Effects of Hypoxic Training on Aerobic Performance and Angiogenesis Biomarkers

Background: Exercise training performed under conditions of reduced ambient or inspired oxygen availability (hypoxic training) has long been proposed as a strategy to enhance aerobic performance beyond the adaptations achieved through equivalent normoxic training. Central to this hypothesis is the hypoxia-inducible factor (HIF) signaling pathway, which upregulates vascular endothelial growth factor (VEGF) and other angiogenic mediators, thereby promoting capillary growth, oxygen delivery, and oxidative capacity in skeletal muscle (۱,۲). However, the translation of these molecular responses into consistent gains in maximal oxygen uptake (V̇O۲max) and sea-level performance remains contested in the human exercise-physiology literature (۱). Methods: This narrative review synthesizes current evidence from animal and human studies examining the physiological and molecular effects of hypoxic training on aerobic performance indices (V̇O۲max, time to exhaustion, peak power output) and circulating or tissue-level angiogenesis biomarkers, including VEGF, matrix metalloproteinases (MMP-۲, MMP-۹), endostatin, and hypoxia-inducible factor-۱α (HIF-۱α). Findings from controlled animal models (۲), acute human exercise trials under normobaric hypoxia (۳), and recent systematic reviews and meta-analyses of intermittent hypoxic training protocols (۱) were critically appraised and integrated. Results: Evidence from rodent models demonstrates that hypoxic training protocols, particularly combined hypoxic exposure with training, upregulate skeletal muscle CD۳۱ and VEGF expression alongside markers of mitochondrial turnover, consistent with enhanced capillarization and oxidative capacity (۲). In humans, acute intensive exercise under normobaric hypoxia differentially modulates angiogenic biomarkers in an altitude-dependent manner, with VEGF, MMP-۲, MMP-۹, and endostatin showing distinct temporal response patterns across simulated altitudes (۳). Despite this molecular plausibility, a recent systematic review and meta-analysis encompassing ۳۵ studies found that aerobic intermittent hypoxic training does not confer a statistically significant advantage over normoxic training for V̇O۲max, peak power output, or time to exhaustion at sea level, with evidence of publication bias favoring positive findings (۱). Conclusion: A clear dissociation exists between the molecular angiogenic signature induced by hypoxic training and its translation into superior sea-level aerobic performance outcomes. While hypoxic stimuli reliably activate HIF-VEGF-mediated angiogenic pathways at the tissue level, current human performance data do not support a consistent ergogenic advantage of hypoxic over normoxic training. Future research should prioritize standardized hypoxic dosing protocols and paired biomarker–performance assessments to clarify this discrepancy.

کلیدواژه ها:

Hypoxic training ، Angiogenesis ، Vascular endothelial growth factor ، Aerobic performance ، Hypoxia-inducible factor