Has melatonin been used in studies for anti-premature ventricular contractions (PVCs)?

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Last updated: September 2, 2025View editorial policy

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Melatonin and Premature Ventricular Contractions: Evidence from Research

Melatonin has shown both antiarrhythmic and proarrhythmic effects in relation to premature ventricular contractions (PVCs), with limited human studies specifically examining this relationship.

Conflicting Evidence on Melatonin's Effects on PVCs

Proarrhythmic Evidence

  • A 2017 case report documented two patients with structurally normal hearts who developed symptomatic PVCs while taking melatonin for sleep disorders. Discontinuation of melatonin resolved the PVCs in both cases, suggesting a potential proarrhythmic effect 1.

Antiarrhythmic Evidence

  • Several animal studies have demonstrated melatonin's antiarrhythmic properties:
    • In rat models, melatonin prevented ventricular tachycardia/fibrillation (VT/VF) during ischemia and reperfusion through receptor-dependent enhancement of impulse conduction 2.
    • Melatonin prevented early ventricular fibrillation in a porcine model of acute myocardial infarction by preventing activation time increases in areas adjacent to ischemic zones 3.
    • Melatonin treatment was associated with lower VT/VF incidence at reperfusion in rat models 4.

Mechanism of Action

  • Melatonin's antiarrhythmic effects appear to be mediated through:

    • Receptor-dependent enhancement of impulse conduction
    • Association with connexin43 phosphorylation
    • Maintenance of resting membrane potential levels
    • Antioxidative properties 2, 4
  • However, blockade of melatonin receptors (MT1/MT2) abolishes its antiarrhythmic effect and can slow ventricular conduction in rat hearts 2.

Clinical Implications

  • For patients with symptomatic PVCs, the American College of Cardiology recommends beta-blockers (e.g., metoprolol, carvedilol) and non-dihydropyridine calcium channel blockers (e.g., verapamil, diltiazem) as first-line therapy 5.
  • Calcium channel blockers like diltiazem have shown effectiveness in reducing PVC frequency, particularly in patients whose PVCs show a positive correlation with heart rate 6.

Caveats and Considerations

  • The human evidence regarding melatonin's effect on PVCs is extremely limited, with only one small case report suggesting a proarrhythmic effect 1.
  • Most evidence comes from animal studies that may not translate directly to human clinical outcomes.
  • The American Academy of Sleep Medicine notes that melatonin is generally considered safe with few serious adverse effects reported in short-term use at doses ≤10 mg/day 7.
  • Patients with existing cardiac conditions should exercise caution when considering melatonin supplementation.

Conclusion

While animal studies suggest potential antiarrhythmic properties of melatonin, the limited human evidence indicates possible proarrhythmic effects in some individuals. Given this conflicting evidence, patients with PVCs should consult with their healthcare provider before using melatonin, and those experiencing new or worsening PVCs while taking melatonin should consider discontinuation and medical evaluation.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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