Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US Food and Drug Administration Warnings | Complementary and Alternative Medicine | JAMA Network Open | JAMA Network
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Bailey  RL, Gahche  JJ, Lentino  CV,  et al.  Dietary supplement use in the United States, 2003-2006.  J Nutr. 2011;141(2):261-266. doi:10.3945/jn.110.133025PubMedGoogle ScholarCrossref
US Food and Drug Administration.  Constituent updates—FDA creates the Office of Dietary Supplement programs and announces new nutrition office leadership. http://wayback.archive-it.org/7993/20171114120120/https://www.fda.gov/Food/NewsEvents/ConstituentUpdates/ucm478303.htm. Published December 21, 2015. Accessed June 2017.
National Institutes of Health, Office of Dietary Supplements.  Dietary supplements: what you need to know. https://ods.od.nih.gov/HealthInformation/DS_WhatYouNeedToKnow.aspx. Published June 17, 2011. Accessed June 2017.
US Food and Drug Administration.  Dietary supplement products & ingredients. http://www.fda.gov/Food/DietarySupplements/ProductsIngredients/default.htm. Updated November 29, 2017. Accessed June 2017.
US Food and Drug Administration.  Information for consumers on using dietary supplements. https://www.fda.gov/Food/DietarySupplements/UsingDietarySupplements/default.htm. Updated November 29, 2017. Accessed June 2017.
US Government Accountability Office, Report to Congressional Requesters.  Dietary supplements: FDA may have opportunities to expand its use of reported health problems to oversee products. http://www.gao.gov/assets/660/653113.pdf. Published March 2013. Accessed June 2017.
US Food and Drug Administration.  Safety: recalls, market withdrawals, & safety alerts: background and definitions. http://www.fda.gov/safety/recalls/ucm165546.htm. Published June 24, 2009. Accessed June 2017.
Geller  AI, Shehab  N, Weidle  NJ,  et al.  Emergency department visits for adverse events related to dietary supplements.  N Engl J Med. 2015;373(16):1531-1540. doi:10.1056/NEJMsa1504267PubMedGoogle ScholarCrossref
Hamburg  MA.  Letter from commissioner of food and drugs to manufacturers of dietary supplements. http://www.fda.gov/downloads/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/MedicationHealthFraud/UCM236985.pdf. Published December 15, 2010. Accessed June 2017.
Interlandi  J.  Consumer reports: supplements can make you sick. http://www.consumerreports.org/vitamins-supplements/supplements-can-make-you-sick/. Published July 27, 2016. Accessed June 2017.
US Food and Drug Administration.  FDA begins posting adverse event report data for foods and cosmetics. http://www.fda.gov/Food/NewsEvents/ConstituentUpdates/ucm531519.htm. Published January 3, 2017. Accessed June 2017.
US Food and Drug Administration.  Tainted products marketed as dietary supplements_CDER. https://www.accessdata.fda.gov/scripts/sda/sdNavigation.cfm?sd=tainted_supplements_cder. Data extracted February 28, 2017. Accessed February 28, 2017.
Viagra [package insert]. New York, NY: Pfizer Inc; 2010.
Cialis [package insert]. Indianapolis, IN: Eli Lilly and Co; 2011.
Levitra [package insert]. West Haven, CT: Bayer Pharmaceuticals Corporation; 2007.
Francis  SH, Corbin  JD.  Molecular mechanisms and pharmacokinetics of phosphodiesterase-5 antagonists.  Curr Urol Rep. 2003;4(6):457-465. doi:10.1007/s11934-003-0027-xPubMedGoogle ScholarCrossref
US Food and Drug Administration.  Rhino 5 plus, maxtremezen and extenzone: recall—undeclared drug ingredients. https://wayback.archive-it.org/7993/20170112164800/http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm375727.htm. Published November 19, 2013. Accessed June 2017.
US Food and Drug Administration.  Questions and answers about FDA’s Initiative Against Contaminated Weight Loss Products. https://wayback.archive-it.org/7993/20170111234801/http://www.fda.gov/Drugs/ResourcesForYou/Consumers/QuestionsAnswers/ucm136187.htm. Updated March 10, 2016. Accessed June 2017.
US Food and Drug Administration.  Detox transforms health and nutrition issues voluntary nationwide recall of dietary supplements due to the presence of undeclared drug ingredients. https://wayback.archive-it.org/7993/20170406095839/https://www.fda.gov/Safety/Recalls/ArchiveRecalls/2015/ucm433513.htm. Published February 9, 2015. Accessed June 2017.
US Food and Drug Administration.  FDA announces rule prohibiting sale of dietary supplements containing ephedrine alkaloids effective April 12. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2004/ucm108281.htm. Published April 12, 2004. Accessed June 2017.
Balunas  MJ, Su  B, Brueggemeier  RW, Kinghorn  AD.  Natural products as aromatase inhibitors.  Anticancer Agents Med Chem. 2008;8(6):646-682. doi:10.2174/187152008785133092PubMedGoogle ScholarCrossref
US Food and Drug Administration.  Reumofan plus: recall—undeclared drug ingredient. https://wayback.archive-it.org/7993/20161022174034/http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm306360.htm. Updated March 14, 2014. Accessed June 2017.
US Food and Drug Administration.  Public notification: mayhem contains hidden drug ingredients. https://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/MedicationHealthFraud/ucm422932.htm. Published February 9, 2015. Accessed June 2017.
Helfand  C.  The coming generics threat to Pfizer's Viagra brand just got scarier. FiercePharma. http://www.fiercepharma.com/sales-and-marketing/coming-generics-threat-to-pfizer-s-viagra-brand-just-got-scarier. Published April 14, 2015. Accessed June 2017.
US Food and Drug Administration.  Public notification: power male sexual stimulant contains hidden drug ingredient. https://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/MedicationHealthFraud/ucm534470.htm. Published December 22, 2016. Accessed June 2017.
McMahon  CG.  Dapoxetine: a new option in the medical management of premature ejaculation.  Ther Adv Urol. 2012;4(5):233-251. doi:10.1177/1756287212453866PubMedGoogle ScholarCrossref
US Food and Drug Administration.  Volcano male enhancement liquid and Volcano male enhancement capsules: recall—undeclared drug ingredients. https://wayback.archive-it.org/7993/20170406124423/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm361854.htm. Published July 22, 2013. Accessed June 2017.
US Food and Drug Administration.  CTV BEST GROUP Inc issues voluntary nationwide recall of dietary supplements Best Slim 40 Pills Lot #109400 exp: Dec 31, 2016 because of potential health risk. https://wayback.archive-it.org/7993/20170406103731/https://www.fda.gov/Safety/Recalls/ArchiveRecalls/2013/ucm364119.htm. Published August 3, 2012. Accessed June 2017.
US Food and Drug Administration.  Warning on body building products marketed as containing steroids or steroid-like substances. https://www.fda.gov/ForConsumers/ConsumerUpdates/ucm173739.htm. Updated February 27, 2015. Accessed June 2017.
US Food and Drug Administration.  Kilosports Inc issues voluntary recall of clomed. https://wayback.archive-it.org/7993/20170406014329/https://www.fda.gov/Safety/Recalls/ArchiveRecalls/2010/ucm225847.htm. Published September 14, 2010. Accessed June 2017.
US Food and Drug Administration.  February 2, 2011: three indicted for selling mislabeled steroids. https://wayback.archive-it.org/7993/20161023232224/http://www.fda.gov/ICECI/CriminalInvestigations/ucm242337.htm. Published February 2, 2011. Accessed June 2017.
Campbell  N, Clark  JP, Stecher  VJ,  et al.  Adulteration of purported herbal and natural sexual performance enhancement dietary supplements with synthetic phosphodiesterase type 5 inhibitors.  J Sex Med. 2013;10(7):1842-1849. doi:10.1111/jsm.12172PubMedGoogle ScholarCrossref
Cohen  PA, Maller  G, DeSouza  R, Neal-Kababick  J.  Presence of banned drugs in dietary supplements following FDA recalls.  JAMA. 2014;312(16):1691-1693. doi:10.1001/jama.2014.10308PubMedGoogle ScholarCrossref
US Food and Drug Administration.  November 19, 2010: Vigor-25: undeclared drug ingredient-sold as natural dietary supplement. https://wayback.archive-it.org/7993/20170112165703/http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm234460.htm. Published November 19, 2010. Accessed August 2018.
US Food and Drug Administration.  March 10, 2016: Questions and answers: Reumofan Plus and Reumofan Plus Premium. https://wayback.archive-it.org/7993/20170722024631/https://www.fda.gov/Drugs/ResourcesForYou/Consumers/BuyingUsingMedicineSafely/MedicationHealthFraud/ucm316478.htm. Last updated March 10, 2016. Accessed August 2018.
US Food and Drug Administration.  December 23, 2013: muscle growth product called Mass Destruction: FDA health risk warning—undeclared ingredients. https://wayback.archive-it.org/7993/20170406124406/https://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm379740.htm. Published December 23, 2013. Accessed August 2018.
Van Gaal  LF, Caterson  ID, Coutinho  W,  et al; SCOUT Investigators.  Weight and blood pressure response to weight management and sibutramine in diabetic and non-diabetic high-risk patients: an analysis from the 6-week lead-in period of the sibutramine cardiovascular outcomes (SCOUT) trial.  Diabetes Obes Metab. 2010;12(1):26-34. doi:10.1111/j.1463-1326.2009.01090.xPubMedGoogle ScholarCrossref
James  WP, Caterson  ID, Coutinho  W,  et al; SCOUT Investigators.  Effect of sibutramine on cardiovascular outcomes in overweight and obese subjects.  N Engl J Med. 2010;363(10):905-917. doi:10.1056/NEJMoa1003114PubMedGoogle ScholarCrossref
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    5 Comments for this article
    Supplement ingredients
    Ben Garcia |
    Great article. Where does a reader find the specific names of the supplements and their manufacturers that were identified as including unapproved ingredients? Surely people would like that information to see if they are taking something that has been banned.
    Squandered medical science
    ARS |
    The focus of this article is further profit of the pharmaceutical industry by proving otc products should be regulated. No point otherwise
    Pharmaceutical fraud
    Frederick Rivara, MD, MPH | University of Washington
    I was very surprised when I saw this study. These companies are committing fraud on the public. Will the FDA step up their efforts to better protect the public?
    CONFLICT OF INTEREST: Editor in Chief, JAMA Network Open
    renal toxicity
    Kunal Malhotra, MD | University of Missouri
    This study is very important from renal point of view. When seeing a patient with decreased GFR, we should ask history of supplements since these unapproved ingredients can lead to Acute Kidney Injury and Chronic Kidney disease. This is specially true for those with pre-existing renal disease. The first step should be to stop all supplements.

    Kunal Malhotra, MD, FASN, FNKF
    Illegal drugs are not dietary supplements
    Haley Chitty | American Herbal Products Association (AHPA)
    The American Herbal Products Association (AHPA) and its members share concerns about health risks presented by unapproved drugs masquerading as dietary supplements.

    However, the article does not make a clear distinction between unlawful, misbranded drugs and legal dietary supplements. Put simply, these products are illegal under current U.S. law and those who knowingly manufacture and distribute them are criminals.

    This is in stark contrast to the regulated dietary supplement industry which is committed to consumer safety. AHPA and its members fully support strict enforcement of all laws and regulations, including those that prohibit illegal, undeclared drugs from being
    sold in any product.

    Since 2011, AHPA has worked to keep consumers informed about illegal products that contain undeclared drug ingredients through our Keep Supplements Clean website. The website lists recalls and health advisories posted by FDA, and by international regulatory organizations in other countries including Canada, Australia, and the United Kingdom. The fact that this is an international concern demonstrates that the U.S. legal and regulatory structure for dietary supplements is not to blame for this issue.

    It is important for consumers to know the difference between these products and I encourage you to help educate your readers to make this distinction in future articles by refraining from identifying these fraudulent products as dietary supplements.
    CONFLICT OF INTEREST: AHPA is a non-profit association for herbal product companies
    Original Investigation
    Public Health
    October 12, 2018

    Unapproved Pharmaceutical Ingredients Included in Dietary Supplements Associated With US Food and Drug Administration Warnings

    Author Affiliations
    • 1Food and Drug Branch, California Department of Public Health, Sacramento
    • 2California Epidemiologic Investigation Service (Cal EIS) Fellowship Program, Sacramento
    JAMA Netw Open. 2018;1(6):e183337. doi:10.1001/jamanetworkopen.2018.3337
    Key Points español 中文 (chinese)

    Question  What are the trends across adulterated dietary supplements associated with a warning released by the US Food and Drug Administration from 2007 through 2016?

    Findings  In this quality improvement study, analysis of the US Food and Drug Administration warnings from 2007 through 2016 showed that unapproved pharmaceutical ingredients were identified in 776 dietary supplements, and these products were commonly marketed for sexual enhancement, weight loss, or muscle building. The most common adulterants were sildenafil for sexual enhancement supplements, sibutramine for weight loss supplements, and synthetic steroids or steroid-like ingredients for muscle building supplements, with 157 products (20.2%) containing more than 1 unapproved ingredient.

    Meaning  Potentially harmful active pharmaceuticals continue to be identified in over-the-counter dietary supplements.


    Importance  Over half of adults in the United States report consuming dietary supplements. The US Food and Drug Administration (FDA) has warned of numerous dietary supplements containing undeclared, unapproved pharmaceutical ingredients. These FDA warnings have not been comprehensively analyzed for recent years.

    Objective  To summarize trends across adulterated (containing unapproved ingredients) dietary supplements associated with a warning released by the FDA from 2007 through 2016.

    Design, Setting, and Participants  In this quality improvement study, data were extracted from the FDA’s Center for Drug Evaluation and Research, Tainted Products Marketed as Dietary Supplements_CDER database from 2007 through 2016. Data from each warning were recorded unless multiple warnings were issued for the same product within a 6-month period. Date, product name, company, hidden ingredient(s), product category, source of sample, and warning document type were recorded for each included warning. Data analysis was conducted from February 2017 to June 2017.

    Results  From 2007 through 2016, 776 adulterated dietary supplements were identified by the FDA and 146 different dietary supplement companies were implicated. Most of these products were marketed for sexual enhancement (353 [45.5%]), weight loss (317 [40.9%]), or muscle building (92 [11.9%]), with 157 adulterated products (20.2%) containing more than 1 unapproved ingredient. The most common adulterants were sildenafil for sexual enhancement supplements (166 of 353 [47.0%]), sibutramine for weight loss supplements (269 of 317 [84.9%]), and synthetic steroids or steroid-like ingredients for muscle building supplements (82 of 92 [89.1%]). There were 28 products named in 2 or 3 warnings more than 6 months apart. Of these products, 19 (67.9%) were reported to contain new unapproved ingredients in the second or third warning, consistent with the assumption that the FDA found the product to be adulterated more than once. In recent years (2014-2016), 117 of 303 adulterated samples (38.6%) were identified through online sampling and 104 of 303 (34.3%) were identified through the examination of international mail shipments.

    Conclusions and Relevance  Active pharmaceuticals continue to be identified in dietary supplements, especially those marketed for sexual enhancement or weight loss, even after FDA warnings. The drug ingredients in these dietary supplements have the potential to cause serious adverse health effects owing to accidental misuse, overuse, or interaction with other medications, underlying health conditions, or other pharmaceuticals within the supplement.