Serious Adverse Events Reported with Dietary Supplement Use in the United States: A 2.5 Year Experience

Abstract

Dietary supplement marketers assure the safety of their products by complying with current good manufacturing practices and a host of federal regulations, including those enforced by the Food and Drug Administration (FDA). Post-market surveillance is a key part of identifying safety problems associated with dietary supplement products. FDA requires dietary supplement marketers to provide a domestic address or phone number on product labels for consumers, family members, or health care professionals to report adverse events (AEs) associated with product use and to report all serious adverse events (SAEs) to the agency within 15 business days of receipt. We aimed to evaluate the characteristics of AEs reported with dietary supplement use, including dietary supplement type and Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) that occur with reported SAEs. A total of 41,121 unique adverse event cases reported to two large, U.S.-based dietary supplement marketers in a 2.5-year period (March 1, 2014–August 31, 2016) were assessed for seriousness using established criteria. Each SAE was assigned one or more MedDRA preferred terms and system organ classes (SOC). The types of supplements most responsible for SAEs were assessed. Of the 41,121 AE cases reported, 203 (0.48%) were SAEs. SAEs tended to occur with products marketed for weight loss (69.0%) and glycemic control (19.2%). SAEs occurred most commonly in the cardiovascular, gastrointestinal, and nervous system disorder SOCs. The percentage of SAEs reported to dietary supplement marketers is low, predominantly among consumers of two types of supplements. Further study is needed among a larger cohort of supplement users to determine causal associations between types of supplement products and serious adverse events.

Keywords:

• adverse event
• CFSAN
• dietary supplement
• DSHEA
• FDA regulation of dietary supplements
• nutravigilance
• serious adverse event
• supplement safety

Acknowledgments

The authors thank Taylor C. Wallace, PhD, for his insightful editorial comments and Christina West for final quality review and final formatting of literature citations and data tables.

Declaration of interest

The authors did not receive compensation to author this paper. SMS and HLL are co-founders and owners of Supplement Safety Solutions, LLC (SSS), an independent regulatory compliance company. SSS receives consulting fees from the manufacturers to assess, analyze, perform safety surveillance, and report SAEs on their behalf. HLL is a principal and officer of the Center for Applied Health Sciences, LLC., a privately held contract research organization that receives external funding from companies in the dietary supplement, natural products, and functional foods/beverages industry. HLL is also co-inventor on multiple patents within the field of dietary supplements, applied nutrition, and bioactive compounds. DM and HN work for the Counsel for Responsible Nutrition (CRN), a Washington D.C.-based trade association and lobbying group representing the dietary supplement and functional food industry. CRN represents more than 100 companies that manufacture dietary ingredients and/or dietary supplements or supply services to those suppliers and manufacturers. CRN’s member companies produce a large portion of the dietary supplements marketed in the United States and globally.

Additional information

Notes on contributors

Stephen M. Schmitz

Stephen M. Schmitz, MD, MPH (Co-Founder, Supplement Safety Solutions, 121 Davis Road, Bedford, MA 01730). He was trained as a family physician and occupational physician, and has worked for 20 years in pharmacovigilance and nutravigilance. Interests include enhancing the safety of dietary supplements through data-driven information, dispelling inaccuracies of supplement safety and assuring access to high-quality products.

Hector L. Lopez

Hector L. Lopez, MD, MS (Co-Founder, Supplement Safety Solutions, 121 Davis Road, Bedford, MA 01730, Co-Owner, The Center for Applied Health Sciences(CAHS), 4302 Allen Road, Suite 120, Stow, OH 44224) is a physiatrist by training, with specialized training in nutrition and anti-aging medicine. Dr. Lopez has received research grants from companies who do business in the dietary supplement, natural products and functional foods industry as a co-owner of CAHS, a contract research organization. Dr. Lopez is also co-inventor on multiple patent applications within the field of dietary supplements, applied nutrition and bioactive compounds.

Douglas Mackay

Douglas Mackay, ND (Senior Vice-President, Scientific and Regulatory Affairs, Council for Responsible Nutrition, 1828 L Street, NW, Suite 810 Washington DC 20036-5114) is a naturopathic physician who oversees CRN's science and regulatory affairs department, ensuring that the association's scientific, policy and legislative positions are based on credible scientific rationale. Dr. MacKay serves on the Advisory Board for the American Botanical Council, the NSF International Joint Committee on Dietary Supplements, and the NIST/NIH Dietary Supplement Laboratory Quality Assurance Program. He is also on the editorial board of three peer-reviewed publications. Interests include dietary supplement use by health care providers, drug-dietary supplement interactions, and dietary supplement safety and regulations.

Haiuyen Nguyen

Haiuyen Nguyen, BS (Senior Director, Scientific & Regulatory Affairs, Council for Responsible Nutrition, 1828 L Street, NW, Suite 810 Washington DC 20036-5114) focuses on developing regulatory and scientific comments on dietary supplement-related topics submitted to federal agencies including the US Food and Drug Administration and US Department of Health and Human Services. Her interests include facilitating industry compliance with dietary supplement regulations, including good manufacturing practices, and engaging in nutrition policy-making processes.

Paula E. Miller

Paula E. Miller, BS, Eng., Esq., (Associate, Finnegan, Henderson, Farabow, Garrett & Dunner, 901 New York Ave NW, Washington, DC 20001) is a practicing attorney, focusing on several areas of patent law, including patent litigation, patent prosecution, and proceedings before the US Patent and Trademark Office.