Recombinant human erythropoietin (rHuEpo) increases haemoglobin mass (Hbmass) and maximal oxygen uptake ( O2 max).PurposeThis study defined the time course of changes in Hbmass, O2 max as well as running time trial performance following 4 weeks of rHuEpo administration to determine whether the laboratory observations would translate into actual improvements in running performance in the field.Methods19 trained men received rHuEpo injections of 50 IU•kg−1 body mass every two days for 4 weeks. Hbmass was determined weekly using the optimized carbon monoxide rebreathing method until 4 weeks after administration. O2 max and 3,000 m time trial performance were measured pre, post administration and at the end of the study.ResultsRelative to baseline, running performance significantly improved by ∼6% after administration (10∶30±1∶07 min:sec vs. 11∶08±1∶15 min:sec, p<0.001) and remained significantly enhanced by ∼3% 4 weeks after administration (10∶46±1∶13 min:sec, p<0.001), while O2 max was also significantly increased post administration (60.7±5.8 mL•min−1•kg−1 vs. 56.0±6.2 mL•min−1•kg−1, p<0.001) and remained significantly increased 4 weeks after rHuEpo (58.0±5.6 mL•min−1•kg−1, p = 0.021). Hbmass was significantly increased at the end of administration compared to baseline (15.2±1.5 g•kg−1 vs. 12.7±1.2 g•kg−1, p<0.001). The rate of decrease in Hbmass toward baseline values post rHuEpo was similar to that of the increase during administration (−0.53 g•kg−1•wk−1, 95% confidence interval (CI) (−0.68, −0.38) vs. 0.54 g•kg−1•wk−1, CI (0.46, 0.63)) but Hbmass was still significantly elevated 4 weeks after administration compared to baseline (13.7±1.1 g•kg−1, p<0.001).ConclusionRunning performance was improved following 4 weeks of rHuEpo and remained elevated 4 weeks after administration compared to baseline. These field performance effects coincided with rHuEpo-induced elevated O2 max and Hbmass.

Recombinant human erythropoietin (rHuEPO) is frequently abused by athletes as a performance-enhancing drug, despite being prohibited by the World Anti-Doping Agency. Although the methods to detect blood doping, including rHuEPO injections, have improved in recent years, they remain imperfect. In a proof-of-principle study, we identified, replicated, and validated the whole blood transcriptional signature of rHuEPO in endurance-trained Caucasian males at sea level (n = 18) and Kenyan endurance runners at moderate altitude (n = 20), all of whom received rHuEPO injections for 4 wk. Transcriptional profiling shows that hundreds of transcripts were altered by rHuEPO in both cohorts. The main regulated expression pattern, observed in all participants, was characterized by a "rebound" effect with a profound upregulation during rHuEPO and a subsequent downregulation up to 4 wk postadministration. The functions of the identified genes were mainly related to the functional and structural properties of the red blood cell. Of the genes identified to be differentially expressed during and post-rHuEPO, we further confirmed a whole blood 34-transcript signature that can distinguish between samples collected pre-, during, and post-rHuEPO administration. By providing biomarkers that can reveal rHuEPO use, our findings represent an advance in the development of new methods for the detection of blood doping.

The purpose of this study was to investigate the relationship between running economy (RE) and performance in a homogenous group of competitive Kenyan distance runners. Maximal aerobic capacity (VO2max) (68.8 ± 3.8 ml∙kg(-1)∙min(-1)) was determined on a motorised treadmill in 32 Kenyan (25.3 ± 5.0 years; IAAF performance score: 993 ± 77 p) distance runners. Leg anthropometry was assessed and moment arm of the Achilles tendon determined. While Achilles moment arm was associated with better RE (r(2) = 0.30, P = 0.003) and upper leg length, total leg length and total leg length to body height ratio were correlated with running performance (r = 0.42, P = 0.025; r = 0.40, P = 0.030 and r = 0.38, P = 0.043, respectively), RE and maximal time on treadmill (t(max)) were not associated with running performance (r = -0.01, P = 0.965; r = 0.27; P = 0.189, respectively) in competitive Kenyan distance runners. The dissociation between RE and running performance in this homogenous group of runners would suggest that RE can be compensated by other factors to maintain high performance levels and is in line with the idea that RE is only one of many factors explaining elite running performance.

BackgroundRecombinant human erythropoietin (rHuEpo) can improve human performance and is therefore frequently abused by athletes. As a result, the World Anti-Doping Agency (WADA) introduced the Athlete Biological Passport (ABP) as an indirect method to detect blood doping. Despite this progress, challenges remain to detect blood manipulations such as the use of microdoses of rHuEpo.MethodsForty-five whole-blood transcriptional markers of rHuEpo previously derived from a high-dose rHuEpo administration trial were used to assess whether microdoses of rHuEpo could be detected in 14 trained subjects and whether these markers may be confounded by exercise (n = 14 trained subjects) and altitude training (n = 21 elite runners and n = 4 elite rowers, respectively). Differential gene expression analysis was carried out following normalisation and significance declared following application of a 5% false discovery rate (FDR) and a 1.5 fold-change. Adaptive model analysis was also applied to incorporate these markers for the detection of rHuEpo.Results ALAS2, BCL2L1, DCAF12, EPB42, GMPR, SELENBP1, SLC4A1, TMOD1 and TRIM58 were differentially expressed during and throughout the post phase of microdose rHuEpo administration. The CD247 and TRIM58 genes were significantly up- and down-regulated, respectively, immediately following exercise when compared with the baseline both before and after rHuEpo/placebo. No significant gene expression changes were found 30 min after exercise in either rHuEpo or placebo groups. ALAS2, BCL2L1, DCAF12, SLC4A1, TMOD1 and TRIM58 tended to be significantly expressed in the elite runners ten days after arriving at altitude and one week after returning from altitude (FDR > 0.059, fold-change varying from 1.39 to 1.63). Following application of the adaptive model, 15 genes showed a high sensitivity (≥ 93%) and specificity (≥ 71%), with BCL2L1 and CSDA having the highest sensitivity (93%) and specificity (93%).ConclusionsCurrent results provide further evidence that transcriptional biomarkers can strengthen the ABP approach by significantly prolonging the detection window and improving the sensitivity and specificity of blood doping detection. Further studies are required to confirm, and if necessary, integrate the confounding effects of altitude training on blood doping.Electronic supplementary materialThe online version of this article (10.1186/s12864-017-4191-7) contains supplementary material, which is available to authorized users.

Four weeks of rHuEpo increased the HGB and HCT of Kenyan endurance runners to a lesser extent than in SCO (~17% vs ~10%, respectively) and these alterations were associated with similar improvements in running performance immediately after the rHuEpo administration (~5%) and 4 weeks after rHuEpo (~3%).