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Purpose:  Ketone bodies are energy substrates produced by the liver during prolonged fasting or low-carbohydrate diet. The ingestion of a ketone ester (KE) rapidly increases blood ketone levels independent of nutritional status. KE has recently been shown to improve exercise performance, but whether it can also promote post-exercise muscle protein or glycogen synthesis is unknown.   Methods:  Eight healthy trained males participated in a randomized double-blind placebo-controlled crossover study. In each session, subjects undertook a bout of intense one-leg glycogen-depleting exercise followed by a 5-h recovery period during which they ingested a protein/carbohydrate mixture. Additionally, subjects ingested a ketone ester (KE) or an isocaloric placebo (PL).   Results:  KE intake did not affect muscle glycogen resynthesis, but more rapidly lowered post-exercise AMPK phosphorylation and resulted in higher mTORC1 activation, as evidenced by the higher phosphorylation of its main downstream targets S6K1 and 4E-BP1. As enhanced mTORC1 activation following KE suggests higher protein synthesis rates, we used myogenic C 2 C 12  cells to further confirm that ketone bodies increase both leucine-mediated mTORC1 activation and protein synthesis in muscle cells.   Conclusion:  Our results indicate that adding KE to a standard post-exercise recovery beverage enhances the post-exercise activation of mTORC1 but does not affect muscle glycogen resynthesis in young healthy volunteers.  In vitro , we confirmed that ketone bodies potentiate the increase in mTORC1 activation and protein synthesis in leucine-stimulated myotubes. Whether, chronic oral KE intake during recovery from exercise can facilitate training-induced muscular adaptation and remodeling need to be further investigated.

Intake of a Ketone Ester Drink during Recovery from Exercise Promotes mTORC1 Signaling but Not Glycogen Resynthesis in Human Muscle