Hypoxic and Hyperoxic Breathing as a Complement to Low-Intensity Physical Exercise Programs: A Proof-of-Principle Study

Abstract

Inflammation is an adaptive response to both external and internal stimuli including infection, trauma, surgery, ischemia-reperfusion, or malignancy. A number of studies indicate that physical activity is an effective means of reducing acute systemic and low-level inflammation occurring in different pathological conditions and in the recovery phase after disease. As a proof-of-principle, we hypothesized that low-intensity workout performed under modified oxygen supply would elicit a "metabolic exercise" inducing a hormetic response, increasing the metabolic load and oxidative stress with the same overall effect expected after a higher intensity or charge exercise. Herein, we report the effect of a 5-week low-intensity, non-training, exercise program in a group of young healthy subjects in combination with the exposure to hyperoxia (30% and 100% pO₂, respectively) or light hypoxia (15% pO₂) during workout sessions on several inflammation and oxidative stress parameters, namely hemoglobin (Hb), redox state, nitric oxide metabolite (NOx), inducible nitric oxide synthase (iNOS), inflammatory cytokine expression (TNF-α, interleukin (IL)-6, IL-10), and renal functional biomarkers (creatinine, neopterin, and urates). We confirmed our previous reports demonstrating that intermittent hyperoxia induces the normobaric oxygen paradox (NOP), a response overlapping the exposure to hypoxia. Our data also suggest that the administration of modified air composition is an expedient complement to a light physical exercise program to achieve a significant modulation of inflammatory and immune parameters, including cytokines expression, iNOS activity, and oxidative stress parameters. This strategy can be of pivotal interest in all those conditions characterized by the inability to achieve a sufficient workload intensity, such as severe cardiovascular alterations and articular injuries failing to effectively gain a significant improvement of physical capacity.

Keywords: hyperoxia; hypoxia; immune response; inflammation; normobaric oxygen paradox; oxidative stress; physical activity; rehabilitation.

Figure 1

Hemoglobin variation after a 5-week exercise program consisting of 20 min low-intensity workout sessions every other day (panel (A)) and hematocrit variation throughout the same program (panel (B)). Histograms display the percentage variation (mean ± standard deviation (SE)) in comparison to the baseline (time 0). ** p < 0.01, *** p < 0.001; for one sample t-test vs. the baseline. Samples were drawn twice a week.

Figure 2

Reactive oxygen species (ROS) production (panel (A)) and total antioxidant capacity (TAC; panel (B)) in human plasma at the end of a 5-week workout program consisting of 20 min low-intensity exercise sessions every other day. Box and Whisker plots indicate the median, 1st quartile, 3d quartile, interquartile range, minimum, and maximum in comparison to the baseline (time 0), which was set at 100%. * p < 0.05, ** p < 0.01 vs. the baseline before oxygen exposure (time 0), according to the Wilcoxon test.

Figure 3

Inducible nitric oxide synthase (iNOS) protein level (panel (A)) and NOx production (panel (B)) in human plasma at the end of a 5-week workout program consisting of 20 min low-intensity exercise session every other day. Box and Whisker plots indicate the median, 1st quartile, 3d quartile, interquartile range, minimum, and maximum in comparison to the baseline (time 0), which was set at 100%. * p < 0.05, ** p < 0.01 vs. the baseline before oxygen exposure (time 0), for the Wilcoxon test.

Figure 4

Interleukin (IL)-6 (panel (A)), IL-10 (panel (B)), and tumor necrosis factor-alpha (TNF-α) (panel (C)) in human plasma after a 5-week workout program consisting of 20 min low-intensity exercise sessions every other day. Box and Whisker plots indicate the median, 1st quartile, 3d quartile, interquartile range, minimum, and maximum in comparison to the baseline (time 0), which was set at 100%. * p < 0.05, ** p < 0.01 vs. the baseline before altered oxygen exposure (time 0), according to the Wilcoxon test.

Figure 5

Creatinine (panel (A)), neopterin (panel (B)), and urates (panel (C)) in human urine at the end of a 5-week workout program consisting of 20 min low-intensity exercise sessions every other day. Box and Whisker plots indicate the median, 1st quartile, 3d quartile, interquartile range, minimum, and maximum in comparison to the baseline (time 0), which was set at 100%. * p < 0.05, ** p < 0.01 vs. the baseline before oxygen exposure (time 0), for the Wilcoxon test.

Figure 6

Longitudinal evaluation of Borg’s perceived excretion rating (mean ± SEM). * p < 0.05, ** p < 0.01, *** p < 0.001; for the Kruskal–Wallis test followed by Dunn’s post hoc test. (red color: 15% vs. 30%; green color: 15% vs. 100%).