Welcome to DOPING.nl, the Anti-Doping Knowledge Center

Effects of erythropoietin on cycling performance of well trained cyclists : a double-blind, randomised, placebo-controlled trial / Jules A.A.C. Heuberger, Joris I. Rotmans, Pim Gal, Frederik E. Stuurman, Juliëtte van 't Westende, Titiaan E. Post, Johannes M.A. Daniels, Matthijs Moerland, Peter L.J. van Veldhoven, Marieke L. de Kam, Herman Ram, Olivier de Hon, Jelle J. Posthuma, Jacobus Burggraaf, Adam F. Cohen

• The Lancet Haematology 4 (2017) 8 (August), p. e374-e386
• PMID: 28669689
• DOI: 10.1016/S2352-3026(17)30105-9

Abstract

Background: Substances that potentially enhance performance (eg, recombinant human erythropoietin [rHuEPO]) are considered doping and are therefore forbidden in sports; however, the scientific evidence behind doping is frequently weak. We aimed to determine the effects of rHuEPO treatment in well trained cyclists on maximal, submaximal, and race performance and on safety, and to present a model clinical study for doping research on other substances.

Methods: We did this double-blind, randomised, placebo-controlled trial at the Centre for Human Drug Research in Leiden (Netherlands). We enrolled healthy, well trained but non-professional male cyclists aged 18-50 years and randomly allocated (1:1) them to receive abdominal subcutaneous injections of rHuEPO (epoetin β; mean dose 6000 IU per week) or placebo (0·9% NaCl) for 8 weeks. Randomisation was stratified by age groups (18-34 years and 35-50 years), with a code generated by a statistician who was not masked to the study. The primary outcome was exercise performance, measured as maximal power output (Pmax), maximal oxygen consumption VO2 max, and gross efficiency in maximal exercise tests with 25 W increments per 5 min, as lactate threshold and ventilatory threshold 1 (VT1) and 2 (VT2) at submaximal levels during the maximal exercise test, and as mean power, VO2, and heart rate in the submaximal exercise tests at the highest mean power output for 45 min in a laboratory setting and in a race to the Mont Ventoux (France) summit, using intention-to-treat analyses. The trial is registered with the Dutch Trial Registry (Nederlands Trial Register), number NTR5643.

Findings: Between March 7, 2016, and April 13, 2016, we randomly assigned 48 participants to the rHuEPO group (n=24) or the placebo group (n=24). Mean haemoglobin concentration (9·6 mmol/L vs 9·0 mmol/L [estimated difference 0·6, 95% CI 0·4 to 0·8]) and maximal power output (351·55 W vs 341·23 W [10·32, 3·47 to 17·17]), and VO2 max (60·121 mL/min per kg vs 57·415 mL/min per kg [2·707, 0·911 to 4·503]) in a maximal exercise test were higher in the rHuEPO group compared with the placebo group. Submaximal exercise test parameters mean power output (283·18 W vs 277·28 W [5·90, -0·87 to 12·67]) and VO2 (50·288 mL/min per kg vs 49·642 mL/min per kg [0·646, -1·307 to 2·600]) at day 46, and Mont Ventoux race times (1 h 40 min 32 s vs 1 h 40 min 15 s [0·3%, -8·3 to 9·6]) did not differ between groups. All adverse events were grade 1-2 and were similar between both groups. No events of grade 3 or worse were observed.

Interpretation: Although rHuEPO treatment improved a laboratory test of maximal exercise, the more clinically relevant submaximal exercise test performance and road race performance were not affected. This study shows that clinical studies with doping substances can be done adequately and safely and are relevant in determining effects of alleged performance-enhancing drugs.

Funding: Centre for Human Drug Research, Leiden.

Clenbuterol storage stability in the bovine urine and liver samples used for European official control in the azores islands (Portugal) / Isabel Pinheir, Bruno Jesuino, Jorge Barbosa, Humberto Ferreira, Fernando Ramos, José Matos, Maria Irene Noronha da Silveira

• Journal of Agricultural and Food Chemistry 57 (2009) 3 (11 February), p. 910-914
• PMID:19138075
• DOI: 10.1021/jf802995e

Abstract

Clenbuterol is a well-known growth promoter, illegally used in farm animals, especially in cattle. Samples collected for the screening of beta(2)-agonist residues in Portuguese Azores Islands must travel through all the nine islands until they reach Azores Central Laboratory. If any suspicious sample is detected, it must be further transported to the National Reference Laboratory in Lisbon for confirmation. As a consequence of these circumstances, samples are submitted to different transport and storage times, as well as different temperature conditions and in some cases successive freezing and thawing cycles. As clenbuterol is the most detected beta(2)-agonist growth promoter in the Portuguese Residue Monitoring Plan, studies were conducted on the stability of this compound in incurred samples (bovine liver and urine) at +4, -20 and -60 degrees C over time. Samples kept at -20 degrees C were also analyzed over time after successive freezing and thawing cycles. The analyses of clenbuterol over time were performed by gas chromatography-mass spectrometry (GC-MS) with selected ion monitoring (SIM). Clenbuterol in incurred urine and liver samples was significantly stable up to 20 weeks at -20 and -60 degrees C and after, at least, six consecutive freezings and thawings. At +4 degrees C, clenbuterol remained stable, at least until 12 weeks in urine and up to 20 weeks in liver.

The prevalence of trimetazidine use in athletes in Poland : excretion study after oral drug administration / Anna Jarek, Marzena Wójtowicz, Dorota Kwiatkowska, Monika Kita, Ewa Turek-Lepa, Katarzyna Chajewska, Sylwia Lewandowska-Pachecka, Andrzej Pokrywka

• Drug Testing and Analysis 6 (2014) 11-12 (November-December), p. 1191-1196
• 32nd Cologne workshop: Advances in sports drug testing
• PMID: 25421604
• DOI: 10.1002/dta.1755

Abstract

Stimulants, together with anabolic androgenic steroids, are regarded as one of the most popular doping substances in sport. Owing to a great variety of these substances and new designer drugs being introduced to the market, each year the World Anti-Doping Agency (WADA) updates the list of substances and methods prohibited in sport. On 1 January 2014, a new doping agent - trimetazidine (TMZ) - was added to the WADA Prohibited List. TMZ, a substance prohibited in competition, is classified in the S6b Specified Stimulant Group. TMZ is used as a well-known cardiologic drug with confirmed biochemical and clinical activity. According to knowledge of the pharmacology and mechanism of TMZ action, TMZ can be used by athletes to improve physical efficiency, especially in the case of endurance sports. This study presents the phenomena of TMZ use by Polish athletes involved in anti-doping control in the WADA-accredited laboratory in Warsaw (Poland) between 2008 and 2013. Samples were taken from the athletes of such disciplines as cycling, athletics, and triathlon. Moreover, the elimination study of TMZ has been conducted to establish the change of TMZ concentration in urine sample after oral administration of a single or double (during the long-term therapy) dose. TMZ was monitored in urine samples by gas chromatography-mass spectrometry-nitrogen phosphorus detection (GC-MS-NPD).

Consumption of anabolic steroids in sport, physical activity and as a drug of abuse : an analysis of the scientific literature and areas of research / V. Agulló-Calatayud, G. González-Alcaide, J.C. Valderrama-Zurián, R. Aleixandre-Benavent

• British Journal of Sports Medicine 42 (2008) 2 (February), p. 103-109
• PMID: 17548372
• DOI: 10.1136/bjsm.2007.036228

Abstract

Objective: The consumption of anabolic steroids (AS) has been growing continuously in recent years. It has gone beyond the sports world; AS are now widely used as drugs of abuse in connection with bodybuilding. This study sets out to assess the state of scientific research in the area.

Design: Bibliometrics were employed to evaluate the literature retrieved from the principal relevant bibliographic databases: MEDLINE, SportDiscus, the Science Citation Index Expanded and the Social Sciences Citation Index. The core journals were identified along with the leading authors and research groups and their institutional affiliations. Techniques based on social network analysis were applied in order to build up a concept map of research.

Results: 1325 documents were retrieved. They were produced by 3131 different researchers giving a Collaboration Index of 3.32. The institutions with the most productive authors were Ball State University (Muncie, IN, USA), the Ecole Nationale Vétérinaire de Nantes (ENVN), the Institut Municipal d'Investigació Mèdica (IMIM) (Barcelona, Spain), the Institute of Biochemistry of the German Sport University Cologne (DSHS), Iowa State University, Maastricht University and the University of Iowa.

Conclusions: It was concluded that there has been an upward trend in the number of research projects. The sources used complemented one another, as 78.04% of the documents retrieved were unique to one source. The productivity ranking was headed by sports medicine journals, followed by journals of chemistry, physiology, endocrinology and substance abuse. Besides sporting activities, the most important research clusters were those connected with bodybuilding and with youth groups.

In October 2023 the India National Anti-Doping Agency (INADA) reported an anti-doping rule violation against the Athlete after his sample tested positive for the prohibited substance Drostanolone.

Following notification a provisional suspension was ordered and the Athlete attended the hearing of the Anti-Doping Disciplinary Panel of India (ADDPI).

The Athlete admitted the violation and denied the intentional use of the substance. He assumed that his supplements had caused the positive test.

The Panel finds that the presence of a prohibited substance has been established in the Athlete's sample and accordingly that he committed an anti-doping rule violation.

The Panel deems that the Athlete failed to demonstrate that the violation was not intentional, nor how the substance had entered his system. 

Therefore the ADDPI decides on 12 April 2024 to impose a 4 year period of ineligibility on the Athlete, starting on the date of the provisional suspension, i.e. on 23 October 2023.

In August 2023 the India National Anti-Doping Agency (INADA) reported an anti-doping rule violation against the Athlete after his sample tested positive for the prohibited substance Methyltestosterone.

Following notification a provisional suspension was ordered. The  Athlete filed a statement in his defence and was heard for the Anti-Doping Disciplinary Panel of India (ADDPI).

The Athlete admitted the violation and denied the intentional use of the substance. He stated that he only had used supplements and requested for a reduced sanction.

The Panel finds that the presence of a prohibited substance has been established in the Athlete's sample and accordingly that he committed an anti-doping rule violation.

The Panel deems that the Athlete failed to demonstrate that the violation was not intentional, nor how the substance had entered his system. 

Therefore the ADDPI decides on 29 April 2024 to impose a 4 year period of ineligibility on the Athlete, starting on the date of the provisional suspension, i.e. on 14 August 2023.

In September 2023 the South African Institute for Drugfree Sport (SAIDS) reported an anti-doping rule violation against the rower Lebone Mokheseng. SAIDS deemed that the Athlete had 3 Whereabouts Failures within a 12 month period:

• a Missed Test and Filing Failure on 8 June 2023;
• a Missed Test and Filing Failure on 14 June 2023; and
• a Missed Test and Filing Failure on 12 September 2023.

After notification a provisional suspension was ordered. The Athlete filed a statement in his defence and he was heard for the Anti-Doping Tribunal of South Africa.

The Athlete admitted the violation and denied that he acted intentionally. He acknowledged that he had not availed himself of the information about the Registered Testing Pool.

He explained that he struggled with personal circumstances and ultimately had to resign from the Rowing South Africa (RSA). He had troubles with the Whereabouts Information and assisting the sample collection.

He complained that he had received no support from RSA in these matters. Moreover he was under the impression that RSA would have notified SAIDS about his resignation.

In view of the evidence the Panel accepts that the Athlete's violation was not intentional due to his personal circumstances. The Panel deems that the Athlete lacked understanding the procedures and the rules and had not communicated his resignation to SAIDS.

Therefore the Panel decides on 29 January 2024 to impose a reduced 1 year period of ineligibility on the Athlete, starting on the date of the provisional suspension, i.e. on 12 September 2023.

The Athlete in this redacted case lived overseas between 2006 and 2021 and played rugby between 2006 and 2015. In 2015 he was forced to stop playing rugby because of physical and mental health issues he suffered and his health deteriorated from then on.

In 2020 still residing overseas he started an aggressive medical regime with prescribed prohibited substances that improved his health. In mid-2021 he returned to New Zealand while he continued his medical treatment.

Following his return to New Zealand he was originally not playing rugby. However he was asked to play rugby in Auckland in 2022 and played as an recreational athlete approximately six club games.

In 2022 the New Zealand Customs Service intercepted a package addressed to the Athlete. Besides permitted substances the package contained three prohibited substances:

• BPC-157;
• Human chorionic gonadotrophin (hCG); and
• Ipamorelin.

After the interception the Athlete was informed by Drug Free Sport New Zealand (DFSNZ) that these substances were prohibited under the Sport Anti-Doping Rules. Thereupon his application for a Retrospective TUE was rejected and a provision suspension was ordered in August 2023.

Following notification the Athlete gave a prompt admission, waived his right for a hearing, accepted a provisional suspension and the sanction proposed by DFSNZ. 

With evidence the Athlete testified about the health issues he suffered and the medical treatment he underwent. He explained that due to the Covid Pandemic Limitation in New Zealand he continued to consult with his overseas specialist at the material time and he imported the prescribed prohibited substances in order to maintain his medical treatment.

In May 2024 the parties in this case reached an agreement and filed a joint memorandum in relation to the sanction for approval into a decision of the New Zealand Rugby Union Anti-Doping Judicial Committee.

In view of the evidence the Judicial Committee determines that the Athlete had admitted the violation and that he acted not intentionally. The Committee agrees that he was unaware that his use of the prohibited substances to treat his medical condition would be an issue as an recreational Athlete.

Therefore the New Zealand Rugby Union Anti-Doping Judicial Committee decides on 9 July 2024 to impose a 2 year period of ineligibility on the Athlete, starting on the date of the provisional suspension, i.e. on 9 August 2023.

In July 2024 the New Zealand Sport Integrity Commission (SIC) reported an anti-doping rule violations against the softball player Isaia Walker-Leawere after her sample tested positive for the prohibited substance Cannabis in a concentration above the WADA threshold.

After notification the Athlete gave a prompt admission, waived her right to be heard, accepted a provisional suspension and the sanction proposed by the SIC.
The parties in this case reached an agreement and filed a joint memorandum in relation to the sanction for approval into a decision of the Sports Tribunal of New Zealand.

The Tribunal considers that the Athlete gave a prompt admission about her out-of-competition use of Cannabis. Further the Committee considers that the Athlete completed a Substance of Abuse treatment programme approved by the SIC.

Therefore the Sports Tribunal of New Zealand decides on 29 August 2024 to impose a 1 month period of ineligibility on the Athlete, ending on 15 August 2024.

In July 2024 World Rugby reported an anti-doping rule violation against the South African rugby player S'Busiso Nkosi after his sample tested positive for the prohibited substance Boldenone.

Following notification the Athlete gave a timely admission, waived his right for a hearing, accepted a provisional suspension and the sanction proposed by World Rugby. 

World Rugby deems that the Athlete's violation was intentional and determines that he shall receive a 1 year reduction for his timely admission of the anti-doping rule violation.

Therefore World Rugby decides on 5 September 2024 to impose a 3 year period of ineligibility on the Athlete, starting on the date of the provisional suspension, i.e. on 16 July 2024.