Long-term melatonin use associated with 90% higher heart failure risk
New research links melatonin use in chronic insomnia patients to serious health risks including heart failure and increased mortality.
1Melatonin and heart health connection
Preliminary research presented at the American Heart Association's 2025 Scientific Sessions revealed that long-term melatonin use increases heart failure risk by 90% in chronic insomnia patients. The study found a 4.6% heart failure incidence in melatonin users over 5 years compared to 2.7% in non-users. Researchers also identified significant associations between melatonin use and higher rates of hospitalization and mortality, challenging the supplement's safety profile for chronic use.
2Research methodology
The study analyzed de-identified electronic health records from the TriNetX Global Research Network. Adults (18+) with chronic insomnia who used melatonin for at least one year were compared to matched non-users. Participants with prior heart failure diagnoses or using other sleep medications were excluded. Geographic locations of participants were unknown due to data anonymization. The research team employed rigorous matching criteria to ensure comparable groups for analysis.
3Persistent risk with prescribed use
In a secondary analysis focusing on participants who filled at least two melatonin prescriptions 90+ days apart, heart failure risk remained 82% higher. This finding is particularly relevant for countries like the UK where melatonin requires prescription. Hospitalization rates were dramatically higher among melatonin users (19.0%) versus non-users (6.6%). These consistent patterns across different analyses strengthen concerns about long-term melatonin safety, especially in vulnerable populations.
4Elevated mortality rates
During the five-year follow-up, all-cause mortality was nearly doubled in the melatonin group (7.8%) compared to non-users (4.3%). Lead author Dr. Ekenedilichukwu Nnadi noted the striking consistency of adverse health outcomes despite controlling for multiple risk factors. The mortality data adds significant weight to concerns about chronic melatonin use, particularly given its widespread perception as a 'natural' and harmless sleep aid in many countries.
5Expert reactions
Dr. Marie-Pierre St-Onge, chair of the AHA's 2025 scientific statement committee, expressed surprise at physicians prescribing melatonin for chronic insomnia, noting it's not FDA-approved for this indication in the U.S. The Columbia University professor emphasized that chronic use without proper medical supervision may pose risks. Experts highlighted regulatory disparities, with melatonin available over-the-counter in some countries (like the U.S.) but prescription-only in others (like the UK).
6Understanding melatonin
Melatonin is a naturally occurring hormone produced by the pineal gland that regulates circadian rhythms. Synthetic melatonin, chemically identical to endogenous melatonin, is commonly used for jet lag and sleep disorders. While available over-the-counter in many countries including the U.S., it's not tightly regulated, leading to potential variability in dosage and purity between products. This lack of standardization may contribute to inconsistent effects and safety profiles observed in different populations.
7Study limitations
Key limitations include the inability to account for geographic variations in melatonin regulation due to de-identified data. The study couldn't assess dosage, formulation, or adherence details. As an observational study, it can't prove causation, only association. Researchers note the need for prospective studies to confirm findings. The electronic health record methodology may also miss some melatonin use (e.g., over-the-counter purchases not documented in medical records).
8Clinical practice implications
These findings suggest clinicians should exercise greater caution when recommending melatonin, particularly for chronic use. While often marketed as 'natural,' the potential cardiovascular risks identified warrant careful risk-benefit assessment, especially in patients with pre-existing conditions. If confirmed, the results may necessitate revisions to sleep aid guidelines and clearer patient communication about potential long-term risks of melatonin supplementation beyond short-term use.