. Therefore, the actual comparison groups may not accurately reflect true melatonin usage patterns.
Hospitalization rates reported in this study were higher than initial heart failure diagnosis rates. Researchers explained that multiple related diagnostic codes might be entered for hospitalizations. These entries might not always include specific codes for new heart failure diagnoses. Additionally, researchers lacked complete information regarding insomnia severity among participants. They also could not determine whether participants had depression, anxiety, or other psychiatric conditions
Understanding Heart Failure and Its Prevalence
The American Heart Association reported that 6.7 million American adults currently have heart failure. Heart failure occurs when the heart cannot pump sufficient oxygen-rich blood to the body’s organs and tissues. When organs fail to receive adequate oxygen-rich blood, they cannot function properly. This common condition ranks as a leading cause of hospital admissions in America.
Symptoms include shortness of breath during activity or while lying down, fatigue, swollen feet and ankles, and a persistent cough. Some patients experience confusion, decreased alertness, or nausea as heart failure progresses. Irregular or rapid heartbeats often accompany the condition. Various factors increase heart failure risk, including hypertension, diabetes, coronary artery disease, and previous heart attacks.
Conflicting Evidence from Prior Research
However, these new findings on melatonin and heart failure have stirred debate within the medical and scientific communities. Previous research literature suggests potentially opposite conclusions about melatonin and cardiovascular health. Several systematic reviews and studies have demonstrated that melatonin possesses antioxidant properties beneficial for the heart. These earlier investigations indicated melatonin might protect heart muscle from damage. Some animal studies showed melatonin reduced cardiac damage following ischemia-reperfusion injury.
Other research suggested melatonin could decrease elevated blood pressure. These findings proposed potential protective cardiovascular effects from melatonin supplementation. Experts familiar with prior literature expressed surprise at the new study’s findings. One researcher noted the new results contradicted previous evidence suggesting cardiovascular benefits. This contradiction between recent findings and prior research has raised questions about what factors might explain the unexpected association.
Dr. Ekenedilichukwu Nnadi led the research team and serves as chief resident in internal medicine. He stated that melatonin supplements may carry risks not previously appreciated by the public. Nnadi emphasized that if confirmed by further research, these findings could fundamentally change how doctors counsel patients. He cautioned that this study cannot prove direct cause-and-effect relationships between melatonin and heart failure.
Dr. Marie-Pierre St-Onge, a sleep medicine expert, offered additional perspective on these findings. St-Onge serves as chair of the American Heart Association’s 2025 scientific statement on multidimensional sleep health. She noted surprise that physicians would prescribe melatonin for extended periods exceeding one year. St-Onge pointed out that melatonin has no FDA-approved indication for treating insomnia in America. She emphasized that over-the-counter melatonin should not be used chronically without proper medical justification.
Additionally, Dr. Idrees Mughal (MBBS, MRes), known online as Dr. Idz, shared his critiques of the study on Instagram. He stressed that the findings are preliminary and were presented at a conference, meaning they have not yet undergone peer review. Dr. Idz also pointed out common limitations of observational research, including difficulty controlling for confounding variables, and noted that supplement quality and dosage inconsistencies in the U.S. market could influence outcomes. He encouraged viewers to interpret the results with caution and to consult a qualified healthcare professional before using melatonin regularly.
For a deeper breakdown of his perspective, be sure to check out the video embedded below.
Possible Explanations for the Observed Association
Researchers acknowledged multiple possible explanations for their surprising findings. One theory suggests that severe, untreated insomnia itself might indicate underlying heart problems. Patients experiencing persistent severe sleep disturbances might be unknowingly developing cardiac dysfunction. These patients might then turn to melatonin seeking sleep relief while their hearts silently deteriorate.
Another possibility involves confounding factors that researchers could not fully control. More severe insomnia, depression, anxiety, or use of other sleep medications might be connected to both melatonin use and increased heart problems. It remains unclear whether melatonin itself causes the increased risk or whether these underlying conditions drive both melatonin use and heart failure.
Nnadi specifically stated that worse insomnia, depression, or anxiety might link to both melatonin use and heart risk. The quality and consistency of melatonin supplements add another complication. In America, over-the-counter supplements do not require government approval for quality or consistency. Different brands of melatonin can vary significantly in strength and purity. Actual melatonin content in marketed supplements may be up to 478% higher than labeled amounts.
What This Study Cannot Prove
The research team emphasized critical limitations regarding causal conclusions. This preliminary study cannot prove that melatonin directly causes heart failure. The study demonstrates only an association or correlation between melatonin use and increased heart failure risk. Showing 2 things occur together does not prove one causes the other. Scientists require randomized controlled trials to establish direct cause-and-effect relationships.
Such trials would need to randomly assign some patients to melatonin and others to inactive placebo treatments. Researchers would then track heart health outcomes over extended periods. Until such definitive studies are completed, scientists must characterize these findings as preliminary and concerning. The study has not been peer-reviewed or published in a scientific journal. Experts consider abstract presentations to be preliminary until researchers publish full manuscripts through peer review.
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Recommendations for Patients and Providers
Medical experts have offered guidance regarding melatonin use based on current knowledge. Doctors and patients should discuss long-term melatonin use more carefully going forward. Dr. Kanika Mody, another physician commenting on these findings, recommended that patients discuss sleep concerns with their healthcare providers. She particularly suggested that patients should undergo sleep tests to rule out conditions like sleep apnea.
Sleep apnea represents an important medical condition that might require different treatment approaches. Patients considering melatonin should understand it was not officially approved for treating insomnia in America. Alternative evidence-based approaches to insomnia management deserve consideration.
Cognitive behavioral therapy for insomnia represents an effective non-medication option. Lifestyle modifications, including regular exercise, sleep schedule consistency, and bedroom environment optimization, help many people. Medical evaluation should identify and treat any underlying conditions contributing to sleep problems.
Future Research Directions
The scientific community recognizes the need for additional investigation following these preliminary findings. Randomized controlled trials represent the next essential step toward understanding any true causal relationship. Such studies would need to enroll participants over long periods and closely monitor cardiac outcomes.
Researchers need to explore specific biological mechanisms that might explain how melatonin use could increase heart failure risk. This investigation would help clarify the contradiction between these findings and prior research suggesting cardiovascular benefits. Scientists should examine whether specific melatonin doses, supplement brands, or formulations might pose greater risk. Additional study focusing on melatonin’s long-term cardiovascular safety in populations without insomnia would provide valuable information.
Researchers should investigate whether the association remains strong when accounting for additional psychiatric conditions like depression. Understanding whether insomnia severity itself serves as an independent risk factor for heart failure would clarify results interpretation. Large prospective studies following people over time would help distinguish between melatonin use as a cause versus a marker of underlying cardiac risk.
Conclusion
The preliminary study linking melatonin use to increased heart failure risk has appropriately raised safety concerns within the medical and scientific communities. Over 130,000 patient records revealed that long-term melatonin users showed substantially elevated heart failure risk compared with matched non-users. The findings included increased hospitalization rates and higher mortality from any cause.
However, important limitations prevent definitive conclusions about direct causation. The study was conducted using electronic health records that may not capture all over-the-counter melatonin use. Results remain preliminary pending peer review and publication. Future research must determine whether melatonin itself causes the increased risk or whether underlying conditions explain the association.
Healthcare providers should counsel patients about melatonin’s uncertain long-term safety profile. Patients taking melatonin chronically without a clear medical indication should discuss this with their doctors. Until more definitive evidence emerges, individuals should consider evidence-based alternative approaches to managing insomnia.
Disclaimer: This information is not intended to be a substitute for professional medical advice, diagnosis or treatment and is for information only. Always seek the advice of your physician or another qualified health provider with any questions about your medical condition and/or current medication. Do not disregard professional medical advice or delay seeking advice or treatment because of something you have read here.
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