Impaired metabolic flexibility to fasting is associated with increased ad libitum energy intake in healthy adults

Abstract Objective We investigated how changes in 24‐h respiratory exchange ratio (RER) and substrate oxidation during fasting versus an energy balance condition influence subsequent ad libitum food intake. Methods Forty‐four healthy, weight‐stable volunteers (30 male and 14 female; mean [SD], age 39.3 [11.0] years; BMI 31.7 [8.3] kg/m 2 ) underwent 24‐h energy expenditure measurements in a respiratory chamber during energy balance (50% carbohydrate, 30% fat, and 20% protein) and 24‐h fasting. Immediately after each chamber stay, participants were allowed 24‐h ad libitum food intake from computerized vending machines. Results Twenty‐four‐hour RER decreased by 9.4% (95% CI: −10.4% to −8.5%; p < 0.0001) during fasting compared to energy balance, reflecting a decrease in carbohydrate oxidation (mean [SD], −2.6 [0.8] MJ/day; p < 0.0001) and an increase in lipid oxidation (2.3 [0.9] MJ/day; p < 0.0001). Changes in 24‐h RER and carbohydrate oxidation in response to fasting were correlated with the subsequent energy intake such that smaller decreases in fasting 24‐h RER and carbohydrate oxidation, but not lipid oxidation, were associated with greater energy intake after fasting ( r = 0.31, p = 0.04; r = 0.40, p = 0.007; and r = −0.27, p = 0.07, respectively). Conclusions Impaired metabolic flexibility to fasting, reflected by an inability to transition away from carbohydrate oxidation, is linked with increased energy intake.