Yes, we all pretend to know the mechanism how ketones may improve cognition in MCI/Alzheimer's, but we don't. Nobody does.
-Preferred fuel? kinda meaningless
-Niacin receptor? if so, where are the studies on niacins or even nicotinamide riboside (the latter is kind of unrelated, but should yield some niacin in vivo) (P.S. blog post on NR in the works).
-Epigenetics? Idk. Of those, I'd say probably all contribute somehow.
Ketogenic Diet Retention and Feasibility Trial #KDRAFT (Taylor et al., 2017)
Study design: 3 months MCT-supplemented ketogenic diet: 70% fat, 20% protein, <10% carbs; then one month on their former diet.
They started with 15-20 grams MCT (~10% of total calories) and gradually increased to 40%.
Of the 15 participants, 5 dropped out; of the 10 remaining, 5 had diarrhea. The former was attributed to the ketogenic diet, the latter to MCTs. This 1/2 of 2/3 [or whatever] was actually their primary objective - IOW, is keto feasible in this population? Secondary objective, which would kinda only matter if the primary objective was affirmative, how does this impact cognition?
Results: 5 people achieved pretty high ketosis for most of the time. Lots of variability, though, which may be due to their "conservative evaluation of ketosis." Ie, instead of just being non-reported, days that ketones weren't reported were counted as zero O_o which, depending how frequently this happened, could've driven down the average.
This part is actually pretty interesting: nearly all participants, especially the most protocol-compliant ones, experienced significant cognitive improvements during the 3-month intervention that promptly declined after one month back on their prior diet.
While fascinating, it does not illuminate the cause of MCI/AD or how ketones may help. It could simply be that the 160 grams of carbs they cut was all industrial food -- that seems likely because although we aren't told what foods they were actually eating, the authors mentioned ketogenic diet cooking classes -- I think that is very important.
Alternatively, ketones seem to have some interesting direct effects as signaling metabolites -- another potential role for ketone supps if this pans out (the other being gout) (I don't see physical performance as ketone supps' strongest suit).
Some other observations: the improved cognition was not associated with any metabolic health parameters. Some liver enzymes and blood glucose actually started creeping upward, and insulin didn't budge.
Of the original 15, the 4 with the most severe dementia all dropped out. It's unclear why, but unfortunate none the less.
"Caregiver burden" was an issue, which is pretty understandable because if neither the caregiver nor patient has extensive experience with a ketogenic diet... let's just say keto a pretty big switch from pretty much any other diet.
They added 10 grams of protein and about 50 more kcals (NS), and lean body mass didn't budge (actually declined a bit [NS]). My rules of thumb on this are: if you're gonna drop carbs in an isocaloric and especially hypocaloric #context: 1) gotta replace some of those calories with protein; and 2) exercise. MCTs & ketones are neither anabolic nor anti-catabolic in this setting. Protein & exercise are both.
Despite being MCI/AD, this population is also elderly and more likely to be frail. Can't have 'em losing muscle mass & function, too.
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