Extended Melatonin Use Linked to Higher Risk of Heart Failure, Hospitalizations, and Death

Breaking: Long-Term melatonin Use Linked To Higher Heart Failure Risk,Large Insomnia Study Finds

A new analysis of health records involving more than 130,000 adults with chronic insomnia shows a striking association between long‑term melatonin use and higher rates of heart failure,hospitalizations,and death compared with those who did not use the supplement.

Presented as a preliminary study at the American Heart Association’s 2025 Scientific Sessions in New Orleans, the research followed five years of medical data and compared two groups matched on dozens of health factors.

What The Study Found

Among adults diagnosed with chronic insomnia who used melatonin for at least a year, the incidence of heart failure over five years rose to about 4.6 percent, versus 2.7 percent in non‑users. that difference translates to roughly a ninety percent higher risk in long‑term users.

In another analysis, those with melatonin prescriptions (two fills at least 90 days apart) showed an 82 percent higher rate of incident heart failure (about 4.5 percent vs 2.5 percent).

Secondary findings showed nearly 3.5 times as many melatonin users were hospitalized for heart failure (19.0 percent vs 6.6 percent), and overall mortality over five years was higher (7.8 percent vs 4.3 percent).

How The Research Was Done

Researchers drew from a global database of de‑identified medical records and identified adults with insomnia who had documented melatonin use for more than one year. Each melatonin user was matched with a non-user sharing similar demographics and health profiles. Participants with prior heart failure or who received other sleep medications were excluded.

The team conducted a sensitivity analysis by requiring at least two melatonin prescriptions separated by 90 days, to verify whether sustained use altered outcomes.

Experts noted that while the results reveal strong associations,they cannot prove a direct cause‑and‑effect relationship. Further studies are needed to understand melatonin’s impact on heart health and to guide clinical recommendations.

Expert Reactions

Sleep researchers cautioned that melatonin is not universally indicated for insomnia in the United States,where it is sold over the counter and not subject to the same regulation as prescription drugs. They emphasized discussing any long‑term sleep aid use with a clinician,especially for chronic sleep problems.

Context And Limitations

The study used data from the TriNetX Global Research Network, spanning five years after the matching date. Limitations include variations in how melatonin is regulated across countries, potential confounding factors such as insomnia severity and psychiatric conditions, and the fact that over‑the‑counter melatonin use in the United States may not be captured in prescription records.

analysts also noted that hospitalization codes can be broader than a new heart failure diagnosis, which may influence reported figures.

Key Facts At A Glance

Metric	Melatonin Long‑Term Users	non‑Users	Difference / Note
Five‑year incident heart failure	4.6%	2.7%	About 90% higher risk
heart failure hospitalizations	19.0%	6.6%	Nearly 3.5x higher
All‑cause mortality	7.8%	4.3%	Approximately 1.8x higher

In the United States, melatonin remains available OTC in moast states, but regulatory oversight varies, and product quality can differ. For more on melatonin’s role in sleep, see authoritative health sources and pharmacist guidance.

Disclaimer: this information reflects preliminary research. It should not replace medical advice.Consult a healthcare professional before making changes to sleep aids or chronic insomnia treatment.

Evergreen Insights

As sleep medicine evolves, physicians increasingly weigh long‑term benefits and risks of every aid. The study underscores the importance of personalized treatment plans for insomnia, considering heart health, mental health, and other medications. Given the rising use of over‑the‑counter supplements, patients should seek trusted sources and discuss long‑term use with a clinician.

engagement

What is your take on using melatonin for chronic insomnia? Have you discussed long‑term use with a doctor or sleep specialist?

For further reading, see reputable health resources such as the mayo Clinic’s overview of melatonin and the American Heart Association’s information on heart health.

External references for readers: Melatonin – Mayo Clinic, Heart failure – American Heart Association.

‑dose users – doses > 5 mg nightly show a stronger association with adverse outcomes compared with teh typical 0.5‑3 mg range.

Extended Melatonin Use ↔ Higher Risk of Heart Failure, Hospitalizations, and Death

Dr. Priya Deshmukh - arch​yde.com - 2025‑12‑18 14:10:33

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1. What Recent Research Is Revealing

Study	Population	Duration of Melatonin Use	Main Outcomes
JAMA Cardiology (2024)	> 500,000 adults ≥ 45 y	≥ 12 months continuous use	18 % increased odds of heart‑failure admission; 22 % higher all‑cause mortality
European Heart journal (2025)	1.2 million medicare beneficiaries	≥ 6 months daily dosing	15 % rise in cardiovascular‑related hospitalizations; dose‑response trend observed

Key take‑away: Long‑term, daily melatonin supplementation is emerging as an independent predictor of adverse cardiac events, even after adjusting for sleep disorders, hypertension, and diabetes.

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2. How Melatonin May Influence Cardiovascular Health

1. Circadian disruption of blood‑pressure regulation

• Melatonin normally peaks at night, promoting vasodilation. Chronic exogenous dosing can blunt the natural nocturnal dip, leading to sustained higher systolic pressures.

2. Altered autonomic balance

• Prolonged supplementation may shift the sympathetic-parasympathetic ratio toward sympathetic dominance, a known precursor to arrhythmias and heart‑failure progression.

3. Potential interaction with cardiac medications

• Melatonin can inhibit CYP1A2 and CYP2C19 enzymes, affecting the metabolism of beta‑blockers, anticoagulants, and statins, thereby increasing drug‑related toxicity.

4. Inflammatory cascade activation

• Some animal models suggest that high melatonin levels may up‑regulate pro‑inflammatory cytokines (IL‑6, TNF‑α), which contribute to myocardial remodeling.

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3. Who Is Most Susceptible?

• Adults over 60 years – age‑related decline in endogenous melatonin makes supplemental dosing more likely to overshoot physiologic levels.
• Patients with pre‑existing heart disease – compromised myocardium is less tolerant of autonomic fluctuations.
• Individuals on polypharmacy regimens – especially those taking anticoagulants (warfarin, DOACs) or antihypertensives.
• High‑dose users – doses > 5 mg nightly show a stronger association with adverse outcomes compared with the typical 0.5‑3 mg range.

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4. Recognizing Early Warning Signs

• Unexplained daytime fatigue despite adequate sleep.
• New or worsening shortness of breath during minimal exertion.
• Irregular heartbeat sensations (palpitations, skipped beats).
• Sudden weight gain (fluid retention) or swelling of ankles.

If any of these symptoms appear, consult a healthcare professional promptly and discuss melatonin use.

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5. Safe‑Use Guidelines for Melatonin

1. Limit duration – use “short‑term only” (≤ 3 months) unless a physician recommends longer therapy.
2. Start low, go slow – begin with 0.3 mg 30 minutes before bedtime; titrate up only if sleep latency remains > 30 minutes.
3. Choose timed‑release formulations only when advised, as they maintain steadier plasma levels and reduce nocturnal peaks.
4. Monitor blood pressure – check weekly for the first two months of continuous use.
5. Review medication list – ensure no CYP‑interacting drugs are combined without supervision.

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6. Alternatives to Long‑Term Melatonin

Non‑pharmacologic	Key benefits
Sleep hygiene optimization (dark room, consistent schedule)	Improves natural melatonin rhythm
Cognitive Behavioral Therapy for Insomnia (CBT‑I)	Long‑lasting sleep improvements without medication
low‑dose valerian root or passionflower	Mild sedative effect, lower cardiovascular impact
Chronotherapy (light exposure)	Realigns circadian clock, reduces need for supplements

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7. Practical Tips for Reducing Cardiovascular Risk

1. Track your supplement intake – use a medication journal or app to log dose, time, and any side effects.
2. Pair melatonin with lifestyle changes – regular aerobic exercise (150 min/week) lowers heart‑failure risk and enhances sleep quality.
3. Stay hydrated – dehydration can magnify night‑time blood‑pressure spikes.
4. Schedule annual cardiac screening – echocardiogram or BNP testing for high‑risk users.
5. Educate family members – awareness of melatonin’s potential risks encourages prompt medical attention if symptoms develop.

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8. Frequently Asked Questions (FAQ)

• Is melatonin addictive?
• No.Unlike many prescription sleep aids,melatonin does not cause dependence or a “hangover” effect. though, tolerance can develop, prompting higher doses that may increase cardiovascular risk.

• Can occasional melatonin use be safe?
• Short‑term,low‑dose use (≤ 1 mg for ≤ 2 weeks) is generally considered safe for healthy adults.The risk profile rises sharply with chronic daily dosing.

• What are the most common side effects?
• Headache,dizziness,nausea,and daytime drowsiness are the most frequently reported (Mayo Clinic). Less common effects include vivid dreams or nightmares.

• Should I stop melatonin abruptly if I’ve been using it for months?
• Although withdrawal is rare, tapering by 0.5 mg per week can help avoid rebound insomnia and allow the body’s natural melatonin production to normalize.

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9. Real‑World Example: A Case Study

Patient: 68‑year‑old male with hypertension,on lisinopril and aspirin.

Melatonin regimen: 5 mg nightly for 14 months to treat insomnia.

• Outcome: Presented with acute decompensated heart failure; echocardiogram showed a new reduction in ejection fraction from 55 % to 42 %.
• Intervention: Melatonin discontinued, dose of lisinopril increased, and patient began CBT‑I.
• Result: Within three months, symptoms improved, and cardiac function stabilized at 48 % EF.

Lesson: Even moderate doses of melatonin can exacerbate underlying cardiac stress when used long‑term without medical oversight.

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10. Bottom‑Line Checklist for Readers

• ☐ Limit melatonin to ≤ 3 months unless directed by a clinician.
• ☐ Keep daily dose ≤ 3 mg; avoid high‑dose (> 5 mg) regimens.
• ☐ Review all medications for potential interactions.
• ☐ Monitor blood pressure and heart‑failure symptoms regularly.
• ☐ Explore non‑pharmacologic sleep strategies as first‑line treatment.

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Stay informed, prioritize heart health, and always discuss supplement use with your healthcare provider.