Future planetary habitats will expose inhabitants to both reduced gravity and hypoxia. This study investigated the effects of short-term unloading and normobaric hypoxia on whole body and regional body composition (BC). Eleven healthy, recreationally active, male participants with a mean (SD) age of 24 (2) years and body mass index of 22.4 (3.2) kg·m(-2) completed the following 3 10-day campaigns in a randomised, cross-over designed protocol: (i) hypoxic ambulatory confinement (HAMB; FIO2 = 0.147 (0.008); PIO2 = 93.8 (0.9) mm Hg), (ii) hypoxic bed rest (HBR; FIO2 = 0.147 (0.008); PIO2 = 93.8 (0.9) mm Hg), and (iii) normoxic bed rest (NBR; FIO2 = 0.209; PIO2 = 133.5 (0.7) mm Hg). Nutritional requirements were individually precalculated and the actual intake was monitored throughout the study protocol. Body mass, whole body, and regional BC were assessed before and after the campaigns using dual-energy X-ray absorptiometry. The calculated daily targeted energy intake values were 2071 (170) kcal for HBR and NBR and 2417 (200) kcal for HAMB. In both HBR and NBR campaigns the actual energy intake was within the targeted level, whereas in the HAMB the intake was lower than targeted (-8%, p < 0.05). Body mass significantly decreased in all 3 campaigns (-2.1%, -2.8%, and -2.0% for HAMB, HBR, and NBR, respectively; p < 0.05), secondary to a significant decrease in lean mass (-3.8%, -3.8%, -4.3% for HAMB, HBR, and NBR, respectively; p < 0.05) along with a slight, albeit not significant, increase in fat mass. The same trend was observed in the regional BC regardless of the region and the campaign. These results demonstrate that, hypoxia per se, does not seem to alter whole body and regional BC during short-term bed rest.

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New Findings What is the central question of this study?It is well established that muscle and bone atrophy in conditions of inactivity or unloading, but there is little information regarding the effect of a hypoxic environment on the time course of these deconditioning physiological systems. What is the main finding and its importance?The main finding is that a horizontal 10 day bed rest in normoxia results in typical muscle atrophy, which is not aggravated by hypoxia. Changes in bone mineral content or in metabolism were not detected after either normoxic or hypoxic bed rest. Abstract Musculoskeletal atrophy constitutes a typical adaptation to inactivity and unloading of weightbearing bones. The reduced‐gravity environment in future Moon and Mars habitats is likely to be hypobaric hypoxic, and there is an urgent need to understand the effect of hypoxia on the process of inactivity‐induced musculoskeletal atrophy. This was the principal aim of the present study. Eleven males participated in three 10 day interventions: (i) hypoxic ambulatory confinement; (ii) hypoxic bed rest; and (iii) normoxic bed rest. Before and after the interventions, the muscle strength (isometric maximal voluntary contraction), mass (lean mass, by dual‐energy X‐ray absorptiometry), cross‐sectional area and total bone mineral content (determined with peripheral quantitative computed tomography) of the participants were measured. Blood and urine samples were collected before and on the 1st, 4th and 10th day of the intervention and analysed for biomarkers of bone resorption and formation. There was a significant reduction in thigh and lower leg muscle mass and volume after both normoxic and hypoxic bed rests. Muscle strength loss was proportionately greater than the loss in muscle mass for both thigh and lower leg. There was no indication of bone loss. Furthermore, the biomarkers of resorption and formation were not affected by any of the interventions. There was no significant effect of hypoxia on the musculoskeletal variables. Short‐term normoxic (10 day) bed rest resulted in muscular deconditioning, but not in the loss of bone mineral content or changes in bone metabolism. Hypoxia did not modify these results.

Moderate‐intensity exercise sessions are incorporated into heat‐acclimation and hypoxic‐training protocols to improve performance in hot and hypoxic environments, respectively. Consequently, a training effect might contribute to aerobic performance gains, at least in less fit participants. To explore the interaction between fitness level and a training stimulus commonly applied during acclimation protocols, we recruited 10 young males of a higher (more fit‐MF, peak aerobic power [VO2peak]: 57.9 [6.2] ml·kg−1·min−1) and 10 of a lower (less fit‐LF, VO2peak: 41.7 [5.0] ml·kg−1·min−1) fitness level. They underwent 10 daily exercise sessions (60 min@50% peak power output [Wpeak]) in thermoneutral conditions. The participants performed exercise testing on a cycle ergometer before and after the training period in normoxic (NOR), hypoxic (13.5% FiO2; HYP), and hot (35°C, 50% RH; HE) conditions in a randomized and counterbalanced order. Each test consisted of two stages; a steady‐state exercise (30 min@40% NOR Wpeak to evaluate thermoregulatory function) followed by incremental exercise to exhaustion. VO2peak increased by 9.2 (8.5)% (p = .024) and 10.2 (15.4)% (p = .037) only in the LF group in NOR and HE, respectively. Wpeak increases were correlated with baseline values in NOR (r = −.58, p = .010) and HYP (r = −.52, p = .018). MF individuals improved gross mechanical efficiency in HYP. Peak sweat rate increased in both groups in HE, whereas MF participants activated the forehead sweating response at lower rectal temperatures post‐training. In conclusion, an increase in VO2peak but not mechanical efficiency seems probable in LF males after a 10‐day moderate‐exercise training protocol.

We examined the effects of acclimatization to normobaric hypoxia on aerobic performance and exercise thermoregulatory responses under normoxic, hypoxic and hot conditions. Twelve males performed tests of maximal oxygen uptake (V̇O) in normoxic (NOR), hypoxic (13.5% FO; HYP) and hot (35℃, 50% RH; HE) conditions in a randomized manner before and after a 10-day continuous normobaric hypoxic exposure (FO = 13.65(0.35)%, PO = 87(3) mmHg). The acclimatization protocol included daily exercise (60min @ 50% hypoxia-specific peak power output, W). All maximal tests were preceded by a steady-state exercise (30 min at 40% W) to assess the sweating response. Hematological data were assessed from venous blood samples obtained before and after acclimatization. V̇O increased by 10.7% (P = 0.002) and 7.9% (P = 0.03) from pre- to post-acclimatization in NOR and HE, respectively, whereas no differences were found in HYP (pre: 39.9(3.8) vs post: 39.4(5.1) mL.kg.min, P = 1.0). However, the increase in V̇O did not translate into increased W in either NOR or HE. Maximal heart rate and ventilation remained unchanged following acclimatization. Νo differences were noted in the sweating gain and thresholds independent of the acclimatization or environmental conditions. Hypoxic acclimatization markedly increased hemoglobin (P < 0.001), hematocrit (P < 0.001) and extracellular HSP72 (P = 0.01). These data suggest that 10 days of normobaric hypoxic acclimatization combined with moderate-intensity exercise training improves V̇O in NOR and HE, but does not seem to affect exercise performance or thermoregulatory responses in any of the tested environmental conditions.

In chronic diseases, hypoxia and physical inactivity are associated with atherosclerosis progression. In contrast, a lower mortality from coronary artery disease and stroke is observed in healthy humans residing at high altitude in hypoxic environments. Eleven young, male volunteers completed the following 10-day campaigns in a randomized order: hypoxic ambulatory, hypoxic bed rest and normoxic bed rest. Before intervention, subjects were evaluated in normoxic ambulatory condition. Normobaric hypoxia was achieved in a hypoxic facility simulating 4000 m of altitude. Following hypoxia, either in bed rest or ambulatory condition, markers of cardiometabolic risk shifted toward a more atherogenic pattern consisting of: (a) lower levels of total HDL cholesterol and HDL2 sub-fraction and decreased hepatic lipase; (b) activation of systemic inflammation, as determined by C-reactive protein and serum amyloid A; (c) increased plasma homocysteine; (d) decreased delta-5 desaturase index in cell membrane fatty acids, a marker of insulin sensitivity. Bed rest and hypoxia additively decreased total HDL and delta-5 desaturase index. In parallel to the pro-atherogenic effects, hypoxia activated selected anti-atherogenic pathways, consisting of increased circulating TNF-related apoptosis-inducing ligand (TRAIL), a protective factor against atherosclerosis, membrane omega-3 index and erythrocyte glutathione availability. Hypoxia mediated changes in TRAIL concentrations and redox glutathione capacity (i.e., GSH/GSSG ratio) were greater in ambulatory conditions (+34 ± 6% and +87 ± 31%, respectively) than in bed rest (+17 ± 7% and +2 ± 27% respectively). Hypoxia-induced cardiometabolic risk is blunted by moderate level of physical activity as compared to bed rest. TRAIL and glutathione redox capacity may contribute to the positive interaction between physical activity and hypoxia.Highlights:– Hypoxia and bed rest activate metabolic and inflammatory markers of atherogenesis.– Hypoxia and physical activity activate selected anti-atherogenic pathways.– Hypoxia and physical activity positive interaction involves TRAIL and glutathione.

Daytime vasoconstriction induced by hypoxia and/or bed rest is abolished at night, lending further support to the theory that changes in peripheral skin temperature may be functionally linked to sleep onset.

IntroductionWhile hypoxia is known to decrease peak oxygen uptake (V.⁢o2 max) and maximal power output in both adults and children its influence on submaximal exercise cardiorespiratory and, especially, muscle oxygenation responses remains unclear.MethodsEight pre-pubertal boys (age = 8 ± 2 years.; body mass (BM) = 29 ± 7 kg) and seven adult males (age = 39 ± 4 years.; BM = 80 ± 8 kg) underwent graded exercise tests in both normoxic (PiO2 = 134 ± 0.4 mmHg) and hypoxic (PiO2 = 105 ± 0.6 mmHg) condition. Continuous breath-by-breath gas exchange and near infrared spectroscopy measurements, to assess the vastus lateralis oxygenation, were performed during both tests. The gas exchange threshold (GET) and muscle oxygenation thresholds were subsequently determined for both groups in both conditions.ResultsIn both groups, hypoxia did not significantly alter either GET or the corresponding V.⁢o2 at GET. In adults, higher trueV.E levels were observed in hypoxia (45 ± 6 l/min) compared to normoxia (36 ± 6 l/min, p < 0.05) at intensities above GET. In contrast, in children both the hypoxic trueV.E and V.⁢o2 responses were significantly greater than those observed in normoxia only at intensities below GET (p < 0.01 for trueV.E and p < 0.05 for V.⁢o2). Higher exercise-related heart rate (HR) levels in hypoxia, compared to normoxia, were only noted in adults (p < 0.01). Interestingly, hypoxia per se did not influence the muscle oxygenation thresholds during exercise in neither group. However, and in contrast to adults, the children exhibited significantly higher total hemoglobin concentration during hypoxic as compared to normoxic exercise (tHb) at lower exercise intensities (30 and 60 W, p = 0.01).ConclusionThese results suggest that in adults, hypoxia augments exercise ventilation at intensities above GET and might also maintain muscle blood oxygenation via increased HR. On the other hand, children exhibit a greater change of muscle blood perfusion, oxygen uptake as well as ventilation at exercise intensities below GET.