Changes in Immature Reticulocytes Aid the Indirect Detection of Microdose Recombinant Erythropoietin Use in Men and Women

Abstract

Purpose We investigated whether immature reticulocyte fraction (IRF) and the immature reticulocytes to red blood cells ratio (IR/RBC) are sensitive and specific biomarkers for microdose recombinant human erythropoietin (rHuEPO) and whether the inclusion of reticulocyte percentage (RET%) and the algorithm “abnormal blood profile score (ABPS)” increased the athlete biological passport (ABP) sensitivity compared with hemoglobin concentration ([Hb]) and the OFF-hr score ([Hb]–60 × √RET%). Methods Forty-eight (♀ = 24, ♂ = 24) participants completed a 2-wk baseline period followed by a 4-wk intervention period with three weekly intravenous injections of 9 IU·kg−1·bw−1 epoetin β (♀ = 12, ♂ = 12) or saline (0.9% NaCl, ♀ = 12, ♂ = 12) and a 10-d follow-up. Blood samples were collected weekly during baseline and intervention as well as 3, 5, and 10 d after treatment. Results The rHuEPO treatment increased [Hb] (time–treatment, P < 0.001), RET% (time–treatment, P < 0.001), IRF (time–treatment, P < 0.001) and IR/RBC (time–treatment, P < 0.001). IRF and IR/RBC were up to ~58% (P < 0.001) and ~141% (P < 0.001) higher compared with placebo, and calculated thresholds provided a peak sensitivity across timepoints of 58% and 54% with ~98% specificity, respectively. To achieve >99% specificity for IRF and IR/RBC, sensitivity was reduced to 46% and 50%, respectively. Across all timepoints, the addition of RET% and ABPS to the ABP increased sensitivity from 29% to 46%. Identification of true-positive outliers obtained via the ABP and IRF and IR/RBC increased sensitivity across all timepoints to 79%. Conclusions In summary, IRF, IR/RBC, RET% and ABPS are sensitive and specific biomarkers for microdose rHuEPO in both men and women and complement the ABP.

Intermittent exogenous ketosis: permissive or stimulatory for skeletal muscle angiogenesis in response to endurance training overload?

“…Although the present study demonstrates a 25% increase in serum EPO concentration in the KE group, the authors did not quantify changes in $${\dot V_{{{\rm{O}}_2}\max }}$$ or total red blood cell mass, making it difficult to draw a link between the increase in EPO and improvements in endurance capacity. However, a recent study reported that intravenous injection of recombinant EPO three times a week for 4 weeks was sufficient to increase peak O 2 uptake and peak aerobic power by 4.2 ± 6.1% and 2.9 ± 4.0%, respectively (Breenfeldt Andersen et al., 2023). Future studies are required to determine changes in haematological outcomes, capillarization and endurance capacity in order to determine whether KE, perhaps via EPO, can augment the adaptive response to prolonged (i.e.…”