Active Voice: Erythropoietin is Performance Enhancing in Kenyan Athletes Living and Training at Altitude
By Yannis Pitsiladis, MMedSci., Ph.D., FACSM

Yannis Pitsiladis, MMedSci., Ph.D., FACSM
Viewpoints presented in SMB commentaries reflect opinions of the authors and do not necessarily represent positions or policies of ACSM.

Yannis Pitsiladis, MMedSci., Ph.D., FACSM, is a professor of sport and exercise science at the University of Brighton in the United Kingdom. His current research priority is the application of “omics” (i.e., genomics, transcriptomics, metabolomics and proteomics) to the detection of drugs in sport. He specifically applies these tools to determine influences upon recombinant human erythropoietin (rHuEpo), blood doping and testosterone. His most recent research is funded by the World Anti-Doping Agency (WADA). Dr. Pitsiladis is a member of the International Olympic Committee (IOC) Medical and Scientific Commission and the Executive Committee, and chair of the Scientific Commission of the International Sports Medicine Federation (FIMS). He also has been a member of two WADA committees and is an active member of ACSM. He has published more than 170 peer-reviewed papers, written and edited several scholarly books and has been featured in numerous televised research documentaries on ESPN, BBC and CNBC.

This commentary presents Dr. Pitsiladis’ views on the topic of a research article which he and his colleagues authored. Their article appears in the February 2019 issue of
Medicine & Science in Sports & Exercise® (MSSE).

The topic of this commentary deals with a very current and critical issue in the area of sports doping, i.e., the ergogenic effects of recombinant human erythropoietin (rHuEpo). Strong scientific evidence exists that rHuEpo increases exercise performance by augmenting total hemoglobin mass (tHb-mass) and, therefore, transport of oxygen to active muscles. Due to this clear, performance-enhancing effect, the use of rHuEpo by athletes has been banned by the World Anti-Doping Agency (WADA). Despite overwhelming research evidence demonstrating the ergogenic effects of rHuEpo on endurance performance, some studies, including that published in The Lancet Haematology by Heuberger et al. in 2017, have questioned the performance enhancing properties of rHuEpo, especially when applied to elite sporting situations. Specifically, these authors advocate that the improvements seen in laboratory-based assessments of maximum oxygen uptake do not translate to real-world improvements in performance (Heuberger et al.; British Journal of Pharmacology, 2017).

Studies of elite athletic performance beyond simple descriptive studies are particularly difficult to conduct. This may explain some of the contradictions in the literature. For example, in the Heuberger et al. study in The Lancet Haematology, participants were administered injections varying from 5,000 to 8,000 IU per dose to elicit a 10-15 percent increase in hemoglobin concentration. Maximum oxygen uptake was increased by 10 percent as a result, but this did not translate into significant improvement in performance compared with a matched control group that completed a fixed 100-km group cycle followed by a mountain climb. However, these authors did not utilize the most appropriate experimental design (i.e., no crossover), so their conclusions in terms of performance should be interpreted with caution. Furthermore, the effects of rHuEpo during moderate altitudes of about 2,000-2,800 meters and typical of the live-high, train-low paradigm utilized by elite endurance athletes also remains unclear.

Our manuscript, published in the February 2019 issue of MSSE, is the first to present evidence that four weeks of rHuEpo administration significantly increases the already relatively high basal hemoglobin concentration and hematocrit values of Kenyan endurance runners living and training at moderate altitude by ~10 percent. The rHuEpo-induced increase in key hematological parameters in these altitude-trained Kenyan endurance runners was blunted compared to Caucasian individuals living and training at or near sea-level. However, the relative improvements of ~5 percent and ~3 percent in running performance, immediately after the rHuEpo administration and four weeks after the last injection, were similar in both cohorts and in line with the great majority of the scientific literature. Although caution is required when extrapolating findings from sub-elite to truly elite athletes, the significant improvements in endurance running performance we report at moderate altitude are in line with performance benefits we and others have previously observed at sea-level. Thus, we have high confidence that these findings would translate into a worthwhile enhancement in elite performance.

Collectively, the findings of our research, interpreted in the context of the extensive scientific literature on rHuEpo, are consistent with enhanced blood oxygen carrying capacity being the mechanism by which rHuEpo improves exercise performance. Amid the increasingly sensitive issue of doping worldwide and inconsistent messages in the scientific literature in terms of mechanisms of enhancement of rHuEpo, our exciting new findings are timely. We are optimistic that this information will help clarify current inconsistencies in the scientific literature and add essential new insights to current antidoping efforts.