Ketone Body Metabolism in Normal Aging and Alzheimer's disease

We are excited to continue our MCT Technical Series. In this issue, we focus on Ketone Body Metabolism in Normal Aging and Alzheimer's disease.  

Background: The brain is the largest user of glucose in the body. Carbohydrates are the major source of glucose. However, as we get older, it becomes harder to utilize glucose. It is established that MCT-derived ketone bodies (KBs) provide an alternative to insulin-dependent energy source for the brain. KBs are water-soluble molecules produced by the liver from fatty acids usually during periods of low food intake (fasting), carbohydrate restrictive ketogenic diets, starvation and prolonged intense exercise.

The KBs are principally beta-hydroxybutyrate (BHB) and acetoacetate (AcAc). KB-derived energy is important during fasting, when glucose is low (for example during endurance exercise), with diabetes (inability to utilize glucose in type 1 and insulin resistance in type 2) and neurologic disorders (chronic glucose hypo metabolism), and with normal aging, where sub-optimal amounts of glucose are taken up by the brain29.

In one of the recent clinical trials, a very high fat ketogenic diet with 4:5:1 ratio of lipids (fats), protein and carbohydrates) was given for four days to healthy adults. The resulting plasma ketone bodies (plasma is the largest component of human blood, comprising about 55 percent, and contains water, salts, enzymes antibodies and other proteins) increased 6-fold7. These energy sources were estimated to provide 1/3 of the brain’s energy needs.

This result paved the way for studies with persons with cognitive impairments. In three studies with mild-to- moderate Alzheimer's disease (AD), brain KB uptake was not impaired relative to age-matched controls, whereas glucose uptake was impaired9. The increase in brain KB uptake in response to a high fat Ketogenic Diet with 20-70 g MCT per day, translated to improved cognitive outcomes9. There is now intense interest to determine if KBs and MCTs can benefit conditions preceding Alzheimer’s including Mild Cognitive Impairment (MCI), and conditions in which cognitive decline have not yet started10. Examples of the latter include young adult carriers of presenilin-1 or apolipoprotein E4, and young adults with mild insulin resistance or with a maternal family history of Alzheimer’s.

A common feature of all these conditions is likely gradual brain glucose exhaustion, which could be remedied with oral ketogenic supplements.

Conclusions: The body of literature showing that MCTs and KETOGENIC DIETS can improve cognition in Mild Cognitive Impairment, Alzheimer’s, and other neurological conditions2 is compelling and growing. With proper dosing, there are seemingly few contraindications for consuming MCTs for these clinical populations, but drug interactions are always a concern with elderly populations. Consultation with a medical doctor is recommended. The possibility that exposure to MCTs and KETOGENIC DIETS before apparent symptoms develop, to slow or prevent cognitive decline, is an exciting and important area of future research and we promise to bring you any new developments in clinical trials.  


2. Benjamin, J.S., et al., A ketogenic diet rescues hippocampal memory defects in a mouse model of Kabuki syndrome. Proceedings of the National Academy of Sciences, 2016.

7. Courchesne-Loyer, A., et al., 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 Cereb Blood Flow Metab, 2016. 9. Cunnane, S.C., et al., Can ketones compensate for deteriorating brain glucose uptake during aging? Implications for the risk and treatment of Alzheimer's disease. Ann N Y Acad Sci, 2016. 1367(1): p. 12-20.

10. Cunnane, S.C., et al., Can Ketones Help Rescue Brain Fuel Supply in Later Life? Implications for Cognitive Health during Aging and the Treatment of Alzheimer's Disease. Front Mol Neurosci, 2016. 9: p. 53.

29. Nugent, S., et al., Relationship of metabolic and endocrine parameters to brain glucose metabolism in older adults: do cognitively-normal older adults have a particular metabolic phenotype? Biogerontology, 2016. 17(1): p. 241-255.

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