Long-Term Melatonin Use Linked to 90% Higher Heart Failure Risk in Insomnia Patients

Introduction

Melatonin, a hormone naturally produced by the body to regulate sleep-wake cycles, is widely available as an over-the-counter supplement. It's often perceived as a harmless, natural remedy for insomnia and jet lag. However, new preliminary research presented at the American Heart Association's Scientific Sessions 2025 raises significant questions about the long-term cardiovascular safety of this popular sleep aid. The study found a striking association between chronic melatonin use and a substantially higher risk of developing heart failure, hospitalization for heart failure, and even death from any cause among individuals with chronic insomnia.

Key Details

• A study of 130,828 adults diagnosed with chronic insomnia found that those with documented long-term melatonin use (12 months or more) had approximately a 90% higher risk of developing heart failure over a five-year period compared to matched non-users.
• Heart failure incidence was 4.6% in the melatonin group versus 2.7% in the non-melatonin group.
• A secondary analysis revealed that individuals using melatonin long-term were nearly 3.5 times more likely to be hospitalized for heart failure (19.0% vs. 6.6%).
• Deaths from any cause were also more common in the melatonin group, with a nearly twofold higher risk (7.8% vs. 4.3%).
• A sensitivity analysis, requiring at least two melatonin prescriptions at least 90 days apart, still showed an 82% higher risk of heart failure, strengthening the association.
• The study utilized de-identified electronic health records from the TriNetX Global Research Network, covering five years of data.
• Participants were adults with chronic insomnia, aged 55.7 years on average, with 61.4% being women. Exclusions included individuals with pre-existing heart failure or those prescribed other sleep medications.

Background

Melatonin is a hormone produced by the pineal gland, crucial for maintaining the body's circadian rhythm. Its synthetic counterpart is widely used to combat insomnia and jet lag. In many regions, including the U.S., melatonin supplements are available without a prescription, leading to varied product strengths and purity levels due to a lack of stringent regulation for supplements. Despite its popularity and perceived safety, robust evidence regarding its long-term cardiovascular effects, especially when used chronically, has been limited. This gap in knowledge prompted the researchers to investigate potential links between prolonged melatonin intake and heart health outcomes in a population already vulnerable due to chronic insomnia.

Impact Analysis

The study's primary finding—a 90% increased risk of heart failure among long-term melatonin users with chronic insomnia—is a significant concern. This elevated risk, coupled with a 3.5-fold increase in heart failure hospitalizations and nearly double the risk of all-cause mortality, suggests that melatonin may not be as benign as commonly believed, particularly for individuals with pre-existing sleep disorders. The consistency of the findings, even after a sensitivity analysis, adds weight to the association. Lead author Dr. Ekenedilichukwu Nnadi noted, “Melatonin supplements may not be as harmless as commonly assumed. If our study is confirmed, this could affect how doctors counsel patients about sleep aids.”

“Melatonin supplements are widely thought of as a safe and 'natural' option to support better sleep, so it was striking to see such consistent and significant increases in serious health outcomes, even after balancing for many other risk factors.”

Broader Context

The widespread use of over-the-counter supplements like melatonin, often without medical supervision, presents a public health challenge. As Dr. Marie-Pierre St-Onge, a sleep researcher not involved in the study, pointed out, “In the U.S., melatonin can be taken as an over-the-counter supplement and people should be aware that it should not be taken chronically without a proper indication.” This highlights a disconnect between consumer perception and clinical guidance. The study's findings, if validated, could necessitate a re-evaluation of recommendations for chronic insomnia management, potentially shifting focus towards non-pharmacological interventions or prescription medications with better-established safety profiles for long-term use.

Future Outlook

While this study provides compelling preliminary evidence, it is crucial to acknowledge its limitations. The observational nature means a direct causal link cannot be definitively established. Furthermore, the reliance on electronic health records means that over-the-counter melatonin use, particularly in countries like the U.S., might have been underreported, potentially biasing the results. Researchers did not have data on the severity of insomnia, other psychiatric comorbidities, or the precise dosage and purity of the melatonin used. Future research should aim to replicate these findings using more controlled study designs, such as randomized controlled trials, and investigate the specific biological mechanisms through which melatonin might impact cardiovascular function. Understanding these mechanisms is key to confirming causality and developing safer treatment strategies.

Conclusion

This preliminary study from the American Heart Association raises a significant red flag regarding the long-term use of melatonin in individuals with chronic insomnia. The observed 90% higher risk of heart failure, alongside increased hospitalizations and mortality, challenges the prevailing notion of melatonin's universal safety. While the findings warrant caution and further investigation, they underscore the importance of consulting healthcare professionals before embarking on long-term supplement use, especially for individuals managing chronic health conditions. More research is imperative to clarify the relationship between melatonin and cardiovascular health.