Leg glucose uptake and substrate utilisation during time trial exercise: Effects of acute hypobaric hypoxia and biological sex

Abstract Hypoxia reduces exercise performance, yet it remains unclear how biological sex and altitude influence substrate utilisation during prolonged maximal exercise. Twenty‐two trained cyclists and triathletes (10 females) completed 30 min time trials (TTs) at low altitude (normoxia; ∼400 m) and moderate altitude (hypoxia; ∼2800 m in a hypobaric chamber) in counterbalanced order. Whole‐body metabolism was estimated from indirect calorimetry, whereas leg glucose uptake and substrate utilisation were derived from arterial and femoral venous blood samples and leg blood flow (thermodilution). Muscle biopsies were obtained from vastus lateralis to measure glycogen utilisation. Across altitudes, females displayed a higher fractional utilisation of during the TTs. TT performance was decreased in hypoxia, and the proportional decrease was smaller in females (−14%) than in males (−18%). Whole‐body substrate utilisation was similar between sexes in normoxia. However, males showed a large decrease in carbohydrate oxidation in hypoxia, whereas females displayed only a modest decrease. Males and females had similar leg metabolic responses to hypoxia: estimated glycogen oxidation decreased, with no change in absolute fat or blood glucose oxidation. However, across altitudes, females showed greater carbohydrate contributions, originating primarily from blood glucose rather than muscle glycogen. Estimates of fat contribution were uncertain but suggested a lower contribution in females than in males. In conclusion, females exercised at a higher relative intensity and derived relatively more energy from blood glucose. Males and females had similar leg metabolic responses to hypoxia, with the lower power output and metabolic rate in hypoxic TTs primarily regulated by reduced estimated glycogen oxidation. image Key points Substrate utilisation during exercise is affected by altitude, sex, training status, food intake and relative intensity. Whether sex‐ and altitude‐related differences in substrate utilisation persist during an ecologically valid maximal time trial in the fed state in trained males and females is unknown. Acute hypobaric hypoxia (∼2800 m) decreased 30 min time trial performance compared to normoxia (∼400 m) in both sexes, with a larger decrement in males. Females completed the time trials at a higher relative intensity than males in normoxia and hypoxia. Hypoxia reduced total metabolic rate primarily by decreasing estimated muscle glycogen oxidation, with no change in fat or blood glucose oxidation. The resulting changes in substrate partitioning were similar between sexes. Across altitudes, females derived relatively more energy from blood glucose despite similar muscle glycogen utilisation between sexes, whereas uncertain estimates suggested a lower contribution of fat in females than in males.