Abbreviations: FDA, US Food and Drug Administration; GABA, γ-aminobutyric acid.
eAppendix. Supplemental Methods
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Cohen PA, Sharfstein J, Kamugisha A, Vanhee C. Analysis of Ingredients of Supplements in the National Institutes of Health Supplement Database Marketed as Containing a Novel Alternative to Anabolic Steroids. JAMA Netw Open. 2020;3(4):e202818. doi:10.1001/jamanetworkopen.2020.2818
Dietary supplements are estimated to be responsible for tens of thousands of emergency department visits each year in the US.1 To identify potentially dangerous supplements and manage their risks, clinicians and consumers require access to accurate information about supplement ingredients. In an effort to provide a resource for researchers, clinicians, and the public, the National Institutes of Health (NIH) maintains an online searchable database of supplement labels.2 To our knowledge, whether supplements categorized as containing novel ingredients in the NIH database are accurately labeled has not been previously studied.
In October 2019, the US Food and Drug Administration (FDA) placed 5-alpha-hydroxy-laxogenin, a synthetic analog of a plant steroid that is marketed as a natural alternative to anabolic steroids,3 on the Dietary Supplement Ingredient Advisory List to alert the public that it does not appear to be a lawful supplement ingredient.4 We analyzed the actual contents of supplements categorized as containing 5-alpha-hydroxy-laxogenin in the NIH database to determine whether they are accurately labeled.
In this case series, supplements categorized as containing 5-alpha-hydroxy-laxogenin in the NIH Dietary Supplement Label Database2 were purchased online in November 2018 and analyzed from January to June 2019 for their chemical contents (excluding expedients, minerals, and plant species) according to previously described methods (eAppendix in the Supplement).5 Quantities were considered accurately labeled if they were within 20% of the labeled quantity. Data analysis was conducted with Excel 2016 (Microsoft Corp). The statistical prerequisite established was the determination of goodness of fit (ie, R2 ≥ 0.95) to conclude that linear calibration lines were fit for estimation purposes within the chosen concentration interval.
A total of 6 supplements were categorized in the NIH database as containing 5-alpha-hydroxy-laxogenin; 4 (67%) were available for purchase (1 [17%] was out of stock; 1 [17%] was discontinued). In total, 16 ingredients, excluding expedients, minerals, and plant species, were declared on the 4 product labels.
Compared with their actual chemical contents, no product was accurately labeled (Table). Of the 16 ingredients, 6 (38%) were not detected in the supplements. Only 4 of 14 ingredients (29%) with quantities provided on the label were present in the specified amounts. Quantities detected ranged from less than 5% to 109% of what was listed on the label. Two products contained an ingredient not declared on the label.
Only 1 product (25%) contained 5-alpha-hydroxy-laxogenin, an ingredient with purported anabolic effects in rats that, to our knowledge, has not been studied in humans. The supplements contained phenibut, an unapproved drug with abuse potential that is used in Russia to treat a variety of neurologic conditions; arimistane, a designer steroid that may function as an aromatase inhibitor; 7-keto dehydroepiandrosterone, a minor metabolite of dehydroepiandrosterone; ecdysterone, a steroid-like compound found in many insects and plants that may have anabolic effects in humans; and diosgenin, a steroid-like compound found in trace amounts in several plants and synthetically produced for use in the industrial production of some commercial steroids (Figure). None of these ingredients has an FDA-approved indication.
Supplements categorized in the NIH supplement database as containing 5-alpha-hydroxy-laxogenin were inaccurately labeled and contained a variety of potentially pharmaceutically active compounds with unpredictable health effects. The NIH database contains the disclaimer that “label information has not been verified or checked for conformity with existing US Food and Drug Administration (FDA) regulations.”2 However, this statement does not accurately capture the breadth of gaps in the database, including supplements that contain ingredients not listed on the label, do not contain ingredients declared on the label, provide inaccurate quantities of ingredients on the label, and contain prohibited ingredients.
Our study was limited because we analyzed only supplements categorized as containing 1 new ingredient at 1 point. Ingredients may vary over time within the same product.6
Our analysis suggests that consumers and clinicians cannot obtain accurate information on novel supplement ingredients with the NIH supplement database. Future efforts to design and update supplement databases should take steps to assure accurate results.
Accepted for Publication: February 13, 2020.
Published: April 15, 2020. doi:10.1001/jamanetworkopen.2020.2818
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2020 Cohen PA et al. JAMA Network Open.
Corresponding Author: Pieter A. Cohen, MD, Department of Medicine, Cambridge Health Alliance, 236 Highland Ave, Somerville, MA 02143 (firstname.lastname@example.org).
Author Contributions: Drs Cohen and Vanhee 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: Cohen, Vanhee.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Cohen.
Critical revision of the manuscript for important intellectual content: All authors.
Obtained funding: Cohen.
Administrative, technical, or material support: Kamugisha, Vanhee.
Conflict of Interest Disclosures: Dr Cohen reported receiving grants from Consumers Union and receiving nonfinancial support from NSF International outside the submitted work and being the subject of a civil suit brought by Hi-Tech Pharmaceuticals, a supplement company, in which the jury found in Dr Cohen’s favor. Dr Sharfstein reported serving as principal deputy commissioner of the US Food and Drug Administration from 2009 to 2011. No other disclosures were reported.
Funding/Support: This research was supported in part by a grant from The PEW Charitable Trusts.
Role of the Funder/Sponsor: The funder 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; and decision to submit the manuscript for publication.
Additional Contributions: Paul Bain, PhD (Harvard Medical School), and Patricia Redd, MLS (Cambridge Health Alliance), helped to obtain obscure references; Xizhao Chen, BS (University of Virginia), helped to identify the supplements; Igor Zakharevich, BA (University of Colorado, Denver), helped to purchase the supplements and assisted with Russian translations; and Michaël Canfyn, BS (Sciensano), assisted with the gas chromatography mass spectrometry. They were not compensated for their time.
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