Mary T Newport1, Theodore B VanItallie2, Yoshihiro Kashiwaya3, Michael Todd King4, Richard L Veech5. 1. Spring Hill Neonatology, Inc, Spring Hill, FL, USA. 2. Department of Medicine, St. Luke's Hospital, New York, NY, USA. 3. Division of Neurology, Tominaga Hospital, Osaka, Japan. 4. Laboratory of Metabolic Control, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. 5. Laboratory of Metabolic Control, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA. Electronic address: rlveech@comcast.net.
Abstract
BACKGROUND: Providing ketone bodies to the brain can bypass metabolic blocks to glucose utilization and improve function in energy-starved neurons. For this, plasma ketones must be elevated well above the ≤ 0.2 mM default concentrations normally prevalent. Limitations of dietary methods currently used to produce therapeutic hyperketonemia have stimulated the search for better approaches. METHOD: Described herein is a new way to produce therapeutic hyperketonemia, entailing prolonged oral administration of a potent ketogenic agent--ketone monoester (KME)--to a patient with Alzheimer's disease dementia and a pretreatment Mini-Mental State Examination score of 12. RESULTS: The patient improved markedly in mood, affect, self-care, and cognitive and daily activity performance. The KME was well tolerated throughout the 20-month treatment period. Cognitive performance tracked plasma β-hydroxybutyrate concentrations, with noticeable improvements in conversation and interaction at the higher levels, compared with predose levels. CONCLUSION: KME-induced hyperketonemia is robust, convenient, and safe, and the ester can be taken as an oral supplement without changing the habitual diet. Published by Elsevier Inc.
BACKGROUND: Providing ketone bodies to the brain can bypass metabolic blocks to glucose utilization and improve function in energy-starved neurons. For this, plasma ketones must be elevated well above the ≤ 0.2 mM default concentrations normally prevalent. Limitations of dietary methods currently used to produce therapeutic hyperketonemia have stimulated the search for better approaches. METHOD: Described herein is a new way to produce therapeutic hyperketonemia, entailing prolonged oral administration of a potent ketogenic agent--ketone monoester (KME)--to a patient with Alzheimer's disease dementia and a pretreatment Mini-Mental State Examination score of 12. RESULTS: The patient improved markedly in mood, affect, self-care, and cognitive and daily activity performance. The KME was well tolerated throughout the 20-month treatment period. Cognitive performance tracked plasma β-hydroxybutyrate concentrations, with noticeable improvements in conversation and interaction at the higher levels, compared with predose levels. CONCLUSION:KME-induced hyperketonemia is robust, convenient, and safe, and the ester can be taken as an oral supplement without changing the habitual diet. Published by Elsevier Inc.
Authors: Kieran Clarke; Kirill Tchabanenko; Robert Pawlosky; Emma Carter; Nicholas S Knight; Andrew J Murray; Lowri E Cochlin; M Todd King; Andrea W Wong; Ashley Roberts; Jeremy Robertson; Richard L Veech Journal: Regul Toxicol Pharmacol Date: 2012-04-11 Impact factor: 3.271
Authors: Konrad Talbot; Hoau-Yan Wang; Hala Kazi; Li-Ying Han; Kalindi P Bakshi; Andres Stucky; Robert L Fuino; Krista R Kawaguchi; Andrew J Samoyedny; Robert S Wilson; Zoe Arvanitakis; Julie A Schneider; Bryan A Wolf; David A Bennett; John Q Trojanowski; Steven E Arnold Journal: J Clin Invest Date: 2012-04 Impact factor: 14.808
Authors: Robert Krikorian; Marcelle D Shidler; Krista Dangelo; Sarah C Couch; Stephen C Benoit; Deborah J Clegg Journal: Neurobiol Aging Date: 2010-12-03 Impact factor: 4.673
Authors: Barbara Tate; Timothy D McKee; Robyn M B Loureiro; Jo Ann Dumin; Weiming Xia; Kevin Pojasek; Wesley F Austin; Nathan O Fuller; Jed L Hubbs; Ruichao Shen; Jeff Jonker; Jeff Ives; Brian S Bronk Journal: Int J Alzheimers Dis Date: 2012-12-19
Authors: Robert J Pawlosky; Martin F Kemper; Yoshihero Kashiwaya; Michael Todd King; Mark P Mattson; Richard L Veech Journal: J Neurochem Date: 2017-03-15 Impact factor: 5.372
Authors: Lavanya B Achanta; Benjamin D Rowlands; Donald S Thomas; Gary D Housley; Caroline D Rae Journal: Neurochem Res Date: 2017-03-18 Impact factor: 3.996
Authors: Martin F Kemper; Shireesh Srivastava; M Todd King; Kieran Clarke; Richard L Veech; Robert J Pawlosky Journal: Lipids Date: 2015-10-26 Impact factor: 1.880