title: Novel ketone diet enhances physical and cognitive performance.
abstract: Ketone bodies are the most energy-efficient fuel and yield more ATP per mole of substrate than pyruvate and increase the free energy released from ATP hydrolysis. Elevation of circulating ketones via high-fat, low-carbohydrate diets has been used for the treatment of drug-refractory epilepsy and for neurodegenerative diseases, such as Parkinson's disease. Ketones may also be beneficial for muscle and brain in times of stress, such as endurance exercise. The challenge has been to raise circulating ketone levels by using a palatable diet without altering lipid levels. We found that blood ketone levels can be increased and cholesterol and triglycerides decreased by feeding rats a novel ketone ester diet: chow that is supplemented with (R)-3-hydroxybutyl (R)-3-hydroxybutyrate as 30% of calories. For 5 d, rats on the ketone diet ran 32% further on a treadmill than did control rats that ate an isocaloric diet that was supplemented with either corn starch or palm oil (P < 0.05). Ketone-fed rats completed an 8-arm radial maze test 38% faster than did those on the other diets, making more correct decisions before making a mistake (P < 0.05). Isolated, perfused hearts from rats that were fed the ketone diet had greater free energy available from ATP hydrolysis during increased work than did hearts from rats on the other diets as shown by using [31P]-NMR spectroscopy. The novel ketone diet, therefore, improved physical performance and cognitive function in rats, and its energy-sparing properties suggest that it may help to treat a range of human conditions with metabolic abnormalities.-Murray, A. J., Knight, N. S., Cole, M. A., Cochlin, L. E., Carter, E., Tchabanenko, K., Pichulik, T., Gulston, M. K., Atherton, H. J., Schroeder, M. A., Deacon, R. M. J., Kashiwaya, Y., King, M. T., Pawlosky, R., Rawlins, J. N. P., Tyler, D. J., Griffin, J. L., Robertson, J., Veech, R. L., Clarke, K. Novel ketone diet enhances physical and cognitive performance.
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom; ajm267@cam.ac.uk.|Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Murray
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Nicholas S
authors.initials: NS
authors.lastname: Knight
authors.affiliation: Department of Chemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Cole
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Lowri E
authors.initials: LE
authors.lastname: Cochlin
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Carter
authors.affiliation: Department of Chemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Kirill
authors.initials: K
authors.lastname: Tchabanenko
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Tica
authors.initials: T
authors.lastname: Pichulik
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Melanie K
authors.initials: MK
authors.lastname: Gulston
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Helen J
authors.initials: HJ
authors.lastname: Atherton
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Marie A
authors.initials: MA
authors.lastname: Schroeder
authors.affiliation: Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom.
authors.forename: Robert M J
authors.initials: RM
authors.lastname: Deacon
authors.affiliation: Laboratory of Metabolic Control, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland, USA.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kashiwaya
authors.affiliation: Laboratory of Metabolic Control, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland, USA.
authors.forename: M Todd
authors.initials: MT
authors.lastname: King
authors.affiliation: Laboratory of Metabolic Control, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Pawlosky
authors.affiliation: Department of Experimental Psychology, University of Oxford, Oxford, United Kingdom.
authors.forename: J Nicholas P
authors.initials: JN
authors.lastname: Rawlins
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Tyler
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.|Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Julian L
authors.initials: JL
authors.lastname: Griffin
authors.affiliation: Department of Chemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Robertson
authors.affiliation: Laboratory of Metabolic Control, National Institutes of Health, National Institute on Alcohol Abuse and Alcoholism, Rockville, Maryland, USA.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Veech
authors.affiliation: Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Kieran
authors.initials: K
authors.lastname: Clarke
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D003071:Cognition / Q000502:physiology*; D004032:Diet; D004040:Dietary Carbohydrates / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism; D002149:Energy Intake / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D007328:Insulin / Q000378:metabolism; D007659:Ketones / Q000008:administration & dosage*; D008297:Male; D017208:Rats, Wistar; D014280:Triglycerides / Q000097:blood
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats; D007328:Insulin; D007659:Ketones; D014280:Triglycerides; D002784:Cholesterol
keywords: energetics; exercise; heart; metabolism; muscle