The benefits of melatonin for promoting nighttime rest are widely known. This hormone, naturally produced by the body, has become one of the most popular options to help regulate the circadian rhythm and improve sleep quality. Its use as a food supplement has spread over the last few decades, and with it, doubts about its safety have also increased.

Next, we’ll share what current science says about this topic.

Year 2025: Does melatonin increase cardiovascular disease risk?

The recent release from the American Heart Association (AHA) Newsroom during the Scientific Sessions 2025, titled “Long-term use of melatonin supplements to support sleep may have negative health effects,” sparked major international controversy. Within days, numerous media outlets and specialized blogs reproduced the news with sensational headlines, misinterpreting the original content.

This is a clear case of the so-called “broken telephone”: each outlet summarized what others published, losing the scientific context and spreading the wrong idea that melatonin could increase cardiovascular disease risk.

Nothing could be further from the truth.

What the study really says

The work presented by the AHA is not a clinical trial or a meta-analysis of controlled studies, but a retrospective observational analysis based on electronic health records. Researchers explored a database including countries where melatonin is prescription-only (like the UK) and others where it’s sold freely and without control (like the US).

The article itself acknowledges that a causal relationship cannot be established between melatonin use and increased cardiovascular disease risk. Observing a statistical association doesn’t mean melatonin is the cause. The authors emphasize this limitation repeatedly, stating their study should be seen as a starting point for future research, not as evidence to change usage recommendations.

Limitations acknowledged by the authors

The study has multiple methodological limitations that prevent drawing solid conclusions:

No geographic control: the patients’ country of origin is unknown, mixing populations with different regulations on melatonin access and control.
Registration bias: only melatonin users with a medical prescription were considered. Everyone taking it as a food supplement was mistakenly classified in the “no melatonin” group, distorting results.
Lack of relevant clinical information: severity of insomnia, presence of psychiatric disorders, or concurrent use of other sleep medications were not recorded, all of which could affect outcomes.
Errors in diagnostic codes: the authors admit hospitalizations for heart failure may be overestimated due to how data was analyzed; many “cardiovascular disease” results might not have been so in reality.

In fact, the lead researcher, Dr. Nnadi, states in the release:

“Our study cannot prove a direct cause-effect relationship. It’s possible that higher rates of insomnia, depression, or anxiety, or the use of other sleep medications, are related both to melatonin use and cardiovascular risk.”

This makes it clear the study does not prove melatonin causes any harm, but simply identifies a statistical correlation that could be explained by external factors. And here’s one of the key points:

Correlation does not imply causation

Understanding this is essential. In scientific research, correlation describes a statistical relationship between two variables, while causation means one directly causes an effect on the other.

Observational studies like this only detect correlations but cannot determine causes. To establish causality, randomized controlled clinical trials (RCTs) are needed, where variables are carefully controlled and other factors excluded.

In this case, people taking melatonin usually do so because they suffer from sleep disturbances or stress, conditions themselves linked to higher cardiovascular risk. So, it’s far more likely the results reflect this circumstance, not a harmful effect of melatonin.

Uncontrolled doses and regulatory context

Another critical aspect is that doses used were not controlled, as this was an observational analysis.

In Europe, food supplements containing up to 2 mg of melatonin per daily dose are authorized and recognized as safe by bodies like the European Commission and the European Food Safety Authority (EFSA), which support their use to help reduce the time needed to fall asleep.

In Spain, the Spanish Agency for Food Safety and Nutrition (AESAN) sets the same limit, ensuring the safety of products on the market. These doses are hundreds of times lower than those used in some clinical contexts and pose no cardiovascular risk.

Lack of physiological mechanism and contrary evidence

Moreover, no physiological mechanism has been described to explain how melatonin could increase cardiovascular disease risk. On the contrary, available scientific evidence points to melatonin having cardioprotective effects.

Experimental studies, like the one published in Frontiers in Pharmacology (PMCID: PMC9251346), describe multiple potential heart protection mechanisms, including antioxidant, anti-inflammatory, and autonomic nervous system regulation.

Even more, recent randomized controlled clinical trials have shown a possible cytoprotective and cardioprotective relationship of melatonin use in patients with high cardiovascular risk (PMCID: PMC12564314). These data directly contradict the alarmist interpretations spread by some media.

Study conclusion

The information spread about a supposed link between melatonin and increased cardiovascular disease risk lacks solid scientific support. The study causing the controversy has serious limitations, explicitly states it cannot prove causality, and should be considered only a preliminary observation.

Melatonin, at doses used in food supplements, is safe, effective, and endorsed by major international health authorities. Available data not only rule out harmful effects but even suggest potential long-term cardiovascular health benefits.

Evidence keeps growing, but so far, there’s no scientific or clinical reason to consider melatonin a risk to heart health.

A hormone as safe as it is natural

Melatonin, also known as the “sleep hormone,” has an excellent safety profile. Numerous clinical studies have shown that its use across a wide dose range is completely safe.

As a food supplement, it doesn’t require a prescription since it’s a natural substance with zero toxicity and very high tolerability even with prolonged use, currently ranking among the most used food supplements worldwide, alongside multivitamins. This means consuming it at recommended doses carries no health risk.

Is a melatonin overdose possible?

No. Melatonin cannot cause an overdose. Its toxicity is zero, and scientific trials have shown that even doses far exceeding those in food supplements don’t cause harmful effects.

This is because melatonin is a molecule the body naturally produces and regulates. When given exogenously in small amounts, it simply supports the physiological sleep process without interfering with other functions.

Does it have contraindications?

In healthy individuals, melatonin has no known contraindications. Its use has been widely studied both short- and long-term, showing it doesn’t disrupt hormonal balance or cause relevant side effects.

In fact, doses of several hundred milligrams daily have been administered for years without any clinical or biochemical parameter alterations. These amounts are much higher than those used in food supplements, confirming its safety.

What about side effects?

At usual doses, no adverse effects have been reported. Melatonin doesn’t cause daytime drowsiness, fatigue, mood changes, or appetite or libido alterations.

Some anecdotal reports of symptoms like fatigue or morning sleepiness are attributed to nocebo effect phenomena—that is, expectations or mistaken associations rather than real body reactions. Available scientific evidence cannot link melatonin use causally to these effects.

When should you consult a professional?

Although melatonin is completely safe, in certain medical exceptions (such as pregnancy, breastfeeding, or chronic drug treatments) it’s advisable to inform a healthcare professional before starting use. This isn’t because melatonin poses risks, but because any food supplement should be considered in the context of medical tests or prescriptions.

Melatonin and rest: a natural connection

Melatonin helps synchronize the sleep-wake cycle, naturally promoting restorative rest. It hasn’t been linked to excessive drowsiness or “waking up tired.” When these symptoms are mentioned, they usually stem from external factors like insufficient rest or poor sleep hygiene.

In people with prolonged insomnia, melatonin can help gradually restore sleep rhythm, alongside good habits.

Does it affect sexual desire or fertility?

No. Melatonin doesn’t reduce sexual desire or affect fertility, in men or women. Theories linking its use to hormonal changes come from experimental studies and have no practical or clinical relevance.

Conclusion

Melatonin is a natural substance with a proven safety profile backed by decades of research. Its use at usual food supplement doses poses no risks or adverse effects and can be taken continuously without medical supervision, except in the specific cases mentioned.

It’s undoubtedly one of the safest and most effective options to promote natural nighttime rest.