Contemporary blood doping: Performance, mechanism, and detection

Blood doping is prohibited for athletes but has been a well-described practice within endurance sports throughout the years. With improved direct and indirect detection methods, the practice has allegedly moved towards micro-dosing, i.e., reducing the blood doping regime amplitude. This narrative review evaluates whether blood doping, specifically recombinant human erythropoietin (rhEpo) treatment and blood transfusions are performance-enhancing, the responsible mechanism as well as detection possibilities with a special emphasis on micro-dosing. In general, studies evaluating micro-doses of blood doping are limited. However, in randomized, double-blinded, placebo-controlled trials, three studies find that infusing as little as 130 ml red blood cells or injecting 9 IU × kg bw^-1 rhEpo three times per week for four weeks improve endurance performance ~4-6 %. The responsible mechanism for a performance-enhancing effect following rhEpo or blood transfusions appear to be increased O₂ -carrying capacity, which is accompanied by an increased muscular oxygen extraction and likely increased blood flow to the working muscles, enabling the ability to sustain a higher exercise intensity for a given period. Blood doping in micro-doses challenges indirect detection by the Athlete Biological Passport, albeit it can identify ~20-60% of the individuals depending on the sample timing. However, novel biomarkers are emerging, and some may provide additive value for detection of micro blood doping such as the immature reticulocytes or the iron regulatory hormones hepcidin and erythroferrone. Future studies should attempt to validate these biomarkers for implementation in real-world anti-doping efforts and continue the biomarker discovery.