Effects of two carbonic anhydrase inhibitors on exercise performance in acute hypoxia.
Level 2 - randomized trial
Individual double-blind randomized crossover trial
PubMed 39480272 · doi:10.1152/japplphysiol.00589.2024
What was done
Fifteen healthy participants completed a double-blind, randomized crossover study comparing the effects of acetazolamide (250 mg three times daily for 2 days), methazolamide (100 mg twice daily for 2 days), and placebo on whole-body exercise performance in acute normobaric hypoxia (fraction of inspired oxygen = 0.15). Following baseline testing and familiarization, participants performed a 5-km hypoxic cycling time trial under each condition. Pre-exercise capillary blood samples and resting quadriceps maximal voluntary contractions were evaluated alongside time-trial duration, ventilation, and oxyhemoglobin saturation.
What was found
Both active drugs induced resting metabolic acidosis compared to placebo, with capillary hydrogen ion concentrations of 47 ± 3 nmol for acetazolamide, 43 ± 2 nmol for methazolamide, and 39 ± 2 nmol for placebo (P < 0.01). Time to complete the 5-km cycling trial was significantly faster on placebo (562 ± 32 s, P < 0.01) than on acetazolamide (577 ± 38 s) and methazolamide (581 ± 37 s), with no significant difference between the two active drugs (P = 0.96). Average ventilation (124 ± 27, 127 ± 24, and 127 ± 19 L/min) and oxyhemoglobin saturation (87 ± 2%, 88 ± 2%, and 88 ± 3%) did not differ significantly between acetazolamide, methazolamide, and placebo, respectively (P > 0.05).
Why it matters
While methazolamide was hypothesized to preserve performance based on normoxic isolated-muscle data, these findings demonstrate that both methazolamide and acetazolamide impair whole-body endurance performance during acute hypoxic exposure.
Limits
The study sample was small (n = 15) and restricted to healthy individuals. Testing relied on simulated normobaric hypoxia rather than terrestrial hypobaric altitude, and the abstract omits participant sex distribution as well as data on maximal voluntary contractions.
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