Acetazolamide attenuates lactate accumulation during high-altitude ascent in the Himalayas: A randomized pilot field...

Exposure to high altitude induces hypobaric hypoxia and consequent ventilatory and metabolic adaptations, including increased anaerobic glycolysis and lactate production. Acetazolamide, a carbonic anhydrase inhibitor widely used for altitude sickness prophylaxis, enhances ventilatory drive through renal bicarbonate excretion and mild metabolic acidosis. We aimed to evaluate its effects on blood lactate accumulation and on complementary ventilatory and oxygenation parameters during progressive high-altitude ascent.

We performed a randomized, placebo-controlled pilot field trial during the Everest Base Camp trek in the Nepal Himalaya. Twelve healthy adults were randomized 1:1 to acetazolamide 250 mg once daily or placebo. Physiological variables were recorded at rest at four specific altitudes: 2550 m, 3853 m, 4325 m, and 5160 m. The main outcome was blood lactate concentration; the secondary outcomes were peripheral oxygen saturation (SpO₂), partial pressure of carbon dioxide (pCO₂), partial pressure of oxygen (pO₂), and heart rate. Between-group comparisons were done using the bootstrap resampling method and an exploratory linear mixed model.

Lactate concentrations increased with altitude in both groups but remained consistently lower in the acetazolamide group, with a mean between-group difference of -0.75 mmol/L (95% CI -1.03 to -0.50). Participants receiving acetazolamide also demonstrated lower pCO₂ (-0.27 kPa, 95% CI -0.52 to -0.02) and directionally higher SpO₂ (+1.6%, 95% CI -0.10-3.15). Altitude was the dominant determinant of physiological changes across all parameters.

In this pilot study, acetazolamide was correlated with reduced lactate accumulation, decreased pCO₂, and increased oxygenation during high-altitude ascent. These results are consistent with increased ventilatory compensation and reduced reliance on anaerobic metabolism. They suggest that larger and adequately powered studies should be conducted.