James, I instinctively love you- a fellow 4/4- devoting his life to figuring out the best prevention strategies for us- with academic chops to boot. We are blessed to have you join the discussion. As an MFT, I have a professionally honed bull-sh@t detector and I have to say, you set off all the alarms with (paraphrasing) “Sure, I’m totally open to hear what those quack jobs have to say.”
I get you. I’m trying to stay open-minded as well. Please call ME on it when I’m not.
To go along with your hypothesis, that ε4s need less fats than other APOE genotypes, I have to suspend what I know about human physiology. I know the human brain is pretty small, about 2% of body weight, but demands 20% of our resting metabolic rate- compared to other organs, it’s a virtual pig. I know it’s comprised of approximately 2/3 fat. I know DHA is the most abundant Omega-3 fatty acid in the brain and it is
criticial for normal brain development. I know APOE’s primary function is to transport lipoproteins and fat soluble vitamins. I also know the ε4 allele transports lipids
less efficiently than the other APOE genotypes. To buy into your hypothesis (
totally supportable by research), I have to believe that ε4 brains have completely different nutritional needs and metabolic demands than those of other APOE genotypes. I’m not there…yet, but, stay tuned, my understanding is constantly evolving
Seriously, I’ve been all over the place with this.
I get how you arrived at your conclusion. Could you inadvertently be missing a slightly bigger picture? When you take into account the idea that our APOE is overall reduced and less efficient at transporting and delivering lipids, is it fair to judge the net effect using the same quantities? For instance, The Three City Study, out of France recently determined that ε4s have to eat 3 times the amount of fish to get the same amount of plasma DHA.
http://www.jlr.org/content/54/9/2559.short I think it’s perfectly reasonable to conduct further research providing ε4s with more DHA before reaching a definite conclusion. I think the same argument can be made for demonstrating benefits of a ketogenic diet, etc.
Duh- thanks for the correction on Peter Attia. I knew that and forgot- seriously.
I still think he’s got an amazing mind (I’m more into ideas than titles) and has devoted his life to preventing illness- primarily CVD, like Dr. Dayspring. The same can be said of the others I listed- although their careers have been aimed at preventing Alzheimer’s. You REALLY think they simply haven’t read the same research we have? I suspect they have (and then some) and have come to different conclusions..perhaps because they are looking at a bigger picture or even the same picture from a different angle.
Ketogenic diets in practice aren't as protective as cell-culture and wild-type animal studies would indicate. Again, if you're predisposed to certain diseases then a ketogenic diet may be better than a standard diet, but in normal animals a standard diet would be at least as good or better than a ketogenic diet
...But we're not normal "animals," we ARE predisposed to Alzheimer's and there IS evidence this diet could help with prevention. Oddly, it occurs to me that I could substitute CR for “Ketogenic Diet” (in your quote above) and come to the same conclusions. But then I’d be ignoring all that I’ve learned about CR… looking beyond the animal studies. FWIW, I (and Dr. Perlmutter per Grain Brain) am sold on both CR/IF and regularly practice them…albeit the higher fat version
Please consider reading more of "Grain Brain" It may change what you thought you knew about ketoadaptation as it relates to dementia- even for our genotype.
An individual may follow a ketogenic diet without consuming more saturated fats, but you'd be hard pressed to do this in a tolerable way. In general, the more fat you consume, which is necessary on a ketogenic diet, the more saturated fat you will consume because even at a low percentage of calories your total fat (and thus saturated fat) increases. I put this in parenthesis to indicate that it's relevance is debatable, but that I believe it plays at least some significant role.
Per Dr. Perlmutter, I’m not on a ketogenic diet- not sure how you define it. My macronutients ratios are 65% fat, 20% protein, 15% carb. I’m mildly keto-adapted at best. It’s actually pretty easy to get there with low saturated fat (6 tbs EVOO & a nice juicy avocado, plus other misc. fats from eggs, proteins, seeds & nuts,) but should e4s be avoiding saturated fat? That’s a bigger question for us all to explore another day. I limit it for now, but am sort of all over the place with regards to my thinking about that too.
The question is if a ketogenic diet is beneficially applicable to ApoE4, and I'd posit that it has both therapeutic and preventative limitations, but that it may also be more harmful in ApoE4 than in other disease models, not because of the ketones per se, but because of the nutritional profile of ketogenic diets.
My plate is almost all vegetables (between 60-70 carbs a day), with small portions of Omega-3 rich proteins, and plant-based fats. So many have such a skewed view of what even a mildly ketogenic diet (like mine) is comprised of- no heavy meats, dairy, SFAs here at the exclusion of antioxidant and fiber rich vegetables. I would argue that my diet is exceptionally nutrient dense. What still remains in question for me… is the heart health compatibility of my diet. Another really important topic I'd love to explore further
I greatly appreciate your input, James. I may very occasionally trespass upon your kindness and ask for help understanding various scientific studies/concepts. As a non-scientist, I very often get stuck. Sigh. I never thought reading ApoE4 research would become my strangely addictive hobby
Trust me, I'm not totally relying on any one authority figure. I'm doing my own research and questioning everything. I suspect, I'll learn a lot from you.
Bleh.
