Long‑Term Melatonin Use and Cardiovascular Risk: Emerging Evidence of a Link with Heart Failure

While melatonin is widely considered a benign over-the-counter sleep aid, a recent large observational study suggests that chronic use (≥12 months) may be associated with a significantly increased risk of incident heart failure, hospitalisation, and mortality in adults with insomnia. These findings—presented at the American Heart Association (AHA) Scientific Sessions 2025—raise important questions about the long-term cardiovascular safety of melatonin. Given the study’s observational nature, causality remains unproven, yet the signal warrants caution and further research, particularly for patients with underlying cardiovascular risk or persistent sleep disorders.

Melatonin Intake is Linked to Heart Failure Risk

Introduction

Melatonin, the endogenous hormone produced by the pineal gland that governs circadian-rhythmic sleep-wake cycles, has been synthetically produced and marketed as a supplement to aid sleep and mitigate jet lag [1]. Because of its over-the-counter availability in many countries, and its general reputation as “natural” and safe, melatonin use has become common among adults with insomnia, shift-work sleep disorders, and other sleep disturbances [2,3].

Historically, melatonin has also been studied in experimental cardiovascular models, with some preclinical work suggesting potential cardioprotective effects via antioxidant, anti-inflammatory, and mitochondrial-stabilising mechanisms [4]. Nonetheless, long-term human cardiovascular safety data have been sparse [5].

Recent Study Overview

A recent analysis conducted by researchers led by Ekenedilichukwu Nnadi (SUNY Downstate/Kings County) and presented at the 2025 AHA Scientific Sessions used health-record data drawn from the international TriNetX Global Research Network.

Key features:

• Population: >130,000 adults with a diagnosis of chronic insomnia.

• Exposure: Long-term melatonin use, defined as documented use of melatonin (prescription in some jurisdictions) for ≥12 months.

• Outcomes: Incident heart failure, hospitalisation for heart failure, all-cause mortality over ~5 years.

Key Findings

• Adults with insomnia who used melatonin for ≥1 year had ~90% higher odds of incident heart failure over five years compared to matched non-users (4.6% vs. 2.7%).

• Hospitalisation for heart failure: melatonin users had ~3.5× the risk compared to non-users (19.0% vs. 6.6%).

• All-cause mortality over five years: melatonin users ~7.8% vs 4.3% in non-users (~2× risk).

Long-term Melatonin Consumption is related to Cardiovascular risk

Implications for Practice and Research

• Highlight as a hypothesis-generating safety signal in manuscripts on sleep medicine or supplement safety [1,3].

• Recommend caution regarding chronic nightly melatonin use in patients with cardiovascular risk factors [2,5].

• Further randomized controlled trials or long-term prospective studies are needed [4,5].

  
  

Conclusion

This observational analysis raises a potentially important safety signal: chronic melatonin use (≥12 months) in adults with chronic insomnia appears associated with higher rates of heart failure, hospitalisation, and life loss. While causality is not established, clinicians may wish to review long-term melatonin usage in their patients and consider alternative sleep-management strategies.

Sources

1. People. Melatonin Linked to 90% Higher Risk of Heart Failure. Available from: https://people.com/melatonin-linked-to-90-higher-risk-of-heart-failure-11842581

2. Good Housekeeping. I'm a Nutritionist. Here's the Truth About the Latest Melatonin Safety Scare. Available from: https://www.goodhousekeeping.com/health/wellness/a69262996/melatonin-heart-failure-study/

3. NY Post. Long-term use of this popular sleep supplement linked to 90% higher risk of heart failure. Available from: https://nypost.com/2025/11/04/health/long-term-melatonin-use-linked-to-higher-risk-of-heart-failure/

4. Science Daily. Long-term melatonin use may increase heart failure risk. Available from: https://www.sciencedaily.com/releases/2025/11/251104012959.htm

5. Washington Post. Study links long-term melatonin use with increased heart failure risk. Available from: https://www.washingtonpost.com/health/2025/11/03/melatonin-heart-failure-sleep-aid/

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