In a randomized, placebo-controlled, double-blind study, we tested a 4-week program in normobaric hypoxia that is commercially offered for the prevention of acute mountain sickness (AMS). Twenty-two male and 18 female healthy subjects [mean age 33 +/- 7 (SD) years] exercised 70 min, 3 x /week for 3 weeks on a bicycle ergometer at workloads of 60% VO2max either in normoxia (normoxia group, NG) or in normobaric hypoxia (hypoxia group, HG), corresponding to altitudes of 2500, 3000, and 3500 m during weeks 1, 2, and 3, respectively. Four passive exposures of 90 min in normoxia (NG) or hypoxia corresponding to 4500 m (HG) followed in week 4. Five days after the last session, subjects ascended within 24 h from sea level to 4559 m (one overnight stay at 3611 m) and stayed there for 24 h. AMS was defined as LL (Lake Louise score) > or =5 and AMS-C > or =0.70. The AMS incidence (70% in NG vs. 60% in HG, p = 0.74), LL scores (7.1 +/- 4.3 vs. 5.9 +/- 3.4, p = 0.34), and AMS-C scores (1.50 +/- 1.22 vs. 0.93 +/- 0.81, p = 0.25) at the study endpoint were not significantly different between the groups. However, the incidence of AMS at 3611 m (6% vs. 47%, p = 0.01) and the functional LL score at 4559 m were lower in HG. SpO2 at 3611 m, heart rate during ascents, and arterial blood gases at 4559 m were not different between groups. We conclude that the tested program does not reduce the incidence of AMS within a rapid ascent to 4559 m, but our data show that it prevents AMS at lower altitudes. Whether such a program would prevent AMS at higher altitudes, but with slower ascent, remains to be tested.

Increased plasma levels of vascular endothelial growth factor (VEGF) due to lower levels of its soluble receptor (sFlt-1) had been suggested to cause vasogenic brain edema and thereby to cause the symptoms of acute mountain sickness (AMS). We tested this hypothesis after active ascent to high altitude. Plasma was collected from 31 subjects at low altitude (100 m) before (LA1) and after (LA2) 4 weeks of aerobic exercise training in normobaric hypoxia or normoxia, and one night after ascent to high altitude (4559 m). Training modalities (hypoxia or normoxia) did not influence VEGF- and sFlt-1-levels. Therefore, data of both training groups were analyzed together. After one night at 4559 m, 18 subjects had AMS (AMS+), 13 had no AMS (AMS-). In AMS+ and AMS-, VEGF was 110 ± 75 (SD) pg/ml vs. 104 ± 82 (p = 0.74) at LA1, 63 ± 40 vs. 73 ± 50 (p = 0.54) at LA2, and 88 ± 62 vs. 104 ± 81 (p = 0.54) at 4559 m, respectively. Corresponding values for sFlt-1 in AMS+ and AMS- were 81 pg/ml ± 13.1 vs. 82 ± 17 (p = 0.97), 79 ± 11 vs. 80 ± 16 (p = 0.92) and 139 ± 28 vs. 135 ± 31 (p = 0.70), respectively. Absolute values or changes of VEGF were not correlated and those of sFlt-1 slightly correlated with AMS scores. These data provide no evidence for a role of plasma VEGF and sFlt-1 in the pathophysiology of AMS. They do, however, not exclude paracrine effects of VEGF in the brain.

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