Impact of one-day fasting, ketogenic diet or exogenous ketones on control of energy balance in healthy participants

Abstract

Oral ketone supplements may mimic the beneficial effects of endogenous ketones on energy metabolism as β-hydroxybutyrate has been proposed to increase energy expenditure and improve body weight regulation. Therefore, our objective was to compare the effects of a one-day isocaloric ketogenic diet, fasting and supplementation with ketone salts on energy expenditure and appetite perception. Eight healthy young adults (4 women, 4 men, age 24±3 years, BMI 24.3±3.1kg/m2) participated in a randomized cross-over trial with four 24 h-interventions in a whole room indirect calorimeter at a physical activity level of 1.65: (i) total fasting (FAST), (ii) isocaloric ketogenic diet (3.1% energy from carbohydrates (CHO), KETO), (iii) isocaloric control diet (47.4% energy from CHO, ISO), and (iv) ISO supplemented with 38.7g/d ketone salts (exogenous ketones, EXO). Effects on serum ketone levels (15 h-iAUC), energy metabolism (total energy expenditure, TEE; sleeping energy expenditure, SEE; macronutrient oxidation) and subjective appetite were measured. Compared to ISO, ketone levels were considerably higher with FAST and KETO and little higher with EXO (all p>0.05). Total and sleeping energy expenditure did not differ between ISO, FAST and EXO whereas KETO increased TEE (+110±54kcal/d vs. ISO, p<0.05) and SEE (+201±90kcal/d vs. ISO, p<0.05). CHO oxidation was slightly decreased with EXO compared to ISO (-48±27g/d, p<0.05) resulting in a positive CHO balance (p<0.05). No differences between the interventions were found for subjective appetite ratings (all p>0.05). A 24 h-ketogenic diet may contribute to maintain a neutral energy balance by increasing energy expenditure. Exogenous ketones in addition to an isocaloric diet did not improve regulation of energy balance. NCT04490226 https://clinicaltrials.gov/.