Evaluation of performance-enhancing drugs seized by Israeli enforcement agencies 2012-2017: implications for policy and regulatory change.

BACKGROUND: Illicit performance-enhancing substances are used mostly by athletes to enhance performance in sports, and by bodybuilders to gain muscle and body mass. Among performance-enhancing substances, the most common and known substances are anabolic-androgenic steroids, which are associated with a range of short and long-term adverse medical and psychiatric effects. While the sale and distribution of performance-enhancing substances are considered criminal offenses per the Israeli local pharmacy ordinance, the use and personal possession of these substances are not. Presently, the Division of Enforcement and Inspection of the Israel Ministry of Health cooperates with police and customs agents in performance-enhancing substance-related enforcement activities, which chiefly include seizures carried out at suspicious sites. Moreover, the Division of Enforcement and Inspection provides professional guidance, lab analysis services, and expert opinions on the toxicological and pharmaceutical nature of products seized. This paper presents a contemporary sub-analysis of registered seizures of performance-enhancing substances carried-out by Israel enforcement agencies. The main aim of this analysis is to characterize current patterns of performance-enhancing substances, thus providing the possibility of better assessment of current enforcement and health policy. METHODS: A sub-analysis of 712 seizures of performance-enhancing substances seized by Israeli enforcement authorities during a six-year period ranging from January 2012 to December 2017. RESULTS: This study demonstrates that Israel faces a challenge regarding the importation and distribution of illicit performance-enhancing substances. The most common substances seized were anabolic androgenic steroids (N = 539). Most seizures were carried out in the central mail processing sites, (38.4%), followed by seizures in private premises such as homes and warehouses (29.6%). Significant differences were found between anabolic-androgenic steroids and other substances, relating to place and year of seizure. Among seizures with known sources (N = 355), the most frequent geographic region given as the source of substances was Eastern Europe (47.6%), followed by East Asia (24.8%), West Asia (19.4%), and Western Europe (5.9%). Bulgaria was the country with the highest frequency of seizures (N = 71) followed by Jordan (N = 45), Thailand (N = 37) and Moldova (N = 36). Significant regional differences were found based on the variables of gender, place of seizure, and type of substance. The most frequent month of seizures was August (N = 129), followed by July (N = 119), and June (N = 118). CONCLUSIONS: While data analysis focused on the supply side of the performance-enhancing substances market, the high number of seizures of performance-enhancing substances in Israel represents evidence of the existence of a high demand and a large consumer base for these products. Consequently, there is a need for developing further enforcement, treatment, and prevention policies that do not currently exist in Israel. Policymakers should consider prioritizing law enforcement action and incentivizing intelligence sharing to monitor suspected shipment sources and specific points of entry. Additionally, the results demonstrate that there is a need in reforming the penal law to discourage the use of performance-enhancing substances. Similar measures have already been applied in countries like Spain, Italy, and Belgium. Furthermore, policy-makers should consider enhancing health ministry agencies with a higher enforcement capacity by giving them further investigative and inquiry authority. Due to the troubling magnitude of the phenomenon, policymakers should also prioritize educational and prevention strategies.

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.

ISSN exercise & sports nutrition review update: research & recommendations.

BACKGROUND: Sports nutrition is a constantly evolving field with hundreds of research papers published annually. In the year 2017 alone, 2082 articles were published under the key words 'sport nutrition'. Consequently, staying current with the relevant literature is often difficult. METHODS: This paper is an ongoing update of the sports nutrition review article originally published as the lead paper to launch the Journal of the International Society of Sports Nutrition in 2004 and updated in 2010. It presents a well-referenced overview of the current state of the science related to optimization of training and performance enhancement through exercise training and nutrition. Notably, due to the accelerated pace and size at which the literature base in this research area grows, the topics discussed will focus on muscle hypertrophy and performance enhancement. As such, this paper provides an overview of: 1.) How ergogenic aids and dietary supplements are defined in terms of governmental regulation and oversight; 2.) How dietary supplements are legally regulated in the United States; 3.) How to evaluate the scientific merit of nutritional supplements; 4.) General nutritional strategies to optimize performance and enhance recovery; and, 5.) An overview of our current understanding of nutritional approaches to augment skeletal muscle hypertrophy and the potential ergogenic value of various dietary and supplemental approaches. CONCLUSIONS: This updated review is to provide ISSN members and individuals interested in sports nutrition with information that can be implemented in educational, research or practical settings and serve as a foundational basis for determining the efficacy and safety of many common sport nutrition products and their ingredients.

Structure and Development of the List of Prohibited Substances and Methods.

The list of prohibited substances and methods (the List) is the international standard that determines what is prohibited in sport both in- and out-of-competition. Since 2004, the official text of the List is produced by the World Anti-Doping Agency (WADA), the international independent organization responsible for promoting, coordinating, and monitoring the fight against doping in sport. Originally based on the prohibited lists established by the International Olympic Committee, the List has evolved to incorporate new doping trends, distinguish permitted from prohibited routes of administration, and adjust to new analytical and pharmacological breakthroughs. In this chapter, the elements that compose the List as well as the updates over the years are presented.

Dietary supplement for energy and reduced appetite containing the ß-agonist isopropyloctopamine leads to heart problems and hospitalisations.

In 2013 the Dutch authorities issued a warning against a dietary supplement that was linked to 11 reported adverse reactions, including heart problems and in one case even a cardiac arrest. In the UK a 20-year-old woman, said to have overdosed on this supplement, died. Since according to the label the product was a herbal mixture, initial LC-MS/MS analysis focused on the detection of plant toxins. Yohimbe alkaloids, which are not allowed to be present in herbal preparations according to Dutch legislation, were found at relatively high levels (400-900 mg kg(-1)). However, their presence did not explain the adverse health effects reported. Based on these effects the supplement was screened for the presence of a ß-agonist, using three different biosensor assays, i.e. the validated competitive radioligand ß2-adrenergic receptor binding assay, a validated ß-agonists ELISA and a newly developed multiplex microsphere (bead)-based ß-agonist assay with imaging detection (MAGPIX(®)). The high responses obtained in these three biosensors suggested strongly the presence of a ß-agonist. Inspection of the label indicated the presence of N-isopropyloctopamine. A pure standard of this compound was bought and shown to have a strong activity in the three biosensor assays. Analysis by LC-full-scan high-resolution MS confirmed the presence of this 'unknown known' ß3-agonist N-isopropyloctopamine, reported to lead to heart problems at high doses. A confirmatory quantitative analysis revealed that one dose of the preparation resulted in an intake of 40-60 mg, which is within the therapeutic range of this compound. The case shows the strength of combining bioassays with chemical analytical techniques for identification of illegal pharmacologically active substances in food supplements.

Performance-Enhancing Drugs I: Understanding the Basics of Testing for Banned Substances.

Whenever athletes willfully or accidentally ingest performance-enhancing drugs or other banned substances (such as drugs of abuse), markers of those drugs can be detected in biological samples (e.g., biofluids: urine, saliva, blood); in the case of some drugs, that evidence can be apparent for many weeks following the last exposure to the drug. In addition to the willful use of prohibited drugs, athletes can accidentally ingest banned substances in contaminated dietary supplements or foods and inadvertently fail a drug test that could mean the end of an athletic career and the loss of a good reputation. The proliferation of performance-enhancing drugs and methods has required a corresponding increase in the analytical tools and methods required to identify the presence of banned substances in biofluids. Even though extraordinary steps have been taken by organizations such as the World Anti-Doping Agency to limit the use of prohibited substances and methods by athletes willing to cheat, it is apparent that some athletes continue to avoid detection by using alternative doping regimens or taking advantage of the limitations in testing methodologies. This article reviews the testing standards and analytical techniques underlying the procedures used to identify banned substances in biological samples, setting the stage for future summaries of the testing required to establish the use of steroids, stimulants, diuretics, and other prohibited substances.

Ultra high performance supercritical fluid chromatography coupled with tandem mass spectrometry for screening of doping agents. I: Investigation of mobile phase and MS conditions.

The conditions for the analysis of selected doping substances by UHPSFC-MS/MS were optimized to ensure suitable peak shapes and maximized MS responses. A representative mixture of 31 acidic and basic doping agents was analyzed, in both ESI+ and ESI- modes. The best compromise for all compounds in terms of MS sensitivity and chromatographic performance was obtained when adding 2% water and 10mM ammonium formate in the CO2/MeOH mobile phase. Beside mobile phase, the nature of the make-up solvent added for interfacing UHPSFC with MS was also evaluated. Ethanol was found to be the best candidate as it was able to compensate for the negative effect of 2% water addition in ESI- mode and provided a suitable MS response for all doping agents. Sensitivity of the optimized UHPSFC-MS/MS method was finally assessed and compared to the results obtained in conventional UHPLC-MS/MS. Sensitivity was improved by 5-100-fold in UHPSFC-MS/MS vs. UHPLC-MS/MS for 56% of compounds, while only one compound (bumetanide) offered a significantly higher MS response (4-fold) under UHPLC-MS/MS conditions. In the second paper of this series, the optimal conditions for UHPSFC-MS/MS analysis will be employed to screen >100 doping agents in urine matrix and results will be compared to those obtained by conventional UHPLC-MS/MS.

Ultra high performance supercritical fluid chromatography coupled with tandem mass spectrometry for screening of doping agents. II: Analysis of biological samples.

The potential and applicability of UHPSFC-MS/MS for anti-doping screening in urine samples were tested for the first time. For this purpose, a group of 110 doping agents with diverse physicochemical properties was analyzed using two separation techniques, namely UHPLC-MS/MS and UHPSFC-MS/MS in both ESI+ and ESI- modes. The two approaches were compared in terms of selectivity, sensitivity, linearity and matrix effects. As expected, very diverse retentions and selectivities were obtained in UHPLC and UHPSFC, proving a good complementarity of these analytical strategies. In both conditions, acceptable peak shapes and MS detection capabilities were obtained within 7 min analysis time, enabling the application of these two methods for screening purposes. Method sensitivity was found comparable for 46% of tested compounds, while higher sensitivity was observed for 21% of tested compounds in UHPLC-MS/MS and for 32% in UHPSFC-MS/MS. The latter demonstrated a lower susceptibility to matrix effects, which were mostly observed as signal suppression. In the case of UHPLC-MS/MS, more serious matrix effects were observed, leading typically to signal enhancement and the matrix effect was also concentration dependent, i.e., more significant matrix effects occurred at the lowest concentrations.