Oxygen delivery enhancers: Past, present, and future

In endurance sport the delivery of oxygen to muscles plays a critical role. Indeed, muscle performance declines during prolonged and intense activity as a consequence of the shift from the aerobic to the anaerobic metabolism with an increase of lactate. To enhance the aerobic capacity 2 alternatives may be used: increasing either the transport or the delivery of oxygen. In this setting, blood doping is the practice of illicitly using a drug or blood product to improve athletic performance. Based on this definition, blood doping techniques may include: 1) blood transfusion (autologous or omologous); 2) erythropoiesisstimulating substances [recombinant human erythropoietin (α, β, ω), darbepoietin-α, continuous erythropoiesis receptor activator, hematide]; 3) blood substitutes (hemoglobin-based oxygen carriers, perfluorocarbon emulsions); 4) allosteric modulators of hemoglobin (RSR-13 and RSR-4); 5) gene doping (human erythropoietin gene transfection); 6) gene regulation (hypoxia-inducible transcription factors pathway). In the present overview we will briefly describe the above-mentioned techniques with the aim of underlining potential hematological alternatives to gene doping for increasing aerobic capacity in sport.