Figure 1.

Acclimatization to high-altitude hypoxia decreases steady-state levels of carboxylic acids in human red blood cells. Twenty-one healthy volunteers (12 male and 9 female) were flown from sea level (Oregon) to Bolivia (>5,260 m) for up to 16 days (A), within the framework of the AltitudeOmics study (28, 29). While all of them successfully acclimatized to high-altitude hypoxia (28, 29), red blood cell (RBC) levels (B) of citrate, alpha-ketoglutarate, hydroxyglutarate, and succinate decrease from sea level to high altitude, proportionally to the duration of stay at over 5,000 m. Transient decrease and progressive increases in fumarate and malate were observed, paralleled by increases in the pyruvate/lactate ratios and reduced/oxidized glutathione (GSH/GSSG) ratios, suggestive of a progressively more reducing environment in the cytosol of RBCs from individuals acclimatizing to high-altitude hypoxia. *p < 0.05; **p < 0.01; ***p < 0.001 (repeated measures ANOVA). All data points on x axis were tested [n for each data point is reported in panel (C)].