New review of ketone neurochemistry and AD

[Julie G]

Michael, I certainly accept your gracious apology...but did look out the window to check for flying pigs

I fully understand that the word "ketosis" conjures a different image than the strategy most here employ. It does take a certain amount of time and dedication to understand our members' strategies; how and why we employ them. You're not the first to misunderstand our use of the term.

Merouleau is right, we don't have a "consensus" per se...but we've worked very hard as a team contributing a path forward for E4 carriers to prevent both Alzheimer's and heart disease- that didn't exist when I began my search three years ago. I'm very proud of our collaboration and care deeply for our members.

When you, who fully admits to knowing little about the E4 allele, came roaring into town denouncing ketosis...it felt very disrespectful. We have members here (myself included) who need some ketones to function. Yeah, we'd all like PROOF of long term efficacy and safety, but some here aren't afforded that luxury. We're doing the best we can in a really difficult situation. You seem to have picked up on that and demonstrate a surprising sensitivity by apologizing. Thank you. Your reformed personna is most welcome anytime.

I assure you that you've made another assumption by suggesting that we are in any way associated with Dr. Perlmutter. Yes, I consulted with him pre Grain Brain and received tremendous help...but he is hardly the focus of my message or platform. He actually avoids or neglects to work on the E4 specific pathology- which IS our focus.

[Stavia]

Well said Merouleau and Julie, much better than I could have. I didn't explain properly what I meant by using the word consensus and reading my post I see it was misleading. I was thinking in the broader sense of the basic strategies both non diet and diet wise and blancinng biomarkers such as glycaemic control and lipids. I see the ketone issue as part of the current dialogue but absolutely not consensus and unlikely to be for some time. And the actual optimal macronutrient composition of our diets IMO will cover a wide range as we are genetically and otherwise diverse.

[MichaelR]

Thanks, Stavia, merouleau, and Juliegee ... Edit: a couple ofquickies:

I do not feel the need to criticise Julie. Hope you didnt mean I did.

Er ... no! I'm looking back at my post, and genuinely baffled as to what I said that might've been interpreted that way. (And to be clear, I didn't and don't think there is any need to do so, and indeed had no intention of doing so -- tho' my comments were possibly taken as implicit or indirect criticism of her).

Michael, I certainly accept your gracious apology...but did look out the window to check for flying pigs

LOL!

We have members here (myself included) who need some ketones to function. Yeah, we'd all like PROOF of long term efficacy and safety, but some here aren't afforded that luxury.

It is, of course, rather a different thing to use them to sustain function than as a preventive strategy per se. It is to the latter use that my post was primarily directed, tho' I'd continue to urge caution about going further into "full-on" keto for the reasons I outlined and others I've not gotten around to yet because they involve more complex argumentation.

We're doing the best we can in a really difficult situation.

Indeed.

I assure you that you've made another assumption by suggesting that we are in any way associated with Dr. Perlmutter. Yes, I consulted with him pre Grain Brain and received tremendous help...but he is hardly the focus of my message or platform. He actually avoids or neglects to work on the E4 specific pathology- which IS our focus.

I didn't really assume that the group was associated w/DP as such (tho' as you know, I was concerned about the appearance of a quote from him on the homepage), nor that he is the focus of your personal approach or advice/input. But (again) he has a bestselling book that has convinced a lot of people that full-onketogenic and/or gluten-free diets are the key to neurological health, and you did just now identify yourself as "a patient of Dr. Perlmutter's."

[marthaNH]

I'm happy to read all of this and just want to note (as Stavia and I discussed yesterday) that this is one of the few places on the internet that I know of where you can find people going off the rails, butting heads, and then actually getting themselves back to a cordial and mutually more or less supportive stance. Which is one reason I hang around here.

[Silverlining]

I am also very, very grateful for the posters here. Most days I am at peace with my double 4's; that initial heart stopping, paralyzing terror that gripped me during those few discovery days is mostly a distant memory. I read almost everything posted and try to break down and absorb it all. It is critical that our community continue to flourish, question and attract diverse opinions for debate. Many members are silent, but we're watching, reading and pondering it all. Big thank you from me to you all!

[TuitNutrition]

Hi Everyone,


Saw some increased traffic to my blog from this site, so I thought I'd pop in again.
My apologies that I haven't had a chance to look thoroughly through this thread, so forgive me if I'm posting something you're already aware of. (Seems like most of you are way ahead of the curve on this stuff and certainly don't need any input from me, but I thought I'd pass this along just in case. Probably old news around here, but you never know...)

A paper came out a couple of months ago where they had a single subject who I assume is Dr. Newport's husband. Basically, it sounds like they changed nothing about his diet, but gave him oral doses of a ketone mono-ester. He is APOE ε4-positive, but they don't say if he's homozygous or heterozygous. (Maybe Dr. Newport discusses this elsewhere, in other papers or her book.) Seems he did have a pretty good response to the elevated ketones:

A new way to produce hyperketonemia: use of ketone ester in a case of Alzheimer's disease.
http://www.ncbi.nlm.nih.gov/pubmed/25301680

From the paper:
"Given the report by Henderson et al. [12] indicating that the APOE ε4-positive subjects in their study failed to show statistically significant improvement in their ADAS-Cog scores in response to MCTG treatment, it is noteworthy that the patient, although APOE ε4-positive, exhibited clear cognitive and behavioral improvement while consuming equivalent or larger quantities of ketogenic MCFAs. The findings of Henderson et al. (which may have lacked the statistical power to detect a change in APOE ε4-positive subjects) do not rule out the possibility that carriers of the ε4 allele could show cognitive improvement if studied for longer periods of time and/or given higher doses of MCTG."

If anyone would like to read the full text and can't access it, feel free to contact me.

And yes, from the few posts I've had a chance to read, you are correct: for AD, I do advocate a lower-carb, higher fat diet, but I do not claim to have all the answers (or even a few) for the specific nuances of E4. Seems like getting ketones higher would be a good thing for ALL genotypes whose brain cells' utilization of glucose has become compromised, but maybe, for whatever reasons, the E4s would do best on a ketone supplement rather than a very low-carb diet. (Or maybe a VLC/KD diet is still a good option, but the optimal fatty acid ratios have yet to be determined...which really makes it no different from the knowledge we have regarding the "optimal diet" [and I use the term loosely] for any other genotype or individual person.)

I dunno. I don't have all the answers, and I certainly don't claim to. But I have at least some potentially helpful information, and it infuriates me that the average family doctor -- not to mention neurologist, for cryin' out loud -- has no clue at all about the cerebral hypometabolism and the role of insulin in the accumulation of AB plaques. People who are literally losing their minds from this neurodegeneration -- and their loved ones and caretakers -- deserve to know about these issues, and all the fancy-schmancy Alzheimer's "foundations" and charities don't seem the least bit interested in shouting this from the rooftops, so we have to do it ourselves.

I have a blog post coming up next week about the study I linked to here. Their big selling point is that the ketone ester would benefit people and they wouldn't have to change their diet. My opinion in a nutshell -- emphasizing that it is just that -- my opinion: it's all well and good to elevate ketones via a drink or infusion, or whatever other method might be effective. But to do that in the absence of making changes to at least some of the other dietary and lifestyle factors that might be having a negative impact (or dare I even say causal relationship) with progression of AD, is the lazy way out. As I said in an article a while back: administering exogenous ketones in the absence of dramatic dietary and lifestyle adjustments is like bailing water out of a leaky boat without stopping to patch the hole -- you merely manage the symptoms while the root causes continue wreaking havoc.

For someone who's 90 years old and is not likely to suddenly give up their morning oatmeal in favor of eggs cooked in coconut oil, then sure, let's dose 'em with a ketone drink. But for someone who's in their late 50s or mid-60s, and might have 25-35 more years of life? If that person doesn't want to make any changes that might stop things from getting much worse, then fine. But my hunch is that the double-whammy, one-two punch, if you will, would come from dietary & lifestyle changes AND the ketone esters. (And if we're talking about mild cognitive impairment, a VLC diet might not even be necessary. For some people, just going lowER carb might be enough -- just enough to reduce insulin resistance, and maybe combine that with better sleep, more physical activity, daylight, time outdoors, stress reduction, etc.

I just think the "carb up & ketone up" isn't much better than the standard diabetes line of "carb up & shoot up" (with insulin).

...slinking back into my hole now.

[Stavia]

Hi Amy, thanks for popping in! And thanks for the information. This is cutting edge stuff, and you know how long it takes for new info to get translated into clinical practice.
If you have any insights we'd love to hear them if you have time to share, and to discuss

[Julie G]

Amy! Nice to see you posting again

Seems like getting ketones higher would be a good thing for ALL genotypes whose brain cells' utilization of glucose has become compromised, but maybe, for whatever reasons, the E4s would do best on a ketone supplement rather than a very low-carb diet. (Or maybe a VLC/KD diet is still a good option, but the optimal fatty acid ratios have yet to be determined...which really makes it no different from the knowledge we have regarding the "optimal diet" [and I use the term loosely] for any other genotype or individual person.)

Absolutely; IMO this is the strongest argument for ketosis for E4s. We are THE known population with decreased cerebral glucose metabolism decades before cognition declines. What gets tricky for us is HOW to best create those ketones without driving up our risk for CAD/CVD as we also tend to hyper-absorb dietary cholesterol. Many of our members practice CR, IF, exercise, reduce starchy carbs, and use MUFAs to more safely create ketone bodies. Ketone supplements, like MCT, can also drive up LDL-P. As you've wisely ascertained, ketone esters MAY end up being our ticket... but even less research has been done there

We're kind of between a rock and a hard place. It's pretty clear that we could greatly benefit from ketones; but we're struggling with how to balance brain health with heart health.

[TuitNutrition]

Okay, I just looked through this thread, so as long as I'm here, a couple more things:

I do think that dietary & lifestyle strategies that might (MIGHT) prevent AD need not be as drastic as those required to slow/delay/stop/potentially reverse it. As they say, "drastic times call for drastic measures." I touched on this in a guest post I did for Robb Wolf's blog a while back. (In response to the first interview he did with Dr. Perlmutter, because Perlmutter was basically advocating a LC/KD for everyone, across the board, and it stirred up a huge hornet's nest: http://robbwolf.com/2013/10/16/carbohyd ... est-trees/)

For someone with severe and longstanding AD, I don't think that's a time to mess around. Hit it hard, and hit it from all angles. For someone who's just beginning to show signs of MCI or early onset AD, and is maybe a younger age, if they wanted to do a VLC or ketogenic diet, I see no reason not to give that a try, but at those early stages, it wouldn't surprise me if just managing blood glucose & insulin levels better would steer the boat back to safer territory. (Plus better sleep, lower stress, appropriate levels of physical activity, etc -- the whole nine yards.) The worse shape somebody's in, the more drastic the interventions would likely need to be. (Speculation on my part, of course.)

I don't think a KD is "required" as Alz therapy for everyone. In my book, I include examples of macronutrient ratios that go as high as 20% carbohydrate. If someone's in the early stages of the condition, but it's recognized that it is happening, and they want to prevent further worsening, and potentially even facilitate reversal (if this proves possible), someone younger and in otherwise decent shape might do just fine at 25-30% or even 35% carbs, all of which are still significantly lower than what the average American is consuming. Obviously, the 30-35% would be for younger and more physically active people. I guess what I'm trying to say is, I think CHO reduction needs to be at least part of a multi-pronged strategy to fight AD, but the degree to which it needs to be done could very well vary. Just like for any other goal -- be it weight loss, diabetes management, mental health, or something else -- the degree of CHO restriction needed will vary from person to person. Some people might do great at 100g/day, while others might need to be below 40g. (And even then, maybe that wouldn't be necessary forever; just long enough to get some therapeutic benefit, and possibly be able to increase a little over time, without negative effects.)

As regards prevention, for someone who shows no signs of MCI or AD, and wants to keep things that way, then I would say they want to stay metabolically flexible -- support mitochondrial health via a low-ISH carb diet and the other lifestyle factors you've probably covered here ad nauseum. That's something else I address in the book -- dietary changes are the cornerstone, but the approach is multifactorial.

Someone mentioned that in terms of helping someone with AD, I am probably more concerned with fueling the brain than with changes to their lipid profile. (Worrisome for the E4 type.) That's an accurate assessment, but that doesn't mean I would ignore lipids. I guess my biggest beef there is that we seem to know less and less about cholesterol and lipoproteins. (You know that phrase: "The more I learn, the less I know.") If people who present with heart disease or a heart attack run the gamut from "low" cholesterol, to "normal" cholesterol, and "high" cholesterol, then I'm not sure we should prioritize keeping cholesterol, particle sizes, or particle numbers within some "safe" window that seems to change with the tides. For someone with no other, potentially more pressing health condition, then yes, let's make lipids the big priority. But for someone whose brain is starving to death? In that case, I must admit, addressing that would be my main focus. (While still keeping an eye on the lipids to make sure things don't get too out of whack.)

Sadly, for me, this is all a moot point, since zero people have contacted me for help with AD.
Am considering sticking with writing and dropping the practice side of things altogether. Very disheartened for a number of reasons.

[Stavia]

Thank you again Amy, for taking the time to put your thoughts down for us. You are echoing my general approach that CONTEXT needs to be considered most carefully and it's never one size fits all.

P.S. May I give you a hug for your disheartened feelings? (((Amy)))