Is melatonin safe for patients with heart failure?

Melatonin Safety in Heart Failure Patients

Current evidence does not support routine melatonin use in heart failure patients, as major cardiology guidelines do not recommend it and the limited clinical trial data shows no clear benefit on cardiac function or clinical outcomes. 1

Guideline Position

• The European Society of Cardiology (ESC) 2012 Heart Failure Guidelines explicitly list melatonin efficacy and safety as an unresolved "gap in evidence" requiring future research. 1

• The Critical Care Medicine Society (2018) makes no recommendation for melatonin use in critically ill adults, including those with heart failure, citing very low quality evidence from three small trials (n=60 total) that showed no discernible improvement in sleep outcomes. 1

• No major heart failure guideline from ESC (2001,2012) or ACC/AHA (2022) includes melatonin in treatment algorithms for heart failure management. 1

Clinical Trial Evidence

The highest quality recent evidence comes from a 2025 meta-analysis of four clinical trials, which found:

• Melatonin showed a non-significant trend toward improved ejection fraction (mean difference 2.39%, p=0.27), meaning no proven cardiac benefit. 2

• NYHA functional class improvement was marginal (OR 4.84, p=0.05, barely reaching statistical significance). 2

• The only consistent benefit was improved quality of life scores (mean difference -5.95, p=0.001), suggesting primarily symptomatic rather than disease-modifying effects. 2

• NT-proBNP reduction and other cardiac parameters showed inconsistent results across studies. 2

Safety Considerations

Melatonin appears relatively safe with few adverse effects reported:

• Common side effects are limited to sedation and headache. 1

• No serious cardiac adverse events have been documented in heart failure trials. 3, 2

• Critical caveat: In the United States, melatonin is not FDA-regulated, raising concerns about product quality, consistency, and actual dosing, which has prevented many hospitals from formulary adoption. 1

Mechanistic Rationale vs. Clinical Reality

While experimental studies suggest melatonin may counteract renin-angiotensin-aldosterone system activation, reduce oxidative stress, and prevent cardiac remodeling 4, 3, 5, these laboratory findings have not translated into meaningful clinical benefits in human trials. 2

• Animal studies show reduced mortality and cardiac remodeling with melatonin in isoproterenol-induced heart failure 5, but human data remains insufficient.

• Observational data suggests melatonin secretion is impaired in advanced heart failure (NYHA III), with negative correlation to NT-proBNP levels 6, but supplementation trials have not proven this deficiency is clinically relevant to correct.

Clinical Recommendation Algorithm

For heart failure patients requesting sleep aids or melatonin:

1. First-line: Optimize guideline-directed medical therapy (beta-blockers, ACE inhibitors/ARNIs, MRAs, SGLT2 inhibitors) as these improve both outcomes and symptoms. 1

2. Address sleep hygiene: Use non-pharmacologic interventions (earplugs, eyeshades, noise reduction) which have better evidence for sleep improvement than melatonin. 1

3. If pharmacologic sleep aid needed: Consider alternatives with established safety profiles rather than melatonin, given lack of proven cardiac benefit.

4. If patient insists on melatonin: It can be used cautiously (3-10 mg at bedtime) given low risk of harm 1, 3, 2, but counsel that it will not improve cardiac function or prognosis and may only provide modest symptomatic benefit for sleep quality.

Key Pitfalls to Avoid

• Do not prescribe melatonin expecting cardiac improvement—the evidence does not support disease modification. 2

• Do not delay or substitute melatonin for proven heart failure therapies (beta-blockers, ACE inhibitors, MRAs, SGLT2 inhibitors). 1

• Verify product quality if prescribing, as unregulated supplements may have inconsistent dosing. 1