Nutritional Ketosis with Ketogenic Diets or Exogenous Ketones: Features, Convergence, and Divergence

Abstract

Athletes, clinicians, and practitioners are increasingly interested in the proposed performance and therapeutic benefits of nutritional ketosis (NK). NK is best operationally defined as a nutritionally induced metabolic state resulting in blood β-hydroxybutyrate concentrations of ≥0.5 mM. Most tissues readily metabolize ketone bodies (KBs), and KBs in turn regulate metabolism and signaling in both a systemic and tissue-specific manner. During fasting, starvation, or ketogenic diets, endogenous synthesis of KBs is amplified resulting in a state of NK. Orally administered exogenous ketone supplements rapidly elevate circulating KBs and produce a similar, but far from identical, metabolic state. NK results in a number of convergent features regardless of endogenous or exogenous induction; however, important differences also are observed. The implications of NK across health, disease, and performance is rapidly becoming more evident, thus acknowledging the convergent and divergent features of NK is critical for fully understanding the potential utility of this metabolic state.

Dose Response of a Novel Exogenous Ketone Supplement on Physiological, Perceptual, and Performance Parameters

“…Interest into the health, disease, and performance impact of exogenous ketone bodies has rapidly expanded due to the multifaceted physiologic and signaling properties ascribed to these metabolites (1,7,36). Various natural and synthetically derived forms currently exist with emergent evidence indicating convergent and divergent impacts across various physiologic and metabolic parameters (1).…”

“…Ketones bodies are metabolic end products of lipid metabolism traditionally produced during fasting/starvation, severe caloric restriction, or low carbohydrate diets (1). Endogenous ketone production is predominantly regulated via insulin and glucagon levels on adipose and hepatic tissue, respectively (2).…”

“…However, dietary restriction can be di cult for some to follow (1). Consequently, exogenous ketone bodies have been developed to circumvent traditional barrier to elevating circulating ketone bodies (1,3,4). Currently, available exogenous ketone bodies include medium chain triglycerides (MCT), betahydroxybutyrate (βHB)-salts and/or amino acids, and esters, all commercially available and generally recognized as safe (GRAS approved) by FDA.…”

Dose Response of a Novel Exogenous Ketone Supplement on Physiological, Perceptual and Performance Parameters

“…The 1,3 butanediol backbone enters hepatic circulation and is subsequently catabolized via alcohol and aldehyde dehydrogenases into βHB. Consequently, all exogenous ketone bodies result in subsequent elevations in circulating ketone body elevations, but with diverse kinetics, tolerance, and application impact [1,3,6,7]. Sport and/or athletic practitioners have been interested in exogenous ketone bodies dating back for almost a half-century when MCT's their potential metabolic and performance impact in isolation or combination with other exogenous nutrients under the hypothesis that providing additional and diverse metabolite availability may augment sport related performance outcomes [5].…”

“…Of interest were the ndings that βHB-salts+MCTs augmented and prolonged elevations in circulating βHB compared to βHB-salts alone, illustrating unique metabolic impact [3]. Additionally, this unique mixture lowers the acute mineral and MCT load, potentially mitigating gastrointestinal impact [1]. Consequently, our group explored the metabolic and performance impact of βHB-salts and MCTs on 5-km running in well trained runners and found that this was well tolerated, altered systemic metabolism, and augmented and attenuated 8/10 and 2/10 5k runner performance, respectively [25].…”