Therapeutic Use of Exercising in Hypoxia: Promises and Limitations.

Abstract

It is well-established that different altitude training modalities can improve convective oxygen (O2) transport capacity and physical fitness of athletes (Millet et al., 2010). Exercising in hypoxia also induces specific muscular adaptations including increased oxidative enzymes (e.g., citrate synthase) activity, mitochondrial density, capillary-to-fiber ratio, and fiber cross-sectional area (Hoppeler et al., 2008). These changes with hypoxic training are mostly modulated via hypoxia-inducible factor 1α (HIF-1α) signaling cascade, which is not activated to the same extent when training is performed in normoxia or by passive hypoxic exposure. Indeed, large body of literature shows that, compared to hypoxic exercise, passive exposure to hypoxia does not provoke similar acute responses. In healthy individuals, both systemic (e.g., performance enhancement), cardiovascular (e.g., maximal O2 uptake, VO2max) or transcriptional muscular responses are minimal with intermittent passive exposures at moderate altitude. On the other hand, there are clear evidences that when hypoxia is combined with exercise, it triggers specific responses, not observed following similar exercise in normoxia (Bartsch et al., 2008; Lundby et al., 2009). In addition, greater specific adaptations have been reported in high-intensity vs. moderate-intensity hypoxic intervention (Faiss et al., 2013) (e.g., improvements in muscle O2 homeostasis and tissue perfusion induced by enhanced mitochondrial efficiency, control of mitochondrial respiration, angiogenesis, and muscle buffering capacity). It seems that the main underlying mechanism is the larger hypoxemia resulting from the combination of muscle deoxygenation (high-intensity exercise) and systemic desaturation (moderate hypoxia). In patients or elderly individuals, altitude is generally associated with increased health risks through enhanced sympathetic vasoconstrictor activation (Blitzer et al., 1996), obstructive sleep apneas (Nespoulet et al., 2012), hypoxemia (Levine et al., 1997), pulmonary hypertension (Valencia-Flores et al., 2004), arrhythmias (Kujanik et al., 2000), and alterations of postural control (Degache et al., 2012). However, several studies have investigated the therapeutic benefits of exercising in mild hypoxia on the blood pressure regulation and the influence of different hypoxic modalities in healthy individuals (Bailey et al., 2001; Wang et al., 2007; Haufe et al., 2008; Nishiwaki et al., 2011; Morishima et al., 2014; Shi et al., 2014) or in patients with different cardiovascular and respiratory risk factors such as chronic obstructive pulmonary disease (COPD) (Haider et al., 2009), obesity (Wiesner et al., 2010), coronary artery disease (Burtscher et al., 2004). Recent studies (Haufe et al., 2008; Wiesner et al., 2010) have also reported that sustained hypoxia may be of benefit to weight management programs of obese patients (Urdampilleta et al., 2012; Kayser and Verges, 2013). Both exercise (Williams et al., 2002) and/or intermittent hypoxia (Burtscher et al., 2004; Shatilo et al., 2008) have been suggested to positively influence age-related alterations in elderly individuals. Finally, living at altitude seems to have contradictory effects on different mortality risk factors. Therefore, this essay summarizes recent evidences suggesting that exercising in hypoxia might be a valuable and viable “therapeutic strategy.” We discuss the benefits and risks/limitations in (i) hypertensive (ii) obese, (iii) elderly individuals. Since the benefits of being active have been extensively investigated in these three groups of individuals (see respective reviews on the effects of physical activity in Cherubini et al., 1998; Baillot et al., 2014; Borjesson et al., 2016), the present article focus on the potential additional health benefits provided by hypoxic exercise, when compared to normoxic exercise. For safety and practical reasons, patients cannot access high altitude (even by using hypoxic devices) and preferably stay at moderate altitude (1800–3000 m). In this setting, exercise is used to increase the overall hypoxia-induced metabolic stress and thereby provide benefits beyond those achievable by normoxic therapeutic training modalities.