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

Article type: Research Article

Authors: Croteau, Etienne^a | Castellano, Christian-Alexandre^a | Richard, Marie Anne^b | Fortier, Mélanie^a | Nugent, Scott^c | Lepage, Martin^b | Duchesne, Simon^{c; d} | Whittingstall, Kevin^e | Turcotte, Éric E.^b | Bocti, Christian^f | Fülöp, Tamàs^{a; f} | Cunnane, Stephen C.^{a; f; *}

Affiliations: [a] Research Center on Aging, Université de Sherbrooke, Sherbrooke, QC, Canada | [b] Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, QC, Canada | [c] Centre de recherche CERVO de l’Institut universitaire en santé mentale de Québec, Québec, QC, Canada | [d] Department of Radiology, Université Laval, Québec, QC, Canada | [e] Department of Radiology, Université de Sherbrooke, Sherbrooke, QC, Canada | [f] Department of Medicine, Université de Sherbrooke, Sherbrooke, QC, Canada

Correspondence: [*] Correspondence to: Stephen C. Cunnane, Research Center on Aging, 1036 Belvedere St South, Sherbrooke, Quebec J1H 4C4, Canada. Tel.: +1 819 780 2220/Ext: 45670; E-mail: stephen.cunnane@usherbrooke.ca.

Abstract: 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 (11C-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.

Keywords: Acetoacetate, Alzheimer’s disease, beta-hydroxybutyrate, brain energy metabolism, [¹¹C]-acetoacetate, cerebral blood flow, [¹⁸F]-fluorodeoxyglucose, ketones, medium chain triglycerides

DOI: 10.3233/JAD-180202

Journal: Journal of Alzheimer's Disease, vol. 64, no. 2, pp. 551-561, 2018