Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype?

Sports Medicine, Jul 2016

Elite athletes and coaches are in a constant search for training methods and nutritional strategies to support training and recovery efforts that may ultimately maximize athletes’ performance. Recently, there has been a re-emerging interest in the role of ketone bodies in exercise metabolism, with considerable media speculation about ketone body supplements being routinely used by professional cyclists. Ketone bodies can serve as an important energy substrate under certain conditions, such as starvation, and can modulate carbohydrate and lipid metabolism. Dietary strategies to increase endogenous ketone body availability (i.e., a ketogenic diet) require a diet high in lipids and low in carbohydrates for ~4 days to induce nutritional ketosis. However, a high fat, low carbohydrate ketogenic diet may impair exercise performance via reducing the capacity to utilize carbohydrate, which forms a key fuel source for skeletal muscle during intense endurance-type exercise. Recently, ketone body supplements (ketone salts and esters) have emerged and may be used to rapidly increase ketone body availability, without the need to first adapt to a ketogenic diet. However, the extent to which ketone bodies regulate skeletal muscle bioenergetics and substrate metabolism during prolonged endurance-type exercise of varying intensity and duration remains unknown. Therefore, at present there are no data available to suggest that ingestion of ketone bodies during exercise improves athletes’ performance under conditions where evidence-based nutritional strategies are applied appropriately.

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Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype?

Sports Med Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype? Philippe J. M. Pinckaers 0 1 2 Tyler A. Churchward-Venne 0 1 2 David Bailey 0 1 2 Luc J. C. van Loon 0 1 2 0 BMC Racing Team , Eke , Belgium 1 NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre ? , P.O. Box 616, 6200 MD Maastricht , The Netherlands 2 & Luc J. C. van Loon Elite athletes and coaches are in a constant search for training methods and nutritional strategies to support training and recovery efforts that may ultimately maximize athletes' performance. Recently, there has been a re-emerging interest in the role of ketone bodies in exercise metabolism, with considerable media speculation about ketone body supplements being routinely used by professional cyclists. Ketone bodies can serve as an important energy substrate under certain conditions, such as starvation, and can modulate carbohydrate and lipid metabolism. Dietary strategies to increase endogenous ketone body availability (i.e., a ketogenic diet) require a diet high in lipids and low in carbohydrates for *4 days to induce nutritional ketosis. However, a high fat, low carbohydrate ketogenic diet may impair exercise performance via reducing the capacity to utilize carbohydrate, which forms a key fuel source for skeletal muscle during intense endurance-type exercise. Recently, ketone body supplements (ketone salts and esters) have emerged and may be used to rapidly increase ketone body availability, without the need to first adapt to a ketogenic diet. However, the extent to which ketone bodies regulate skeletal muscle bioenergetics and substrate metabolism during prolonged endurance-type exercise of varying intensity and duration remains unknown. Therefore, at present there are no data available to suggest that ingestion of ketone bodies during exercise improves athletes' performance under conditions where evidence-based nutritional strategies are applied appropriately. 1 Introduction Nutrients consumed before and during exercise training can support optimal performance by delaying the onset of fatigue and assisting in the recovery process by replenishing endogenous substrates stores. Particularly for endurance-type sports characterized by high rates, and absolute levels of energy expenditure, appropriate nutrient intake is essential to fuel exercise, delay the deterioration in performance, and promote post-exercise recovery [1–5]. For endurance-type sports, research has focused on improving carbohydrate availability to better meet the anticipated fuel demands of the competition [6]. However, alternative fueling strategies based on adaptation to a highfat carbohydrate-restricted diet increase fat oxidation during exercise and, as such, may help to spare the body’s limited glycogen stores [7]. Although the focus of fat-based fueling strategies has been to enhance the capacity for fat oxidation during exercise, extreme carbohydrate restriction (e.g., \50 g/day) [8] also increases the production of ketone bodies, which may provide an additional energy substrate for the brain and skeletal muscle tissue [9, 10]. Recently, the ingestion of ketone body supplements has emerged as an alternative strategy to induce hyperketonemia [11], with considerable media speculation about ketone body supplements being used by professional cyclists [12]. This article will discuss what is currently known regarding ketone bodies within the context of exercise metabolism and performance, with an emphasis on the proposed use of ketone body supplements to improve exercise performance. 2 What are Ketone Bodies? Ketone bodies are lipid-derived organic compounds that can serve as a circulating energy source for tissues during starvation/fasting or prolonged exercise [13]. Under physiological conditions in which ample carbohydrate is available, or after an overnight fast, circulating ketone body concentrations are relatively low (*0.1–0.5 mmol/L) [14, 15]. However, under conditions of limited carbohydrate availability such as starvation (i.e., depletion of muscle and liver glycogen stores), fatty acid mobilization from adipose tissue is increased as a means to supply energy. Under these circumstances, some of the acetylCoA derived from fatty acids is converted to ketone bodies via hepatic mitochondria (up to *150 g/day) [16, 17]. The ketone body acetoacetate (AcAc) can subsequently be enzymatically converted to b-hydroxybutyrate (b-OHB) or spontaneously degraded to acetone which is less abundant [13]. For clarification, although the term ‘‘ketone bodies’’ refers to the compounds AcAc, b-OHB, and acetone which are derived from acetyl-CoA, only AcAc and acetone are actual ‘‘ketones’’ containing a carbonyl group with two hydrocarbon atoms. b-OHB is a ketone body, but is technically not a ketone since one of its hydrocarbon atoms is replaced by a hydroxyl group [18]. While the majority of acetone is secreted through urine and lost (...truncated)


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Philippe J. M. Pinckaers, Tyler A. Churchward-Venne, David Bailey, Luc J. C. van Loon. Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype?, Sports Medicine, 2016, pp. 383-391, Volume 47, Issue 3, DOI: 10.1007/s40279-016-0577-y