Micro‐doses of Recombinant Human Erythropoietin Enhance Endurance Performance While Indirect Detection by The Athlete Biological Passport Is Improved by Including The Immature Reticulocyte Fraction

Abstract

Recombinant human erythropoietin (rHuEPO) is ergogenic but micro-doses remain a challenge for anti-doping authorities. Here, we investigated the hypothesis that frequent micro-doses of rHuEPO enhance maximal oxygen consumption (VO2max) and time trial performance and that the combination of immature reticulocyte fraction (IRF) and the Athlete's Biological Passport (ABP) would enhance detection compared to the ABP alone. In a randomized, double-blinded, placebo-controlled design, 34 trained (VO2max: 52 ± 7 ml×min-1×kg-1, mean ± SD) adults received either rHuEPO (rHuEPO: epoetin-β, 9 IU/kg, n = 16) or placebo (PLA: 0.9% NaCl, n = 18) three times a week for four weeks. Before and after the intervention, VO2max, mean power output during a 400-kcal time trial and total hemoglobin mass (tHb) were measured. Venous blood samples were collected before, each week during rHuEPO administration, and 3, 5 and 10 days after the last injection. Hematological values were evaluated using dedicated ABP software. VO2max increased by 4.7% (p<0.01) and tHb increased by 6.8% (p<0.001) in the rHuEPO group when compared to the PLA group where no changes were evident. Mean power output during the time trial increased by 4.0% (p<0.01) in the rHuEPO group with no changes observed in the PLA group. Inclusion of IRF thresholds improved ABP sensitivity from 47% to 73%, yielding a peak sensitivity during the first two weeks of the rHuEPO treatment and 10 days after cessation of treatment. In conclusion, these findings show that four weeks of rHuEPO micro-doses are sufficient to induce considerable ergogenic effects on both VO2max and time trial performance in trained adults. The inclusion of IRF thresholds into the ABP improved sensitivity during treatment and the viability of including IRF into the ABP should be considered although more studies are needed.