Optimizing Intermittent Hypoxic–Hyperoxic Training for Safety and Feasibility: An Exploratory Pilot Study

Background: Intermittent Hypoxic–Hyperoxic Training (IHHT) induces physiological adaptations. While its efficacy in athletic performance remains debated, IHHT improves health markers in pathological and geriatric populations. This Exploratory Pilot Study aimed to explore the safety and feasibility of two IHHT protocols through preliminary responses. Methods: Twelve healthy volunteers completed a 4-week intervention (two sessions/week, 45 min/session) combining IHHT simultaneously during low-intensity exercise. The study compared a Training Group (TG: 30 min hypoxia, 7.5 min normoxia, 7.5 min hyperoxia) with a Conditioning Group (CG: 15 min hypoxia, 22.5 min normoxia, 7.5 min hyperoxia). Outcomes assessed included cardiorespiratory parameters, Acute Mountain Sickness symptoms, Perceived Exertion, a comprehensive biochemical panel, systemic inflammation, oxidative stress, and renal status. Results: Both protocols were well-tolerated. The TG exhibited significantly greater oxygen desaturation than the CG (p = 0.048). Moreover, the CG demonstrated a significantly attenuated increase in Interleukin-6 (p = 0.021) compared to the TG. Additionally, preliminary variations highlighted an interesting reduction in lipid parameters (TC, LDL, and Apo A1/B ratios) in both groups, although these did not reach statistical significance after FDR correction. Conclusions: While both protocols proved feasible and safe, a more balanced hyperoxic-to-hypoxic exposure (CG) showed better acute physiological tolerability, attenuating cardiovascular strain and mitigating systemic pro-inflammatory responses compared to the unbalanced exposure (TG). Finally, the preliminary variations observed in lipid parameters provide a rationale that warrants further controlled investigations.