β-Hydroxybutyrate Oxidation in Exercise Is Impaired by Low-Carbohydrate and High-Fat Availability

David J Dearlove; David Holdsworth; Tom Kirk; Leanne Hodson; Evelina Charidemou; Eline Kvalheim; Brianna Stubbs; Andrew Beevers; Julian L Griffin; Rhys Evans; Jeremy Robertson; Kieran Clarke; Pete J Cox

doi:10.3389/fmed.2021.721673

β-Hydroxybutyrate Oxidation in Exercise Is Impaired by Low-Carbohydrate and High-Fat Availability

Front Med (Lausanne). 2021 Nov 25:8:721673. doi: 10.3389/fmed.2021.721673. eCollection 2021.

Authors

Affiliations

¹ Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom.
² Oxford Centre for Diabetes, Endocrinology and Metabolism, Oxford NIHR Biomedical Research Centre, University of Oxford, Oxford, United Kingdom.
³ Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, MRC Human Nutrition Research, Cambridge, United Kingdom.
⁴ Department of Chemistry, University of Oxford, Oxford, United Kingdom.
⁵ Research and Development Department, Sterling Pharma Solutions Ltd., Cramlington, United Kingdom.

Abstract

Purpose: In this study, we determined ketone oxidation rates in athletes under metabolic conditions of high and low carbohydrate (CHO) and fat availability. Methods: Six healthy male athletes completed 1 h of bicycle ergometer exercise at 75% maximal power (WMax) on three occasions. Prior to exercise, participants consumed 573 mg·kg bw^-1 of a ketone ester (KE) containing a ¹³C label. To manipulate CHO availability, athletes undertook glycogen depleting exercise followed by isocaloric high-CHO or very-low-CHO diets. To manipulate fat availability, participants were given a continuous infusion of lipid during two visits. Using stable isotope methodology, β-hydroxybutyrate (βHB) oxidation rates were therefore investigated under the following metabolic conditions: (i) high CHO + normal fat (KE+CHO); (ii) high CHO + high fat KE+CHO+FAT); and (iii) low CHO + high fat (KE+FAT). Results: Pre-exercise intramuscular glycogen (IMGLY) was approximately halved in the KE+FAT vs. KE+CHO and KE+CHO+FAT conditions (both p < 0.05). Blood free fatty acids (FFA) and intramuscular long-chain acylcarnitines were significantly greater in the KE+FAT vs. other conditions and in the KE+CHO+FAT vs. KE+CHO conditions before exercise. Following ingestion of the ¹³C labeled KE, blood βHB levels increased to ≈4.5 mM before exercise in all conditions. βHB oxidation was modestly greater in the KE+CHO vs. KE+FAT conditions (mean diff. = 0.09 g·min^-1, p = 0.03; d = 0.3), tended to be greater in the KE+CHO+FAT vs. KE+FAT conditions (mean diff. = 0.07 g·min^-1; p = 0.1; d = 0.3) and were the same in the KE+CHO vs. KE+CHO+FAT conditions (p < 0.05; d < 0.1). A moderate positive correlation between pre-exercise IMGLY and βHB oxidation rates during exercise was present (p = 0.04; r = 0.5). Post-exercise intramuscular βHB abundance was markedly elevated in the KE+FAT vs. KE+CHO and KE+CHO+FAT conditions (both, p < 0.001; d = 2.3). Conclusion: βHB oxidation rates during exercise are modestly impaired by low CHO availability, independent of circulating βHB levels.

Keywords: exercise; exogenous ketosis; ketone; ketosis; oxidation.

Abstract

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