Trends in Use of Melatonin Supplements Among US Adults, 1999-2018

Exogenous supplementation of melatonin, one of the key hormones governing circadian rhythm, is indicated for treatment of circadian rhythm sleep disorders¹ and, despite insufficient evidence,² is widely used as an over-the-counter sleep aid. Evidence of antioxidant and anti-inflammatory properties of melatonin³ has prompted investigation of its therapeutic value in multiple diseases.⁴ Although melatonin is generally regarded as safe, adverse effects have been reported, and data on long-term use and high-dose use are scarce.⁵ The heterogeneity in over-the-counter formulations⁶ further supports the need for a broader understanding of consumption of exogenous melatonin in the population.

We examined reported prevalence and trends in use of melatonin supplements among US adults from 1999 through 2018. Because the recommended dosage of melatonin typically does not exceed 5 mg/d, we additionally evaluated prevalence and trends in use of greater than 5 mg/d of melatonin.

We used data from the 1999-2000 through 2017-2018 cycles of the National Health and Nutrition Examination Survey (NHANES), a series of cross-sectional, stratified, multistage probability sample surveys of the noninstitutionalized US population, with response rates ranging from 51.9% (2017-2018) to 84.0% (2001-2002). Participants younger than 20 years (n = 46 235) or without available dietary supplement data (n = 58) were excluded. For the analysis on greater than 5 mg/d of melatonin use, we additionally excluded those reporting melatonin use but without daily dose information (n = 2). The National Center for Health Statistics Institutional Review Board approved the NHANES protocol and all participants provided written informed consent. Data on dietary supplement use during the past 30 days and daily dose used when taking the supplements were collected through in-home interview, and to aid reporting, participants were required to show supplement containers.

For each survey cycle, we computed weighted prevalences and 95% CIs of melatonin use in the overall sample and across sex and age categories. Prevalences and 95% CIs of greater than 5 mg/d of melatonin use was also estimated. P values for linear and quadratic trends were calculated using linear regression modeling with survey cycle as a continuous variable. To determine if trends varied by demographic characteristics, interaction effects were assessed using weighted logistic regression. R version 4.0.1 (R Foundation) and SPSS version 20.0 (IBM Corp) were used for analysis, and a 2-sided P < .05 was considered statistically significant.

Data from 55 021 adults (mean age, 47.5 [SD, 17.1] years; 52.0% women) from 10 NHANES cycles were included. The number of participants included in each cycle ranged from 4865 to 6214 (Table), and supplement containers were verified by interviewers for 93.9% of self-reported melatonin users. The overall reported weighted prevalence of melatonin use increased from 0.4% (95% CI, 0.2%-1.0%) in 1999-2000 to 2.1% (95% CI, 1.5%-2.9%) in 2017-2018 (linear P = .004) (Figure), with an increase beginning in 2009-2010 (quadratic P < .001). Trends were similar across sex and age groups (interaction P > .05 for all) (Table).

Melatonin use of greater than 5 mg/d was not reported before 2005-2006. The reported prevalence of melatonin use greater than 5 mg/d increased from 0.08% (95% CI, 0.02%-0.38%) in 2005-2006 to 0.28% (0.13%-0.60%) in 2017-2018 (linear P = .005) (Figure).

Among US adults, reported prevalence of melatonin supplement consumption significantly increased from 1999-2000 to 2017-2018 across all demographic groups. Although it remained very low, prevalence of self-reported use of greater than 5 mg/d of melatonin also increased over time. These estimates may raise safety concerns, especially given that the actual content of melatonin in marketed supplements may be up to 478% higher than the labeled content⁶ and that evidence supporting melatonin use for sleep disturbances is weak.² The growing use of exogenous melatonin in the general population and its expanding therapeutic potential⁴ provide impetus for the acquisition of robust evidence of long-term safety of melatonin supplementation. Limitations include self-reported use of melatonin, although supplement containers were verified in nearly all participants. Because of the small number of melatonin users in some subgroups, results of stratified analyses should be interpreted with caution. Reliable estimates of trends in melatonin use across racial/ethnic groups cannot be provided. Also, reasons for use were not available in all cycles.

Corresponding Author: Naima Covassin, PhD, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55902 (covassin.naima@mayo.edu).

Accepted for Publication: December 13, 2021.

Author Contributions: Drs Covassin and Li had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Li, Somers, Lopez-Jimenez, Covassin.

Acquisition, analysis, or interpretation of data: Li, Covassin.

Drafting of the manuscript: Li, Covassin.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Li.

Administrative, technical, or material support: Somers, Covassin.

Supervision: Covassin.

Conflict of Interest Disclosures: Dr Somers reported having served as a consultant for Respicardia, Baker Tilly, Bayer, and Jazz Pharmaceuticals and serving on the Sleep Number Research Advisory Board. No other disclosures were reported.

Funding/Support: Dr Li is supported by grant 82004301 from the National Natural Science Foundation of China. Dr Somers is supported in part by grants HL65176, HL134885, and HL134808 from the National Institutes of Health, grants from Sleep Number Corporation to Mayo Clinic, and the Alice Sheets Marriott Professorship. Dr Covassin is supported by grants HL134885 and HL134808 from the National Institutes of Health, a Mayo Clinic Marie Ingalls Research Career Development Award, and a grant from Sleep Number Corporation to Mayo Clinic.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Additional Information: This work was done when Dr Li was a visiting fellow at Mayo Clinic.