Nutritional Ketoacidosis During Incremental Exercise in Healthy Athletes.

David J Dearlove,Kieran Clarke,Pete J Cox,Olivia K Faull,Edward Rolls

doi:10.3389/fphys.2019.00290

Abstract

Purpose: Ketosis, achieved through ingestion of ketone esters, may influence endurance exercise capacity by altering substrate metabolism. However, the effects of ketone consumption on acid-base status and subsequent metabolic and respiratory compensations are poorly described.Methods: Twelve athletically trained individuals completed an incremental bicycle ergometer exercise test to exhaustion following the consumption of either a ketone ester [(R)-3-hydroxybutyrate-(R)-1,3-butanediol] or a taste-matched control drink (bitter flavoured water) in a blinded, cross-over study. Respiratory gases and arterialised blood gas samples were taken at rest and at regular intervals during exercise.Results: Ketone ester consumption increased blood D-β-hydroxybutyrate concentration from 0.2 to 3.7 mM/L (p < 0.01), causing significant falls versus control in blood pH to 7.37 and bicarbonate to 18.5 mM/L before exercise. To compensate for ketoacidosis, minute ventilation was modestly increased (p < 0.05) with non-linearity in the ventilatory response to exercise (ventilatory threshold) occurring at a 22 W lower workload (p < 0.05). Blood pH and bicarbonate concentrations were the same at maximal exercise intensities. There was no difference in exercise performance having consumed the ketone ester or control drink.Conclusion: Athletes compensated for the greater acid load caused by ketone ester ingestion by elevating minute ventilation and earlier hyperventilation during incremental exercise.

Highlights

Ketosis is our metabolic adaptation to starvation (Cahill, 1970)
Supplementing athletes with nutritional ketones mimics some of the advantageous aspects of starvation ketosis by reducing glycolysis and increasing fat oxidation in working skeletal muscle
The acidaemia resulting from prolonged starvation or nutritional ketosis is distinctly different to that observed in uncontrolled endogenous ketoacidosis, such as diabetic crisis, where ketone concentrations of ≥20 mM/L may cause blood pH to fall below 6.9 (Koul, 2009)

Summary

Introduction

Ketosis is our metabolic adaptation to starvation (Cahill, 1970). The production of the lipid-derived ketone bodies, D-β-hydroxybutyrate (D-βHB) and acetoacetate, prolongs survival during starvation by providing a supplementary oxidisable carbon source for nerve tissue, subsequently slowing the catabolism of finite glycogen and gluconeogenic skeletal muscle (Owen et al, 1967; Cahill, 1970). As with starvation, where serum ketone levels plateau at approximately 7.5 mM/L (Robinson and Williamson, 1980), high circulating concentrations of nutritional ketones causes a mild metabolic acidosis (ketoacidosis) (Stubbs et al, 2017). The acidaemia resulting from prolonged starvation or nutritional ketosis is distinctly different to that observed in uncontrolled endogenous ketoacidosis, such as diabetic crisis, where ketone concentrations of ≥20 mM/L may cause blood pH to fall below 6.9 (Koul, 2009)

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Conclusion