Contemporary blood doping—Performance, mechanism, and detection

Abstract

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, that is, 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 4 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 O2 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.

Annual banned‐substance review 16th edition—Analytical approaches in human sports drug testing 2022/2023

“…A consensus appears to exist in the perception that applying direct as well as biomarker-based indirect test methods (as provided, e.g., by the ABP hematological module) enables the identification of doping practices while clearly recognizing biomarker variabilities originating from factors other than doping. However, the consensus extends also to the observation that new, complementary biomarkers would be beneficial to enhance the sensitivity of the ABP, [158][159][160]…”

Indirect biomarkers of blood doping: A systematic review

“…77 Included in the ABP, the 14 current variables of the hematological module remain the only biomarkers actually used for the indirect detection of blood doping. 152 However, although numerous studies confirmed the sensitivity of the ABP to multiple blood doping protocols, [153][154][155] the hematological module of the ABP has shown its limitation to identify rhEPO microdoses 156 and direct detection opportunities remain possible. 14 In addition, consistently adjusted by the body, plasma volume (PV) plays a key role in the variability of many markers of the ABP, 157 especially on [Hb] and the resulting OFF score.…”

“…For instance, the Abnormal Blood Profile Score or the ON/OFF scores have been specially designed to identify the early days and cessation phases of rhEPO intake 77 . Included in the ABP, the 14 current variables of the hematological module remain the only biomarkers actually used for the indirect detection of blood doping 152 . However, although numerous studies confirmed the sensitivity of the ABP to multiple blood doping protocols, 153–155 the hematological module of the ABP has shown its limitation to identify rhEPO microdoses 156 and direct detection opportunities remain possible 14 .…”

Prediction of plasma volume and total hemoglobin mass with machine learning

“…CBC is a rapid and relatively inexpensive method that offers important information regarding the diagnosis of different pathologies or conditions. Notably CBC, and [Hb], can be used to detect athletes using blood doping to increase their performance (3,4), to identify individuals at risk of stroke in vulnerable populations (5,6), to help patients hospitalization decision (7) or to regulate patient blood management (PBM) (8)(9)(10). But most importantly, CBC is used to diagnose hemoglobin disorders such as anemia.…”