Nutrition Notes

A New Application of Ketones – Muscle Regeneration

Without question, ketone bodies acetoacetate (AcAc) and β-hydroxybutyrate (βHB) are popular nutritional subjects. Researchers seem to be delving into the various health effects and nutritional applications of these compounds and their discoveries are exciting. In this blog, the attention will be focused on the anti-catabolic effects of ketones in human skeletal muscle. With sarcopenia being a rising health problem among the elderly, athletes continually seeking out better ways to repair and rebuild muscle, and the average adult seeking to maintain muscle mass, ketones may support yet another chief health concern among various populations.

Ketone bodies are naturally an alternative fuel source for the brain, heart, and skeletal muscle, being endogenously produced from fatty acids when the supply of glucose is limited. Starvation, low carb diets, and intense physical exercise are the most common causes for the body to turn toward ketone bodies for energy; however, researchers are discovering that even when glucose is available, ketones still may exert a positive influence on these tissues. Their use may not be limited that of an alternative fuel source, but rather, their presence may actually attenuate proteolysis in skeletal muscle.

Skeletal muscle has been shown to have a high affinity for ketone bodies and is able to metabolize a majority of the available ketone bodies in plasma while in a resting state. Under normal conditions, the availability of ketone bodies is low, forcing skeletal muscle to utilize glucose or free fatty acids; however, when the quantity is raised – either endogenously from dietary manipulation or extreme exercise, or via exogenous ketones – the potential for skeletal muscle to “bank in” on the benefits of ketones is also greater.

Athletes also have a greater ability to utilize ketone bodies. In animal studies, the activity of ketolytic enzymes was greatest in the skeletal muscle of animals that engaged in intense aerobic exercise training. Further, when compared to sedentary rats, the ketone body activity in type 2A skeletal muscle fibers was sixfold greater in animals that performed 12 weeks of treadmill running. Ketone body uptake by skeletal muscles also increases in direct proportion to the intensity of the exercise. Therefore, athletes have a unique advantage of using exogenous ketones to both fuel and maintain skeletal muscle.

So how do ketone bodies help rebuild and maintain skeletal muscle? One suggestion is that the presence of ketone bodies inhibits glycolysis and increases the conversion of glucose to glycogen. After exercise, metabolism shifts in skeletal muscle to resynthesize glycogen in preparation for the next workout; however, the presence of ketone bodies enhances this recovery. Not only do ketone bodies enhance the recovery of muscle glycogen, but they also limit proteolysis and support muscle protein synthesis, evidenced by the reduction in the oxidation of alanine and leucine during starvation or ketosis.

More recent studies are finding that the ketone body AcAc, specifically, accelerates muscle regeneration by regulating skeletal muscle satellite cell proliferation as well as inhibiting histone deacetylases, an important regulator of the adaptive response to exercise in skeletal muscle. Satellite cells are a type of adult stem cell found abundantly in skeletal muscle and are responsible for muscle cell regeneration after muscle damage. They are not only important for exercise recovery, but also for various muscle wasting conditions such as muscular dystrophy. In a rat study, the ketone body AcAc was able to stimulate skeletal muscle satellite cells and support their proliferation and differentiation. This activity was confirmed in a rat study, which found that treating muscular dystrophin-deficient mdx mice with AcAc significantly ameliorated muscular dystrophy as evidenced by an improvement in muscle integrity, recovered muscle strength, and enhanced exercise performance.

Ketone bodies, though a natural fuel source that the body most likely utilized often during eras when primal diets were customary, are still a relatively new phenomenon in research. However, as we continue to unravel their biological mysteries, the health applications are diverse and exciting. Their role in promoting and maintaining skeletal muscle is yet another discovery that could make the use of exogenous ketones beneficial for numerous individuals including athletes and those experiencing or at risk for various conditions of muscle degeneration.