Repeated exposure to mild intermittent hypoxia enhances walking endurance and microvascular function in OSA patients for up to 4 - 8 weeks post therapy

Background: Obstructive sleep apnea (OSA) is an ever-growing problem affecting an estimated one billion people worldwide. This condition is often associated with comorbidities such as hypertension (HTN) and increased vulnerability to fatigue, which can be linked to reduced oxygen availability and impaired exercise performance. In our previous work, we found that daily exposure to mild intermittent hypoxia (MIH) led to an immediate waning of symptoms, improvement in sleep quality, and reduction in blood pressure after three weeks of treatment. These reductions in symptoms may be accompanied by improvements in microvascular function, fatigability, and exercise performance. Objective: In the present investigation we explored if daily exposure to MIH improves other symptoms of fatigue (i.e. walking endurance) and if the improvements in endurance were associated with improvements in microvascular function. Finally, we evaluated if the improvements were sustained for 8 weeks following daily MIH treatment in individuals with OSA and HTN. Methods: To achieve our objective, both males and females with severe OSA and hypertension were randomly assigned to receive MIH intervention (n=13) or Sham MIH (n=13). Within each group, half of the participants were also randomly assigned to receive nightly CPAP treatment, creating 4 groups to be evaluated. The MIH protocol consisted of twelve 2-minute hypoxic episodes (PETO2 ~50 mmHg), alternated with 2 minutes of normoxia, administered daily for 15 days. PETCO2 was maintained 2 mmHg above baseline throughout the protocol. To measure the effects of MIH participants underwent vascular occlusion tests with near-infrared spectroscopy (NIRS) to assess microvascular function and oxygen-carrying capacity, and a 10-minute walk test (10 MWT) to assess fatigability before therapy, as well as, 4 days, 4 weeks, and 8 weeks following the treatment. Results: No significant differences in distance, speed, or fatigue were observed before therapy. After treatment, the MIH groups walked further (p = 0.008), faster (p = 0.006), and experienced less fatigue (p = 0.007, p = 0.009), with improvements lasting up to 8 weeks, while the groups treated with sham MIH showed no changes. The slope of the rate of desaturation was steeper in those participants treated with MIH + CPAP (p = 0.019). Similarly, the time constant of the decrease in oxygen saturation was faster in both groups treated with MIH compared to those participants treated with Sham MIH, 4 days after treatment (p=0.017). The maximum hyperemic response was increased within the MIH group 4 days after treatment (p=0.003) and the area under the curve of the hyperemic response increased in the groups treated with MIH, 4 days (p=0.027) and 4 weeks (p=0.016) after treatment. Conclusion: Our results show that distance, speed and performance fatigue are improved following treatment with MIH and that these improvements are sustained for 8 weeks. In addition, MIH treatment lead to an improved utilization of oxygen 4 days after treatment and improved vascular responsiveness 4 weeks following treatment. In summary, MIH improves muscle endurance and microvascular function, allowing patients with OSA and HTN to walk faster, for longer durations, and with less fatigue for up to 8 weeks following 15 days of treatment. J.H.M. is supported by the United States Department of Veterans Affairs (I01CX000125, IK6CX002287) and the National Institute of Heart, Lung and Blood (R01HL085537) This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.