Impact of Erythropoietin on Hematological Adaptations and Physical Performance

Negative hematological adaptations due to prolonged periods of strenuous physical activity may, in part, contribute to declines in physical performance during military operations. Exogenous erythropoietin (EPO) is a potential intervention that may be used to maintain hemoglobin (hgb), hematocrit (Hct), and physical performance during periods of high physical activity. The objective of the current study is to determine the ability of EPO to maintain hgb, Hct, and physical performance compared to baseline measures. Additionally, EPO may result in non-hematological adaptations which increase mitochondria biogenesis and alter substrate oxidation. As such, this study will also assess the influence of EPO on whole-body and skeletal muscle substrate oxidation. Eight healthy physically active individuals will be recruited to participate in this longitudinal trial. After exercise practice sessions, volunteers will complete baseline physical performance (time trial) and substrate oxidation testing. Participants will then receive EPO injections 3 times per week for 4 weeks. Diet and exercise will be controlled during the injection period. Participants will undergo four weeks of an intense physical training exercise program. Every seventh day during the injection period a safety blood sample, assessing hematocrit, will be drawn, and participants will complete a 5 km time trial to determine the time course of changes in physical performance can be detected. After the 4 weeks of EPO injections volunteers will complete the same physical performance and substrate oxidation testing. Substrate oxidation will be assessed during 90-min steady-state load carriage (30% body mass) exercise on a treadmill at 55 ± 5% of VO2peak. 6-6-[2H2] glucose tracer technique and indirect calorimetry will be used measure substrate oxidation. Muscle biopsies will be performed to measure muscle glycogen, enzyme activity, and molecular markers of metabolism and inflammation before, and immediately and 3-hrs post exercise. Multiple blood samples will be collected throughout the study to determine alterations in hemoglobin, hematocrit, and markers of substrate metabolism, and inflammation. All study procedures will occur at USARIEM. The primary risks associated with this study include those associated with EPO injection, exercise, blood draws, and muscle biopsies.