On November 3, 2025, the American Heart Association (AHA) turned heads with a large-scale analysis that tracked more than 130,000 adults with chronic insomnia over five years. The finding that caught everyone’s attention: people who took melatonin for at least a year faced higher rates of heart failure diagnosis, hospitalization, and death from any cause compared to similar adults who didn’t use the supplement. The numbers tell a stark story—4.6% of long-term users developed heart failure versus 2.7% of non-users over the study period. Even when researchers tightened their criteria, requiring evidence of two melatonin prescriptions at least 90 days apart, the pattern held steady.
Yet the AHA was careful to pump the brakes on panic. This was observational research presented at a conference, not a peer-reviewed publication, and it can’t prove melatonin actually causes heart problems. The study has real limitations that matter. Many people buy melatonin over the counter without prescriptions, potentially skewing the “non-user” group. The researchers couldn’t fully account for how severe people’s insomnia was or what other health conditions might have influenced the results. Still, the association is strong enough that sleep and heart specialists are advising caution—particularly for people with existing cardiovascular risks—while we wait for more definitive research.¹
The media response has been appropriately measured, highlighting both the concerns and the context. Coverage has reminded readers that poor sleep itself damages cardiovascular health, that American melatonin supplements vary wildly in dose and purity because they’re regulated like vitamins rather than medications, and that we need better studies before making sweeping changes to how we use melatonin. This is a warning sign worth investigating, not a reason to throw out every bottle overnight.²
How the current flare-up compares to earlier melatonin controversies
While the cardiac angle feels fresh, debates about melatonin’s proper role have been brewing for years. The supplement’s regulatory status in the United States has long frustrated researchers and clinicians alike. Unlike prescription medications, supplements don’t face the same pre-market testing requirements, which means the melatonin you buy might contain significantly more or less than what’s on the label—and sometimes other compounds entirely. This regulatory gap makes it nearly impossible to know whether research findings about “melatonin” apply to what people are actually taking.¹
The question of long-term use has been another persistent concern, particularly when it comes to children and vulnerable populations. Review after review has pointed out the same glaring issue: most clinical trials last only a few weeks, maybe a month or two at most. While short-term side effects appear mild—some drowsiness here, a headache there—we simply don’t have robust data on what happens when people take melatonin nightly for years. This knowledge gap isn’t new; researchers have been flagging it for over a decade. The current heart failure study hits exactly this nerve, examining the kind of extended real-world use that controlled trials haven’t addressed.³ ⁶
Then there’s the complex relationship between melatonin and cardiovascular function. Pharmacology textbooks have long described melatonin’s Jekyll-and-Hyde effects on blood pressure, heart rate, and blood sugar regulation. Depending on the dose, the time of day, and which receptors get activated, melatonin can constrict or dilate blood vessels, raise or lower blood pressure, and shift metabolic patterns in ways that could theoretically help or harm. This biological complexity means that the same supplement that helps one person sleep might subtly stress another person’s cardiovascular system—especially when taken at the wrong time or in the wrong amount.⁴ ⁵
Mechanisms: why timing and dose matter
Understanding melatonin means understanding its receptors. The hormone primarily works through two molecular doorways called MT1 and MT2, which are scattered throughout the brain and body. In the brain’s master clock—the suprachiasmatic nucleus—these receptors help coordinate when we feel sleepy and when we feel alert. But they’re also found in blood vessels, the heart, the gut, and other tissues where their activation can have unexpected consequences. Melatonin also interacts with nuclear receptors that influence immune function and cell growth, and there’s even a mysterious partner protein called GPR50 that can interfere with normal melatonin signaling when it binds to MT1 receptors.
This molecular complexity translates into practical consequences. Take melatonin at the wrong time relative to your body’s natural rhythm, and you might trigger vasoconstriction when you need vasodilation, or vice versa. Take too much for too long, and you might gradually shift your glucose metabolism or blood pressure regulation in unhelpful directions. The timing matters as much as the dose because melatonin is fundamentally a time-keeping molecule, not just a sleep inducer. When you disrupt that temporal signaling with poorly timed or excessive supplementation, you risk throwing off multiple physiological systems that depend on circadian coordination.³ ⁴ ⁵
Effectiveness: where melatonin reliably helps—and where it only helps a little
After decades of research, we know melatonin works best as a chronobiotic—a substance that shifts biological timing—rather than as a traditional sleep medication. For people with circadian rhythm disorders, such as delayed sleep-wake phase disorder, or for travelers crossing time zones, carefully timed melatonin can genuinely reset the body clock. The key is taking it at the right time relative to your body’s natural melatonin production, which typically begins in dim evening light.
For ordinary insomnia, the picture is murkier. Yes, melatonin can help people fall asleep a bit faster—maybe 10 to 15 minutes on average—but the effect is modest and varies widely between individuals. That’s why cognitive behavioral therapy for insomnia (CBT-I) remains the gold standard treatment; it addresses the underlying thoughts and behaviors that perpetuate sleep problems rather than just providing a chemical nudge toward drowsiness.
One area where melatonin truly shines is in treating REM sleep behavior disorder (RBD), a condition where people physically act out their dreams, sometimes injuring themselves or their bed partners. Studies suggest that around 3 mg of melatonin nightly can significantly reduce these dangerous episodes, offering a gentler alternative to benzodiazepines. For sleep apnea or excessive daytime sleepiness, however, melatonin shows little benefit, and standard treatments like CPAP machines remain essential.³
Safety: short-term looks mild; long-term is the question mark
In controlled trials lasting weeks to a few months, melatonin’s side effect profile appears reassuring. Most people tolerate it well, experiencing at worst some daytime grogginess, mild headaches, or dizziness that resolves when they stop taking it. Serious adverse events are rare in these short-term studies.
But here’s the catch: those trials weren’t designed to detect problems that emerge after months or years of nightly use, and many were conducted before modern safety reporting standards. Review authors consistently note this blind spot, warning that we lack high-quality, long-duration safety data in people with multiple health conditions—exactly the population that a large electronic health record study can examine, albeit with all the limitations of observational research.³ ⁶
Earlier toxicology reviews raised additional concerns about chronic exposure, particularly regarding dose-dependent effects on blood vessels and metabolism. There are also documented interactions to consider—melatonin can affect how the body processes certain medications, and it may interact problematically with NSAIDs or some chemotherapy drugs. The takeaway isn’t that melatonin is dangerous, but that “natural” doesn’t mean “harmless,” especially when taken indefinitely.⁴ ⁵
Putting the new heart-failure signal in context
So where does this leave clinicians, patients, and anyone trying to make sense of the headlines? First, we need to resist jumping to conclusions. The AHA-featured study raises an important question about long-term safety that deserves serious investigation through prospective, controlled trials. Association isn’t causation, but it’s often where causation first shows its face.
Second, we shouldn’t dismiss this signal, especially for people already at cardiovascular risk. The findings align uncomfortably well with known mechanisms by which melatonin could theoretically affect heart function over time, and they spotlight exactly the safety gap that systematic reviews have been warning about for years.
Third, we need to be smarter about matching melatonin to the right problems. For chronic insomnia in otherwise healthy adults, CBT-I offers more lasting benefits than any pill. When melatonin makes sense—for jet lag, circadian disorders, or RBD—proper timing often matters more than dose, and use should be purposeful rather than indefinite.
Finally, in markets where melatonin is sold as a supplement, product selection matters more than many people realize. Choose brands that undergo third-party testing, resist the temptation to increase doses without medical guidance, and monitor blood pressure, blood sugar, and overall sleep quality during regular check-ups.¹–⁶
The most honest assessment is that we’re dealing with uncertainty, not certainty. Short-term use appears safe for most people, benefits are clearest for specific sleep-timing disorders and RBD, and the wisdom of taking melatonin every night for years remains an open question. The 2025 heart-failure signal transforms what was a theoretical concern into an urgent research priority—and a practical reminder to use melatonin thoughtfully, respecting both its power and its complexity as a timekeeper molecule.
Endnotes
- American Heart Association (press release): “Long-term use of melatonin supplements to support sleep may have negative health effects.” Newsroom.heart.org, November 3, 2025. https://newsroom.heart.org/news/long-term-use-of-melatonin-supplements-to-support-sleep-may-have-negative-health-effects
- NBC News coverage: “What taking melatonin could reveal about your heart health.” NBC News, November 2025. https://www.nbcnews.com/health/health-news/taking-melatonin-reveal-heart-health-rcna241132
- Xie Z., et al. “A review of sleep disorders and melatonin.” Neurological Research (2017). (Uploaded file: “A review of sleep disorders and melatonin.pdf”.)
- Guardiola-Lemaître B. “Toxicology of Melatonin.” (1997). (Uploaded file: “guardiola-lemaitre-1997-toxicology-of-melatonin.pdf”.)
- Emet M., Özcan H., Özel L., Yayla M., Halici Z., Hacimuftuoglu A. “A Review of Melatonin, Its Receptors and Drugs.” The Eurasian Journal of Medicine 48(2):135–141 (2016). (Uploaded file: “eajm-48-2-135.pdf”.)
- Besag F.M.C., Vasey M.J., Lao K.S.J., Wong I.C.K. “Adverse events associated with melatonin for the treatment of primary or secondary sleep disorders: a review.” (Manuscript PDF; 2020 file timestamp). (Uploaded file: “Wong_Melatonin_AEs_FINAL_RESUBMIT_1.7_CLEAN_DET_REFS.pdf”.)
This article is for general information and not medical advice. Readers considering melatonin—especially for long-term nightly use or with heart, blood-pressure, or glucose issues—should speak with a licensed clinician.