Ketogenic Medium Chain Triglycerides Increase Brain Energy Metabolism in Alzheimer's Disease

被引:101
作者
Croteau, Etienne [1 ]
Castellano, Christian -Alexandre [1 ]
Richard, Marie Anne [2 ]
Fortier, Melanie [1 ]
Nugent, Scott [3 ]
Lepage, Martin [2 ]
Duchesne, Simon [4 ]
Whittingstall, Kevin [5 ]
Turcotte, Eric E. [2 ]
Bocti, Christian [6 ]
Fulop, Tamas [1 ,6 ]
Cunnane, Stephen C. [1 ,6 ]
机构
[1] Univ Sherbrooke, Res Ctr Aging, Sherbrooke, PQ, Canada
[2] Univ Sherbrooke, Dept Nucl Med & Radiobiol, Sherbrooke, PQ, Canada
[3] Inst Univ Sante Mentale Quebec, Ctr Rech CERVO, Quebec City, PQ, Canada
[4] Univ Laval, Dept Radiol, Quebec City, PQ, Canada
[5] Univ Sherbrooke, Dept Radiol, Sherbrooke, PQ, Canada
[6] Univ Sherbrooke, Dept Med, Sherbrooke, PQ, Canada
关键词
Acetoacetate; Alzheimer's disease; beta-hydroxybutyrate; brain energy metabolism; C-11]-acetoacetate; cerebral blood flow; F-18]-fluorodeoxyglucose; ketones; medium chain triglycerides; CEREBRAL-BLOOD-FLOW; POSITRON-EMISSION-TOMOGRAPHY; KETONE-BODIES; GLUCOSE; VOLUME; MILD; PET; HYPOMETABOLISM; DEMENTIA; MRI;
D O I
10.3233/JAD-180202
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: In Alzheimer's disease (AD), it is unknown whether the brain can utilize additional ketones as fuel when they are derived from a medium chain triglyceride (MCT) supplement. Objective: To assess whether brain ketone uptake in AD increases in response to MCT as it would in young healthy adults. Methods: Mild-moderate AD patients sequentially consumed 30 g/d of two different MCT supplements, both for one month: a mixture of caprylic (55%) and capric acids (35%) (n = 11), followed by a wash-out and then tricaprylin (95%; n = 6). Brain ketone (C-11-acetoacetate) and glucose (FDG) uptake were quantified by PET before and after each MCT intervention. Results: Brain ketone consumption doubled on both types of MCT supplement. The slope of the relationship between plasma ketones and brain ketone uptake was the same as in healthy young adults. Both types of MCT increased total brain energy metabolism by increasing ketone supply without affecting brain glucose utilization. Conclusion: Ketones from MCT compensate for the brain glucose deficit in AD in direct proportion to the level of plasma ketones achieved.
引用
收藏
页码:551 / 561
页数:11
相关论文
共 36 条
[1]   Recommended Implementation of Arterial Spin-Labeled Perfusion MRI for Clinical Applications: A Consensus of the ISMRM Perfusion Study Group and the European Consortium for ASL in Dementia [J].
Alsop, David C. ;
Detre, John A. ;
Golay, Xavier ;
Guenther, Matthias ;
Hendrikse, Jeroen ;
Hernandez-Garcia, Luis ;
Lu, Hanzhang ;
MacIntosh, Bradley J. ;
Parkes, Laura M. ;
Smits, Marion ;
van Osch, Matthias J. P. ;
Wang, Danny J. J. ;
Wong, Eric C. ;
Zaharchuk, Greg .
MAGNETIC RESONANCE IN MEDICINE, 2015, 73 (01) :102-116
[2]   USE OF R-BETA-[1-C-11]HYDROXYBUTYRATE IN PET STUDIES OF REGIONAL CEREBRAL UPTAKE OF KETONE-BODIES IN HUMANS [J].
BLOMQVIST, G ;
THORELL, JO ;
INGVAR, M ;
GRILL, V ;
WIDEN, L ;
STONEELANDER, S .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1995, 269 (05) :E948-E959
[3]   A 3-Month Aerobic Training Program Improves Brain Energy Metabolism in Mild Alzheimer's Disease: Preliminary Results from a Neuroimaging Study [J].
Castellano, Christian-Alexandre ;
Paquet, Nancy ;
Dionne, Isabelle J. ;
Imbeault, Helene ;
Langlois, Francis ;
Croteau, Etienne ;
Tremblay, Sebastien ;
Fortier, Melanie ;
Matte, J. Jacques ;
Lacombe, Guy ;
Fueloep, Tamas ;
Bocti, Christian ;
Cunnane, Stephen C. .
JOURNAL OF ALZHEIMERS DISEASE, 2017, 56 (04) :1459-1468
[4]   Lower Brain 18F-Fluorodeoxyglucose Uptake But Normal 11C-Acetoacetate Metabolism in Mild Alzheimer's Disease Dementia [J].
Castellano, Christian-Alexandre ;
Nugent, Scott ;
Paquet, Nancy ;
Tremblayd, Sebastien ;
Bocti, Christian ;
Lacombe, Guy ;
Imbeault, Helene ;
Turcotte, Eric ;
Fulop, Tamas ;
Cunnane, Stephen C. .
JOURNAL OF ALZHEIMERS DISEASE, 2015, 43 (04) :1343-1353
[5]   Inverse relationship between brain glucose and ketone metabolism in adults during short-term moderate dietary ketosis: A dual tracer quantitative positron emission tomography study [J].
Courchesne-Loyer, Alexandre ;
Croteau, Etienne ;
Castellano, Christian-Alexandre ;
St-Pierre, Valerie ;
Hennebelle, Marie ;
Cunnane, Stephen C. .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2017, 37 (07) :2485-2493
[6]   Stimulation of mild, sustained ketonemia by medium-chain triacylglycerols in healthy humans: Estimated potential contribution to brain energy metabolism [J].
Courchesne-Loyer, Alexandre ;
Fortier, Melanie ;
Tremblay-Mercier, Jennifer ;
Chouinard-Watkins, Raphael ;
Roy, Maggie ;
Nugent, Scott ;
Castellano, Christian-Alexandre ;
Cunnane, Stephen C. .
NUTRITION, 2013, 29 (04) :635-640
[7]   A cross-sectional comparison of brain glucose and ketone metabolism in cognitively healthy older adults, mild cognitive impairment and early Alzheimer's disease [J].
Croteau, E. ;
Castellano, C. A. ;
Fortier, M. ;
Bocti, C. ;
Fulop, T. ;
Paquet, N. ;
Cunnane, S. C. .
EXPERIMENTAL GERONTOLOGY, 2018, 107 :18-26
[8]   Brain fuel metabolism, aging, and Alzheimer's disease [J].
Cunnane, Stephen ;
Nugent, Scott ;
Roy, Maggie ;
Courchesne-Loyer, Alexandre ;
Croteau, Etienne ;
Tremblay, Sebastien ;
Castellano, Alex ;
Pifferi, Fabien ;
Bocti, Christian ;
Paquet, Nancy ;
Begdouri, Hadi ;
Bentourkia, M'hamed ;
Turcotte, Eric ;
Allard, Michele ;
Barberger-Gateau, Pascale ;
Fulop, Tamas ;
Rapoport, Stanley I. .
NUTRITION, 2011, 27 (01) :3-20
[9]   Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer's Disease [J].
Cunnane, Stephen C. ;
Courchesne-Loyer, Alexandre ;
Vandenberghe, Camille ;
St-Pierre, Valerie ;
Fortier, Melanie ;
Hennebelle, Marie ;
Croteau, Etienne ;
Bocti, Christian ;
Fulop, Tamas ;
Castellano, Christian-Alexandre .
FRONTIERS IN MOLECULAR NEUROSCIENCE, 2016, 9
[10]   Different regional patterns of cortical thinning in Alzheimer's disease and frontotemporal dementia [J].
Du, An-Tao ;
Schuff, Norbert ;
Kramer, Joel H. ;
Rosen, Howard J. ;
Gorno-Tempini, Maria Luisa ;
Rankin, Katherine ;
Miller, Bruce L. ;
Weiner, Michael W. .
BRAIN, 2007, 130 :1159-1166