A Ketone Ester Drink Increases Postexercise Muscle Glycogen Synthesis in Humans

INTRODUCTION: Physical endurance can be limited by muscle glycogen stores, in that glycogen depletion markedly reduces external work. During carbohydrate restriction, the liver synthesises 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 post-exercise glycogen synthesis in human skeletal muscle. METHODS: Following an interval-based glycogen-depletion exercise protocol, 12 well-trained male athletes completed a randomized, 3-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 two hours. The three post-exercise 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 two-hour clamps. RESULTS: The ketone ester drink increased blood D-β-hydroxybutyrate concentrations to a maximum of 5.3 vs. 0.7 mM for the control drink (p < 0.0001). During the two-hour glucose clamps, insulin levels were two-fold higher (31 vs. 16 mU/l, p < 0.01) and glucose uptake 32% faster (1.66 vs. 1.26 g/kg, p<0.001). The ketone drink increased by 61 g the total glucose infused over 2 h, from 197 g to 258 g, and muscle glycogen was 50% higher (246 vs.164 mmoles glycosyl units/kg 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.