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      Drug-Induced Liver Injury Associated With Alpha Bolic (RAD-140) and Alpha Elite (RAD-140 and LGD-4033)

      case-report
      , MD 1 , 2 , , MD 3 , , MD, MPH 1 , 2 ,
      ACG Case Reports Journal
      Wolters Kluwer

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          ABSTRACT

          We report a 52-year-old man who developed drug-induced liver injury after taking Alpha Bolic (contains RAD-140) and Alpha Elite (contains both RAD-140 and LGD-4033) supplements. Liver biopsy demonstrated diffuse centrilobular canalicular cholestasis, prominent ductular reaction, and mild lobular inflammation with rare non-necrotizing epithelioid granuloma suggestive of drug-induced liver injury. Liver enzymes returned to normal levels approximately 3 months after the patient stopped both supplements. We present the mechanism of drug-induced liver injury associated with 2 selective androgen receptor modulators, including RAD-140 and LGD 4033.

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          Most cited references9

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          Selective Androgen Receptor Modulators: Current Knowledge and Clinical Applications

          Selective androgen receptor modulators (SARMs) differentially bind to androgen receptors depending on each SARM's chemical structure. As a result, SARMs result in anabolic cellular activity while avoiding many of the side effects of currently available anabolic steroids. SARMs have been studied in the treatment of breast cancer and cachexia and have also been used as performance-enhancing agents. Here, we evaluate and summarize the current literature on SARMs.
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            Criteria of drug-induced liver disorders. Report of an international consensus meeting.

            International reporting of adverse drug reactions by pharmaceutical manufacturers to national drug regulatory authorities requires internationally accepted standard definitions of reactions and criteria for assessment of causality. The Council for International Organizations of Medical Sciences (CIOMS) undertook a pilot project to prepare such definitions and criteria, and proposed to use as its model a series of expert consensus meetings organized in France by the pharmaceutical company, Roussel Uclaf, with the participation of the official French network of pharmacovigilance. Under CIOMS auspices, an international meeting was organized to test the feasibility of adapting for international use the outcome of the French consensus meetings on drug-induced liver disorders. The meeting resulted in a series of proposed standard designations of drug-induced liver disorders and criteria of causality assessment.
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              Chemical Composition and Labeling of Substances Marketed as Selective Androgen Receptor Modulators and Sold via the Internet

              Question What types and quantity of ingredients are found in products sold through the internet and advertised to contain selective androgen receptor modulators? Findings Chemical analyses of 44 products sold via the internet as selective androgen receptor modulators revealed that only 52% contained selective androgen receptor modulators and another 39% contained another unapproved drug. In addition, 25% of products contained substances not listed on the label, 9% did not contain an active substance, and 59% contained substance amounts that differed from the label. Meaning Selective androgen receptor modulators, which have not been approved by the US Food and Drug Administration, were available through the internet and were inaccurately labeled. Importance Recent reports have described the increasing use of nonsteroidal selective androgen receptor modulators, which have not been approved by the US Food and Drug Administration (FDA), to enhance appearance and performance. The composition and purity of such products is not known. Objective To determine the chemical identity and the amounts of ingredients in dietary supplements and products marketed and sold through the internet as selective androgen receptor modulators and compare the analyzed contents with product labels. Design and Setting Web-based searches were performed from February 18, 2016, to March 25, 2016, using the Google search engine on the Chrome and Internet Explorer web browsers to identify suppliers selling selective androgen receptor modulators. The products were purchased and the identities of the compounds and their amounts were determined from April to August 2016 using chain-of-custody and World Anti-Doping Association–approved analytical procedures. Analytical findings were compared against the label information. Exposures Products marketed and sold as selective androgen receptor modulators. Main Outcomes and Measures Chemical identities and the amount of ingredients in each product marketed and sold as selective androgen receptor modulators. Results Among 44 products marketed and sold as selective androgen receptor modulators, only 23 (52%) contained 1 or more selective androgen receptor modulators (Ostarine, LGD-4033, or Andarine). An additional 17 products (39%) contained another unapproved drug, including the growth hormone secretagogue ibutamoren, the peroxisome proliferator-activated receptor-δ agonist GW501516, and the Rev-ErbA agonist SR9009. Of the 44 tested products, no active compound was detected in 4 (9%) and substances not listed on the label were contained in 11 (25%). In only 18 of the 44 products (41%), the amount of active compound in the product matched that listed on the label. The amount of the compounds listed on the label differed substantially from that found by analysis in 26 of 44 products (59%). Conclusions and Relevance In this limited investigation involving chemical analyses of 44 products marketed as selective androgen receptor modulators and sold via the internet, most products contained unapproved drugs and substances. Only 52% contained selective androgen receptor modulators and many were inaccurately labeled. This study conducted web-based searches for products marketed as selective androgen receptor modulators, which are performance-enhancing drugs that have not been approved by the US Food and Drug Administration, and compared the chemical identities and the amount of ingredients in each product with those listed on the product label.
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                Author and article information

                Journal
                ACG Case Rep J
                ACG Case Rep J
                ACGCRJ
                ACGCRJ
                AC9
                ACG Case Reports Journal
                Wolters Kluwer (Maryland, MD )
                2326-3253
                June 2020
                18 June 2020
                : 7
                : 6
                : e00409
                Affiliations
                [1 ]Margaret M. and Albert B. Alkek Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX
                [2 ]Michael E. DeBakey Department of Surgery, Division of Abdominal Transplantation, Baylor College of Medicine, Houston, TX
                [3 ]Department of Pathology and Immunology, Baylor College of Medicine, Houston, TX
                Author notes
                Correspondence: Ayse L. Mindikoglu, MD, MPH ( Ayse.Mindikoglu@ 123456bcm.edu ).
                Article
                ACGCR-19-0868 00020
                10.14309/crj.0000000000000409
                7535764
                33062783
                bbd83bf2-e8de-48b3-ba4a-b962659555aa
                © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

                History
                : 12 December 2019
                : 08 April 2020
                Categories
                Case Report
                Liver
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