Long-Term Melatonin Use Linked to Higher Heart Failure Risk in Insomnia Cohort
Long-term melatonin use was associated with a higher rate of heart failure diagnosis, heart failure hospitalization and all-cause death in adults with chronic insomnia, raising fresh questions about the cardiovascular safety of a supplement many patients consider benign. The analysis, drawn from a large real-world electronic health record network, followed more than 130,000 adults over five years and found persistent differences between people with insomnia who had documented melatonin use and those who did not.
The signal was not subtle. Among adults with insomnia, incident heart failure appeared in 4.6% of the melatonin group versus 2.7% of matched non-users. Hospitalization for heart failure reached 19.0% in the melatonin group compared with 6.6% among controls, and death from any cause was 7.8% versus 4.3% over the same follow-up period. In a field where patients often reach for supplements because they seem low-risk, those gaps demand careful interpretation rather than casual reassurance.
What the Database Comparison Actually Measured
Investigators used the TriNetX Global Research Network to review five years of de-identified health records from adults with chronic insomnia. The melatonin cohort included people whose records showed at least one melatonin prescription and documented use for at least a year; the comparison cohort included patients with insomnia who never had melatonin recorded in their medical records. Patients with prior heart failure or with other sleep medications, including benzodiazepines, were excluded.
The final analysis included 130,828 adults, with an average age of 55.7 years and 61.4% women. Half of the sample, 65,414 participants, fell into the melatonin group. The groups were matched on 40 factors, including demographic characteristics, cardiovascular and neurologic diseases, medications, blood pressure and body mass index. That design strengthens the comparison, but it cannot erase the usual limitations of observational research, especially when exposure is defined through routine documentation rather than direct pill counts or verified adherence.
One sentence captures the clinical tension here: melatonin is widely perceived as gentle, yet the long-term safety question remains unsettled.
Why the Heart Failure Signal Matters Clinically
The association extended beyond a single outcome definition. A sensitivity analysis that required at least two melatonin prescriptions filled 90 days apart produced a similar pattern, with an 82% higher chance of incident heart failure in the melatonin group. That consistency matters because it suggests the signal was not limited to one loose exposure definition.
From a bedside perspective, the concern is straightforward. Insomnia itself often travels with cardiometabolic disease, autonomic stress, mood disorders and fragmented sleep architecture, all of which can strain the cardiovascular system. If melatonin use simply marks people with more severe sleep disturbance or heavier psychiatric burden, the supplement may be a proxy rather than a cause. If, however, long-term melatonin exposure itself participates in physiologic pathways that affect myocardial function, vascular tone or fluid regulation, the public health implications would be broader.
The study cannot distinguish between those possibilities. It does, however, place long-term melatonin use inside the same conversation as other sleep-related exposures that deserve tighter scrutiny before they are assumed to be harmless.
The Safety Questions Behind a Common Over-the-Counter Habit
Melatonin is a naturally occurring hormone produced by the pineal gland and used synthetically to support sleep and jet lag management. In the U.S., it is sold over the counter, and supplement products do not require the same premarket government approval used for prescription drugs to ensure consistency in strength and purity. That regulatory difference matters because real-world exposure may vary from one product to the next, even when patients believe they are taking the same agent every night.
Marie-Pierre St-Onge, who was not involved in the analysis, said physicians should be cautious about chronic use because melatonin is not indicated for insomnia in the U.S. Her point aligns with the larger clinical concern: patients often treat supplement use as self-limited and risk-free, yet prolonged nightly use can become de facto long-term therapy without the kind of monitoring that typically accompanies prescription sleep treatment.
Why the Findings Should Be Read as Preliminary
This was a research abstract scheduled for presentation at the American Heart Association’s Scientific Sessions 2025, not a peer-reviewed full manuscript. The findings are therefore preliminary. The investigators also acknowledged several important caveats. Patient geography was unavailable in the de-identified data, even though melatonin access differs substantially across countries. In places where melatonin requires a prescription, it would be more likely to appear in the medication record; in settings such as the U.S., over-the-counter use could be missed and mistakenly placed in the non-melatonin group.
That limitation could blunt the exposure classification and distort estimates in either direction. Hospitalization coding also carries noise, because admission records may include related diagnostic codes without always capturing a new heart failure diagnosis cleanly. The database did not provide insomnia severity or information on psychiatric comorbidity, leaving open the possibility that depression, anxiety, worse sleep burden or other sleep-enhancing medicines contributed to both melatonin use and cardiovascular risk.
Those missing details matter because insomnia rarely arrives alone. Patients with the most persistent sleep disruption are often the same patients who carry higher cardiometabolic risk, use multiple medications and live with stressors that complicate sleep treatment choices.
What Clinicians May Need to Reconsider
The clinical takeaway is not to panic over occasional melatonin use. It is to stop assuming that chronic nightly use is automatically benign, especially when the medication has been taken for a year or longer without a clear indication or reassessment. The current analysis raises a question that clinicians already encounter in practice: when a patient uses melatonin for months or years, are they treating insomnia, masking a deeper sleep disorder or accumulating an exposure whose cardiovascular effects have not been adequately studied?
For now, the data support caution, not causality. More research is needed to test whether the association reflects direct harm, residual confounding or both, and whether any cardiovascular risk differs by dose, formulation, duration or patient phenotype. Until then, long-term melatonin use should be viewed less as a trivial habit and more as a therapy that deserves the same clinical scrutiny applied to any chronic sleep intervention.