My knowledge of the effects of ketone salts & esters is virtually zero, so I don't feel qualified to comment on that at all. I would just echo Julie's advice to go slowly. I agree that the degree of ketonemia that might be beneficial for preventing cognitive decline might be less than we think. In the absence of herculean measures, it's pretty difficult to have super elevated ketones for any appreciable amount of time. (Like 4-8mM.) But I don't know that that's necessary. If the "normal" level of ketones in someone eating an average mixed diet is closer to 0.2-ish, then even getting to the neighborhood of 1.0-2.0 is ten times as much. I can't imagine that wouldn't have at least some
noticeable effect. It's just guesswork at this point, but don't let that intimidate you. Go slowly and see how you do.
I wish there were more trials looking at ketone supplements in conjunction with reduced CHO diets. When some results have shown that E4s don't respond as well to ketone salts/esters, those studies usually employ the ketones with no other changes to diet and lifestyle. I have a hunch that even if blood ketone levels weren't sky-high, the efficacy of ketone supplements combined with a lowER carb diet, exercise, and other interventions might be far more impressive. I haven't written much about the topic of metabolic/mitochondrial flexibility, but someone who's been on a relatively lowER carb diet for a while -- especially when combined with exercise, good sleep, and possibly some intermittent fasting -- probably has more of the "metabolic machinery" in place to USE those ketones. (I am not an expert on this, but what good do ketones do if we're "wasting" them in the breath and urine? We want our cells to use
them. Someone who's 70 years old, sedentary, and eats upward of 250g of CHO a day is probably NOT metabolically flexible. So we dose them with exogenous ketones, and maybe they get a small
benefit. But would we see a much bigger (read: better/more effective) benefit in giving the same ketone dose to someone whose mitochondria are primed to be able to use that fuel properly? We tend to forget that we can't just shove certain compounds into our bodies and expect to automatically get the intended benefit. Certain physiological/biochemical mechanisms have to be in place in order to use them effectively. (Enzymes, etc.) This is why I think the combination of outside ketones and a lower carb diet (and exercise, and anything else that improves insulin sensitivity and metabolic flexibility) would show much more promise than we've seen so far in studies where they administer ketones but require no other changes to diet or lifestyle.
(Maybe Bredesen will do this in the future -- add ketones to the existing protocol.) The caveat I would give is that this would have to be a fairly long-term study, especially if the subjects are much older. The younger someone is, the more likely they can adapt more quickly to a dietary change. For someone of advanced age, and advanced AD, it would probably take longer for them to bring the metabolic machinery up to speed. I would hate to have a trial go for 6 weeks and it be determined that this "doesn't work," when it might have been golden at 4 months...
See J. Stanton's presentation on metabolic flexibility: http://www.gnolls.org/3637/what-is-metabolic-flexibility-and-why-is-it-important-j-stantons-ahs-2013-presentation-including-slides/
(His focus is more on weight, metabolic syndrome, and overall health, but he's got some really good insights that I think are applicable to overall fueling of the body and brain.)
I've been careful to make the distinction between prevention versus slowing/reversal of symptoms because, in different "audiences," people have some pretty militant reactions on both sides of the argument. Some will argue for VLC diets for everyone, across the board, regardless of family history, athletic pursuits, body comp goals, or even anything at all to do with Alzheimer's. (Nora Gedgaudas seems to be in this camp.) And then, we have long-lived and healthy
people who consume fruit, legumes, and other starches. It's a very tough road to walk. I've had some experience with clients who fall into the "orthorexia" category, and I like to talk them down from the ledge, so to speak, and encourage them not to focus so much
on "not dying" that they forget to actually live
. So there's a quality of life aspect to all this, too. From what I've gathered in my limited time on this forum, though, it's clear that most of you are far more motivated and disciplined than most average folks, and with the E4, you do have reason to be more careful and more concerned than ... pardon my saying, but someone with no known risk factors for much of anything, but who's terrified that half a sweet potato now and then might take them from a dress size 2 to a size 4. :-/
To Stavia: thanks for the hugs! Kind of embarrassed to admit how badly I need them.
P.S. Sorry that all my posts are so long! Let's just say that some days, I do freelance work from home, and I am starved for human communication, hehheh!