Lifelong High-Altitude Hypoxia Does Not Prevent Aerobic Trainability in Native Andean Cyclists

Lifelong exposure to high-altitude hypoxia imposes a persistent challenge to aerobic metabolism, yet the capacity of native high-altitude athletes to further improve their aerobic performance remains insufficiently characterized. We investigated within-participant changes in aerobic performance, skeletal muscle oxygenation, hematological and biochemical profiles, and mitochondrial respiration in peripheral blood mononuclear cells (PBMCs) over six weeks of supervised high-intensity interval training (HIIT) in 12 native Andean cyclists (six women and six men) permanently residing at 3600 m in La Paz, Bolivia. Maximal oxygen uptake (VO2max) increased by 15.9%, with no statistically significant changes in hematological or biochemical parameters after correction for multiple comparisons. High-resolution respirometry revealed increased Complex IV-supported mitochondrial respiration and a reduced Complex I+II/Complex IV respiratory ratio in PBMCs. Near-infrared spectroscopy identified significant increases in muscle deoxygenated hemoglobin and myoglobin signals and muscle oxygen saturation, without significant sex × training interactions. Together, these findings demonstrate substantial aerobic responsiveness accompanied by measurable changes in circulating cell mitochondrial respiration and local muscle oxygenation in native Andean athletes. Although the absence of a nonintervention control group prevents attributing these changes exclusively to HIIT, and the lack of matched sea-level controls precludes comparisons of training responsiveness across altitude populations, neither limitation negates the longitudinal improvements documented within this high-altitude cohort. Our findings establish that aerobic performance can improve in athletes exposed to lifelong high-altitude hypoxia.