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

Mark Evans, Tyler S. McClure, Andrew P. Koutnik & Brendan Egan

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.

 Conclusions

There is little doubt that AcAc and R-βHB have wide-ranging metabolic and molecular effects on organs such as the brain, heart, and skeletal muscle, and that the commercial availability of ingestible EKS has led to the recent interest in KBs in athletic contexts, and resurgent interest in KBs in therapeutic contexts. Despite the mechanistic bases for potential beneficial effects of EKS, the evidence at present is overwhelmingly against EKS being an ergogenic aid for athletic performance. Yet questions remain about whether there are optimal dosing strategies (especially using ketone esters), specific athletic populations, or specific exercise challenges in which acute ingestion of EKS may provide a performance benefit. Additionally, future research should investigate whether there are other athletic contexts where EKS are efficacious given the positive, albeit preliminary, data from studies on overreaching, acute hypoxic exposure, and traumatic brain injury.