Carbohydrate and Fat Oxidation in Muscle Assessed with Exercise Calorimetry in 6465 Subjects

Background/Objectives: Exercise calorimetry provides a means to quantify the relative contributions of lipid and carbohydrate (CHO) oxidation across a range of exercise intensities. Although lipid oxidation capacity has been widely studied—particularly in relation to exercise prescription for individuals with obesity—the factors governing CHO oxidation during exercise are less clearly defined. This study therefore aimed to investigate, within a large single-center cohort, not only the established determinants of maximal lipid oxidation (LIPOXmax) but also those influencing CHO oxidation. Methods: Exercise calorimetry was performed in a cohort of 6465 individuals (4561 women and 1904 men; mean age 46.5 years; mean BMI 33.6 kg/m2). Two principal physiological indices were derived: LIPOXmax, defined as the exercise intensity eliciting maximal rates of fat oxidation, and the carbohydrate cost of the watt (CCW), defined as the slope characterizing the relationship between CHO oxidation and power output. Results: LIPOXmax showed positive associations with lean and muscle mass, and negative associations with fat mass and age, supporting the notion that greater muscle mass enhances the capacity for fat oxidation. Although men demonstrated higher absolute maximal fat oxidation rates, adjustment for body composition revealed that women exhibited relatively higher lipid oxidation (+30%, p < 0.001), occurring at a greater percentage of V˙O2max (+9.2%, p < 0.001). Furthermore, the carbohydrate cost of the watt was significantly elevated in women (+17.8% compared with men). CCW was positively correlated with BMI, fat mass, and age, and negatively correlated with muscle mass, LIPOXmax, and the crossover point—that is, the exercise intensity at which CHO becomes the predominant substrate. Discussion and Conclusions: Individuals with higher adiposity exhibited a greater reliance on carbohydrate oxidation, whereas leaner individuals preferentially oxidized lipids at comparable exercise intensities. These observations reinforce the reciprocal interplay between lipid and carbohydrate metabolism during exercise and highlight the substantial influence of body composition, age, and sex. Notably, this study provides the first comprehensive characterization of the determinants of CHO oxidation during exercise, identifying sex, age, and adiposity as major contributing factors. This underexplored facet of metabolic flexibility may hold practical relevance in clinical contexts such as obesity or susceptibility to exercise-induced hypoglycemia.