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A Ketone Ester Drink Increases Postexercise Muscle Glycogen Synthesis in Humans

HOLDSWORTH, DAVID A.1; COX, PETER J.1; KIRK, TOM1; STRADLING, HUW1; IMPEY, SAMUEL G.2; CLARKE, KIERAN1

Medicine & Science in Sports & Exercise: September 2017 - Volume 49 - Issue 9 - p 1789–1795
doi: 10.1249/MSS.0000000000001292
Basic Sciences

Introduction: Physical endurance can be limited by muscle glycogen stores, in that glycogen depletion markedly reduces external work. During carbohydrate restriction, the liver synthesizes the ketone bodies, D-β-hydroxybutyrate, and acetoacetate from fatty acids. In animals and in the presence of glucose, D-β-hydroxybutyrate promotes insulin secretion and increases glycogen synthesis. Here we determined whether a dietary ketone ester, combined with plentiful glucose, can increase postexercise glycogen synthesis in human skeletal muscle.

Methods: After an interval-based glycogen depletion exercise protocol, 12 well-trained male athletes completed a randomized, three-arm, blinded crossover recovery study that consisted of consumption of either a taste-matched, zero-calorie control or a ketone monoester drink, followed by a 10-mM glucose clamp or saline infusion for 2 h. The three postexercise conditions were control drink then saline infusion, control drink then hyperglycemic clamp, or ketone ester drink then hyperglycemic clamp. Skeletal muscle glycogen content was determined in muscle biopsies of vastus lateralis taken before and after the 2-h clamps.

Results: The ketone ester drink increased blood D-β-hydroxybutyrate concentrations to a maximum of 5.3 versus 0.7 mM for the control drink (P < 0.0001). During the 2-h glucose clamps, insulin levels were twofold higher (31 vs 16 mU·L−1, P < 0.01) and glucose uptake 32% faster (1.66 vs 1.26 g·kg−1, P < 0.001). The ketone drink increased by 61 g, the total glucose infused for 2 h, from 197 to 258 g, and muscle glycogen was 50% higher (246 vs 164 mmol glycosyl units per kilogram dry weight, P < 0.05) than after the control drink.

Conclusion: In the presence of constant high glucose concentrations, a ketone ester drink increased endogenous insulin levels, glucose uptake, and muscle glycogen synthesis.

1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UNITED KINGDOM; and 2Research Institute for Sport and Exercise Sciences, Liverpool John Moore's University, Liverpool, UNITED KINGDOM

Address for correspondence: David A. Holdsworth, B.M., B.C.h., Department of Physiology, Anatomy and Genetics, Sherrington Building, University of Oxford, Parks Road, Oxford OX1 3PT, United Kingdom; E-mail: david.holdsworth@dpag.ox.ac.uk.

Submitted for publication January 2017.

Accepted for publication March 2017.

This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

© 2017 American College of Sports Medicine