Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease

Annals of the New York Academy of Sciences
Stephen C CunnaneChristian-Alexandre Castellano

Abstract

Brain glucose uptake is impaired in Alzheimer's disease (AD). A key question is whether cognitive decline can be delayed if this brain energy defect is at least partly corrected or bypassed early in the disease. The principal ketones (also called ketone bodies), β-hydroxybutyrate and acetoacetate, are the brain's main physiological alternative fuel to glucose. Three studies in mild-to-moderate AD have shown that, unlike with glucose, brain ketone uptake is not different from that in healthy age-matched controls. Published clinical trials demonstrate that increasing ketone availability to the brain via moderate nutritional ketosis has a modest beneficial effect on cognitive outcomes in mild-to-moderate AD and in mild cognitive impairment. Nutritional ketosis can be safely achieved by a high-fat ketogenic diet, by supplements providing 20-70 g/day of medium-chain triglycerides containing the eight- and ten-carbon fatty acids octanoate and decanoate, or by ketone esters. Given the acute dependence of the brain on its energy supply, it seems reasonable that the development of therapeutic strategies aimed at AD mandates consideration of how the underlying problem of deteriorating brain fuel supply can be corrected or delayed.

References

Apr 1, 1991·Journal of Neurochemistry·N AuestadJ Edmond
Sep 1, 1986·Journal of Gerontology·E D LondonS I Rapoport
Nov 1, 1986·The American Journal of Clinical Nutrition·T B SeatonR G Campbell
Oct 1, 1974·The Journal of Clinical Investigation·A J GarberO E Owen
Jan 1, 1972·Diabetes·J P Flatt
Oct 1, 1972·The Journal of Clinical Investigation·E J DrenickA S Brickman
Oct 1, 1967·The Journal of Clinical Investigation·O E OwenG F Cahill
Jun 1, 1983·The Journal of Clinical Investigation·J W RoweJ S Flier
Nov 1, 1982·The American Journal of Clinical Nutrition·A C Bach, V K Babayan
Jul 1, 1996·Journal of the Neurological Sciences·M OgawaJ Kimura
Feb 24, 2000·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·K A TraulD Nakhasi
Jun 1, 2000·Current Pharmaceutical Design·R E GibsonC Ryan
Feb 1, 1974·The Journal of Clinical Investigation·G A ReichardW M Bortz
Sep 25, 2001·IUBMB Life·R L VeechG F Cahill
Jun 18, 2002·American Journal of Physiology. Endocrinology and Metabolism·G BlomqvistK Ekberg
May 21, 1960·Lancet·S A HASHIMT B VAN ITALLIE
Dec 23, 2003·Proceedings of the National Academy of Sciences of the United States of America·Eric M ReimanJohn Hardy
Feb 11, 2004·Prostaglandins, Leukotrienes, and Essential Fatty Acids·Toshiyuki FukaoGrant A Mitchell
May 5, 2004·Neurobiology of Aging·Mark A RegerSuzanne Craft
Mar 23, 2005·Molecular Genetics and Metabolism·Fanny MochelJean-Marie Saudubray
Nov 25, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Rodney A VelliquetteRobert Vassar
Jun 10, 2006·Journal of Inherited Metabolic Disease·Henri Brunengraber, Charles R Roe
Jun 30, 2006·Annals of Neurology·Kristopher J BoughRaymond J Dingledine
Aug 1, 2006·Lancet·Kaj BlennowHenrik Zetterberg
Jul 17, 2007·Neurobiology of Aging·Grégoria KalpouzosBéatrice Desgranges
Jul 16, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Samuel T Henderson
Dec 17, 2008·Annals of the New York Academy of Sciences·John P Blass
Mar 21, 2009·The Journal of Nutrition, Health & Aging·E FreemantleS C Cunnane
Sep 15, 2010·Proceedings of the National Academy of Sciences of the United States of America·S Neil VaishnaviMarcus E Raichle
Nov 3, 2010·Nutrition·Stephen CunnaneStanley I Rapoport
Dec 7, 2010·Neurobiology of Aging·Robert KrikorianDeborah J Clegg
Dec 22, 2011·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Gerald A Dienel
May 9, 2012·Regulatory Toxicology and Pharmacology : RTP·Kieran ClarkeRichard L Veech

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Citations

Jul 20, 2016·Journal of Oleo Science·Yudai NonakaShin Terada
Jul 28, 2016·Frontiers in Molecular Neuroscience·Stephen C CunnaneChristian-Alexandre Castellano
Jan 7, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Jens V AndersenHelle S Waagepetersen
Feb 9, 2017·Canadian Journal of Physiology and Pharmacology·Camille VandenbergheStephen C Cunnane
Sep 16, 2016·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Alexandre Courchesne-LoyerStephen C Cunnane
Jan 29, 2017·Metabolism: Clinical and Experimental·Theodore B VanItallie
Feb 15, 2017·Neuroscience and Biobehavioral Reviews·Mortimer Mamelak
Feb 6, 2017·Journal of Alzheimer's Disease : JAD·Christian-Alexandre CastellanoStephen C Cunnane
Aug 9, 2017·Experimental Physiology·Kurt J Smith, Philip N Ainslie
Dec 1, 2017·Frontiers in Molecular Neuroscience·Marwa ElaminPaola Sacchetti
Dec 19, 2017·Frontiers in Aging Neuroscience·Alice HardingSim K Singhrao
Apr 7, 2017·Journal of the American Heart Association·Konrad KochJochen Klein
Jan 24, 2019·Journal of Neurovirology·Bianca CottoDianne Langford
Mar 17, 2019·Military Medicine·Richard A LaFountainJeff S Volek
May 22, 2019·Journal of Endocrinological Investigation·M CaprioUNKNOWN Cardiovascular Endocrinology Club of the Italian Society of Endocrinology
Jun 13, 2019·Acta Neuropsychiatrica·Brian E Leonard, Gregers Wegener
Nov 16, 2019·Journal of the American Veterinary Medical Association·Kimberly A May, Dorothy P Laflamme
Dec 8, 2019·BMJ : British Medical Journal·Elizabeth Joe, John M Ringman
Apr 28, 2019·Alzheimer's & Dementia : the Journal of the Alzheimer's Association·Mélanie FortierStephen C Cunnane
Mar 30, 2019·Alzheimer's & Dementia : Diagnosis, Assessment & Disease Monitoring·Seth Stoykovich, Kelly Gibas
Jun 22, 2016·Brain Pathology·Susana CardosoPaula I Moreira
Jun 28, 2020·BMJ : British Medical Journal·Amy JenningsAnne Marie Minihane
May 19, 2017·Frontiers in Aging Neuroscience·Roger J MullinsDimitrios Kapogiannis
Aug 14, 2019·International Journal of Molecular Sciences·Marta RusekStanisław J Czuczwar
Feb 23, 2020·Frontiers in Nutrition·Camille VandenbergheStephen C Cunnane
Jun 23, 2020·Journal of Alzheimer's Disease : JAD·Maggie RoyMaxime Descoteaux
Nov 23, 2017·Frontiers in Aging Neuroscience·Bryan J Neth, Suzanne Craft
Mar 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·Lilianne R Mujica-ParodiKieran Clarke
Dec 20, 2016·PloS One·Marcin StudnickiDariusz Stępkowski
May 4, 2017·Journal of Neuroscience Research·Yuri Zilberter, Misha Zilberter
Oct 21, 2017·Pharmaceuticals·Chiara LucchiGiuseppe Biagini
Nov 14, 2018·Oxidative Medicine and Cellular Longevity·Senthilkumar SivanesanJayakumar Rajadas
Mar 5, 2019·Frontiers in Aging Neuroscience·Christian-Alexandre CastellanoStephen C Cunnane
Feb 26, 2020·European Psychiatry : the Journal of the Association of European Psychiatrists·Gerwyn MorrisBasant K Puri
Aug 8, 2020·Nordic Journal of Psychiatry·Magnus G ChristensenAnders Fink-Jensen

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