The Role and Regulation of Hemoglobin Mass in Endurance Exercise

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Endurance performance relies on sustained oxygen delivery to skeletal muscles. Consequently, the maximum capacity to deliver oxygen is closely related to the total amount of hemoglobin (Hb) in the circulation, hemoglobin mass (Hbmass). Experimental reduction of Hbmass results in lowered oxygen delivery in maximal exercise and hence a lower maximal oxygen uptake (V̇O2max). At submaximal intensities, compensatory adjustments can be employed in response to Hbmass reduction to maintain oxygen delivery, potentially lessening the impact on intensities below V̇O2max; however, data relating to these effects are lacking. While females have a lower [Hb] and lower Hbmass than males, the influence of sex on hematological properties has not been thoroughly investigated. In addition, the regulation of Hb turnover in endurance training is poorly understood, owing to methodological limitations. The purpose of this thesis was to expand on the current understanding about the role and regulation of Hbmass in facilitating endurance exercise. In Study 1 (n=16), reducing effective [Hb] by ~5% using low-dose carbon monoxide inhalation destabilized the maximal lactate steady state. This effect was more prominent in trained individuals, suggesting higher sensitivity to impairments in oxygen delivery. In Study 2 (n=17), Hbmass was reduced by withdrawal of 7% of blood volume through phlebotomy. In a 60-min exercise bout, ventilation, lactate, and heart rate were increased in a time-dependent manner, and time-to-task failure in a subsequent maximal task was reduced. Study 3 explored sex-differences in a pooled analysis (n=79) of four datasets. This cross-sectional study revealed that, due to sex differences in hematological variables, females must achieve a similar fat-free mass-normalized V̇O2max with a lower Hbmass than males. Study 4 (n=5) piloted the use of deuterated water as a metabolic label to quantify the fractional synthetic rate (FSR) of Hb in vivo. The preliminary data showed that this 28-day protocol was feasible and yielded expected FSR values (<1%∙day-1). Future research should explore the mechanisms behind impaired submaximal exercise performance after reduced oxygen delivery; how males and females employ specific strategies to reach a given oxygen uptake; and how Hb synthesis is influenced by sex and regulated in response to exercise training.
exercise, endurance, oxygen, hemoglobin, sex difference, protein synthesis, cycling
Kontro, H. (2024). The role and regulation of hemoglobin mass in endurance exercise (Doctoral thesis, University of Calgary, Calgary, Canada). Retrieved from