Study Findings on Long-Term Melatonin Use and Cardiovascular Risk
New research presented at the American Heart Association’s 2025 Scientific Sessions warns of potential health risks associated with long-term melatonin supplementation. An analysis of over 130,000 adults with insomnia from multiple countries found that those prescribed melatonin for more than one year had an 89 percent higher risk of heart failure diagnosis within five years compared to those not prescribed melatonin. Additionally, long-term users faced nearly triple the risk of hospitalization due to heart failure and a twofold increase in all-cause mortality.
Melatonin, a hormone naturally secreted by the pineal gland, regulates the body’s circadian rhythm and sleep-wake cycle. Synthetic melatonin supplements are commonly used to alleviate insomnia and jet lag. While short-term use (typically 1 to 2 months) is widely considered safe and well-tolerated, evidence supporting the safety of prolonged supplementation has been limited.
Contextualizing Melatonin’s Role in Cardiovascular Health
Contrasting with the new observational findings, prior research has shown that melatonin’s biological functions extend beyond sleep regulation. Melatonin exhibits antioxidant, anti-inflammatory, and metabolic regulatory properties. Several experimental studies suggest it may confer protection against cardiovascular conditions such as ischemia-reperfusion injury, hypertension, atherosclerosis, and heart failure through multiple mechanisms including the reduction of oxidative stress and modulation of lipid metabolism.
These findings hint at a complex relationship between melatonin and cardiovascular health, with therapeutic potential noted in preclinical and some clinical contexts. However, the new large-scale epidemiological data highlight a potential risk associated with long-term exogenous melatonin use that warrants further rigorous investigation.
Limitations and Expert Commentary
The study’s design, relying on electronic health records to classify melatonin use, introduces notable limitations. It is unclear whether patients classified as non-users include individuals self-administering over-the-counter melatonin, particularly in countries like the United States where the hormone is widely available without prescription. This could confound comparisons and risk estimates.
Carlos Egea, President of the Spanish Federation of Sleep Medicine Societies, emphasizes the need for prospective randomized controlled trials to confirm these associations and clarify melatonin’s safety profile when used chronically. Despite methodological caveats, the findings challenge the common perception of melatonin as an entirely benign supplement for long-term use and suggest caution in clinical recommendations.
Implications for Public Health and Clinical Practice
Melatonin is one of the most popular natural supplements in the United States and increasingly worldwide. Its accessibility without medical supervision raises public health concerns about unmonitored prolonged use, especially in vulnerable populations such as older adults or those with pre-existing cardiovascular conditions.
Healthcare providers should be aware of emerging evidence suggesting potential adverse effects from long-term melatonin use. Patients using melatonin for chronic insomnia or sleep disorders should engage in discussions with their clinicians to weigh benefits and risks carefully and consider alternative evidence-based treatments when appropriate.
Next Steps in Research
Given melatonin’s widespread use and the new findings associating long-term use with increased heart failure and mortality risks, further studies are urgently needed. Well-designed prospective clinical trials and mechanistic research will help determine causality, optimal dosing regimens, and identify patient groups for whom melatonin supplementation might be safe or harmful.
This research highlights a critical gap in knowledge about the long-term safety of a commonly used supplement and underscores the importance of rigorous evaluation before endorsing chronic use.
For comprehensive information on melatonin’s effects and safety, readers can consult health experts such as the World Health Organization and guidance from major medical institutions.
Read more on Globally Pulse Health for the latest updates on sleep aids and cardiovascular research.
