Proceedings of The Physiological Society

Physiology 2015 (Cardiff, UK) (2015) Proc Physiol Soc 34, PC217

Poster Communications

Nutritional ketosis increases intramuscular fat oxidation during exercise

P. J. Cox1, K. Willerton1, T. Kirk1, S. McLure1, B. J. Stubbs1, D. Dearlove1, K. Clarke1

1. Physiology Anatomy and Genetics, University of Oxford, Oxford, Oxfordshire, United Kingdom.

Introduction: Human metabolic responses to energy crisis are hardwired to favour ketosis[1]. Ketone bodies act as substrates and signals to conserve glucose stores by altering substrate competition for respiration[2]. Endurance exercise performance may be constrained by the same metabolic considerations pertinent to starvation, albeit occurring on an accelerated scale[3]. We investigated whether acute nutritional ketosis could mimic starvation physiology and increase fat oxidation in muscle during exercise, without restricting carbohydrate intake. Methods: After providing informed consent, and after an overnight fast, 7 highly trained male volunteers (age 29.7 y, VO2 max 4.8 L/min) drank 1.14 g/kg BW of ketone ester (KE) and dextrose, or isocaloric carbohydrates alone (CHO), in a randomised, blinded, crossover design. After 30 min, athletes performed 2 h of bicycle exercise at a fixed intensity of 70% Wmax. Blood samples were obtained via an intravenous catheter at regular intervals during exercise, and assayed for β-hydroxybutyrate (BHB), lactate, glucose, insulin, cortisol and free fatty acids (FFA). Indirect calorimetry (Cortex, Metalyser) was performed at identical times to quantify respiratory quotient (RQ) and VO2. Muscle biopsies of the vastus lateralis were obtained before and after exercise. Muscle samples were cryosectioned, stained for intramuscular triacylglycerol (IMTAG), glycogen, and fibre type, and quantified using confocal microscopy. A 2-way repeated measures ANOVA with post-Hoc Tukey correction was used to determine statistical significance (considered as p<0.05). Results: Blood BHB rose from 0.1 to 2.2 mM (p<0.01) following KE ingestion, reaching 3.2 mM after 2 h of exercise. BHB concentration remained unchanged on CHO throughout exercise (0.1 ± 0.05 mM, p<0.01 vs. KE). Blood lactate concentrations were significantly lower on KE vs. CHO (p<0.05). FFA were identical for the first 60 min of exercise but increased on CHO vs. KE by 2 h (p<0.05). No differences in cortisol, blood glucose or insulin were observed between CHO and KE. Mean exercise RQ was significantly lower on KE vs. CHO (0.89 ± 0.02 vs. 0.97 ± 0.02, p<0.05). IMTAG and glycogen were not significantly different between conditions at baseline, however IMTAG fell by 24% on KE vs. 1% on CHO (p<0.01) after 2 h of exercise. There was a direct relationship between IMTAG oxidation and % of slow type muscle fibre content (r = 0.65, p<0.05) on KE. Conclusion: Nutritional ketosis is able to harness the innate metabolic response to starvation, increasing IMTAG oxidation 20-fold during exercise in the presence of normal muscle glycogen, co-ingested carbohydrate and elevated insulin. These findings may have important implications not just for endurance exercise performance, but for conditions of dysregulated fatty acid oxidation such as insulin resistance.

Where applicable, experiments conform with Society ethical requirements