In January 2021, an interesting paper was published in Translational Research & Clinical Interventions titled, “A ketogenic supplement improves white matter energy supply and processing speed in mild cognitive impairment”. The authors aimed to answer the questions, “Does a ketogenic supplement improve ketone metabolism by white matter fascicles (bundles that connect regions) in the brain?” and “Is uptake of glucose or ketones in the brain associated with cognitive outcomes and white matter structural properties?”. As far as studies go, this is the first to see how a ketogenic supplement impacts the brain and cognition.
In this 6-month study, 17 participants with mild cognitive impairment were randomized to receive a supplement that provided 30 g/d of medium-chain triglycerides (60% caprylic acid [C8] and 40% capric acid [C10]) in lactose-free skim milk and 16 to a placebo containing high-oleic acid sunflower oil (a long-chain fatty acid). The supplement containing the medium-chain triglycerides is ketogenic because the body cannot store these fats, and thus, they are shunted to the mitochondria for b-oxidation. As a result of the increased breakdown of these medium-chain fats, an accumulation of acetyl CoA occurs which then results in the production of ketones. On the other hand, unless the diet is excessively low in carbohydrates (ketogenic), long-chain fatty acids, such as those in the placebo group, tend to be stored rather than burned for fuel.
One issue here is that the authors did not collect dietary or physical activity data on the participants. At least 300 kcal/d extra was being consumed by participants. Since there were no changes in weight, there must have been adaptations to the extra calories via diet and/or activity levels. Ideally, the adaptations between the two groups were similar, but without the data, one cannot be certain. Before and after the 6-month intervention, participants underwent neurocognitive testing and brain imaging, which included an MRI and dual tracer (ketone and glucose) PET-CT. They found that the MCT supplement increased ketone uptake in the brain, specifically in white matter and gray matter fascicles. These improvements were associated with improvements in processing speed. The authors state that these results indicate an improvement in myelin integrity. The results of this study are very interesting and show promise in the treatment of cognitive impairment by MCTs. The mechanisms by which these improvements occur remain to be determined but this study certainly provides important insight.
Roy M, et al. A ketogenic supplement improves white matter energy supply and processing speed in mild cognitive impairment. Alzheimers Dement (N Y). 2021 Nov 17;7(1):e12217. doi: 10.1002/trc2.12217. PMID: 34869825; PMCID: PMC8596139.