Mike Montemarano, Associate Editor 04.25.23
In 25 products containing either melatonin or a combination of melatonin and cannabidiol (CBD), just three products were labeled accurately within a ±10% window of accuracy, according to a research letter published in JAMA.
Led by Pieter A. Cohen, MD, researchers analyized 25 dietary supplements formulated as gummies with “melatonin” on the label. Products were found through the National Institutes of Health Dietary Supplement Label Database and researchers purchased them online.
One sample of each product was analyzed for concentrations of melatonin, CBD, and serotonin utilizing ultra high-performance liquid chromatography-photodiode array analyses. The authors screened for serotonin as it was previously found as a contaminant in melatonin-containing products, the authors reported.
Of the 25 products which met the authors’ inclusion criteria, one product didn’t contain any detectable levels of melatonin, but contained 31.3 mg of CBD.
In the remaining products, melatonin ranged from 1.3 mg to 13.1 mg per serving size. Product inaccuracies, defined as being greater or less than 10% off of label claims, ranged from 74% to 347% of labeled quantity. Based on this definition of accuracy, only three products were accurately labeled, the authors concluded.
The quantity of CBD ranged from 10.6 mg to 31.3 mg per serving, and doses were substantially more accurate, ranging from 104% to 118% of labeled quantities.
No serotonin was found in any of the products tested.
The authors of the study were primarily concerned with the potential for children to consume excessive amounts of melatonin due to the overages observed. Additionally, they were concerned about the presence of CBD in these products, given that it has only been approved to treat refractory seizures in children and is not approved for any indication in a healthy pediatric population.
“Administration of as little as 0.1 mg to 0.3 mg of melatonin to young adults can increase plasma concentrations into the normal nighttime range. Consuming melatonin gummies as directed could expose children to between 40- and 130-times higher quantities of melatonin. Unintentional ingestions could lead to consumption that greatly exceeds these dosages of melatonin,” the authors concluded.
They noted that since only one sample of each brand was analyzed, the results aren’t generalizable to brands or to other product types, such as capsules and tablets.
“Clinicians should advise parents that pediatric use of melatonin gummies may result in ingestion of unpredictable quantities of melatonin and CBD,” the authors noted.
This study is not the first in recent years concerned with unpredictable quantities of melatonin.
A study on Canadian natural health products containing melatonin published in 2017, for instance, yielded similar findings on melatonin overages.
Meanwhile, the Centers for Disease Control (CDC) noted that poison control center reports of pediatric melatonin ingestions increased by 530% from 2012 to 2021. However, certain conclusions were met with some criticism as the outcomes assessed were voluntary self-reporting by nature, and of all reported ingestions, only 1.6% resulted in serious outcomes. In those serious outcomes, no comorbidities or any other medical data were reported.
With a Grain of Salt
According to the Council for Responsible Nutrition (CRN), the research letter raises “unnecessary concern” about melatonin, given the safety profile of the ingredient established for users of all ages. It also conflates standards of overages used in pharmaceutical products with how overages are handled for dietary supplements, the trade association said in a statement.
Further, the study shouldn’t be concerned about pediatric populations for products labeled for adult use, CRN said.
While the authors didn’t disclose the names of the products they tested, CRN was able to match the product descriptions with labels in the Dietary Supplements Label Database, and found that “almost all of the 25 products sampled contained adult servings and are expressly labeled for use in adults, yet the authors conflate their findings with pediatric data,” CRN reported.
The association also noted that the authors used FDA’s drug standard for overages and shortages of ingredients (10% more or less than declared content on a label). Dietary supplement regulations require products to meet at least 100% of ingredient contents claimed on a label for the duration of a product’s shelf-life, and it is standard practice in the industry to include an overage of an ingredient as degradation naturally occurs.
According to CRN, overages are permitted in products for that reason, so long as those overages align with current Good Manufacturing Practices (cGMPs).
CRN said in its statement that the study may lead to confusion about the safety profile of melatonin products, given that study authors mentioned the CDC’s study on poison control center calls. Consumers shouldn’t connect presumable “overdose” levels observed in the CDC study with the overages which were reported in the present research letter, the association said.
“This report does a complete disservice to a safe product when it is used according to manufacturer’s instructions,” said Steve Mister, president and CEO of CRN. “Supplement companies go to great lengths to ensure their products contain safe and consistent levels of dietary ingredients, as labeled. And while there may be some variability in overages as companies adhere to the FDA’s requirements regarding shelf life and potency, it does not mean there is a risk in taking these products as intended. It’s a misleading comparison to look at scenarios where kids, for example, got their hands on an entire bottle of adult gummies and became ill after eating multiple servings, versus having slightly more of an ingredient in a single serving that, if taken as directed, would pose no harm.”
Led by Pieter A. Cohen, MD, researchers analyized 25 dietary supplements formulated as gummies with “melatonin” on the label. Products were found through the National Institutes of Health Dietary Supplement Label Database and researchers purchased them online.
One sample of each product was analyzed for concentrations of melatonin, CBD, and serotonin utilizing ultra high-performance liquid chromatography-photodiode array analyses. The authors screened for serotonin as it was previously found as a contaminant in melatonin-containing products, the authors reported.
Of the 25 products which met the authors’ inclusion criteria, one product didn’t contain any detectable levels of melatonin, but contained 31.3 mg of CBD.
In the remaining products, melatonin ranged from 1.3 mg to 13.1 mg per serving size. Product inaccuracies, defined as being greater or less than 10% off of label claims, ranged from 74% to 347% of labeled quantity. Based on this definition of accuracy, only three products were accurately labeled, the authors concluded.
The quantity of CBD ranged from 10.6 mg to 31.3 mg per serving, and doses were substantially more accurate, ranging from 104% to 118% of labeled quantities.
No serotonin was found in any of the products tested.
The authors of the study were primarily concerned with the potential for children to consume excessive amounts of melatonin due to the overages observed. Additionally, they were concerned about the presence of CBD in these products, given that it has only been approved to treat refractory seizures in children and is not approved for any indication in a healthy pediatric population.
“Administration of as little as 0.1 mg to 0.3 mg of melatonin to young adults can increase plasma concentrations into the normal nighttime range. Consuming melatonin gummies as directed could expose children to between 40- and 130-times higher quantities of melatonin. Unintentional ingestions could lead to consumption that greatly exceeds these dosages of melatonin,” the authors concluded.
They noted that since only one sample of each brand was analyzed, the results aren’t generalizable to brands or to other product types, such as capsules and tablets.
“Clinicians should advise parents that pediatric use of melatonin gummies may result in ingestion of unpredictable quantities of melatonin and CBD,” the authors noted.
This study is not the first in recent years concerned with unpredictable quantities of melatonin.
A study on Canadian natural health products containing melatonin published in 2017, for instance, yielded similar findings on melatonin overages.
Meanwhile, the Centers for Disease Control (CDC) noted that poison control center reports of pediatric melatonin ingestions increased by 530% from 2012 to 2021. However, certain conclusions were met with some criticism as the outcomes assessed were voluntary self-reporting by nature, and of all reported ingestions, only 1.6% resulted in serious outcomes. In those serious outcomes, no comorbidities or any other medical data were reported.
With a Grain of Salt
According to the Council for Responsible Nutrition (CRN), the research letter raises “unnecessary concern” about melatonin, given the safety profile of the ingredient established for users of all ages. It also conflates standards of overages used in pharmaceutical products with how overages are handled for dietary supplements, the trade association said in a statement.
Further, the study shouldn’t be concerned about pediatric populations for products labeled for adult use, CRN said.
While the authors didn’t disclose the names of the products they tested, CRN was able to match the product descriptions with labels in the Dietary Supplements Label Database, and found that “almost all of the 25 products sampled contained adult servings and are expressly labeled for use in adults, yet the authors conflate their findings with pediatric data,” CRN reported.
The association also noted that the authors used FDA’s drug standard for overages and shortages of ingredients (10% more or less than declared content on a label). Dietary supplement regulations require products to meet at least 100% of ingredient contents claimed on a label for the duration of a product’s shelf-life, and it is standard practice in the industry to include an overage of an ingredient as degradation naturally occurs.
According to CRN, overages are permitted in products for that reason, so long as those overages align with current Good Manufacturing Practices (cGMPs).
CRN said in its statement that the study may lead to confusion about the safety profile of melatonin products, given that study authors mentioned the CDC’s study on poison control center calls. Consumers shouldn’t connect presumable “overdose” levels observed in the CDC study with the overages which were reported in the present research letter, the association said.
“This report does a complete disservice to a safe product when it is used according to manufacturer’s instructions,” said Steve Mister, president and CEO of CRN. “Supplement companies go to great lengths to ensure their products contain safe and consistent levels of dietary ingredients, as labeled. And while there may be some variability in overages as companies adhere to the FDA’s requirements regarding shelf life and potency, it does not mean there is a risk in taking these products as intended. It’s a misleading comparison to look at scenarios where kids, for example, got their hands on an entire bottle of adult gummies and became ill after eating multiple servings, versus having slightly more of an ingredient in a single serving that, if taken as directed, would pose no harm.”
