Melatonin Gummies Sold in the U.S. Contain Inconsistent and Mostly Excessive Quantities of the Ingredient

Melatonin is a hormone that occurs naturally in the human body, and has a role in regulating awake and sleep cycles.[1] Accordingly, and more broadly because of its effects on brain function, melatonin supplementation is used for various conditions, including jet lag, insomnia, sleep disturbances related to late-night work, seasonal affective disorders, dementia and seizures. However, research has shown that melatonin supplements are only safe and effective for jet lag, not for other conditions, as discussed in a 2020 Worst Pills, Best Pills News article.[2]

Melatonin is regulated as a dietary supplement rather than as a drug, and thus it is available over the counter, including in oral gummy formulations.[3] A 2022 Worst Pills, Best Pills News article highlighted an increase in ingestion of melatonin supplements by children, sometimes leading to hospitalizations.[4] Adding to concerns about unintended melatonin consumption, recent research published in JAMA found that melatonin gummies almost always have quantities of this ingredient that are higher than those indicated on the product label.[5]

Recent information on melatonin’s effectiveness

The Cochrane Library is a respected online repository of medical evidence, including a searchable database of systematic reviews.[6] Since 2002, melatonin’s effectiveness for a variety of illnesses has been the subject of nearly 30 Cochrane reviews, many of which were reviewed by Worst Pills, Best Pills News in 2020. Since 2020, several updated and new reviews continue to indicate that melatonin is ineffective or only marginally useful for conditions other than jet lag. These reviews include those examining the use of melatonin to prevent or treat: weight gain, depression, anxiety and subfertility (difficulty becoming pregnant). The Cochrane reviews found only small studies regarding each of these proposed uses, and did not identify substantial evidence of effectiveness.

For example, a review of treatments for weight gain associated with the use of antipsychotic medications identified only one randomized trial of melatonin versus placebo with just 36 patients. The study found a small (3-kilogram) weight reduction with eight weeks of treatment with melatonin, as compared to a placebo.[7] Another study with just 60 patients indicated that melatonin may be equivalent to the benzodiazepine diazepam (VALIUM and generics) in treating recurrent febrile seizures in children, but the Cochrane researchers noted, as they did in all of the recent melatonin reviews, that further research was needed.[8] For the treatment of depression in persons with chronic conditions,[9] melatonin was tested in just one small trial. Although the trial found that melatonin may have a beneficial effect on depression in women being treated for breast cancer, only 43 subjects completed the trial.[10] Another Cochrane review of drug therapies for sleep disturbance in patients with dementia identified five trials with a total of 222 patients and “found no evidence for beneficial effects of melatonin.”[11]

Given its antioxidant properties, one recent Cochrane review considered melatonin (and many other drugs) as treatments for subfertility.[12] That review identified three randomized trials involving 270 women that showed no significant increases in live births from melatonin treatment as compared with placebo (two trials) or no treatment (one trial).

Finally, a 2020 Cochrane review found that melatonin may reduce presurgical anxiety by about 12 points on a 100-point scale, and post-operative anxiety by about 5 points. The presurgical estimates for melatonin were derived from 18 trials with 1,264 patients; post-operative estimates were derived from seven trials with 524 patients.[13] The certainty of this evidence was rated as low to moderate, and of questionable clinical importance.

The quantity of melatonin in melatonin gummies[14]

A research letter in the April 25, 2023 issue of JAMA assessed the quantity of melatonin in melatonin gummies sold in the United States. In September 2022, the researchers obtained a list, from the National of Institutes of Health’s Dietary Supplement Label Database, of 30 uniquely branded melatonin gummy products. Of these products, 25 were confirmed to contain melatonin and were available for purchase online. Once obtained, each product was tested to quantify the amount of melatonin, cannabidiol (CBD), which was sometimes included as a co-supplement, and serotonin (a suspected contaminant).

Of the 25 products, only 3 contained a quantity of melatonin that was within 10% of the quantity listed on the product label. Moreover, the amount of melatonin ranged from 74% to 347% of the amount that was listed on the label.[15] In the five products with CBD, the amount was 104% to 118% of the amount that was listed on the label. No serotonin was detected in any of the products.

These results were consistent with a separate Canadian study of 16 melatonin brands that found that the actual amounts of melatonin were 17% to 478% of the amounts listed on the label. The JAMA researchers thus concluded that “the great majority of melatonin gummy products [in the US] were inaccurately labeled with most products exceeding the declared amounts of melatonin and CBD.”

What You Can Do

Although melatonin dietary supplements may be useful for short-term treatment of jet lag, there is no to little evidence that they are effective for other conditions. Consumers should be aware that gummy and other melatonin supplements may contain substantially higher amounts of the ingredient than stated on the product label. Signs of excessive melatonin intake include headache, elevated or reduced blood pressure, drowsiness, vomiting and worsening of alopecia areata (an autoimmune disorder causing hair loss).[16] If you are concerned about a potential excess melatonin ingestion for yourself or your child, stop using the supplement and contact your local poison control center or your clinician.
 

References

[1] Melatonin dietary supplements: Useful for jet lag, not for other conditions. Worst Pills, Best Pills News. July 2020. https://www.worstpills.org/newsletters/view/1342. Accessed September 5, 2023.

[2] Ibid.

[3] Cohen PA, Avula B, Wang YH et al. Quantity of melatonin and CBD in melatonin gummies sold in the US. JAMA. 2023;329(16):1401-1402.

[4] News brief: Pediatric ingestion of melatonin is increasing. Worts Pills, Best Pills News. December 2022. https://www.worstpills.org/newsletters/view/1508. Accessed September 5, 2023.

[5] Cohen PA, Avula B, Wang YH et al. Quantity of melatonin and CBD in melatonin gummies sold in the US. JAMA. 2023;329(16):1401-1402.

[6] Cochrane Library. www.cochranelibrary.com. Accessed September 5, 2023.

[7] Agarwal SM, Stogios N, Ahsan ZA, et al. Pharmacological interventions for prevention of weight gain in people with schizophrenia. Cochrane Database of Syst Re. 2022;10(10):CD013337.

[8] Offringa M, Newton R, Nevitt SJ, Vraka K. Prophylactic drug management for febrile seizures in children. Cochrane Database of Syst Rev. 2021;6(6):CD003031.

[9] Kampling H, Baumeister H, Bengel J, Mittag O. Prevention of depression in adults with long-term physical conditions. Cochrane Database of Syst Rev. 2021;3(3):CD011246.

[10] Hansen MV, Andersen LT, Madsen MT, et al. Effect of melatonin on depressive symptoms and anxiety in patients undergoing breast cancer surgery: a randomized, double-blind, placebo-controlled trial. Breast Cancer Res Treat. 2014;145(3):683-695.

[11] McCleery J, Sharpley AL. Pharmacotherapies for sleep disturbances in dementia. Cochrane Database of Syst Rev. 2020;11(11):CD009178.

[12] Showell MG, Mackenzie-Proctor R, Jordan V, Hart RJ. Antioxidants for female subfertility. Cochrane Database of Syst Rev. 2020;8(8):CD007807.

[13] Madsen BK, Zetner D, Møller AM, Rosenberg J. Melatonin for preoperative and postoperative anxiety in adults. Cochrane Database of Syst Rev. 2020;12(12):CD009861.

[14] Cohen PA, Avula B, Wang YH, et al. Quantity of melatonin and CBD in melatonin gummies sold in the US. JAMA. 2023;329(16):1401-1402.

[15] Erland LA, Saxena PK. Melatonin natural health products and supplements: presence of serotonin and significant variability of melatonin content. J Clin Sleep Med. 2017;13(2):275-281.

[16] Pacheco D, Singh A. Can you overdose on melatonin? August 9, 2023. https://www.sleepfoundation.org/melatonin/melatonin-overdose. Accessed September 5, 2023.