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

Buga, Alex, Kackley, Madison L., Crabtree, Christopher D., Sapper, Teryn N., Mccabe, Lauren, Fell, Brandon, LaFountain, Rich A., Hyde, Parker N., Martini, Emily R., Bowman, Jessica, Pan, Yue, Scandling, Debbie, Brownlow, Milene L., O'Connor, Annalouise, Simonetti, Orlando P., Kraemer, William J., Volek, Jeff S.·2021·Frontiers in Nutrition
DOI 10.3389/fnut.2021.618520PMC PMC8044842
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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.

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Figure 1 Fasting capillary BHB responses to a ketogenic diet plus ketone salt (KD + KS) vs. placebo (KD + PL). Values at each week represent mean (± SEM) of 7-day BHB values. Primary Statistics: 2 (group) × 7 (time point) ANOVA followed by secondary 3×7 ANOVA that included a third low-fat diet (LFD) group (dashed line). Time effects: ***p < 0.001 from WK0 for primary statistics only. Interaction effects: distinct letters at each time point denote between group differences (p < 0.05).
Figure 1 Fasting capillary BHB responses to a ketogenic diet plus ketone salt (KD + KS) vs. placebo (KD + PL). Values at each week represent mean (± SEM) of 7-day BHB values. Primary Statistics: 2 (group) × 7 (time point) ANOVA followed by secondary 3×7 ANOVA that included a third low-fat diet (LFD) group (dashed line). Time effects: ***p < 0.001 from WK0 for primary statistics only. Interaction effects: distinct letters at each time point denote between group differences (p < 0.05).CC BY · PubMed Central
Figure 2 Diet effects on body weight and weight loss composition. Solid lines are primary KD outcomes; dashed lines show LFD for comparison. Results are presented as absolute change (± SEM) from baseline. Panels: (A) scale body weight, (B) DXA whole-body fat and (C) DXA whole-body lean mass. Statistics: 2 (group) × 4 (time) ANOVA. Time effects: ***p < 0.001 from WK0. Body weight and fat mass decreased steadily and significantly between each timepoint after WK0 (p < 0.001). Lean mass decreased significantly by WK2 (p < 0.001), followed by no other significant reductions thereafter. With LFD included in the secondary 3 (group) × 4 (time) ANOVA analysis – No major changes were detected besides a higher FFM WK2 value compared to WK6 (p < 0.05).
Figure 2 Diet effects on body weight and weight loss composition. Solid lines are primary KD outcomes; dashed lines show LFD for comparison. Results are presented as absolute change (± SEM) from baseline. Panels: (A) scale body weight, (B) DXA whole-body fat and (C) DXA whole-body lean mass. Statistics: 2 (group) × 4 (time) ANOVA. Time effects: ***p < 0.001 from WK0. Body weight and fat mass decreased steadily and significantly between each timepoint after WK0 (p < 0.001). Lean mass decreased significantly by WK2 (p < 0.001), followed by no other significant reductions thereafter. With LFD included in the secondary 3 (group) × 4 (time) ANOVA analysis – No major changes were detected besides a higher FFM WK2 value compared to WK6 (p < 0.05).CC BY · PubMed Central
Figure 3 Diet effects on urinary nitrogen and nitrogen balance. Solid lines are primary KD outcomes; dashed lines show LFD for comparison. Panels: (A) 24 h urine urea nitrogen standardized per gram of creatinine; (B) nitrogen balance derived from validated formula. Primary analysis: 2 (group) × 4 (time) ANOVA. WK2 UUN was significantly higher than WK4 (p < 0.05) and WK6 (p < 0.01). Group effects show on average 8% lower UUN during KD + KS compared to KD + PL (p = 0.082). With LFD included in the secondary 3 (group) × 4 (time) ANOVA analysis – Time effects: *p < 0.05 from WK0. Between-group effects: KD + PL had significantly higher UUN than LFD (p = 0.004) and trended higher than KD + KS (p = 0.076).
Figure 3 Diet effects on urinary nitrogen and nitrogen balance. Solid lines are primary KD outcomes; dashed lines show LFD for comparison. Panels: (A) 24 h urine urea nitrogen standardized per gram of creatinine; (B) nitrogen balance derived from validated formula. Primary analysis: 2 (group) × 4 (time) ANOVA. WK2 UUN was significantly higher than WK4 (p < 0.05) and WK6 (p < 0.01). Group effects show on average 8% lower UUN during KD + KS compared to KD + PL (p = 0.082). With LFD included in the secondary 3 (group) × 4 (time) ANOVA analysis – Time effects: *p < 0.05 from WK0. Between-group effects: KD + PL had significantly higher UUN than LFD (p = 0.004) and trended higher than KD + KS (p = 0.076).CC BY · PubMed Central
Figure 4 Change in normalized plasma 3-methylhistidine relative to baseline. Values were subtracted from WK0 plasma 3MH concentrations and analyzed for significant covariance effects. Primary statistic: 2 (group) × 4 (time) ANOVA with normalized baseline held as covariate. No significant effects were detected between KD groups. With LFD included in the secondary 3 (group) × 4 (time) ANOVA – Time effect: *p < 0.05; **p < 0.01 from WK0.
Figure 4 Change in normalized plasma 3-methylhistidine relative to baseline. Values were subtracted from WK0 plasma 3MH concentrations and analyzed for significant covariance effects. Primary statistic: 2 (group) × 4 (time) ANOVA with normalized baseline held as covariate. No significant effects were detected between KD groups. With LFD included in the secondary 3 (group) × 4 (time) ANOVA – Time effect: *p < 0.05; **p < 0.01 from WK0.CC BY · PubMed Central

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Citations

Cites

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Metadata

Authors
Buga, A., Kackley, M. L., Crabtree, C. D., Sapper, T. N., Mccabe, L., Fell, B., LaFountain, R. A., Hyde, P. N., Martini, E. R., Bowman, J., Pan, Y., Scandling, D., Brownlow, M. L., O'Connor, A., Simonetti, O. P., Kraemer, W. J., & Volek, J. S.
Venue
Frontiers in Nutrition
Publisher
Frontiers Media SA
Published
2021-03-24
Volume
8
ISSN
2296-861X
DOI
10.3389/fnut.2021.618520
PMC
PMC8044842
Cited by
38
References
10
Licence
creativecommons.org/licenses/by/4.0/ (vor)

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