A recent observational study has revealed a notable association between long-term use of the sleep-aid hormone supplement Melatonin and elevated risks of heart failure, hospitalisation, and even death among adults with chronic insomnia. Researchers emphasise that this is not proof of causation, but the findings nevertheless raise important warning flags.
What the researchers did
The team led by Ekenedilichukwu Nnadi (internal medicine resident at SUNY Downstate/Kings County Primary Care in New York) analysed five years’ worth of electronic health-record (EHR) data from approximately 130,828 adults whose average age was about 56. These participants had documented insomnia diagnoses.
Within this cohort, those identified as “long-term melatonin users” were defined as individuals whose records indicated use (prescription or recorded supplement use) for at least 12 months. The comparison group consisted of insomnia patients with no recorded melatonin usage.
Key findings included:
- Incident heart-failure occurred in 4.6% of the long-term melatonin group over five years, compared with 2.7% in the non-melatonin group. That’s roughly a 90% higher relative risk.
- Hospitalisation for heart failure was markedly higher: 19.0% in the melatonin group versus 6.6% in the non-use group (≈ 3.5 times higher).
- All-cause mortality during the study period was also higher: 7.8% among long-term users versus 4.3% in non-users (≈ twice as likely to die).
The research was presented at the upcoming American Heart Association Scientific Sessions 2025 (in New Orleans) and has not yet undergone full peer review.
Why the findings matter (and what they don’t tell us)
Why they matter:
- Melatonin is widely regarded as benign — a popular “natural” sleep aid; the fact that its long-term use is associated with serious cardiovascular events is surprising and demands attention.
- Insomnia and poor sleep are themselves known risk factors for cardiovascular problems (via elevated blood pressure, increased stress hormones, inflammation). Researchers emphasise that the need to take melatonin for a long stretch might itself be a marker of deeper health issues.
What it does not tell us:
- The study cannot prove that melatonin causes heart failure — it only demonstrates an association. The lead researcher explicitly stated: “This doesn’t prove that melatonin directly causes heart failure.”
- The dose and regimen of melatonin use were not consistently recorded in the EHR data. So we don’t know how much, how often, or how reliably people took the supplement.
- The data may not capture all melatonin use — in the U.S., melatonin is available over-the-counter, and many users may never have it recorded in their medical record. This could misclassify users as non-users, muddying the comparison.
- It is unclear what sub-type of heart failure (for example, reduced vs preserved ejection fraction) the subjects developed, or how other sleep-related conditions (sleep-apnoea, restless-legs) factored in.
What may be going on — the plausible mechanisms
Given that melatonin has often been studied as beneficial to cardiovascular health, the findings may appear contradictory. Meshing the evidence:
- Historically, melatonin (endogenous and exogenous) has been shown in animal and early human‐studies to have antioxidant, anti-inflammatory, anti-fibrotic, and cardioprotective mechanisms. For example, melatonin receptors play a role in modulating the renin-angiotensin system, sympathetic overactivity, and mitochondrial dysfunction — all relevant to heart failure.
- However, this purely mechanistic benefit doesn’t necessarily line up with long‐term supplement use in real-world populations. Several factors may explain the observed association:
- Underlying insomnia: Chronic insomnia itself increases cardiovascular risk. The longer one uses melatonin, perhaps the more severe or persistent the sleep disorder is — thereby the higher the risk.
- Residual confounding: People using melatonin long-term may differ in unmeasured ways: more comorbidities (hypertension, diabetes), medications, lifestyle factors (night-shift work), or underlying sleep-apnoea. One study emphasised that unknown variables might make people both more likely to take melatonin and more susceptible to heart failure.
- Misclassification and usage patterns: As noted above, OTC use without prescription could mislead categorisation. Duration, dose, sleep hygiene, and adherence are ambiguous.
- Potential direct adverse effect (less proven): Some case reports suggest melatonin might affect heart rate, blood pressure, or autonomic tone — for instance one case of bradycardia after 20 mg melatonin in a young healthy adult.
- The paradox of beneficial vs harmful in context: Laboratory models showing benefit do not automatically translate to long‐term everyday use in heterogeneous humans. What was protective under tightly controlled doses and conditions might not be the same in broad, real-world application.
Melatonin use and sleep-health landscape
- Usage of melatonin supplements has grown considerably. For instance, a 2022 survey by the Sleep Foundation found that up to 27% of U.S. adults and 4% of children reported melatonin use.
- The supplement status of melatonin means that it is less strictly regulated compared to prescription drugs. As the Food and Drug Administration (FDA) treats it as a dietary supplement in the U.S., doses, purity, timing and quality vary widely.
- Established clinical guidance has emphasised that melatonin is generally safe for short-term use, but the evidence for long‐term use remains limited. The Mayo Clinic states melatonin is “generally safe when used short‐term,” but also notes the need to address underlying causes of insomnia rather than rely solely on the supplement.
- Importantly, many clinical bodies warn that chronic insomnia warrants evaluation rather than simply pill solutions. Lifestyle interventions (sleep hygiene, cognitive behavioural therapy for insomnia = CBT-I) are front-line. For example, the American Academy of Sleep Medicine emphasises non-drug therapies for persistent insomnia.
What this means for individuals
If you or someone you know has been taking melatonin regularly—especially nightly or for more than a year—these findings suggest some actionable considerations:
- Don’t panic — but do take notice. These results are not a verdict of harm but a signal for deeper evaluation.
- Talk with your physician or sleep specialist. Mention the fact of long-term melatonin use, and ask whether underlying sleep disorders (e.g., obstructive sleep apnoea, restless-legs syndrome, circadian rhythm disorders) might be present.
- Investigate underlying causes of sleep disturbance, rather than treating sleep solely with pills. Good sleep hygiene, regular sleep schedule, limiting screen time before bed, managing stress/anxiety, addressing caffeine/alcohol—all matter.
- Review cardiovascular risk: If you’re already using melatonin long-term, this may warrant review of heart-health risk factors — hypertension, high cholesterol, diabetes, obesity, family history of heart failure — and perhaps screening or monitoring as appropriate.
- Re-evaluate melatonin dosing, timing, and duration: Ask whether you still need to be on it nightly or whether you might taper or use it as “when needed.” Some clinicians suggest reserving melatonin for specific situations (jet-lag, shift changes) rather than chronic nightly use.
- Be aware the study is evolving: Because this is preliminary and not peer‐reviewed, indefinite changes aren’t mandated yet—but caution is wise.
- Keep updated: Further research, including prospective trials, will provide greater clarity. The observation here is a call-to-action for the research community, but not a definitive clinical guideline yet.
Key Take-aways
- Adults with chronic insomnia who used melatonin for 12 months or more had about a 90 % higher relative risk of developing heart failure over five years (4.6% vs 2.7%).
- They were also ≈ 3.5 times more likely to be hospitalised for heart failure and ~twice as likely to die during the follow‐up period compared to non-users.
- The study does not prove melatonin causes heart failure; the underlying insomnia or other health conditions may be driving the association.
- Real‐world use of melatonin is poorly regulated and often unmonitored, complicating interpretation.
- Individuals using melatonin long-term should consult healthcare professionals, re-assess their underlying sleep issues, and review cardiovascular risk, rather than simply continuing nightly use without oversight.
The Information is Collected from NBC News and Yahoo.
