Of 25 gummy products analyzed, 22 (88%) were inaccurately labeled, with only three products containing an amount of melatonin within 10% of the quantity declared on the label, according to Dr. Pieter Cohen, of Cambridge Health Alliance, in Somerville, Massachusetts, and co-authors.
One product did not contain any detectable level of melatonin but did contain 31.3 mg of CBD, Cohen and colleagues reported in a JAMA research letter.
The analysis was prompted by a recent report showing that the number of calls about pediatric melatonin ingestions to U.S. Poison Control Centers jumped by 530% from 2012 to 2021.
These calls were associated with 27,795 emergency department and clinic visits, 4,097 hospitalizations, 287 intensive care unit admissions and two deaths.
“Given that the poison control centers have received more than a quarter million calls regarding pediatric ingestions, it behooves us to learn precisely what are in melatonin products and consider what might be done to decrease the risk melatonin poses to children,” Cohen told MedPage Today.
The analysis examined gummies marketed to both adults and children.
“We included all newly introduced melatonin gummies listed at the NIH’s dietary supplement label database regardless if the product was specifically marketed to children or not,” Cohen said. “In the poison control center study, they did not have data on what formulations were consumed, but given that gummies are easier for children to ingest, intentionally or otherwise, we decided to focus on that form of melatonin.”
The findings call into question the confidence medical providers and patients can have in melatonin products, observed Naima Covassin, Ph.D., of the Mayo Clinic in Rochester, Minnesota, who wasn’t involved with the study.
“It may be advisable to use only supplements for which content, purity; and consistency have been independently verified to obtain the desired treatment effects and minimize health risks,” Covassin told MedPage Today
Melatonin products are not approved by the FDA and are sold as dietary supplements or food.
“Over-the-counter melatonin is typically used as a sleep aid but, paradoxically, taking melatonin in excess may actually worsen sleep rather than improving it, because too much melatonin can disrupt our circadian rhythms,” Covassin noted. “Additionally, although melatonin is generally safe, negative health effects have been reported.”
Cohen and colleagues identified melatonin gummies in the National Institutes of Health Dietary Supplement Label Database in September 2022 and purchased 30 unique brands online. The team examined product labels after buying and excluded products that did not include the word “melatonin.”
The researchers reconstituted the gummies in methanol and an aqueous mixture of acetonitrile-methanol, then assessed their levels of melatonin, CBD and serotonin. They screened for serotonin as it previously was reported to be a contaminant in melatonin products.
Of the 30 gummy brands identified, four were unavailable for purchase and one did not contain “melatonin” on the actual label, leaving 25 products in the analysis. One contained CBD but no melatonin. In products that contained melatonin, the actual amount ranged from 74% to 347% of the labeled quantity.
Five products declared CBD as an ingredient; the actual quantity of CBD was 104% to 118% of what was reported on the label. Serotonin was not found in any product.
Melatonin can have interactions with other medications — for example, with anti-seizure medications or blood thinners in adults — noted Dr. Gautam Ganguly, a neurologist in private practice in Whittier, California, and a member of the American Academy of Sleep Medicine Public Safety Committee.
“This paper provides valuable information for physicians,” Ganguly told MedPage Today. “We’ve speculated that the actual melatonin dose in supplements was all over the place, and this paper shows us that what we thought over the years is definitely true. Now we have evidence we can show to parents as well as other patients.”
As little as 0.1 mg to 0.3 mg of melatonin administered to young adults can increase plasma concentrations into the normal nighttime range, Cohen and colleagues noted. Consuming melatonin gummies as directed could expose children to between 40 and 130 times higher quantities of melatonin. And while a purified, pharmaceutical grade of CBD is approved for rare seizure disorders, the FDA has not approved CBD for any indication in healthy children, the team added.
In 2022, the AASM issued a health advisory encouraging parents to seek medical advice before giving melatonin or any supplement to children.
“Melatonin is not equivalent to a warm glass of milk,” Cohen said. “Melatonin should be treated by what it truly is, a medication. Just as parents would not casually give Benadryl to children to help them go to sleep, the same approach should be taken toward melatonin.”
“Clinicians should caution parents that melatonin should be stored with prescription medications away from children,” he continued. “In addition, clinicians should advise parents that purchasing high-quality melatonin in the U.S. is difficult because it is sold as a dietary supplement. One tip is to look for products that are certified by USP [U.S. Pharmacopeia] as these products should contain accurate information about the product on the label.”
This study has limitations, including its small sample size. Only one sample of each brand was tested and only gummies were analyzed, the researchers acknowledged.
Whether results apply to melatonin products sold as tablets and capsules is unknown.