Exogenous Ketone Supplements in Athletic Contexts: Past, Present, and Future

Abstract

The ketone bodies acetoacetate (AcAc) and β-hydroxybutyrate (βHB) have pleiotropic effects in multiple organs including brain, heart, and skeletal muscle by serving as an alternative substrate for energy provision, and by modulating inflammation, oxidative stress, catabolic processes, and gene expression. Of particular relevance to athletes are the metabolic actions of ketone bodies to alter substrate utilisation through attenuating glucose utilisation in peripheral tissues, anti-lipolytic effects on adipose tissue, and attenuation of proteolysis in skeletal muscle. There has been long-standing interest in the development of ingestible forms of ketone bodies that has recently resulted in the commercial availability of exogenous ketone supplements (EKS). These supplements in the form of ketone salts and ketone esters, in addition to ketogenic compounds such as 1,3-butanediol and medium chain triglycerides, facilitate an acute transient increase in circulating AcAc and βHB concentrations, which has been termed 'acute nutritional ketosis' or 'intermittent exogenous ketosis'. Some studies have suggested beneficial effects of EKS to endurance performance, recovery, and overreaching, although many studies have failed to observe benefits of acute nutritional ketosis on performance or recovery. The present review explores the rationale and historical development of EKS, the mechanistic basis for their proposed effects, both positive and negative, and evidence to date for their effects on exercise performance and recovery outcomes before concluding with a discussion of methodological considerations and future directions in this field.

Fig. 1

Factors influencing the time course and magnitude of transient changes in circulating concentrations of ketone bodies after acute ingestion of exogenous ketone supplements, and mechanisms of potential benefit and impairment of consequent effects in athletic contexts. ATP adenosine triphosphate, KB ketone bodies, MPB muscle protein breakdown, MPS muscle protein synthesis, mTORC mechanistic target of rapamycin complex, PDH pyruvate dehydrogenase