Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation

Abstract

Optimising training and performance through nutrition strategies is central to supporting elite sportspeople, much of which has focused on manipulating the relative intake of carbohydrate and fat and their contributions as fuels for energy provision. The ketone bodies, namely acetoacetate, acetone and β-hydroxybutyrate (βHB), are produced in the liver during conditions of reduced carbohydrate availability and serve as an alternative fuel source for peripheral tissues including brain, heart and skeletal muscle. Ketone bodies are oxidised as a fuel source during exercise, are markedly elevated during the post-exercise recovery period, and the ability to utilise ketone bodies is higher in exercise-trained skeletal muscle. The metabolic actions of ketone bodies can alter fuel selection through attenuating glucose utilisation in peripheral tissues, anti-lipolytic effects on adipose tissue, and attenuation of proteolysis in skeletal muscle. Moreover, ketone bodies can act as signalling metabolites, with βHB acting as an inhibitor of histone deacetylases, an important regulator of the adaptive response to exercise in skeletal muscle. Recent development of ketone esters facilitates acute ingestion of βHB that results in nutritional ketosis without necessitating restrictive dietary practices. Initial reports suggest this strategy alters the metabolic response to exercise and improves exercise performance, while other lines of evidence suggest roles in recovery from exercise. The present review focuses on the physiology of ketone bodies during and after exercise and in response to training, with specific interest in exploring the physiological basis for exogenous ketone supplementation and potential benefits for performance and recovery in athletes.

Metabolite Concentration Changes in Humans After a Bout of Exercise: a Systematic Review of Exercise Metabolomics Studies

“…Ketone bodies are "energy metabolites" synthesized from acetyl-CoA or ketogenic amino acids such as leucine in the liver. Ketone bodies are used in particular in brain and muscle when carbohydrates are limited, e.g., during fasting or prolonged exercise [54].…”

Metabolic and molecular framework for the enhancement of endurance by intermittent food deprivation

“…Competition for limited food sources has been a driving force for evolution, with selection for individuals capable of high levels of physical performance under conditions of intermittent food deprivation (IF). In response to controlled energy restriction for more than 12 to 16 h and/or extended exercise, a major cellular fuel source switches from glucose to fats as liver glycogen stores are depleted, and fatty acids are metabolized to the ketones 3b-hydroxybutyrate (BHB) and acetoacetate (4)(5)(6). This switch to fatty acids as a fuel source manifests as a reduction in the respiratory exchange ratio (RER; ratio of CO 2 produced to O 2 consumed).…”

Insulin, glucose and beta-hydroxybutyrate responses to a medium-chain triglyceride-based sports supplement: A pilot study

“…In the case of supplements such as PF, the goal is to provide a readily oxidisable calorie source that does not negatively affect the athlete's underlying physiology. As ketones are actively transported into the exercising muscle to support aerobic work, 11 and the enzymes of ketolysis are upregulated by endurance exercise, 39 it is likely that PF can provide a calorie source to support longer endurance efforts in the low-carb athlete without ever causing unnecessary deviations in blood glucose or BHB.…”

“…Other factors such as the hepatic NAD+/NADH ratio will determine the relative abundances of BHB and acetoacetate (AcAc, which can also be decarboxylated to acetone), 38 the latter of which is less routinely measured in the blood outside of the laboratory setting. Importantly, as support increases for the use of performance-enhancing supplements that increase ketone levels exogenously, 39 it is worth noting that the pure elevation of blood BHB levels is not the goal of supplementation -any additional ketone bodies must also be readily available as an efficient metabolic substrate. In the case of supplements such as PF, the goal is to provide a readily oxidisable calorie source that does not negatively affect the athlete's underlying physiology.…”