title: Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes.
abstract: Ketosis, the metabolic response to energy crisis, is a mechanism to sustain life by altering oxidative fuel selection. Often overlooked for its metabolic potential, ketosis is poorly understood outside of starvation or diabetic crisis. Thus, we studied the biochemical advantages of ketosis in humans using a ketone ester-based form of nutrition without the unwanted milieu of endogenous ketone body production by caloric or carbohydrate restriction. In five separate studies of 39 high-performance athletes, we show how this unique metabolic state improves physical endurance by altering fuel competition for oxidative respiration. Ketosis decreased muscle glycolysis and plasma lactate concentrations, while providing an alternative substrate for oxidative phosphorylation. Ketosis increased intramuscular triacylglycerol oxidation during exercise, even in the presence of normal muscle glycogen, co-ingested carbohydrate and elevated insulin. These findings may hold clues to greater human potential and a better understanding of fuel metabolism in health and disease.
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK; Department of Cardiovascular Medicine, University of Oxford, Oxford OX3 9DU, UK. Electronic address: petejcox456@gmail.com.
authors.forename: Pete J
authors.initials: PJ
authors.lastname: Cox
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Kirk
authors.affiliation: Department of Biochemistry & Cambridge Systems Biology Centre, University of Cambridge & MRC Human Nutrition Research, Cambridge CB1 9NL, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Ashmore
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
authors.forename: Kristof
authors.initials: K
authors.lastname: Willerton
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
authors.forename: Rhys
authors.initials: R
authors.lastname: Evans
authors.affiliation: UK Sport, 40 Bernard Street, London WC1N 1ST, UK.
authors.forename: Alan
authors.initials: A
authors.lastname: Smith
authors.affiliation: Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murray
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
authors.forename: Brianna
authors.initials: B
authors.lastname: Stubbs
authors.affiliation: Department of Biochemistry & Cambridge Systems Biology Centre, University of Cambridge & MRC Human Nutrition Research, Cambridge CB1 9NL, UK.
authors.forename: James
authors.initials: J
authors.lastname: West
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
authors.forename: Stewart W
authors.initials: SW
authors.lastname: McLure
authors.affiliation: Laboratory of Metabolic Control, NIAAA/NIH, Rockville, MD 20852, USA.
authors.forename: M Todd
authors.initials: MT
authors.lastname: King
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Dodd
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK; Department of Cardiovascular Medicine, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: Cameron
authors.initials: C
authors.lastname: Holloway
authors.affiliation: Department of Cardiovascular Medicine, University of Oxford, Oxford OX3 9DU, UK.
authors.forename: Stefan
authors.initials: S
authors.lastname: Neubauer
authors.affiliation: UK Sport, 40 Bernard Street, London WC1N 1ST, UK.
authors.forename: Scott
authors.initials: S
authors.lastname: Drawer
authors.affiliation: Laboratory of Metabolic Control, NIAAA/NIH, Rockville, MD 20852, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Veech
authors.affiliation: Department of Biochemistry & Cambridge Systems Biology Centre, University of Cambridge & MRC Human Nutrition Research, Cambridge CB1 9NL, UK.
authors.forename: Julian L
authors.initials: JL
authors.lastname: Griffin
authors.affiliation: Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford OX1 3PT, UK.
authors.forename: Kieran
authors.initials: K
authors.lastname: Clarke
mesh_terms: D050154:Adiposity; D056352:Athletes; D002241:Carbohydrates; D002331:Carnitine / Q000378:metabolism; D004032:Diet; D004734:Energy Metabolism; D015444:Exercise; D005260:Female; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D007657:Ketone Bodies / Q000378:metabolism; D007662:Ketosis / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D010807:Physical Endurance; D012146:Rest
chemical_list: D002241:Carbohydrates; D007657:Ketone Bodies; D006003:Glycogen; D002331:Carnitine