Acetazolamide reduces exercise capacity following a 5-day ascent to 4559 m in a randomised study.
Level 2 - randomized trial
Individual randomized controlled trial with matched pairs
PubMed 29387446 · doi:10.1136/bmjsem-2017-000302
What was done
Twenty healthy adults (aged 36±20 years, range 21–77) were paired by age, sex, weight, and acute mountain sickness susceptibility in a double-blind, randomized trial comparing acetazolamide (500 mg daily) to placebo. Participants ascended over 5 days to 4559 m, then performed a cycle ergometer exercise test to exhaustion while breath-by-breath gas measurements were recorded. Comparisons were evaluated using Mann-Whitney U and Pearson's chi-square tests.
What was found
Compared with paired placebo controls at altitude, subjects taking acetazolamide showed: - A greater reduction in maximum power output (Pmax) relative to sea-level values: 65±14.1% vs 76.6±7.4% (P=0.007) - Lower VO2max: 20.7±5.2 vs 24.6±5.1 mL/kg/min (P<0.01) - Smaller change in VO2 from rest to Pmax: 9.8±6.2 vs 13.8±4.9 mL/kg/min (P=0.04) - Lower heart rate at Pmax: 154±25 vs 167±16 bpm (P<0.01) In the acetazolamide group, increasing age correlated with greater reductions in Pmax (r = -0.83, P<0.005) and peak heart rate (r = -0.71, P=0.01).
Why it matters
Although acetazolamide prevents acute mountain sickness, a standard 500 mg daily dose impairs peak exercise capacity at high altitude, an adverse effect that is especially pronounced in older adults.
Limits
The study had a very small sample size (n=20 total, 10 pairs) across a wide age spread (21 to 77 years). It tested only a 500 mg daily regimen rather than lower doses (e.g., 250 mg or 125 mg daily) and did not measure serum drug concentrations to confirm the pharmacokinetic hypothesis.
Cited by
- supports Diamox (acetazolamide) causes mild metabolic acidosis and increases SpO2, but reliably reduces cognitive and physical performance.