Melatonin and Heart Failure: Current Evidence
Melatonin is not included in any established heart failure treatment guidelines and should not be used as therapy for heart failure outside of research protocols. 1, 2, 3
Guideline-Directed Medical Therapy Remains the Standard
The established treatment for heart failure with reduced ejection fraction (HFrEF) consists of:
- ACE inhibitors or ARBs as first-line therapy combined with beta-blockers (bisoprolol, metoprolol succinate, carvedilol, or nebivolol) 1, 3
- Aldosterone antagonists, ARBs, or hydralazine-nitrate combinations as second-line therapy, depending on severity, ethnicity, and comorbidities 1, 3
- Diuretics for symptomatic fluid overload (pulmonary congestion or peripheral edema) 1, 3
For heart failure with preserved ejection fraction (HFpEF), focus on managing comorbid conditions including hypertension, ischemic heart disease, and diabetes 1, 3
Experimental Evidence on Melatonin
While melatonin is absent from clinical guidelines, recent research suggests potential mechanisms of benefit:
Proposed Mechanisms (Preclinical Data)
- Melatonin may counteract renin-angiotensin-aldosterone system and sympathetic overactivity, which are key pathological processes in heart failure 4
- Antioxidant and anti-inflammatory properties have been demonstrated in rodent models of cardiac injury 5, 6, 7
- Reduction in cardiac remodeling and fibrosis was shown in rat models of isoproterenol-induced heart failure, with improved survival rates 8
- Protection against ischemia-reperfusion injury has been documented in animal studies 6, 7
Clinical Trial Status
- The MeHR trial (Melatonin for Heart Failure with Reduced Ejection Fraction) is an ongoing double-blind randomized controlled trial evaluating 10 mg daily melatonin versus placebo in 90 outpatients over 24 weeks 4
- Primary outcomes include echocardiographic indices and NT-proBNP levels, with secondary endpoints of mortality, hospitalization, and quality of life 4
- No completed clinical trials have yet demonstrated efficacy or safety of melatonin in human heart failure patients 5
Critical Caveats
- All current evidence supporting melatonin comes from animal studies or theoretical mechanisms—there is no human clinical trial data demonstrating benefit 5, 6, 7, 8
- Potential drug interactions with guideline-directed medical therapy (ACE inhibitors, beta-blockers, ARBs) have not been adequately studied 4
- Safety profile in heart failure patients remains unknown, particularly regarding effects on blood pressure and cardiac rhythm 4, 5
Clinical Recommendation
Do not prescribe melatonin for heart failure management. Instead, optimize guideline-directed medical therapy with ACE inhibitors/ARBs, beta-blockers, and aldosterone antagonists as indicated 1, 3. If patients inquire about melatonin, explain that while animal research shows promise, human clinical trials are still ongoing and no evidence currently supports its use outside of research protocols 4, 5.