Melatonin: should its safety for heart health be re-examined?

Controversial preliminary research has found a link between prolonged use of melatonin for sleep and certain heart problems.

Prolonged intake of a widely used supplement to promote sleep – melatonin – may be linked to negative effects on heart health. Preliminary (and not peer-reviewed) research presented at the American Heart Association Scientific Sessions in New Orleans suggests that the heart safety of long-term melatonin use should be investigated more carefully, given the popularity of the safe, low-dose sleep supplement.

The study is a review of 5 years of health data from more than 130,000 adults with chronic insomnia, who had used melatonin to fall asleep more easily for at least a year. These people were at greater risk of heart failure (the inability of the heart to supply adequate blood to the body), of being hospitalized for the condition, or of dying from any cause, compared to an equal number of insomniacs who had not used melatonin.

Melatonin: what it is and why it is used

Melatonin is a hormone produced by the pineal gland, which is located at the base of the brain. It serves to regulate the sleep-wake cycle: its concentrations begin to increase with the onset of darkness and decrease with exposure to light.

The side effects of melatonin-based supplements are considered almost nil. If the study were confirmed as it is even after the review processes, it would therefore be worth studying the safety aspects of melatonin for heart health, and verifying that the association found does not instead depend on other factors.

Necessary precautions

The study, which was presented in the form of an abstract and is still waiting to be published in a scientific journal, was coordinated by the SUNY Downstate Health Sciences University (Primary Care) Program Brooklyn, New York and does not reflect the official positions of the American Heart Association, an organization that works to reduce deaths caused by heart problems and stroke.

The work is limited to detecting an association between long-term continuous use of melatonin, taken for 12 months or more by prescription (as occurs in some countries) and an increased incidence of heart failure over the 5 years documented by patient data.

Those who had taken the sleep supplement for a year or more had a 90% higher risk of having an episode of heart failure, and a similar result (82% higher risk) occurred when the researchers analyzed a different sample, i.e. people who had had at least 2 melatonin prescriptions at least 90 days apart.

A second analysis suggests that participants who took melatonin for over a year had a 3.5 times higher risk of being hospitalized for heart failure than those who did not take it, and a nearly double risk of death from any cause compared to the control group over the 5 years considered.

Heavy melatonin users and control patients were matched for age, sex, ethnicity, heart or nervous system disease and the drugs taken to treat it, blood pressure and body mass index.

An association to be explored further

In patients with chronic insomnia there may be upstream factors that encourage prolonged melatonin use and at the same time are linked to poor heart health. “A worsening of insomnia, depression/anxiety or the use of other drugs that promote sleep could be linked to both the use of melatonin and cardiac risk” explains Ekenedilichukwu Nnadi, doctor and first author of the work.

«Although the association found raises concerns about the safety of this widely used supplement, our study cannot demonstrate a direct cause-and-effect relationship. More research is needed to test the safety of melatonin for the heart.”

Several limitations

The research has several limitations. The database used in the study took into consideration both countries in which melatonin is prescribed for insomnia (such as the United Kingdom), and countries in which it is purchased as an over-the-counter supplement, such as the USA, without however specifying the origin of the patients from time to time. Since those who had it prescribed were users of melatonin, the patients who purchased it without a prescription could have ended up in the control group, that of insomniacs who do not use it.

Furthermore, there was no indication on the severity of insomnia or the presence of psychiatric diseases that may be associated with cardiac risk.

In short, as much as the association is impressed, it is a safe bet that we will still hear a lot of discussion about these results.