Melatonin and Heart Health: New Study Sparks Concern, But Experts Urge Calm

Melatonin—the over-the-counter sleep aid millions rely on—has long enjoyed a reputation as one of the safest supplements on pharmacy shelves. But a new study published last week in Journal of Clinical Sleep Medicine has thrust the hormone into an unfamiliar spotlight, reporting a 42% higher risk of heart failure among regular users compared to non-users. Headlines blared warnings; social media threads filled with anxious insomniacs tossing amber bottles into drawers. Yet within 48 hours, cardiologists, sleep specialists, and pharmacologists issued a near-unanimous counter-message: don’t panic—yet.The Study at a GlanceResearchers at the University of Eastern Finland analyzed electronic health records from 2015–2023, covering 987,000 adults aged 40–79. After adjusting for age, sex, BMI, smoking, alcohol use, diabetes, hypertension, and baseline cardiovascular disease, the hazard ratio for incident heart failure among those filling at least four melatonin prescriptions annually stood at 1.42 (95% CI: 1.31–1.54). The association strengthened with cumulative dose: individuals exceeding 730 defined daily doses (typically 2 mg) over the study period faced a 68% elevated risk.On the surface, the numbers appear damning. Heart failure currently affects 6.7 million Americans and costs the healthcare system $30.7 billion yearly; any modifiable risk factor demands scrutiny. Yet population-level epidemiology is a blunt instrument, and this study—despite its size—carries caveats that temper alarm.Correlation, Not Causation“Observational data can only generate hypotheses, not conclusions,” stresses Dr. Sanjiv Narayan, professor of cardiovascular medicine at Stanford University. “People reach for melatonin because they can’t sleep. Chronic insomnia itself is a known predictor of heart failure through sympathetic overdrive, inflammation, and endothelial dysfunction. The study adjusted for many confounders, but residual confounding by indication remains plausible.”In plain terms: sicker, more stressed individuals are both more likely to take melatonin and more likely to develop heart failure. The Finnish team attempted to mitigate this by excluding anyone with a sleep apnea diagnosis—common among heart failure patients—but insomnia severity, restless legs syndrome, shift-work status, and over-the-counter purchases (not captured in prescription databases) slipped through the statistical net.Dose and Duration Matter—Or Do They?The risk gradient with higher cumulative exposure initially suggests a dose-response relationship, a hallmark of causality. Yet melatonin pharmacokinetics complicate the picture. The hormone’s half-life is roughly 45 minutes; typical bedtime doses (1–5 mg) produce supra-physiologic plasma peaks 100–200 times above natural nocturnal levels, then rapidly decline. Chronic low-dose exposure—the pattern most strongly linked to heart failure in the study—rarely occurs with standard use.“Most Americans take melatonin intermittently,” notes Dr. Cathy Goldstein, sleep neurologist at University of Michigan. “Four or more annual prescriptions likely flags a subset with refractory insomnia, psychiatric comorbidity, or polypharmacy—precisely the patients at elevated cardiovascular risk independent of the supplement.”Biological Plausibility: A Mixed BagMelatonin receptors (MT1 and MT2) populate cardiac myocytes and vascular endothelium. Preclinical models demonstrate antioxidant, anti-inflammatory, and blood-pressure-lowering effects—properties that should protect the heart. Human trials, albeit small, have shown improved endothelial function in hypertensive patients given 3 mg controlled-release melatonin nightly.Counter-evidence emerges from melatonin’s chronobiotic role. Shifting circadian phase in night-shift workers raises cardiovascular risk; exogenous melatonin could theoretically exacerbate misalignment in susceptible individuals. Additionally, high-dose melatonin mildly suppresses sympathetic tone acutely but may trigger rebound tachycardia upon clearance—a phenomenon documented in ICU settings.Still, no prior randomized trial has reported heart failure as an adverse event. A 2022 meta-analysis of 1,682 participants across 26 RCTs found no increase in serious cardiovascular outcomes with melatonin up to 10 mg nightly for durations up to two years.Expert Consensus: Keep Taking It (For Now)The American Academy of Sleep Medicine, European Sleep Research Society, and World Heart Federation issued a joint statement November 1: “Current evidence does not support discontinuing melatonin for insomnia based on this single observational study. Patients concerned about cardiovascular risk should discuss non-pharmacologic sleep hygiene and cognitive behavioral therapy for insomnia (CBT-I) with their physician.”Dr. Phyllis Zee, chief of sleep medicine at Northwestern University, adds a practical algorithm: “Reserve melatonin for short-term use (≤2 weeks) in jet lag or shift work. For chronic insomnia, prioritize CBT-I. If melatonin is necessary long-term, opt for the lowest effective dose—0.3 to 1 mg—and take it 30–60 minutes before desired bedtime to mimic physiologic release.”Who Should Worry—and Who Shouldn’tLow Concern: Occasional users (≤3 nights/week), Doses ≤1 mg, Age <65, no cardiovascular risk factors, No history of arrhythmia or QT prolongation.Heightened Vigilance: Known heart failure or reduced ejection fraction, Concurrent use of QT-prolonging medications, Daily use >3 mg for >3 months, Night-shift workers with irregular schedules.What the Data Really Tell UsTo contextualize the 42% relative risk increase, absolute risk matters more for individual decision-making. In the Finnish cohort, the baseline 8-year heart failure incidence was 2.1% among non-users. A hazard ratio of 1.42 translates to an absolute risk difference of roughly 0.9%—or 9 additional cases per 1,000 regular users over eight years. For a healthy 50-year-old, that incremental risk pales against the 15–20% lifetime heart failure probability conferred by hypertension or diabetes alone.Moreover, the study’s reliance on prescription fills excludes the majority of U.S. melatonin consumption, which occurs over-the-counter. A 2023 National Health Interview Survey found 19.4 million American adults used melatonin in the past 30 days; fewer than 5% obtained it via prescription. If OTC users mirror prescription patterns, the exposed population balloons, diluting per-person risk further.Alternative Explanations AboundSeveral unmeasured variables could explain the association. Socioeconomic status predicts both supplement use and healthcare access; lower-income individuals may fill prescriptions more reliably while facing higher heart failure rates due to delayed care. Genetic polymorphisms in melatonin receptor genes (MTNR1A/B) influence both sleep architecture and cardiovascular reactivity—potentially creating a spurious link in observational data.Perhaps most critically, reverse causation looms large. Early heart failure symptoms—paroxysmal nocturnal dyspnea, orthopnea—disrupt sleep months before formal diagnosis. Patients self-medicating with melatonin during this prodromal phase would appear as “exposed” cases despite the supplement playing no causal role.The Road Ahead: What Studies We NeedRandomized controlled trials remain the gold standard. Two are already underway: the MEL-HEART trial (n=1,200) testing 2 mg controlled-release melatonin versus placebo in patients with heart failure with preserved ejection fraction, and the CIRCA-MEL study (n=800) examining cardiovascular biomarkers in chronic insomnia patients randomized to CBT-I, melatonin, or both. Results expected 2027–2028.In the interim, pharmacovigilance databases offer reassurance. The FDA’s FAERS system logs fewer than 50 cardiovascular serious adverse event reports linked to melatonin since 2010—versus thousands for common NSAIDs. European Medicines Agency data mirror this safety signal (or lack thereof).Practical Takeaways for ConsumersDon’t abruptly stop melatonin if it’s helping your sleep. Sudden cessation can worsen insomnia and elevate cortisol, indirectly stressing the cardiovascular system. Audit your dose. Most adults need only 0.3–1 mg to advance sleep phase; higher doses primarily increase side effects like morning grogginess. Time it right. Take melatonin 30–60 minutes before desired bedtime to align with natural secretion patterns. Immediate-release formulations better mimic physiology than sustained-release for sleep onset. Layer non-drug strategies. CBT-I—available via apps like Sleepio or in-person therapists—outperforms melatonin long-term for chronic insomnia. Core components: sleep restriction, stimulus control, cognitive restructuring. Monitor for red flags. Discontinue and consult a physician if you experience palpitations, edema, or exertional dyspnea while using melatonin. Special populations exercise caution. Older adults (>75), those with bradycardia, or patients on beta-blockers should start at 0.5 mg maximum and monitor heart rate. The Bottom LineScience thrives on replication, not single studies. The Finnish analysis raises a legitimate signal warranting investigation but falls far short of proving melatonin causes heart failure. For the vast majority of users—particularly those taking low doses occasionally—the benefits for sleep likely outweigh theoretical risks.As Dr. Narayan summarizes: “Melatonin remains one of the best-tolerated compounds in our pharmacopeia. Let’s not allow one observational study to undo decades of safety data—especially when the real villain may be the sleeplessness driving people to take it.”