Food is medicine: The science behind melatonin

Key takeaways:

• Research suggests that melatonin supplementation is a safe, effective insomnia treatment.
• Providers have asked for clearer guidance on its use, especially as it becomes more popular among children.

Melatonin is one of the most popular and easily accessible supplements today.

Justin Tondt, MD, an assistant professor in the department of family and community medicine at Penn State College of Medicine, Penn State Milton S. Hershey Medical Center, told Healio that melatonin — a naturally occurring compound in humans — “is extremely important for our sleep-wake cycle (circadian rhythm).”

The brain produces melatonin in response to darkness, according to the NIH. As such, melatonin supplements are commonly used for the treatment of sleep issues like circadian rhythm disorders or insomnia, said Tondt, who is also a member of the Healio Primary Care Peer Perspective Board.

“The typical dose is 3 to 5 mg taken 30 minutes prior to bedtime,” he said. “It typically has only a mild effect but is extremely safe, making the benefits easily outweigh the risks.”

Enlarge 

Previous research has shown that melatonin is also present in eggs, fish, nuts and some mushrooms and cereals.

Notably, although the American Academy of Sleep Medicine (AASM) and American College of Physicians have stated that they do not recommend the supplement as an insomnia treatment on account of the strength of the evidence, a 2022 survey found that about 70% of primary care physicians believe it is.

"I have many patients who have tried melatonin,” Tondt said. “Although it doesn’t work for all of them, it does help a lot of them get better sleep.”

Popular among children

Additionally, the supplement has gained popularity as a sleep aid for children. Results from a survey published in JAMA Pediatrics in November 2023 showed that about one in five school-aged children and preteens take it — a surprisingly high prevalence, according to researchers. AASM recommended in September 2022 that parents should talk to health care professionals about melatonin before giving it to their children. Providers have called for clearer guidelines on its use in younger populations.

Some research has indicated that rising use of over-the-counter melatonin could put children at risk. A 2022 report from the CDC showed that, from 2012 to 2021, the annual number of pediatric melatonin ingestions was 260,435 — an increase of 530%. Serious adverse outcomes and pediatric hospitalizations also increased, largely due to rising unintentional melatonin ingestions in children aged 5 years or younger.

However, Tondt said he does not have “any issues with how popular melatonin is with children. Sleep hygiene is usually more effective, but melatonin is very safe, so there isn’t harm in using it.”

More evidence

According to the NIH, melatonin supplements can also help with delayed sleep-wake phase disorder, jet lag and even anxiety around a surgery. Recent investigations into the safety and efficacy of melatonin have shed some additional light on the benefits of the supplement.

For example, a double-blind, randomized, placebo-controlled study published in Sleep Medicine in 2020 evaluated melatonin’s effectiveness on sleep disturbances in middle-aged primary insomnia. The researchers found that a 3 mg fast-release melatonin supplement significantly improved several objective aspects of sleep quality, including early wake time, total sleep time and percentage of rapid eye movement. However, they also wrote that the patients’ experiences with subjective sleep was different — nearly all subjective sleep variables were unaffected by the melatonin treatment, particularly for patients with insomnia. The researchers also noted that melatonin was safe: regarding the incidence of adverse events, there was no significant difference between the melatonin and placebo groups. In fact, “no clinically relevant changes in vital signs and laboratory blood and urine tests were observed,” they said.

In 2022, researchers conducted the first systematic review and a series of meta-analyses that evaluated melatonin’s impact on people with sleep or mental health disorders, finding evidence that melatonin significantly improved sleep-onset latency and total sleep time. The researchers additionally found that melatonin significantly improved total sleep time and sleep-onset latency in adolescents and children who had a variety of neurodevelopmental disorders, including autism spectrum disorder, intellectual disability and ADHD. They did not find evidence that melatonin is efficacious for those with other mental health disorders like depression and anxiety, contrary to other “studies pointing to anxiolytic properties of melatonin” and “anecdotal evidence.”

When looking at evidence for children specifically, a meta-analysis of randomized controlled trials published in 2019 revealed that melatonin was an effective and tolerable drug in the short-term treatment of sleep-onset insomnia in this population. The evidence also indicated that melatonin improved total sleep time, advancing sleep-onset time, dim light melatonin onset and sleep-onset latency.

Some research has been critical of melatonin as a dietary supplement. For example, a research letter published in JAMA revealed that a “great majority of melatonin gummy products were inaccurately labeled, with most products exceeding the declared amount of melatonin and CBD.”

Editor’s Note: Healio is highlighting the clinical value of various supplements. See other installments of the series here:

• Omega-3
• Zinc and other supplements for immune health
• Vitamin D
• Calcium
• Ashwagandha
• Magnesium
• Folic Acid
• Vitamin B12
• Iodine
  

References:

• Cohen PA, et al. JAMA. 2023;doi:10.1001/jama.2023.2296.
• Lelak K, et al. MMWR Morb Mortal Wkly Rep. 2022; doi:10.15585/mmwr.mm7122a1.
• Kamfar WW, et al. Heliyon. 2024;doi:10.1016/j.heliyon.2024.e24266.
• Melatonin: What you need to know. https://www.nccih.nih.gov/health/melatonin-what-you-need-to-know. Accessed Jan. 25, 2024.
• Meng X, et al. Nutrients. 2017; doi: 10.3390/nu9040367.
• Salanitro M, et al. Neurosci Biobehav Rev. 2022;doi:10.1016/j.neubiorev.2022.104723.
• Sietten TL, et al. PLoS Med. 2018;doi:10.1371/journal.pmed.1002587.
• Wei S, et al. Sleep Med. 2019;doi:10.1016/j.sleep.2019.02.017.
• Xu H, et al. Sleep Med. 2020;doi:10.1016/j.sleep.2020.10.018.