Topic: MCT, Ketones and Brain Energy Rescue during Aging

Stephen C. Cunnane  Bio
Department of Medicine and Research Center on Aging
Université de Sherbrooke, Sherbrooke, Québec, CANADA

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Despite massive effort and investment, no new therapeutics have been approved for Alzheimer’s disease (AD) in over 20 years. The main focus of this effort has been on stopping AD neuropathology (plaques and tangles). In the past 10-15 years, increasing attention is being paid to an alternative issue confronting the aging brain: a gap between its energy needs and the uptake of its main fuel – glucose. This energy gap begins to widen to about 10% in mild cognitive impairment (MCI), the prodromal state of AD, and widens further to ˃20% in AD. In 2015, we reported that in contrast to glucose, the capacity of the AD brain to use the alternative fuel, ketones (acetoacetate and beta-hydroxybutyrate), was completely normal and tightly linked to the availability of ketones in the blood. This discovery gave impetus to renew earlier attempts to use ketones to delay the onset of MCI or its progression to AD. To correct the brain energy gap, additional ketones need to be provided either by dietary energy restriction, severe carbohydrate restriction or by an exogenous ketogenic supplement. We took the latter route and recently reported the results of a 6-month RCT using a ketogenic medium chain triglyceride in MCI. The MCI group performed significantly better in 4/5 cognitive domains and in direct relation to the plasma and/or brain level of ketones achieved. Brain energy rescue may be an essential prerequisite for therapeutic progress in AD. 

Acknowledgements: SCC thanks his research team, collaborators and study participants, and CIHR, FRQS, NSERC, MITACS, the Alzheimer Society of Canada, the Alzheimer Association USA, Nestlé Health Science, Bulletproof, Abitec for financial and in-kind support of his research program.

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