A five-year review of health records links the long-term use of melatonin supplements with a higher risk of heart failure diagnosis and hospitalization, as well as death from any cause in chronic insomnia. However, experts and industry associations call for “caution and context” in interpreting the preliminary study’s findings on the popular sleep supplement.
Although the observational study cannot prove a cause-and-effect relationship, the authors note that it raises safety concerns regarding the use of melatonin and may warrant further research. The complete research will be presented at the American Heart Association’s Scientific Sessions (Nov 7–10) in New Orleans, US.
The study included 130,828 adults diagnosed with insomnia, with an average age of 55.7 years. Of these participants, 65,414 had been prescribed melatonin and reported taking the sleep aid for at least a year. Compared with matched non-users, these people had a 90% higher chance of incident heart failure over five years, 4.6% instead of 2.7%.
Both the Natural Products Association (NPA) and the Council for Responsible Nutrition (CRN) caution against overinterpretation of these findings, as the study focused on individuals with a specific disease.
“Chronic insomnia — a condition shared by all study participants — may itself be a contributing factor to heart health outcomes, raising more questions than answers,” states CRN.
Daniel Fabricant, Ph.D., president and CEO of NPA, notes that established literature demonstrates the safety of short-term melatonin use. “NPA agrees that consumers should not take melatonin supplements for chronic insomnia without a proper indication and in close consultation with a medical professional.”
Natural sleep aid
Melatonin is a hormone produced in the body by the pineal gland to help regulate the sleep-wake cycle. Hormone levels increase during darkness and decrease during daylight. Melatonin supplements are available over the counter in many countries to help people fall and stay asleep.
The researchers reviewed electronic health records of adults with chronic insomnia who had a recorded use of melatonin and used it for over a year (the melatonin group). They matched these with individuals in the same TriNetX Global Research Network database who had insomnia but did not have melatonin recorded in their health records (the non-melatonin group).
NPA and CRN note that melatonin is deemed safe for short-term use, but that supplements cannot treat diseases like chronic insomnia.The authors used 40 factors to match people in both groups, including demographics, health conditions, and medications. The team excluded people who had been diagnosed with heart failure or had been prescribed other sleep medications.
According to the preliminary findings, people taking melatonin were nearly 3.5 times as likely to be hospitalized for heart failure as people in the non-melatonin group (19% vs. 6.6%, respectively). Moreover, people in the melatonin group had a 7.8% risk of dying from any cause compared to 4.3% among non-melatonin users.
“Melatonin supplements are widely thought of as a safe and ‘natural’ option to support better sleep, so it was striking to see such consistent and significant increases in serious health outcomes, even after balancing for many other risk factors,” says lead author Ekenedilichukwu Nnadi, M.D. and chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn, New York, US.
Safe, short-term use
CRN underscores that melatonin supplements are not intended to treat chronic insomnia or other sleep disorders. The organization’s 2024 voluntary melatonin labeling guidelines include advisory statements such as “For occasional and/or intermittent use only” and “Consult a healthcare professional if you are experiencing long-term sleep difficulties.”
“Decades of consumer experience and multiple clinical studies indicate that low-dose, short-term supplementation is safe for healthy adults when used as directed, “ states the organization. CRN notes that the observational data in the preliminary study do not alter that safety profile.
Although CRN supports ongoing scientific research to understand long-term use of supplements, it cautions: “No single study — especially a preliminary abstract — should serve as the basis for broad conclusions or alarmist headlines about dietary supplements.”
Further research needed
The study researchers acknowledge that the database used includes countries that require a prescription for melatonin, such as the UK, and countries like the US that don’t. They clarify that “patient locations were not part of the de-identified data available to the researchers.” Therefore, it did not include the use of unprescribed melatonin.
Carlos Egea, president of the Spanish Federation of Sleep Medicine Societies, also notes that recorded melatonin use may be biased. Egea was not part of the study.
“It is possible that the control group (without melatonin) included many patients who take melatonin without a prescription (the percentage is unknown, which could be a very significant bias) and is not reflected in their medical records.”
US supplements are subject to cGMP to confirm their identity, purity, strength, and composition, and ensure they don’t contain harmful adulterants.Data on hospitalization may also not have been correct, and the researchers lacked data on insomnia severity and the presence of other psychiatric disorders.
“Worse insomnia, depression/anxiety, or the use of other sleep-enhancing medicines might be linked to both melatonin use and heart risk,” details Nnadi. “Also, while the association we found raises safety concerns about the widely used supplement, our study cannot prove a direct cause-and-effect relationship. This means more research is needed to test melatonin’s safety for the heart.”
Other study limitations highlighted by CRN include a lack of data on melatonin dose, insomnia severity, and psychiatric comorbidities.
Egea also says that, unlike publications in indexed medical journals, the conference abstract has not been filtered by two independent reviewers.
“Therefore, these findings challenge the perception of melatonin as a benign chronic therapy and only highlight the need for a prospective trial with a control group to clarify its safety profile,” he details.
Supplement regulations
The NPA adds that it was “disappointed” in the American Heart Association’s statement that over-the-counter supplements in the US “are not regulated.” The association stresses that supplements, including those containing melatonin, are subject to current good manufacturing practices (cGMP) to confirm their identity, purity, strength, and composition, and ensure they don’t contain harmful adulterants.
According to the organization, the US FDA inspects hundreds of supplement companies each year to review their manufacturing processes.
Moreover, the NPA emphasizes that supplements sold in the US are not intended to treat, cure, or prevent disease; therefore, it does not promote melatonin supplements for a disease population, nor for the treatment of chronic insomnia or any other disease.
“NPA and its members take very seriously the industry’s responsibility to manufacture quality products based on cGMP requirements that FDA enforces,” details Fabricant.
“This is part of the robust regulatory framework created over 30 years ago under DSHEA (the 1994 Dietary Supplement Health and Education Act), which created a clear distinction between products to support health and wellness and those to treat disease, the subject of the preliminary study announced by the American Heart Association.”
