How Ketone Bodies Fuel Muscle Adaptation

 Instructing at the University of South Florida, Dominic D’Agostino is a professor who pursues basic science research and clinical applications of ketone ester supplementation, ketone salts and related ketone technologies. A particular area of interest for Dominic D’Agostino is muscle function and its pivotal role in augmenting performance and overall metabolic health. When a body goes into ketogenesis under carb-restricted dietary conditions, ketone bodies such as beta-hydroxybutyrate (BHB), acetoacetate (AcAc), and acetone are generated by the liver and provide a energetic reserve and important tissue signaling functions.

During exercise, the muscles no longer primarily rely on glycogen (high intensity workout) or lipids and muscle protein amino acids (low intensity workout) for generating the fuel adenosine triphosphate (ATP). Rather, ketone bodies are gradually employed by working muscles as fuel, with the capacity to oxidize the ketone bodies for energy increasing as muscle is trained. Part of being in a keto-adapted state is the increases levels of ketogenesis, ketone transport and tissue ketone utilization (ketolysis).

Beyond this muscle-fueling purpose, ketone bodies serve as signaling molecules for regulating the body’s gene expression and adaptive responses to energetic stress and exercise intervention. One study demonstrated that ketone BHB offers a shield against oxidative stress. It prevents the accumulation of intramuscular fat and decreases muscle wasting, while boosting oxidative metabolism as one ages. In tandem with this, BHB was shown to upregulate the genes associated with muscle atrophy and reduce anabolic gene expression. In this context the elevation of ketones helps to spare energy reserves. Ultimately, it is shown that the ketogenic diet has different effects on skeletal muscle that are partially explained by muscle fiber type, while the ketogenic diet can lead to a change in the fiber type ratio in the muscle itself. While currently the data is contradictory on the ketogenic diet’s benefits and adverse effects on muscle tissue, there is still room for discovery to be made in how the ketogenic diet impacts muscle metabolism in states outside of prolonged fasting and starvation. Based upon what we know about the anti-catabolic effects of ketones, and their multifunctional role during starvation, the benefits of being in ketosis appear to have the greatest effect during metabolic stress associated with disease states and exercise-induced stress. In this context the ketone-induced effects are protective and may confer a longevity advantage when it comes to longevity and long term preservation of muscle structure and function.