The Effects of a 6-Week Controlled, Hypocaloric Ketogenic Diet, With and Without Exogenous Ketone Salts, on Body Composition Responses

Alex Buga; Madison L Kackley; Christopher D Crabtree; Teryn N Sapper; Lauren Mccabe; Brandon Fell; Rich A LaFountain; Parker N Hyde; Emily R Martini; Jessica Bowman; Yue Pan; Debbie Scandling; Milene L Brownlow; Annalouise O'Connor; Orlando P Simonetti; William J Kraemer; Jeff S Volek

doi:10.3389/fnut.2021.618520

The Effects of a 6-Week Controlled, Hypocaloric Ketogenic Diet, With and Without Exogenous Ketone Salts, on Body Composition Responses

Front Nutr. 2021 Mar 24:8:618520. doi: 10.3389/fnut.2021.618520. eCollection 2021.

Authors

Alex Buga¹, Madison L Kackley¹, Christopher D Crabtree¹, Teryn N Sapper¹, Lauren Mccabe¹, Brandon Fell¹, Rich A LaFountain¹, Parker N Hyde¹, Emily R Martini¹, Jessica Bowman¹, Yue Pan^{2

3

4}, Debbie Scandling^{2

3

4}, Milene L Brownlow⁵, Annalouise O'Connor⁵, Orlando P Simonetti^{2

3

4}, William J Kraemer¹, Jeff S Volek¹

Affiliations

¹ Department of Human Sciences, The Ohio State University, Columbus, OH, United States.
² Department of Radiology, Davis Heart & Lung Research Institute, The Ohio State University, Columbus, OH, United States.
³ Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University, Columbus, OH, United States.
⁴ Department of Radiology, Wexner Medical Center, The Ohio State University, Columbus, OH, United States.
⁵ Research and Development Department, Metagenics, Inc., Aliso Viejo, CA, United States.

Abstract

Background: Ketogenic diets (KDs) that elevate beta-hydroxybutyrate (BHB) promote weight and fat loss. Exogenous ketones, such as ketone salts (KS), also elevate BHB concentrations with the potential to protect against muscle loss during caloric restriction. Whether augmenting ketosis with KS impacts body composition responses to a well-formulated KD remains unknown. Purpose: To explore the effects of energy-matched, hypocaloric KD feeding (<50 g carbohydrates/day; 1.5 g/kg/day protein), with and without the inclusion of KS, on weight loss and body composition responses. Methods: Overweight and obese adults were provided a precisely defined hypocaloric KD (~75% of energy expenditure) for 6 weeks. In a double-blind manner, subjects were randomly assigned to receive ~24 g/day of a racemic BHB-salt (KD + KS; n = 12) or placebo (KD + PL; n = 13). A matched comparison group (n = 12) was separately assigned to an isoenergetic/isonitrogenous low-fat diet (LFD). Body composition parameters were assessed by dual x-ray absorptiometry and magnetic resonance imaging. Results: The KD induced nutritional ketosis (>1.0 mM capillary BHB) throughout the study (p < 0.001), with higher fasting concentrations observed in KD + KS than KD + PL for the first 2 weeks (p < 0.05). There were decreases in body mass, whole body fat and lean mass, mid-thigh muscle cross-sectional area, and both visceral and subcutaneous adipose tissues (p < 0.001), but no group differences between the two KDs or with the LFD. Urine nitrogen excretion was significantly higher in KD + PL than LFD (p < 0.01) and trended higher in KD + PL compared to KD + KS (p = 0.076), whereas the nitrogen excretion during KD + KS was similar to LFD (p > 0.05). Conclusion: Energy-matched hypocaloric ketogenic diets favorably affected body composition but were not further impacted by administration of an exogenous BHB-salt that augmented ketosis. The trend for less nitrogen loss with the BHB-salt, if manifested over a longer period of time, may contribute to preserved lean mass.

Keywords: advanced imaging; body composition; exogenous ketones; ketogenic diet; obesity.