Our first guest: Dr. Thomas Dayspring...

Insights and discussion from the cutting edge with reference to journal articles and other research papers.
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Gilgamesh
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Re: Our first guest: Dr. Thomas Dayspring...

Post by Gilgamesh »

Stavia, OK, got it! Yes, those four options would capture what we've discussed best.
thumperama wrote:@Stavia
That's a good suggestion and it may, in fact, be what Dr Dayspring recommends. The purpose for the question structured in such a way was to reflect a general bifurcation of the ApoE4 "expert" dietary recommendations and approaches by members of our forum community.
Note, though it's only a bifurcation among a certain subset of us who happen to havce posted a lot recently. There are plenty of members of our community who think the data comparing Strat. A and B aren't useful because the diets weren't isocaloric in most of the studies, esp. the long-term studies. What do long-lived populations (ε4-carriers or not) have in common? CR and exercise (of some kind) -- that's it!

Perhaps that could be an additional question to Dr. D: Given that calorie restriction is the most robust experimental method of retarding the aging process (including dementia), and given that human data is consistent with these results (one primate study hasn't yet yielded strong results, though; but ther study appears to be flawed), what data is there that shows that altering fat levels -- for epsilon-4 carriers, or non-carriers -- at a given level of caloric intake yields health benefits as measure by medium- or long-term biomarkers (if not actual health outcomes)? Second question: if we vary the level of caloric intake, does the relation of dietary constituents to health outcomes change? In other words, low- or high-fat CR produces the same benefits, perhaps (I'd say it likely does), but maybe dietary constituents matter more att higher levels of energy intake.
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Post by Stavia »

Ok...so its various combinations of calories and fat percentages.
In fact there are SIX permutations.
CR low fat,,middle fat and high fat
AND notCR low fat, middle fat and high fat.
If we ask Dr Dayspring just HF vs HC I know exactly what he will say already. He's very focused on insulin resistance and rightly so. But most of us have beaten fasting insulins right down on an interestingly varied selection of diverse approaches. There's more than one way to skin this cat imo.
Please please please can we ask him to comment on the whole range of possibilities.
Prettt please
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Re: Our first guest: Dr. Thomas Dayspring...

Post by Julie G »

Yes, we absolutely can ask Dr. Daysping (and all of our guests) more questions. Dayspring charges $500 per hour. (He's very graciously offered to answer 3 questions for free.) We could set up a Pay Pal account and perhaps allow members to submit questions in the future in either a written or audio format.

I hear your frustration with the process. Thumperama and I worked hard on these questions to obtain the most information we could without paying a fee. Please note that Strategy A & Strategy B are both Practicing CR with optimal nutrition. We tried to present both strategies in their best light. I am much less convinced of Dayspring's answer, Stavia. He typically recommends LDL-P to be low in "high risk" groups. That may very well be us and he may subsequently recommend strategy A.

His response will be interestng, but just one expert's highly educated and experienced opinion. We plan to solicit MANY experts and hope to ultimately prompt more research in this area.
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Re: Our first guest: Dr. Thomas Dayspring...

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Hi all

All great thoughts, questions and hypotheses.

Dr Dayspring offered to respond to three questions when we asked him about an interview. Since he is on record as having an opinion about the traditional messages for ApoE4 genotypes, particularly dietary macronutrient ratios as they relate to CVD; the questions have been focused in that way.

We hope this is only the beginning of outreach and engagement with professionals who possess knowledge that can be helpful to the members of this forum and those impacted by ApoE4 in general. But it is going to take a lot of work.

Please read these first three questions to Dr Dayspring with this context. They are certainly not inclusive of every members' objectives. But they are a start.
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Re: Our first guest: Dr. Thomas Dayspring...

Post by Gilgamesh »

And, to repeat: thanks for setting this up! We'll learn a lot whatever questions are asked. GB
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Post by Stavia »

I hear you Julie.
Go with what you have and let's see what he says
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Re: Our first guest: Dr. Thomas Dayspring...

Post by Julie G »

Enormous thanks to Dr. Dayspring for generously taking the time to answer our questions. We are honored to have his expertise in helping us determine our best dietary prevention strategy. You'll find his answers below in red. (If you are interested in extending the conversation with Dr. Dayspring, please let us know. We can discuss the best way to make that happen.)

Questions
1. Is there a general dietary recommendation that you would give to ApoE 4 variant individuals (and are there differences between a 3/4 and a 4/4) to reduce their likelihood of Alzheimer’s Disease/dementia and cardiovascular disease. It’s quite common for members of the ApoE4.info forums to take one of two paths to address their disposition to these diseases:

Much of the dietary info that has been used to advise apoE 4 folks comes from older, weak, poorly done studies. Be careful believing the conclusions

Strategy A: Focus on strictly lowering dietary fat to address our population's tendency towards higher LDL-C/P. Some hypothesize that this may also prevent amyloid plaque deposition. Some members who employ this strategy are also vegetarians/vegans. Rice and/or beans are often staples. Caloric restriction is sometimes concurrently employed to avoid insulin resistance.

Strategy B: Focus on increasing healthy fats (MUFAs, nuts) to address/prevent insulin resistance and induce mild ketosis. Members who
employ this strategy tend to be omnivores, who eat small amounts of proteins rich in Omega-3s and plentiful non-starchy vegetables. Many of these members concurrently employ caloric restriction to overcome our propensity for higher LDL-C/P and to further enhance mitochondrial function.

The only thing we know is that in general the CV risk is higher in patients with E4 alleles compared to the others. We also know that as a generality those with E4 alleles tend to hyperabsorb sterols (cholesterol and xenosterols). Almost all of the cholesterol one absorbs comes from endogenous cellular production which through various pathways finds its way to the gut lumen (on average half excreted in stool, half reabsorbed). Very little ingested cholesterol gets absorbed (as it is such a tiny component on the intestinal pool of cholesterol that is available for absorption). However in patients with hyperabsorption of cholesterol (including those with E4) dietary phytosterols which can also be atherogenic are hypothetically worsening their risk with a vegan diet if they significantly raise plant phytosterol levels (campesterol and sitosterol)

My advice - Before any diet check absorption/synthesis status: do markers of cholesterol synthesis (desmosterol and or lathosterol) and markers of absorption (campesterol, sitosterol, cholestanol). If one is a hyperabsorber - avoid plant sterol supplements at all costs. If apoB or LDL-P is high consider ezetimibe (Zetia), a cholesterol absorption blocker as part of the therapy. Plant stanols (Benecol) can also be used - unlike plant sterols they are not readily absorbed.

With respect to fat in take - if one wants to choose that for part of a low carb diet or ketogenic diet because they have insulin resistance - one would have to monitor apoB and LDL-P. If they go up, especially if accompanied by increased desmosterol or lathosterol levels (indicating a sat fat induced hyperabsorption of cholesterol) then one could consider reducing saturated fat intake

I am not aware that caloric restriction by itself is a sane solution to insulin resistance - I think it is the type of calories that matters more than the amount of calories -- carb calories being way more dangerous in causing obesity in an IR pattern than fat calories

I have no comment on types of fats ingested and amyloid - for sure high carbs and IR are a major part of the dementia story. So ingeneral I think carbs are way more dangerous


2. Given the recent research that suggests it’s the amount and function of an individual's ApoE that convey dementia risks rather than the underlying genotype, do you have suggestions for how individuals concerned about this should go about testing for ApoE and therapies that may benefit them by increasing the ApoE levels?

Well we are early in that game - If true we will have to start ordering apoE mass concentrations and I am not aware of any lab that is currentlly offering that. So we are all on hold right now. If there is a sudden demand for this biomarker labs will offer it. It is a very easy assay to get up and running. Right now the best clues to future dementia are family history, insulin resistance, low serum desmosterol levels (most common cause is high dose statins) and low omega 3 index. Anyone on a statin should monitor desmosterol and if suppressed back off on the statin and use other Rx to control apoB and LDL-P (like ezetimibe)

3. If ALL other risk factors are minimized (high HDL-C/P, low glucose markers and inflammation markers, low Lp[a]); is it OK for those who carry an E4 variant to have slightly higher LDL-P/ApoB?

High HDL-C has no meaning without also checking total HDL-P. One could have a very high HDL-C due to just a few very large HDL particles -- HDL-C is high in the face of a low HDL-P: that is associated with CV risk. High HDL-C in the face of increased HDL-P is desirable and usually indicative of low CV risk. Inflammatory markers tell you little about HDL particle associated risk. Lower levels of Lp(a)-P are not a risk factor in any circumstance. However it is possible, to have a high Lp(a)-P and not have a high Lp(a) mass. Most docs do not understand the difference between Lp(a) mass and Lp(a)-P. Right now in every single group of people studied apoB and total LDL-P are major independent CV risk predictors. Of course there are always exceptions but there is no way now to ascertain who with a high apoB or LDL-P may not be at CV risk. High levels have to be respected. You ask slightly higher -- whether one should worry about a given apoB or LDL-P that is not above the 80th percentile (automatic high risk) - one has to do a total risk assessment using all other tools available (history, physical, imaging and multiple other CV biomarkers) - The higher the risk the more one should worry about a given apoB or LDL-P


Huge thanks to Thumperama for spearheading this project. He has an impressive list of other top AD/CVD experts he plans to query on our behalf. Those who've been here long enough realize that there is a tremendous lack of peer reviewed science providing APOE ε4 carriers with a consensus on preventing either disease. As Dr. Dayspring points out, the few studies that have been done are old, weak, and poorly constructed. Even more frustrating, the advice from experts is often wildly contradictory. Our activism on this initiative will hopefully begin to move the scientific community towards conducting potentially lifesaving research on our behalf. In the meantime, our goal is to get some top minds working on this puzzle with us.
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Re: Our first guest: Dr. Thomas Dayspring...

Post by Julie G »

I’ll be the first to jump in with comments/questions. Please feel free to do the same. My red text indicates a request for further clarification from Dr. Dayspring.

Once again, I’m very grateful to Dr. Dayspring for his participation in promoting advanced discussion on this important topic. We’ve been circling the high fat/low fat debate for APOE ε4 carriers for a number of years. In the absence of well constructed studies examining this topic, we’ve been left to read the older, poorly constructed studies and conduct our own n=1 examinations. We truly are the modern day canaries the coal mine. I appreciate having an expert voice in the discussion.

Dr. Dayspring helped clarify some things for me, but left me with more unanswered questions.
However in patients with hyperabsorption of cholesterol (including those with E4) dietary phytosterols which can also be atherogenic are hypothetically worsening their risk with a vegan diet if they significantly raise plant phytosterol levels (campesterol and sitosterol)
For most of us vegetables (primarily non-starchy for me) are the mainstay of our diets. If we hyperabsorb. Dr. Dayspring seems to suggest that we focus on eating vegetables that are LOW in plant sterols. I wonder if I’m understanding that correctly? What else could we safely replace vegetables with?

-Linus Pauling primer on phytosterols: http://lpi.oregonstate.edu/infocenter/p ... s/sterols/

-Ranking of foods highest in phytosterols: http://nutritiondata.self.com/foods-000 ... 000-1.html (Green leaf lettuce is #1 :shock: )

Regarding his take on the best way to utilize caloric restriction, his message seems clear here:
I am not aware that caloric restriction by itself is a sane solution to insulin resistance - I think it is the type of calories that matters more than the amount of calories -- carb calories being way more dangerous in causing obesity in an IR pattern than fat calories

I have no comment on types of fats ingested and amyloid - for sure high carbs and IR are a major part of the dementia story. So in general I think carbs are way more dangerous
I found THIS statement to be the most compelling of his responses:
Right now the best clues to future dementia are family history, insulin resistance, low serum desmosterol levels (most common cause is high dose statins)and low omega 3 index. Anyone on a statin should monitor desmosterol and if suppressed back off on the statin and use other Rx to control apoB and LDL-P (like ezetimibe.)
I can reverse that information to read that we need to work on modifiable factors: insulin resistance, serum desmosterol levels, and Omega 3 index levels. This is a strong argument against statins that DECREASE desmosterol levels. This appears to be a biomarker, we need to be tracking.

His comment on HDL-C/P clears up any misunderstanding and substantiates papers we’ve recently shared. His comment further solidifies the benefit of high HDL-P:
High HDL-C has no meaning without also checking total HDL-P. One could have a very high HDL-C due to just a few very large HDL particles -- HDL-C is high in the face of a low HDL-P: that is associated with CV risk. High HDL-C in the face of increased HDL-P is desirable and usually indicative of low CV risk.
Dr. Dayspring’s comment on the importance of LDL-P/apoB when other risk factors are minimized is very telling. He makes no bones that LDL-P/apoB are vitally important, but need to be analyzed in context:
Right now in every single group of people studied apoB and total LDL-P are major independent CV risk predictors. Of course there are always exceptions but there is no way now to ascertain who with a high apoB or LDL-P may not be at CV risk. High levels have to be respected. You ask slightly higher -- whether one should worry about a given apoB or LDL-P that is not above the 80th percentile (automatic high risk) - one has to do a total risk assessment using all other tools available (history, physical, imaging and multiple other CV biomarkers) - The higher the risk the more one should worry about a given apoB or LDL-P
I like that Dr. Dayspring defines high LDL-P as above the 80%ile. Per NMR LipoProfile reference that is above 1600. Given the collective information he's shared, I’m left with the feeling that chasing down the lowest possible LDL-P/apoB levels while concurrently raising LP-IR is NOT a good idea for our population. Maintaining low IR markers, low inflammation markers, low Lp(a)-P, high Omega 3 index levels, high HDL-P appears to be desirable and seems to make higher LDL-P/apoB less worrisome. If all of those other risk factors were well managed, perhaps levels below 1300 (50th%ile) might be acceptable- with the understanding that lower is less risky?

NMR Reference: http://www.liposcience.com/sites/defaul ... Report.pdf
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Re: Our first guest: Dr. Thomas Dayspring...

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Juliegee wrote: For most of us vegetables (primarily non-starchy for me) are the mainstay of our diets. If we hyperabsorb. Dr. Dayspring seems to suggest that we focus on eating vegetables that are LOW in plant sterols. I wonder if I’m understanding that correctly? What else could we safely replace vegetables with?
Seems clear that for these hyperabsorber folks Zetia should be seriously considered. From what I understand it binds inside the colon. I've never looked for negative interactions within the body, but perhaps if leaky gut then Zetia would need to be reexamined.

If we hyperabsorb because we're in ketosis? Ketosis clearly comes under a heavier burden. Phytosterols are not really discussed much but some think they are worse than oxLDL. Does anyone know the genes to check the transporters (ABCG5 and ABCG8) that he mentions?

To think how dumb I was for years. Constant low level insulin provocation with heavy levels of greens. Hope that I had transporters that were effective.

Thanks for setting this up! Eye opening, to say the least.
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Re: Our first guest: Dr. Thomas Dayspring...

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I will just briefly comment that I didn't read Dayspring's consideration of the hypothetical possibility of vegan diets raising phytosterol levels the same way as some others have. (Standard disclaimer as to my level of expertise, which is nil.)

His emphasis seemed to me to be all about testing absorption/synthesis status and avoiding the sterol supplements. So even though I am almost certainly a hyperabsorber and eat a lot of vegetables, I just don't hear a suggestion in his comments that we start looking for alternatives to vegetables.

On the other hand, I have no idea what Lance is talking about regarding greens and transporters; I didn't know that ketosis causes us to hyperabsorb (where might I read about that?); and I had only heard distant rumblings of concerns about phytosterols. I can't find any reference in Dayspring's replies to the transporters ABCG5 and ABCG8 that Lance mentions. So I have missed something.

Evidence suggests I am completely clueless, in which case, ignore me. But I am pathetically eager to follow any explicit advice given by anyone authoritative (my middle name is Compliant) and I just didn't hear anybody warning me off vegetables.

[PS -- excellent idea to get clarification, then, innit?]
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