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

Background & aims: Oral ketone supplements may mimic the beneficial effects of endogenous ketones on energy metabolism as b-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.Methods: Eight healthy young adults (4 women, 4 men, age 24 +/- 3 years, BMI 24.3 +/- 3.1 kg/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 38.7 g/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.Results: 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 +/- 54 kcal/d vs. ISO, p < 0.05) and SEE (+201 +/- 90 kcal/d vs. ISO, p < 0.05). CHO oxidation was slightly decreased with EXO compared to ISO (-48 +/- 27 g/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).Conclusion: 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.Clinical trial registration: NCT04490226 https://clinicaltrials.gov/.(c) 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.