Strenuous Training Combined With Exogenous Erythropoietin Expands Blood Volume And Reduces Iron Stores In Males

PURPOSE: Strenuous training increases total blood volume (BV) by expanding red cell volume (RCV) and plasma volume (PV). In contrast, exogenous erythropoietin (EPO) increases RCV but decreases PV, rendering BV stable or slightly decreased. This study aimed to determine the combined effects of strenuous training and EPO on BV and markers of systemic and muscle iron homeostasis. METHODS: In this longitudinal study, 8 healthy non-anemic males (mean ± SD; age: 20.1 ± 2.1 y, BMI: 25.2 ± 3.1 kg/m2) were treated with EPO (50 IU/kg body mass, 3x/wk, subcutaneously) across 28 days of strenuous training (4x/week, exercise energy expenditures of 1334 ± 24 kcal/d through 2-3 exercise sessions/d) while consuming a controlled diet providing 39.5 ± 4.4 mg/d iron. Before (PRE) and after (POST) intervention, BV and its components (RCV, PV) were determined by the optimized CO-rebreathing method, and protein markers of iron homeostasis were assessed in blood and skeletal muscle (vastus lateralis). Outcomes were compared PRE vs. POST by paired t-tests. RESULTS: Strenuous training combined with EPO increased BV (5894 ± 578 vs. 6207 ± 662 mL, P = 0.006) by increasing RCV (2314 ± 301 vs. 2612 ± 371 mL, P = 0.0005) from PRE to POST. There was no change in PV (3580 ± 305 vs. 3594 ± 306 mL, P = 0.86). Plasma concentrations of ferritin (42.4 ± 26.3 vs. 8.3 ± 4.1 ng/mL, P = 0.004) and hepcidin (26.5 ± 18.3 vs. 11.3 ± 3.8 ng/mL, P = 0.034) decreased from PRE to POST, while plasma soluble transferrin receptor (TfR) concentrations increased (17.7 ± 1.6 vs. 36.2 ± 3.6 nM, P < 0.0001) from PRE to POST. Skeletal muscle protein abundance of ferritin (iron storage protein) decreased (2.9 ± 0.5 vs. 2.4 ± 0.8 AU, P = 0.044), and muscle TfR (iron import protein) abundance increased (0.9 ± 0.6 vs. 1.1 ± 0.6 AU, P = 0.011) from PRE to POST. CONCLUSIONS: Our novel findings illustrate that strenuous training combined with EPO treatment results in both increased total oxygen carrying capacity and hypervolemia in young healthy males. Decreased ferritin and increased TfR in plasma and muscle suggest that the marked upregulation of erythropoiesis alters systemic and tissue iron homeostasis, resulting in a decline in whole-body and skeletal muscle iron stores. DISCLOSURE: Views expressed do not necessarily reflect positions and policies of the USARIEM, US Army, or Department of Defense. US Army Medical Research and Development Command