A study found long-term melatonin users had a higher risk of heart failure over five years, but experts urge caution, saying more investigation is needed. Photo / 123rf
Experts say new research findings suggesting that long-term use of melatonin could be associated with increased risk of heart failure need further investigation.
A study that reviewed health records for tens of thousands of adults with chronic insomnia found that people who took prescribed melatonin for more than a year had a higher chance of heart failure over five years compared with people who were identified as non-users, the American Heart Association announced Monday. The researchers behind the study also reported that people taking melatonin were more likely to be hospitalised for heart failure and die of any cause than those who did not use the supplement.
But the study, which has not yet been peer-reviewed, has drawn mixed reactions from sleep medicine experts and cardiologists, who are urging the public not to panic and are calling for more research into using melatonin for long periods.
The preliminary results, which appear to contradict existing research suggesting that melatonin might have health benefits for people with heart failure, are from a research abstract that is expected to be presented at the American Heart Association’s Scientific Sessions, a conference for cardiovascular science and medicine. Several experts who reviewed the study also noted limitations that make it challenging to determine whether and how long-term melatonin use could influence heart failure, which is when your heart isn’t pumping as well as it should.
“The findings are certainly provocative and warrant attention, especially given the widespread perception of melatonin as a benign, ‘natural’ sleep aid,” said Muhammad Rishi, an associate professor of clinical medicine and spokesperson for the American Academy of Sleep Medicine, who was not involved in the study. “However, the study is observational and based on electronic health record data, which limits its ability to establish causality.”
Melatonin is a hormone secreted by the brain’s pineal gland in the evening and serves as a signalling mechanism that it’s time for sleep. But some doctors do not recommend using melatonin supplements to treat chronic insomnia, noting that evidence for its efficacy is limited and inconsistent, and there is a lack of data on long-term safety.
Sleep specialists typically suggest low doses of melatonin to help treat sleep-timing problems that people experience through jet lag or shift work. Unlike some other countries, melatonin doesn’t require a prescription in the United States. Prescription and over-the-counter supplements have the same active ingredients, but depending on the country, prescription melatonin is more regulated to meet pharmaceutical standards for more consistency in purity and dose.
Getting quality sleep is critical for heart health, said Joyce Oen-Hsiao, an associate professor of cardiovascular medicine at Yale School of Medicine. Research has found that people who don’t sleep well tend to have higher heart rates and blood pressure, and experience more cardiovascular events, Oen-Hsiao said.
Melatonin is also a well-known antioxidant, she said, and could have benefits for protecting against coronary artery disease, which can lead to heart failure. Taken at a specific time and dose, some research suggests melatonin supplements can also help regulate blood pressure.
The new study appears to be “the only one that is saying that melatonin can cause heart failure,” said Oen-Hsiao, who was not involved in the research.
While the existing research is valuable and adds to the understanding of melatonin’s biological effects, many of the studies were small, short-term or experimental, said Ekenedilichukwu Nnadi, the lead author of the new report and chief resident in internal medicine at SUNY Downstate/Kings County Primary Care in Brooklyn. Previous studies also often used controlled, pharmaceutical-grade melatonin in animals or select patient groups, Nnadi said.
The study relied on an international database of health records and analysed five years of data for more than 130,000 adults diagnosed with insomnia. Researchers identified about 65,000 participants who had been prescribed melatonin at least once and reported taking it for at least a year. Over the course of five years, about 3000 people who were taking prescription melatonin experienced heart failure for the first time, compared with nearly 1800 people who were identified as non-users.
People were excluded from the study if they had been already diagnosed with heart failure or prescribed other sleep medications.
Patients identified as melatonin users were matched with others in the database who also had insomnia but didn’t have melatonin use recorded in their health records. The researchers noted that they accounted for a variety of factors that could influence a person’s risk for heart failure, including other health conditions.
“What stood out most was that we found any association at all,” Nnadi said. “Melatonin is generally viewed as a very safe supplement, as something people, and even physicians, don’t usually worry much about, so we honestly didn’t expect to see a clear signal linking long-term use with higher rates of heart failure, hospitalisations and death.”
Nnadi emphasised that the study’s findings show association, not causation.
“This doesn’t prove that melatonin directly causes heart failure,” he said. “It simply shows that people with chronic insomnia who took melatonin long term were more likely to experience these outcomes. It’s an unexpected and important signal that needs to be studied further, ideally in randomised trials.”
The study’s authors noted several limitations, including that the group of people who did not have an official record of melatonin use could have included individuals who purchased supplements over the counter.
“The most problematic part” of the study, said David Neubauer, a sleep expert at Johns Hopkins University who was not involved in the research, “is we don’t know whether or not those people in the control group were taking melatonin”.
Only using prescriptions to identify melatonin users means it’s possible that people who take over-the-counter melatonin supplements were classified as non-users, Rishi said. This could result in findings that inflated risk, he said.
The health record data also did not capture details about whether patients with insomnia who were prescribed melatonin reported changes in their sleep, Oen-Hsiao said.
“If they had such bad insomnia that they needed prescription-dose melatonin, were they actually getting the benefit of the melatonin for sleep?” she said. “And if the answer is no, then you cannot have a correlation that melatonin causes heart failure.”
It’s more likely, she said, that the insomnia could be contributing to declining heart health and leading to heart failure. She added that the study did not appear to distinguish what type of heart failure patients were diagnosed with.
The study’s data also did not include how much melatonin was prescribed. Dose information was not consistently available in the health records, Nnadi said.
The limitations are “why we need randomized, prospective trials to confirm whether melatonin itself is contributing to these risks,” he said.
Experts who were not involved in the study agreed that further investigation into long-term melatonin use and the risk of heart failure is necessary.
The associations observed in the new research “raise questions as to whether long-term use of melatonin is harmful or not as benign as one would think,” said Marie-Pierre St-Onge, a professor of nutritional medicine at Columbia University who studies the association between lifestyle behaviours, such as diet and sleep, and cardio-metabolic risk.
“These questions deserve investigation to determine causality,” St-Onge said.
In the meantime, some experts urged people and health care providers not to make any drastic changes.
“Right now, we don’t have enough information to blanketly say all people should stop using melatonin,” Oen-Hsiao said.
Several experts said melatonin should be used cautiously and under medical supervision, especially if people have cardiovascular risk factors. For chronic insomnia, cognitive behavioural therapy remains the recommended treatment, according to the American Academy of Sleep Medicine.
“It’s difficult because many patients are searching for help with insomnia,” said Kelly Gill, a sleep medicine specialist at Northwestern Medicine. People often don’t want more prescriptions and consider melatonin a natural and easily accessible option.
“Now, we have to be careful about how we recommend it and how patients utilise it, especially in the context of heart failure,” Gill said.
Low-dose melatonin supplements, amounts usually under five milligrams, taken over short periods are generally regarded as safe, experts said. Keep in mind that melatonin, considered a dietary supplement, is not regulated by the Food and Drug Administration as a prescription or over-the-counter drug.
If you’re taking melatonin, timing matters, Neubauer said. It should be taken one to two hours before the time that you want to be asleep. There also don’t appear to be clear advantages to taking higher doses.
“Melatonin is not a sedating substance,” Neubauer said. “You don’t get more sedated by taking more.”
Nnadi encouraged people who have been taking melatonin for years, especially if they have heart disease or risk factors, to talk with their doctors.
“The takeaway isn’t that melatonin is ‘bad’ or that everyone should stop taking it,” he said. “It’s that we shouldn’t assume something is risk-free just because it’s natural or sold over the counter.”