Generic Pharmaceuticals as a Source of Diuretic Contamination in Athletes Subject to Sport Drug Testing.

This paper describes nine instances of positive anti-doping tests that could be accounted for by the use of permitted generic prescription drugs contaminated with diuretics, which are prohibited in sport at all times under the WADA Prohibited List. The contamination levels found in the medications are reported and were below FDA limits for manufacturers that are based primarily on safety considerations. These cases demonstrate that great care must be taken to identify the source of low-level anti-doping positives for diuretics reported by WADA-accredited laboratories, and possibly other prohibited substances as well, in order to avoid sanctioning innocent athletes. An evaluation of the cases in this paper supports an approach which establishes a laboratory minimum reporting level (MRL) for diuretics found most commonly in medications. A global consensus after extensive review of similar anti-doping cases has resulted in implementation of a recently announced solution regarding potential diuretic contamination cases.

Essential Features of Third-Party Certification Programs for Dietary Supplements: A Consensus Statement.

The presence of performance-enhancing drugs in dietary supplements poses serious anti-doping and health risks to athletes and military service members. A positive drug test, suboptimal health, or adverse event can ruin a career in either setting. These populations need to be certain in advance that a product is of high quality and free from performance-enhancing drugs and other banned substances. However, no regulatory authority conducts or mandates a quality review before dietary supplements are sold. Under the Food Drug and Cosmetic Act, the Food and Drug Administration does not have a role in the premarket safety review of dietary supplements. Due to the increasing demand for high-quality, properly labeled dietary supplements, multiple companies have stepped into this void by offering testing and quality review programs for dietary supplements. Each of these third-party programs has its own quality assurance program with varying testing components. It is difficult for consumers in the sport and military settings to assess whether a particular certification program reduces the risks enough so that they can use a product with confidence. This article puts forward the consensus of the authors on current best practices for third-party certification programs for dietary supplements consumed by athletes and military service members. Also discussed are important ways that third-party programs can develop in the future to improve access to safe, high-quality dietary supplements for these populations.

Chemical Composition and Labeling of Substances Marketed as Selective Androgen Receptor Modulators and Sold via the Internet.

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.

Adulterated dietary supplements threaten the health and sporting career of up-and-coming young athletes.

The authors provide the perspective of the United States Anti-Doping Agency on the actions youth sport organizations should take to protect the health of developing young athletes.

Variability of Stimulant Levels in Nine Sports Supplements Over a 9-Month Period.

Many studies have found that some dietary supplement product labels do not accurately reflect the actual ingredients. However, studies have not been performed to determine if ingredients in the same dietary supplement product vary over time. The objective of this study was to assess the consistency of stimulant ingredients in popular sports supplements sold in the United States over a 9-month period. Three samples of nine popular sports supplements were purchased over the 9-month period. The 27 samples were analyzed for caffeine and several other stimulants (including adulterants). The identity and quantity of stimulants were compared with stimulants listed on the label and stimulants found at earlier time points to determine the variability in individual products over the 9-month period. The primary outcome measure was the variability of stimulant amounts in the products examined. Many supplements did not contain the same number and quantity of stimulants at all time points over the 9-month period. Caffeine content varied widely in five of the six caffeinated supplements compared with the initial measurement (-7% to +266%). In addition, the stimulants-synephrine, octopamine, cathine, ephedrine, pseudoephedrine, strychnine, and methylephedrine-occurred in variable amounts in eight of the nine products. The significance of these findings is uncertain: the sample size was insufficient to support statistical analysis. In our sample of nine popular sports supplements, the presence and quantity of stimulants varied over a 9-month period. However, future studies are warranted to determine if the variability found is significant and generalizable to other supplements.

Pelargonium oil and methyl hexaneamine (MHA): analytical approaches supporting the absence of MHA in authenticated Pelargonium graveolens plant material and oil.

Methylhexaneamine (MHA) has been marketed in dietary supplements based on arguments that it is a constituent of geranium (Pelargonium graveolens) leaves, stems, roots or oil, and therefore qualifies as a dietary ingredient. The purpose of this study is to determine whether P. graveolens plant material (authenticated) or its oil contains detectable quantities of MHA. Two analytical methods were developed for the analysis of MHA in P. graveolens using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry. The results were further confirmed using liquid chromatography-high-resolution mass spectrometry. Twenty commercial volatile oils, three authenticated volatile oils and authenticated P. graveolens leaves and stems (young and mature, and fresh and dried) were analyzed for MHA content. In addition, three dietary supplements containing MHA that alleged P. graveolens as the source are analyzed for their MHA content. The data show that none of the authenticated P. graveolens essential oils or plant material, nor any commercial volatile oil of Pelargonium (geranium oil) contain MHA at detectable levels (limit of detection: 10 ppb). The dietary supplements that contained MHA as one of their ingredients (allegedly from geranium or geranium stems) contained large amounts of MHA. The amounts of MHA measured are incompatible with the use of reasonable amounts of P. graveolens extract or concentrate, suggesting that MHA was of synthetic origin.

Case reports: Death of active duty soldiers following ingestion of dietary supplements containing 1,3-dimethylamylamine (DMAA).

Dietary supplements and their associated adverse events are not uncommon in the U.S. military, and selected dietary supplements have been associated with a number of nontraumatic deaths in service members. Specific ingredients and dietary supplement products in the civilian community are often associated with multiple adverse events and some have subsequently been removed from the marketplace; the most notable in the last decade is ephedra. We present case reports for two soldiers who were taking commercially available dietary supplements containing multiple ingredients to include the sympathomimetic, 1,3-dimethylamylamine (DMAA); both collapsed during physical exertion from cardiac arrest and ultimately died. A presentation of their clinical courses and a discussion of the history and pharmacology of dietary supplement ingredients, including DMAA, are provided. Our cases highlight concerns that DMAA in combination with other ingredients may be associated with significant consequences, reminiscent of previous adverse events from other sympathomimetic drugs previously removed from the market.