Acetazolamide reduces exercise capacity following a 5-day ascent to 4559 m in a randomised study

Abstract

Objective: To assess whether acetazolamide (Az), used prophylactically for acute mountain sickness (AMS), alters exercise capacity at high altitude.

Methods: Az (500 mg daily) or placebo was administered to 20 healthy adults (aged 36±20 years, range 21-77), who were paired for age, sex, AMS susceptibility and weight, in a double-blind, randomised manner. Participants ascended over 5 days to 4559 m, then exercised to exhaustion on a bicycle ergometer, while recording breath-by-breath gas measurements. Comparisons between groups and matched pairs were done via Mann-Whitney U and Pearson's χ² tests, respectively.

Results: Comparing paired individuals at altitude, those on Az had greater reductions in maximum power output (P_max) as a percentage of sea-level values (65±14.1 vs 76.6±7.4 (placebo); P=0.007), lower VO_2max (20.7±5.2 vs 24.6±5.1 mL/kg/min; P<0.01), smaller changes from rest to P_max for VO₂ (9.8±6.2 vs 13.8±4.9 mL/kg/min; P=0.04) and lower heart rate at P_max (154±25 vs 167±16, P<0.01) compared with their placebo-treated partners. Correlational analysis (Pearson's) indicated that with increasing age P_max (r=-0.83: P<0.005) and heart rate at P_max (r=-0.71, P=0.01) reduced more in those taking Az.

Conclusion: Maximum exercise performance at altitude was reduced more in subjects taking Az compared with placebo, particularly in older individuals. The age-related effect may reflect higher tissue concentrations of Az due to reduced renal excretion. Future studies should explore the effectiveness of smaller Az doses (eg, 250 mg daily or less) in older individuals to optimise the altitude-Az-exercise relationships.

Keywords: altitude; elderly people; exercise.

Figure 1

Numbers of individuals taking placebo or acetazolamide (Az) completing each exercise stage (ranging from 23% to 90% of baseline values) at 4559 m. For example, at 68% of baseline power, the test was completed by three Az and nine placebo individuals. P=0.03 by Mann-Whitney U test for differences of means.

Figure 2

Studies at 4559 m showing maximum heart rate (HR) for the matched pairs of participants. Pairs <50 years are shown as solid lines and >50 years are shown as dotted lines. Pearson’s χ² test for observed differences between matched pairs at altitude.

Figure 3

Studies on paired participants (placebo vs acetazolamide (Az)) for P_max at altitude showing (A) the relationship between mean age of each pair and within pair differences for maximum heart rate (HR_max), and similarly for (B) mean age of each pair and differences in reduction in maximum power (P_max) from baseline (Pearson’s correlation).