Females have better metabolic flexibility in different metabolically challenging stimuli

The first aim was to explore the difference in metabolic flexibility between sexes in response to changing exercise intensity under control conditions. The second aim was to evaluate metabolic flexibility between sexes in response to exercise intensity adding two different metabolically challenging stimuli (glycogen depletion and heat). Eleven males (22 ± 3 years, 176.2 ± 4 cm, 68.4 ± 4.9 kg, and 60.2 ± 4.1 mL/kg FFM/min) and nine females (22 ± 2 years, 166.7 ± 4.5 cm, 61.9 ± 2.9 kg, and 64.2 ± 5.6 mL/kg FFM/min) performed a maximal incremental exercise test (30 W every 3 min) on a cycle ergometer under three conditions: control (24 h high-carbohydrate diet followed by the incremental test), glycogen depletion (glycogen-depletion protocol followed by 24 h low-carbohydrate diet and then the incremental test), and heat (24 h high-carbohydrate diet followed by 30 min passive heating and then the incremental test in heat). In the last minute of each step, lactate was analysed, fat (FATox/FFM) and carbohydrate oxidation (CHox/FFM), and energy expenditure (EE/FFM) normalized to fat-free mass (FFM) was estimated by indirect calorimetry. Females presented a greater FATox/FFM as exercise intensity increases across conditions (control, glycogen depletion, and heat) (<i>p</i> = 0.006). In contrast, CHox/FFM was not significantly different between sexes at any specific intensity across conditions (<i>p</i> > 0.05). Consequently, EE/FFM was higher in females throughout the different intensities across conditions (<i>p</i> = 0.002). Finally, lactate concentration was not different between sexes at the same intensities across conditions (<i>p</i> = 0.87). In conclusion, females present a greater metabolic flexibility, due to the higher FATox/FFM throughout the different intensities, regardless of whether the test is performed in conditions emphasizing the oxidative pathway (glycogen depletion) or the glycolytic pathway (heat). Clinical trials: NCT05703100.