A dazzling analysis of common, over-the-counter sleep aids finds they contain wildly variable amounts of melatonin, with packaging up to 347 percent of the labeled amount.
The study, published Tuesday in JAMA, found that 22 of 25 melatonin gummy products analyzed — 88 percent — were labeled inaccurately. That is, they contain more than 10 percent more or less melatonin than stated on the package. Together, the nutritional supplements contain a melatonin range of 1.3 mg to 13.1 mg per serving. And those actual amounts represented a range of 74 percent to 347 percent of what they were supposed to contain based on their labeling.
The finding points to a greater concern about the quality, safety and effectiveness of dietary supplements, which have not been vetted or approved by the Food and Drug Administration, such as over-the-counter drugs, such as ibuprofen and allergy medicines. The multibillion-dollar industry has long shrugged off substantial concerns about quality control, safety, lack of effectiveness data, and hyped health claims.
While the consequences of a melatonin overdose are unlikely to be acutely dangerous or life-threatening, the finding is concerning because melatonin can have unpleasant side effects and is commonly used in children. Gummy versions of the supplement, the focus of the current study, will be given to children in particular.
Melatonin is a hormone produced by the brain in response to darkness, and supplement manufacturers have marketed it as a potential sleep aid and relaxant. While there are some studies indicating that melatonin supplements are better than a placebo at helping children sleep, the data is sparse and there is a lot of uncertainty about its use. Unknowns include the ideal dose and its timing, as well as its long-term effects and whether it could alter hormonal development in children and young adults.
Rough awakening
Side effects and side effects are also not well documented. But in children, experts say melatonin’s risks include excessive sleepiness and increased bedwetting, plus many things that can disrupt sleep, such as headaches, nausea, nightmares, dizziness and mood swings.
“Administration of as little as 0.1 mg to 0.3 mg of melatonin to young adults can raise plasma concentrations to the normal nocturnal range,” wrote the authors of the JAMA study, led by Pieter Cohen, a supplement safety expert at Cambridge Health Alliance. Yet the amounts in the gummies were 40 to 130 times higher than those amounts.
Cohen and colleagues note that an estimated 1.3 percent of American children used melatonin before the pandemic, and that number likely increased during the stressful health crisis. Between 2012 and 2021, calls to poison control centers for children taking melatonin increased by 530 percent, according to data published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report. Those calls were associated with 27,795 emergency department and clinic visits, 4,097 hospitalizations, 287 intensive care unit admissions, and two deaths.
The new JAMA study has limitations; it only looked at gummy products and didn’t do batch-to-batch analysis. But a 2017 study by Canadian researchers looking at 31 melatonin supplements in chewable, capsule, and liquid forms found similar wild variability in products. The melatonin content ranged from 83 percent to 478 percent of what was written on the labels, and the content varied as much as 465 percent from batch to batch. In addition, 26 percent of the products also contained secret amounts of serotonin, a neurotransmitter that can be harmful even in small amounts.
Last year, the American Academy of Sleep Medicine issued a health advisory on the use of melatonin, particularly in children. Parents are advised to talk to pediatricians before using the hormone, which is also recommended by the American Academy of Pediatrics.
