New Study Links Long-Term Melatonin Use to Increased Heart Failure Risk

HOW LONG CAN YOU SAFELY TAKE MELATONIN? THE HIDDEN HEART RISK DOCTORS NEED TO KNOW

If there’s one pill that patients believe is completely harmless, it’s melatonin. Sold in nearly every pharmacy, marketed as “natural,” and casually recommended in hospital corridors, it’s the one sleep aid that even doctors reach for on sleepless nights without hesitation. After all, it’s not a sedative, it’s a hormone — one your body already makes. How bad could it be?

But new data suggest that the story isn’t as innocent as we thought. Research presented at the 2025 American Heart Association Scientific Sessions has revealed a concerning association between long-term melatonin use and the development of heart failure. Yes, heart failure — not merely grogginess or hormonal imbalance. For years, we reassured our patients (and ourselves) that melatonin was the safest aid for chronic insomnia. Now, that assumption may require urgent revision.

When “Natural” Doesn’t Mean Harmless
As doctors, we’ve seen this story before: vitamin E, omega-3s, herbal supplements — all once hailed as “protective,” later shown to carry unanticipated risks when used chronically or at unregulated doses. Melatonin may be following the same path.

The study that drew global attention analyzed a massive health record database of over 130,000 adults diagnosed with insomnia. It compared those who used melatonin for a year or longer to those who did not. The results were striking: long-term users showed about a 90% higher incidence of new-onset heart failure over a five-year follow-up period.

To be clear, this doesn’t prove causation. But as clinicians, we cannot ignore such a signal, especially when it involves a hormone that directly influences the cardiovascular and autonomic systems. The heart, after all, keeps time with circadian rhythm as faithfully as the pineal gland does.

Melatonin and the Heart: A Physiological Connection
Melatonin isn’t just the “sleep hormone.” It’s a major regulator of circadian rhythm, influencing nearly every organ system, including the cardiovascular system. Melatonin receptors (MT1 and MT2) are present in the heart, blood vessels, and endothelial tissues.

In normal physiology, endogenous melatonin rises at night, helping the cardiovascular system “rest.” Blood pressure dips, heart rate slows, and oxidative stress decreases. However, exogenous melatonin — taken inconsistently, in supraphysiologic doses, or at the wrong circadian phase — can disrupt this balance.

Chronically supplementing melatonin might blunt receptor sensitivity, alter nocturnal sympathetic activity, or interfere with the body’s natural rhythm of cardiovascular repair. Some researchers even hypothesize that excessive melatonin may flatten the natural day-night blood pressure variation — a pattern known to increase cardiovascular risk.

In essence, what we thought of as a “sleep vitamin” is a potent chronobiologic signal. And when you tamper with biological clocks, the heart listens — sometimes, with consequences.

The Data Doctors Can’t Ignore
The American Heart Association presentation wasn’t the only alarm bell. The Washington Post recently covered growing concerns about over-the-counter melatonin misuse, noting how widespread and under-regulated its consumption has become. It’s now one of the top-selling supplements in the United States, with an estimated millions of adults and children taking it nightly, often without medical supervision.

What’s more concerning is that melatonin is not regulated as a prescription drug in most countries. As a dietary supplement, it escapes rigorous quality testing. Independent lab analyses have found that many products contain up to 400–600% of their labeled dose, while some contain none at all. Imagine if any prescription drug had that kind of variability — it would never reach the market.

So when patients say, “I just take a small melatonin every night,” we have no real idea how much they’re actually ingesting. Some might be taking pharmacologic doses every evening for years.

The Problem With Chronic “Shortcuts” to Sleep
Sleep is not simply the absence of wakefulness; it’s a highly regulated biological process involving neuroendocrine feedback loops, immune signaling, and metabolic restoration. Melatonin nudges the body toward sleep, but it doesn’t create restorative sleep architecture on its own.

When patients rely on melatonin nightly, they often neglect underlying causes of insomnia: anxiety, circadian misalignment, caffeine overuse, chronic stress, obstructive sleep apnea, or heart failure itself. Ironically, the same patients who later develop heart failure may have been using melatonin to manage symptoms of poor sleep due to undiagnosed cardiovascular dysfunction.

That creates a dangerous loop. The fatigue worsens, melatonin use increases, and subtle cardiovascular symptoms go unnoticed — until overt heart failure emerges. The pill meant to help you rest might mask the warning signs of the disease itself.

Pathophysiologic Hypotheses: How Could This Happen?
While we can’t yet prove causality, several biological explanations make sense.

1. Circadian Disruption and Autonomic Imbalance
Melatonin regulates the timing of sympathetic and parasympathetic activity. Long-term supplementation might desynchronize these systems, leading to persistent sympathetic tone and higher nocturnal blood pressure — both known contributors to ventricular remodeling and heart failure.

2. Receptor Desensitization
Continuous exposure to high melatonin levels could desensitize MT1/MT2 receptors, reducing the heart’s ability to respond to normal circadian signals. This could disturb endothelial function, vascular relaxation, and oxidative balance.

3. Interaction with Cardiac Medications
Melatonin can interact with anticoagulants, antiplatelets, beta-blockers, and calcium channel blockers. Chronic co-use may alter their efficacy or pharmacokinetics.

4. Sleep Architecture Alteration
Melatonin may shorten REM latency but does not reliably increase deep restorative sleep in chronic insomnia. The illusion of “better sleep” without physiologic recovery could perpetuate fatigue, inflammation, and stress hormone elevation — indirect risk factors for cardiovascular disease.

5. Supplement Contamination and Dosing Errors
Unregulated melatonin products may contain unpredictable amounts or even contaminants that exert unrecognized effects on the cardiovascular system. Unlike prescription medications, they are rarely batch-tested for purity.

Fatigue, Insomnia, and the Modern Doctor’s Dilemma
Every physician knows this paradox personally: we preach sleep hygiene, yet we’re often the most sleep-deprived professionals on earth. Many of us have quietly relied on melatonin during residency or long call weeks, believing it harmless. But if chronic use truly carries cardiovascular implications, doctors are both advisors and subjects of concern.

Chronic partial sleep deprivation leads to hormonal chaos — cortisol surges, insulin resistance, altered leptin-ghrelin ratios, and sympathetic dominance. Adding exogenous melatonin into that storm may not fix the problem — it may just confuse the body further.

We need to stop thinking of melatonin as a sleeping pill and start treating it as what it is: a powerful chronobiologic signal. It should be used with the same caution as any hormone replacement therapy — indicated for specific conditions, at precise times, in the right doses, for limited duration.

The Clinical Translation: How to Counsel Your Patients
When patients mention melatonin, many physicians nod and move on. It’s time to stop doing that. Here’s how the new data should shape our clinical conversations:

1. Ask, don’t assume.
Always ask your patients — especially those with cardiovascular risk factors — whether they use melatonin, how often, at what dose, and for how long. Most won’t volunteer it.

2. Explain that “natural” doesn’t mean safe.
Patients associate the word “natural” with harmless. Gently educate them that many potent substances — digitalis, cyanide, morphine — are natural too. The issue is dose, duration, and physiology.

3. Treat insomnia, not sleep deprivation.
Address underlying causes before reaching for supplements. Screen for obstructive sleep apnea, depression, anxiety, pain disorders, medication side effects, and circadian misalignment.

4. Short-term, not lifelong.
If melatonin is necessary, use it for short durations (weeks, not years), at the lowest effective dose (ideally 0.3–1 mg). Higher doses don’t improve efficacy and may increase desensitization.

5. Review heart health regularly.
For patients using melatonin long-term — especially those over 50 with hypertension, obesity, or diabetes — schedule cardiovascular monitoring. Include blood pressure checks, echocardiography if indicated, and review for subtle heart failure symptoms (fatigue, orthopnea, ankle swelling).

6. Prefer regulated brands.
If melatonin is to be continued, recommend pharmacy-verified brands with known consistency, rather than unregulated supplements purchased online.

7. Encourage natural circadian regulation.
Light exposure therapy, consistent sleep-wake times, reduced nighttime screen use, and morning sunlight are often more effective than chronic hormonal supplementation.

Why Doctors Should Pay Attention to This Warning
As clinicians, our culture often overlooks subtle warning signs until they become crises. We tell our patients to take melatonin instead of benzodiazepines because it “can’t hurt.” Yet this new signal shows it might.

Think about how often we see older adults with both insomnia and diastolic dysfunction. For years, they’ve been told to “just take melatonin.” Now, those same patients are the ones showing up with mild heart failure. Is it a coincidence, or did we miss the connection?

Medicine is full of these hindsight lessons — NSAIDs and renal failure, PPIs and B12 deficiency, hormone therapy and thromboembolic disease. Melatonin may soon join the list: a once-beloved fix that turned out to carry hidden costs.

What We Still Don’t Know

1. Causality: The association between melatonin and heart failure doesn’t prove that melatonin causes it. Randomized controlled trials are needed.
   
   
2. Dosing thresholds: We don’t know whether risk rises with higher doses, longer duration, or erratic use.
   
   
3. Population specificity: The study focused on adults with insomnia — a group already at higher cardiovascular risk. Whether findings apply to general users remains unclear.
   
   
4. Reversibility: If melatonin is discontinued after years of use, does the risk decline?
   
   
5. Pharmaceutical vs supplement forms: Data rarely differentiate between prescribed pharmaceutical melatonin (used in some countries) and over-the-counter supplements of inconsistent potency.
   

Until these questions are answered, prudence is our best guide.

What This Means for the Future of Sleep Medicine
The melatonin story underscores a broader truth about medicine’s relationship with fatigue: we’re quick to patch symptoms, slow to fix systems. Sleep deprivation in modern life has become so normalized that we’ve built an industry of chemical shortcuts.

Yet true sleep restoration is not biochemical — it’s behavioral, environmental, and psychological. Melatonin might help recalibrate the clock, but it cannot restore the soul of human rest: consistent circadian rhythm, darkness, quiet, and recovery.

For healthcare professionals, the takeaway is not to demonize melatonin, but to re-contextualize it — to see it as a temporary bridge, not a lifestyle anchor. Prescribe it with respect, not casualness. Question the reflex. Watch the heart as closely as the eyelids.

Because sometimes the most dangerous drugs are the ones we don’t consider drugs at all.