Is Melatonin Linked to Heart Failure?

In November 2025, a headline swept through cardiology circles and mainstream media alike: long-term melatonin use linked to 89% higher risk of heart failure. The study, presented at the American Heart Association's annual Scientific Sessions, covered more than 130,000 patients and triggered genuine alarm — melatonin is taken by an estimated 6% of US adults, and many had considered it one of the safest things in their medicine cabinet. But a closer look at the actual data reveals a story that is both more reassuring and more complicated than the headline suggests — one where "linked" does not mean "caused," where the same year's peer-reviewed RCT evidence points in the opposite direction, and where the real lesson is about how you use melatonin, not whether it exists in your home.

Table of Contents

1. The Study That Started the Alarm: What It Actually Found
2. The Myth Examined: Why "Linked" Is Not "Caused"
3. The Evidence Running the Other Way
4. How Melatonin Interacts With the Heart
5. Melatonin Drug Interactions for Heart Patients
6. Who Should Be Most Cautious
7. Dose, Format, and Duration: Why They Change the Risk Equation
8. Frequently Asked Questions
9. Conclusion
10. Research References

1. The Study That Started the Alarm: What It Actually Found

The research at the centre of the 2025 melatonin panic was presented at the American Heart Association's Scientific Sessions in November 2025. Researchers queried the TriNetX Global Research Network — an international database of electronic health records — identifying 130,828 adults with diagnosed chronic insomnia. They matched 65,414 people who had at least one melatonin prescription and at least 365 days of documented use against 65,414 non-users, balancing them across more than 40 variables: demographics, 15 comorbidities, medications, lab values, and vital signs.

Over five years, new-onset heart failure occurred in 4.6% of melatonin users versus 2.7% of controls — a hazard ratio of 1.89, or roughly 89% higher relative risk. Hospitalization for heart failure was 19.0% in the melatonin group versus 6.6% in controls, about 3.5 times higher. All-cause mortality was also elevated at 7.8% versus 4.3%. The American College of Cardiology put the absolute risk difference in context: 1.9 percentage points for new-onset heart failure over five years — meaningful at population scale, but a different way of reading the same numbers that generated "89% higher risk" headlines.

It is worth holding the study population in mind throughout: every single participant had diagnosed chronic insomnia — a condition independently associated with elevated cardiovascular risk through higher night-time heart rates, elevated blood pressure, and systemic inflammation. The melatonin group specifically consisted of people whose insomnia was serious enough for a clinician to prescribe melatonin and document it in an electronic health record. This is not the population of a healthy adult taking melatonin for occasional jet lag.

2. The Myth Examined: Why "Linked" Is Not "Caused"

The word "linked" in the AHA headline is doing enormous work — and understanding what it can and cannot mean is the core of this article. The study was observational: it identified a statistical association between melatonin use and heart failure in one specific population. It did not — and cannot, by design — establish that melatonin caused any of those heart failure cases. The AHA's own press release acknowledged this explicitly, describing the results as "preliminary" and stating the study "cannot prove a cause-and-effect relationship." Crucially, the study has not yet been published in a peer-reviewed journal; it was presented as a conference abstract, which undergoes less rigorous scientific vetting than a standard journal submission.

The most significant methodological flaw identified by independent researchers involves the control group. In the United States, melatonin is an over-the-counter supplement — no prescription required. That means millions of Americans who buy melatonin at a pharmacy or online would be coded as "non-users" in a health records database, because there is no prescription entry to capture their use. The Council for Responsible Nutrition identified this as a severe exposure misclassification problem: the "non-user" group was not a clean control, but likely contained large numbers of OTC melatonin users — which would compress the apparent difference between groups and make the melatonin effect look larger than it may actually be.

Several other critical data points were simply absent: no information on melatonin dose (1mg nightly versus 20mg nightly are treated identically), no data on insomnia severity, no psychiatric comorbidity data (depression and anxiety are both independent heart disease risk factors common in insomnia patients), and no sleep apnea status. As UR Medicine cardiologist Dr. Andrew Mathias observed: people prescribed long-term melatonin may simply have had more severe underlying health problems to begin with — not heart problems caused by the supplement.

3. The Evidence Running the Other Way

What received far less coverage than the AHA abstract was peer-reviewed research published the same year reaching the opposite conclusion. The Daliri et al. 2025 meta-analysis, published in Clinical Cardiology, analyzed randomized controlled trials of melatonin in patients who already had heart failure. Across 166 participants in RCTs, melatonin significantly improved quality of life (p=0.001), reduced fatigue, lowered NT-Pro BNP (a key heart failure severity biomarker), and improved NYHA functional class scores. The authors concluded melatonin "could be advised as a novel drug for treatment and palliating heart failure." This is peer-reviewed, RCT-based, and published after the AHA abstract — not fringe research.

A broader body of evidence also points toward cardioprotective effects. A 2022 review in Antioxidants found that melatonin administered within 2.5 hours of chest pain onset reduced infarct size by approximately 40% in clinical studies. A 2021 systematic review and meta-analysis in Frontiers in Cardiovascular Medicine found melatonin reduced troponin levels — a marker of cardiac injury — and showed potential to preserve ejection fraction in patients undergoing cardiac revascularization. Melatonin's antioxidant mechanisms are well-established: it scavenges free radicals, suppresses pro-inflammatory cytokines including TNF-α, IL-6, and IL-1β, and reduces LDL cholesterol oxidation.

The apparent contradiction between these findings and the AHA abstract is not actually a contradiction in the data — it reflects the fundamental difference between an observational study of a confounded insomnia population and controlled trials measuring melatonin's direct biological effects. Observational studies capture everything correlated with being prescribed long-term melatonin for insomnia, including severe sleep disorders and possible undetected cardiac disease. RCTs isolate melatonin's effect by controlling for those variables. The honest current state of knowledge: melatonin appears to have genuine cardioprotective mechanisms in controlled settings, while long-term chronic use in an insomnia context — where insomnia itself is a cardiac risk factor — warrants more rigorous study.

4. How Melatonin Interacts With the Heart

Understanding why the evidence is so mixed requires understanding how melatonin interfaces with cardiovascular physiology. It is not simply a sleep hormone — it is a signaling molecule with receptors (MT1 and MT2) expressed throughout the cardiovascular system, including in vascular smooth muscle, coronary arteries, and cardiac tissue. Clinical research shows melatonin can modulate the renin-angiotensin-aldosterone system (RAAS), stimulate nitric oxide production, and reduce sympathetic nervous system activity — all pathways with direct blood pressure and cardiac output implications.

Natural melatonin production declines with age by as much as 80% between ages 20 and 70. This decline is clinically meaningful: lower melatonin levels in older adults correlate with disrupted circadian rhythm, poorer sleep quality, and reduced antioxidant defence — all of which independently increase cardiovascular risk. Restoring melatonin toward physiological levels in a deficient older adult is a different biological act than pushing levels far above the body's natural range in a younger person with normal production. That distinction matters enormously in assessing risk — and most OTC melatonin products in the US, offered in 5mg to 20mg doses, deliver far more than what the body typically produces (natural peak secretion is approximately 0.1–0.3mg per night).

Blood pressure effects illustrate this dose-and-context dependency clearly. A placebo-controlled study in Hypertension found that 2.5mg nightly melatonin reduced nocturnal systolic blood pressure by 6 mmHg and diastolic by 4 mmHg in untreated hypertensive patients. Yet a separate RCT in the British Journal of Clinical Pharmacology found that melatonin raised 24-hour systolic blood pressure by 6.5 mmHg in patients already on the calcium channel blocker nifedipine. Same molecule, opposing cardiovascular outcomes — depending entirely on what else was in the clinical picture.

5. Melatonin Drug Interactions for Heart Patients

For anyone on cardiovascular medications, the interaction question is often more immediately practical than the long-term heart failure question. Mayo Clinic identifies several clinically relevant interactions. The most clearly documented involves anticoagulants: melatonin can enhance the blood-thinning effects of warfarin and similar drugs, increasing bleeding risk. Patients on warfarin who add melatonin may need more frequent INR monitoring — the interaction should be disclosed to a prescriber before starting.

Blood pressure drug interactions are less predictable and depend heavily on drug class. Calcium channel blockers (amlodipine, nifedipine, diltiazem, verapamil) appear particularly susceptible, with research suggesting melatonin can blunt their antihypertensive efficacy. Clonidine combined with melatonin can produce excessive blood pressure and heart rate reduction. Other relevant interactions for heart patients include:

• Antiplatelet drugs (aspirin, clopidogrel): additive bleeding risk
• Immunosuppressants (used after heart transplant): melatonin may interfere by stimulating immune function
• Antiarrhythmics metabolised via shared hepatic enzymes: potential concentration changes requiring monitoring

The practical message is not to avoid melatonin categorically if you have heart disease — it is to treat melatonin as a pharmacologically active substance, not a benign supplement, when you are already on a cardiovascular medication regimen. A review of your full medication list with a cardiologist or pharmacist before starting is the baseline standard of care.

6. Who Should Be Most Cautious

Based on the current evidence, certain groups carry meaningfully higher risk and should approach melatonin with heightened care and explicit medical supervision. People on anticoagulant therapy — warfarin, apixaban, rivaroxaban — face the most clearly documented interaction risk. The blood-thinning potentiation is real, documented, and actionable: disclose melatonin use to your prescriber before starting. People on calcium channel blockers for hypertension or arrhythmia management are a second high-priority group, given the evidence that melatonin may partially offset these drugs' antihypertensive effect.

Adults over 65 warrant particular attention. The NIH NCCIH specifically recommends this age group speak with a healthcare provider before taking any melatonin supplement, as older adults were underrepresented in most safety trials and may clear melatonin more slowly — meaning standard doses can produce higher-than-expected blood levels and more prolonged effects. This is why 0.5mg can be an appropriate starting dose for an older adult where a younger person might use 1–3mg.

The group the AHA 2025 data is most directly relevant for is people considering long-term nightly melatonin use specifically to manage chronic insomnia. Both the American Academy of Sleep Medicine and VA guidelines recommend against melatonin for chronic insomnia due to insufficient evidence. Persistent insomnia deserves a medical evaluation — it may signal underlying conditions, including cardiac ones, that melatonin supplementation would not address and could potentially mask.

7. Dose, Format, and Duration: Why They Change the Risk Equation

If the evidence points toward any consistent safety principle, it is this: the risk profile of melatonin is not fixed — it is heavily shaped by how much you take, how often, and in what form. The AHA 2025 data studied people using melatonin for at least 365 consecutive days for a condition it is not approved to treat in the US. That is a fundamentally different picture than a healthy adult taking melatonin for three nights after a transatlantic flight. Most of the OTC melatonin market offers doses between 5mg and 10mg — sometimes 20mg — despite the body's natural nightly production peaking at approximately 0.1–0.3mg. Supraphysiological doses taken chronically represent the riskiest pattern the evidence identifies.

Delivery format affects how much of a given dose actually reaches the bloodstream. Standard oral tablets have bioavailability of approximately 15–20%, meaning the majority of what is swallowed is lost to first-pass liver metabolism. BioAbsorb Liposomal Liquid Melatonin uses liposomal encapsulation to achieve 80–95% bioavailability — the same therapeutic effect at a significantly lower actual dose. Its graduated dropper delivers 1.5mg per full 1ml pull with increments of approximately 0.25mg, enabling the precise low-dose titration that cautious clinicians and sleep researchers consistently recommend. Starting at 0.5mg with a high-bioavailability format is a meaningfully different proposition than swallowing a 10mg tablet every night for a year.

Manufactured in a Health Canada-approved, GMP-certified Canadian facility with every batch third-party tested and COAs available on request, BioAbsorb's formulation is non-GMO, vegan, gluten-free, and free from artificial flavours and colours. At $29.99 for 100ml (100 full-dropper servings, considerably more at lower doses), it provides quality-controlled, precision-dosable melatonin at a price point that does not incentivise overuse. For anyone with cardiovascular concerns who gets medical clearance to use melatonin, starting low and staying short — with a format that actually delivers what it says at the dose it says — is the most evidence-aligned approach currently available.

Frequently Asked Questions

Does melatonin cause heart failure?

No study has proven melatonin causes heart failure. The 2025 AHA abstract found an association in a specific chronic insomnia population — but the AHA itself states it "cannot prove a cause-and-effect relationship." The study was observational, not peer-reviewed, contained no dose data, and almost certainly misclassified OTC melatonin users as non-users in the control group. The scientific community's response has been consistent: this warrants randomized controlled trials, not a conclusion that melatonin is cardiotoxic.

Should I stop taking melatonin because of the 2025 study?

If you use melatonin occasionally for jet lag or short-term circadian disruption, the AHA study is not directly relevant to your situation — it studied people with chronic insomnia taking prescription melatonin for over a year. If you have been using melatonin nightly for months as a primary insomnia treatment and have cardiovascular risk factors, that is worth a conversation with your doctor — both because of the AHA signal and because melatonin is not recommended for chronic insomnia in the first place.

Is there evidence melatonin actually helps people with heart failure?

Yes, from peer-reviewed RCT data. A 2025 meta-analysis in Clinical Cardiology found melatonin significantly improved quality of life (p=0.001), reduced fatigue, and lowered NT-Pro BNP in people already diagnosed with heart failure. A 2021 meta-analysis of RCTs also found reduced troponin levels and potential ejection fraction preservation in cardiac patients. These findings do not mean heart failure patients should self-prescribe — they mean the cardiovascular story is not one-sided.

Can I take melatonin if I'm on blood pressure medication?

It depends on the specific drug. Mayo Clinic notes melatonin may worsen blood pressure control in some patients on antihypertensives, particularly calcium channel blockers. A separate clinical RCT found nightly melatonin reduced nocturnal blood pressure by 6 mmHg in untreated hypertensive patients — pointing in the opposite direction. The effect is drug-specific and not predictable without knowing your full medication list, which is precisely why a prescriber review is essential before combining the two.

What dose is safest if I have heart concerns?

No dose has been specifically established as safe for cardiac patients, but the consistent evidence-based principle is to start as low as possible — 0.5mg is a reasonable starting point for most adults, well below the 5–10mg common in OTC products. Lower doses reduce the risk of supraphysiological blood levels and minimise the magnitude of any drug interactions. Anyone with heart conditions should determine dose with a cardiologist who knows their complete medication list.

How does the 2025 AHA study compare to other melatonin research?

It sits in direct tension with several peer-reviewed meta-analyses published around the same time. The Daliri et al. 2025 meta-analysis found melatonin beneficial in heart failure patients; the 2021 Frontiers meta-analysis found cardioprotective effects in RCTs. The AHA abstract was larger in scale but weaker in design — observational rather than controlled, and not yet peer-reviewed. The scientific community's response has been that the signal warrants further investigation, not a clinical recommendation to avoid melatonin.

Conclusion

The 2025 AHA headline was accurate in a narrow sense and misleading in a broader one. The link is real in the observational data; what is not real is the implied causation, and what is missing from the coverage is the peer-reviewed evidence from the same year showing melatonin may benefit people who already have heart failure. The honest answer to "is melatonin linked to heart failure?" is: there is an association worth taking seriously in one specific population using it one specific way — and a body of controlled evidence that tells a more protective story. How you use melatonin — the dose, the duration, the format, and whether you are on cardiovascular medications — changes the risk calculation substantially. Short-term, low-dose use for circadian purposes remains well-supported. Long-term nightly use for chronic insomnia was already not recommended before 2025, and the AHA data adds another reason to heed that guidance. If you have a heart condition, start with a cardiologist conversation; if you get the green light, start low, stay short, and use a format you can trust.

Research References

1. Effect of Long-term Melatonin Supplementation on Incidence of Heart Failure in Patients with Insomnia. Circulation (AHA Scientific Sessions 2025 Abstract), Vol. 152, Suppl. 3 (2025). Nnadi et al. Observational study of 130,828 insomnia patients finding an 89% higher hazard of incident heart failure in long-term melatonin users; authors confirm this cannot establish causation. Not yet peer-reviewed.
2. Melatonin as a Novel Drug to Improve Cardiac Function and Quality of Life in Heart Failure Patients: A Systematic Review and Meta-Analysis. Clinical Cardiology, Vol. 48 (2025). Daliri et al. Meta-analysis of RCTs demonstrating melatonin significantly improved quality of life (p=0.001), reduced fatigue and NT-Pro BNP, and improved NYHA functional class in heart failure patients.
3. Role of the Antioxidant Activity of Melatonin in Myocardial Ischemia-Reperfusion Injury. Antioxidants (Basel), Vol. 11, No. 4 (2022). Reviews preclinical and clinical evidence showing melatonin's antioxidant mechanisms reduce infarct size by approximately 40% in early-administration cardiac studies.
4. Melatonin and Cardioprotection in Humans: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Frontiers in Cardiovascular Medicine, Vol. 8 (2021). Systematic review of RCTs finding melatonin reduced troponin levels and showed potential to preserve ejection fraction in cardiac revascularization patients.
5. Daily Nighttime Melatonin Reduces Blood Pressure in Male Patients With Essential Hypertension. Hypertension (AHA journal), Vol. 43 (2004). Placebo-controlled crossover RCT demonstrating 2.5mg nightly melatonin reduced nocturnal systolic blood pressure by 6 mmHg and diastolic by 4 mmHg in untreated hypertensive patients.
6. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. British Journal of Clinical Pharmacology, Vol. 49 (2000). RCT demonstrating melatonin raised 24-hour systolic BP by 6.5 mmHg and heart rate by 3.9 beats/min in patients on nifedipine, establishing a clinically relevant drug-supplement interaction.
7. The Effect of Melatonin Supplement on High Arterial Blood Pressure: An Overview from Clinical Trials. Vascular Health and Risk Management, Vol. 20 (2024). Clinical trial overview finding melatonin modulates RAAS, nitric oxide production, and sympathetic nervous system activity, with mixed blood pressure results that are dose- and duration-dependent.
8. Melatonin: What You Need to Know. National Institutes of Health — National Center for Complementary and Integrative Health (2023). Official NIH overview confirming short-term melatonin use appears safe while long-term safety remains incompletely established.
9. Melatonin — Drug Interactions and Safety. Mayo Clinic (2021). Clinical reference identifying drug interactions relevant to heart patients including anticoagulants, blood pressure medications, immunosuppressants, and antiplatelets.

About the Author

David Kimbell is a health writer, digital entrepreneur and former aerospace engineer, based in Ottawa, Canada. He loves translating complex science into clear, actionable guidance for consumers seeking evidence-based solutions.

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Important Disclaimers

Medical Disclaimer: This article provides educational information only and is not intended as medical advice. Always consult with a qualified healthcare provider before starting any new supplement, especially if you have existing health conditions, take medications, or are pregnant or nursing.

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