Margolis · Metabolism: clinical and experimental 2020 · randomized crossover trial · n=8

Acute hypoxia reduces exogenous glucose oxidation, glucose turnover, and metabolic clearance rate during steady-state aerobic exercise.

Cited 19 times in the scientific literature.

Level 2 - randomized trial

Randomized crossover trial in humans

PubMed 31778707 · doi:10.1016/j.metabol.2019.154030 · record verified 2026-08-30

What was done

Eight healthy male native lowlanders (age 23 ± 2 years, body mass 87 ± 10 kg) participated in a randomized crossover study comparing sea level (757 mmHg) with acute high-altitude exposure (460 mmHg, after a 5-hour exposure). Participants ingested 145 g of glucose (1.8 g/min) during 80 minutes of metabolically matched steady-state treadmill exercise (oxygen consumption: 1.66 ± 0.14 L/min at sea level vs 1.59 ± 0.10 L/min at high altitude). Substrate oxidation rates and glucose turnover kinetics were evaluated using indirect calorimetry and dual-stable isotope tracers (oral 13C-glucose and continuous intravenous [6,6-2H2]-glucose infusion).

What was found

Total carbohydrate oxidation was significantly higher at high altitude compared to sea level (2.15 ± 0.32 vs 1.39 ± 0.14 g/min, P < 0.05), driven by higher muscle glycogen oxidation (1.67 ± 0.26 vs 0.83 ± 0.13 g/min, P < 0.05). Conversely, exogenous glucose oxidation was lower at high altitude (0.35 ± 0.07 vs 0.44 ± 0.05 g/min, P < 0.05). High altitude also led to lower total glucose rate of appearance (12.3 ± 1.5 vs 13.8 ± 2.0 mg/kg/min, P < 0.05), exogenous glucose rate of appearance (8.9 ± 1.3 vs 10.9 ± 2.2 mg/kg/min, P < 0.05), rate of disappearance (12.7 ± 1.7 vs 14.3 ± 2.0 mg/kg/min, P < 0.05), and metabolic clearance rate (9.0 ± 1.8 vs 12.1 ± 2.3 mL/kg/min, P < 0.05), alongside higher circulating glucose and insulin concentrations.

Why it matters

These findings indicate that impaired peripheral tissue glucose uptake and clearance contribute to the reduction in exogenous carbohydrate oxidation during exercise under acute hypoxia.

Limits

The study included only 8 young, healthy male participants, limiting generalizability to females and broader populations. It evaluated short-term (5-hour) simulated altitude exposure, which does not reflect long-term acclimatization dynamics.

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