Acetazolamide Reduces Endurance Despite Higher Oxygen Saturation in Normobaric Hypoxia

Abstract Acetazolamide is recommended for the prevention of acute mountain sickness, but its effects on endurance performance at prophylactic doses remain unclear. Twelve male physical education students completed a randomized, double-blind, placebo-controlled crossover trial with a 1-week washout. Acetazolamide was administered as three 125-mg doses within 24 hours before testing. Following 30 minutes of seated normobaric hypoxia (FiO2=0.13; ~3,800 m simulated altitude), participants performed constant-load cycling at 60% of peak power output under normobaric hypoxia until exhaustion. Time to exhaustion and mean rating of perceived exertion were analyzed using linear mixed models accounting for treatment, period, and sequence. Time to exhaustion was lower with acetazolamide than with placebo (249.6±36.2 vs. 364.7±71.8 s; p<0.001). Mean rating of perceived exertion was higher with acetazolamide (14.50±1.64 vs. 11.81±1.57; p=0.002). Peripheral oxygen saturation was higher with acetazolamide during resting hypoxia, exercise, and at exhaustion (all p≤0.001), whereas the heart rate was higher with acetazolamide only during exercise (p=0.049). No period or sequence effects were detected for time to exhaustion or perceived exertion. Acetazolamide reduced endurance performance and increased early perceived exertion despite higher peripheral oxygen saturation during acute normobaric hypoxia.