Hyperbaric oxygen therapy and cardiorespiratory fitness: the strongest prognostic markers of health and ageing improve across more than 1,000 patients, consistent with controlled trials

Introduction Cardiorespiratory fitness (CRF), assessed via cardiopulmonary exercise testing (CPET), is a powerful objective marker associated with biological aging, healthspan, and all-cause mortality. Controlled trials have reported improvements in CRF following hyperbaric oxygen therapy (HBOT) protocols utilizing hyperoxic–hypoxic paradox (HHP) principles in healthy athletes and older adults; whether similar changes are observed in a broad, heterogeneous clinical population remained unknown. Methods Retrospective cohort study of 1,032 consecutive patients with valid maximal/peak effort CPET before and after HBOT (2018–2025). Within-subject changes were quantified across general and indication-specific CPET parameters and stratified by clinical indication, age (<45 to ≥75 years), and sex; effect sizes were benchmarked against sham- and control-anchored trials of the identical protocol. Results All seven prognostic CPET parameters improved significantly post-treatment at the whole cohort level (all p < 0.001; dz = 0.23–0.74), with aerobic-capacity gains evident across clinical indications, age groups and sexes. Peak aerobic capacity (VO 2 max/kg) rose by +2.29 mL·kg -1 ·min -1 (95% CI +2.10 to +2.47) and submaximal ventilatory threshold capacity (VO 2 at VT1) by +2.12 mL·kg -1 ·min -1 (95% CI +1.94 to +2.30), with parallel improvements in oxygen pulse (+0.79 mL/beat) and ventilatory efficiency (VE/VCO 2 slope −1.07); these represent medium-to-large within-subject effects (dz = 0.74 and 0.73 for peak and threshold capacity). Using magnitude-based thresholds, 53.9% of patients increased VO 2 max/kg by ≥ 0.5 MET and 26.6% by ≥ 1 MET (82.9% showed some increase); improvement in peak or threshold oxygen uptake occurred in 94.4%. Conclusion In the largest CPET-based HBOT cohort reported, completion of the HHP-HBOT protocol (2.0 ATA with intermittent air breaks over a mean of 58.8 sessions) was associated with significant within-subject improvements in VO 2 max and multiple complementary measures of cardiorespiratory fitness. These findings extend prior controlled observations to a large, heterogeneous real-world clinical cohort. Given the retrospective, uncontrolled design, prospective controlled studies are required to determine the specific contribution of HBOT to these changes.