Melatonin has long been viewed as one of the safest and most commonly used supplements for sleep. Over time, its reputation expanded beyond sleep support to include roles in aging, immune regulation, brain health, and antioxidant defense. Recently, however, new headlines have raised concerns that melatonin use may be associated with an increased risk of heart failure and mortality. These claims have caused understandable confusion among individuals who rely on melatonin for sleep or overall wellness.

This article examines what the research actually shows, why recent findings may be misinterpreted, and how melatonin fits into a broader discussion of cardiovascular health, aging, and circadian biology.

Why Melatonin Suddenly Became Controversial

The concern stems from a large observational study presented at a major cardiology conference in 2025. Media coverage quickly amplified the most alarming conclusions, suggesting that long-term melatonin use could increase the risk of heart failure and death. As is often the case with preliminary research, nuance was lost in translation.

The study analyzed health records from over 130,000 adults diagnosed with insomnia who had used melatonin for at least one year. According to the data, melatonin users appeared to have higher rates of cardiovascular events, hospitalizations for heart failure, and all-cause mortality when compared with matched non-users.

At first glance, these statistics seem concerning. However, understanding how the study was designed is essential before drawing conclusions.

Observational Studies vs. Cause and Effect

The study in question was observational, meaning researchers examined existing medical records rather than assigning participants to treatment groups. Observational studies are useful for identifying correlations, but they cannot establish causation.

Several limitations are inherent in this type of research:

• No random assignment of participants
• No control over dosage, formulation, or timing
• Reliance on medical records rather than direct monitoring
• Inability to account for all confounding health factors

In this case, the study evaluated individuals already diagnosed with insomnia—a condition independently associated with increased cardiovascular risk. Chronic sleep disruption has been linked to hypertension, inflammation, metabolic dysfunction, and arrhythmias.

When melatonin use is examined without adequately separating it from the underlying condition of insomnia, the supplement itself may be incorrectly blamed for risks that originate elsewhere.

Insomnia as a Cardiovascular Risk Factor

Extensive research has shown that chronic insomnia is associated with higher rates of cardiovascular disease. Poor sleep quality and duration can elevate cortisol levels, disrupt autonomic nervous system balance, and promote systemic inflammation.

Individuals with existing heart disease frequently experience sleep disturbances and are more likely to use sleep aids, including melatonin. This creates a classic example of confounding by indication—where the reason for using a supplement is itself linked to worse health outcomes.

Without controlling for insomnia severity, comorbid conditions, psychological stress, medication use, and lifestyle factors, it is impossible to determine whether melatonin contributes to cardiovascular risk or merely appears alongside it.

Dosing Matters More Than Headlines Suggest

Another critical issue is dosing. Melatonin is commonly taken in doses ranging from 0.5 to 5 milligrams, which closely resemble physiological nighttime production. These lower doses are generally intended to support circadian rhythm signaling rather than act as sedatives.

Higher doses—often exceeding 10 milligrams—are sometimes used in clinical or experimental settings for conditions unrelated to sleep, including immune modulation and oxidative stress. These doses are not representative of typical over-the-counter use for insomnia.

The observational data did not adequately differentiate between:

• Low-dose vs. high-dose use
• Short-term vs. long-term supplementation
• Over-the-counter vs. prescription formulations

Without this differentiation, conclusions about safety become overly broad and potentially misleading.

Melatonin as a Hormone, Not Just a Sleep Aid

Melatonin is a hormone produced primarily by the pineal gland in response to darkness. While its role in sleep regulation is well known, melatonin also functions as a powerful antioxidant and cellular protector.

Unlike many antioxidants that act in the bloodstream, melatonin readily crosses the blood-brain barrier and enters mitochondria—the energy-producing centers of cells. There, it neutralizes free radicals at their source and activates antioxidant enzymes such as glutathione.

Research suggests that melatonin may be more effective than vitamins C and E at reducing mitochondrial oxidative stress, a key driver of aging and chronic disease.

Aging, Melatonin Decline, and Cardiovascular Health

Melatonin production naturally declines with age, often beginning in mid-adulthood. This decline coincides with lighter sleep, increased inflammation, slower recovery, and greater oxidative damage.

Loss of melatonin signaling has been associated with:

• Disrupted circadian rhythms
• Increased oxidative stress
• Reduced cellular repair
• Higher inflammatory burden

Rather than accelerating aging, melatonin decline may be one of the factors that allows age-related dysfunction to progress. Supporting healthy melatonin signaling may therefore play a role in longevity and disease prevention.

Melatonin and Cancer, Brain Health, and Inflammation

Low melatonin levels have been associated with increased cancer risk, particularly in populations exposed to chronic light at night, such as shift workers. Melatonin influences estrogen signaling, inhibits cancer cell proliferation, and supports DNA repair.

In the brain, melatonin contributes to:

• Reduction of neuroinflammation
• Improved clearance of metabolic waste during sleep
• Support for memory consolidation
• Protection against oxidative damage

These effects help explain why restorative sleep leaves the brain feeling clearer and more resilient.

Why More Is Not Always Better

Although melatonin is generally well tolerated, excessive dosing can disrupt natural circadian rhythms. High doses may flatten normal nighttime peaks, cause morning grogginess, intensify dreams, and reduce sensitivity to endogenous melatonin.

Melatonin works best as a gentle biological signal, not a pharmacological hammer.

Using the lowest effective dose consistently tends to support natural rhythms more effectively than intermittent high-dose use.

Does Melatonin Suppress Natural Production?

Unlike steroid hormones, melatonin supplementation does not shut down endogenous production through negative feedback. The pineal gland responds primarily to light exposure, not circulating melatonin levels.

However, chronic high-dose use may reduce circadian sensitivity, making timing more important than production itself. This distinction explains why appropriate dosing and consistent schedules matter.

Supporting Natural Melatonin Production

Supplementation works best when combined with lifestyle strategies that reinforce circadian biology:

• Morning sunlight exposure to anchor circadian rhythm
• Consistent sleep and wake times
• Reduced screen exposure 1–2 hours before bed
• Complete darkness during sleep

These habits improve melatonin signaling naturally and may reduce the need for higher supplemental doses.

What the Current Evidence Really Suggests

The recent observational findings do not prove that melatonin causes heart failure. Instead, they highlight the complexity of studying sleep, supplements, and chronic disease in real-world populations.

Most clinicians continue to view short-term, low-dose melatonin as safe when used appropriately. Chronic insomnia itself remains a far stronger and better-established cardiovascular risk factor than melatonin supplementation.

Until randomized controlled trials clarify causality, melatonin should be evaluated within the context of individual health status, sleep quality, and overall lifestyle—not judged solely by preliminary headlines.

Authoritative Evidence and Context

Research on melatonin’s antioxidant and mitochondrial effects has been widely published in peer-reviewed literature, including analyses available through the National Institutes of Health and PubMed databases.

For example, a comprehensive review on melatonin’s role in mitochondrial protection and aging can be found via the National Library of Medicine:
https://pubmed.ncbi.nlm.nih.gov/30363194/

Additionally, the NIH has documented the relationship between sleep disorders and cardiovascular disease risk:
https://www.nhlbi.nih.gov/health/sleep-deprivation

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