41 replies to this topic

[nowayout]

Well, if you were E3/E3, you might have had a good lipid response to oatmeal:

http://www.ncbi.nlm..../pubmed/1334101

or perhaps even better if you were a carrier of E2:

http://www.ncbi.nlm....2?dopt=Abstract

But we would be making a mistake to base decisions on APoE SNPs alone. There are several other genes that are thought to affect lipid response to diet:

http://www.ajcn.org/.../77/5/1098.full

The latter article congains some implicit criticism of the table the OP posted. That table should be taken with a grain of salt.

Edited by viveutvivas, 07 February 2012 - 08:06 PM.

[niner]

But we would be making a mistake to base decisions on APoE SNPs alone. There are several other genes that are thought to affect lipid response to diet:

http://www.ajcn.org/.../77/5/1098.full

The latter article congains some implicit criticism of the table the OP posted. That table should be taken with a grain of salt.

I wouldn't make all dietary decisions based on ApoE genotype alone, but it certainly gives you a decent starting point. One would still want to keep an eye on blood lipids. There is now a great deal of data on the consequences of ApoE genotype, and it is clearly an important gene. The 2003 ajcn paper linked here is reference 2 on the chart.

[smithx]

The only good evidence on niacin actually working which I'm aware of is of the regular old flush-producing kind.

Niacins which don't produce a flush also have not been shown to produce the results you want.

I think for now it's either deal with the flush or don't bother.

BTW, some researchers have theorized that the flush itself may be beneficial.

I've added 500 mg flush-free niacin (this one) to my supplements. Is there any way I can go back and edit this into my original post? I've also added 400 mg green tea extract (this one) and potassium plus iodine (this one).

[James Cain]

I haven't posted in a long time, but I still read the forums regularly. I'll be following along as I am ApoE 4/4 and this is one of the most recent active discussions on ApoE4 on the web, and I think the people in this forum could contribute to what is a fairly obscure topic. I mean, there's plenty of research, but there is relatively little serious discussion about the genotype with regards to diet.

My cholesterol seems to track fairly well with yours. That is: total cholesterol ~190-220, LDL ~140-160, HDL ~40-50, Triglycerides ~50-75. These are my numbers on mostly "real" food with fat being anywhere from 40-60% of my diet, from MUFA and SFA primarily (eggs, meat, butter, yogurt, and olive oil). There was a time when I did a very low fat diet with Chol ~150, LDL ~115, HDL ~35, TAG ~75. From what I've read it would seem most people with ApoE4 who respond poorly to dietary fat have quite high cholesterol levels. It seems I can consume a few thousand calories each day of a high fat diet and not have sky-high numbers, so I've recently been considering the trade off in lower total and LDL cholesterol for higher numbers with a probably better density profile.

Of course there is a lot more than overt numbers to go by. I'm reminded of a study showing mice transfected with human ApoE4 (IMO, a very relevant model) had the same cholesterol profiles as WT mice but had much greater progression of atherosclerosis.

[Elus]

I wouldn't make all dietary decisions based on ApoE genotype alone, but it certainly gives you a decent starting point. One would still want to keep an eye on blood lipids. There is now a great deal of data on the consequences of ApoE genotype, and it is clearly an important gene. The 2003 ajcn paper linked here is reference 2 on the chart.

Hey niner,

Would it be possible for you to give me editing privileges on my post? I'd like to edit my additional supplements in.

[Elus]

The only good evidence on niacin actually working which I'm aware of is of the regular old flush-producing kind.

Niacins which don't produce a flush also have not been shown to produce the results you want.

I think for now it's either deal with the flush or don't bother.

BTW, some researchers have theorized that the flush itself may be beneficial.

Hmm, I suppose I'll just have to test it then. If it doesn't work out, I'll simply switch over to the regular niacin. Thanks for the heads up.

I haven't posted in a long time, but I still read the forums regularly. I'll be following along as I am ApoE 4/4 and this is one of the most recent active discussions on ApoE4 on the web, and I think the people in this forum could contribute to what is a fairly obscure topic. I mean, there's plenty of research, but there is relatively little serious discussion about the genotype with regards to diet.

My cholesterol seems to track fairly well with yours. That is: total cholesterol ~190-220, LDL ~140-160, HDL ~40-50, Triglycerides ~50-75. These are my numbers on mostly "real" food with fat being anywhere from 40-60% of my diet, from MUFA and SFA primarily (eggs, meat, butter, yogurt, and olive oil). There was a time when I did a very low fat diet with Chol ~150, LDL ~115, HDL ~35, TAG ~75. From what I've read it would seem most people with ApoE4 who respond poorly to dietary fat have quite high cholesterol levels. It seems I can consume a few thousand calories each day of a high fat diet and not have sky-high numbers, so I've recently been considering the trade off in lower total and LDL cholesterol for higher numbers with a probably better density profile.

Of course there is a lot more than overt numbers to go by. I'm reminded of a study showing mice transfected with human ApoE4 (IMO, a very relevant model) had the same cholesterol profiles as WT mice but had much greater progression of atherosclerosis.

Hey, thanks for posting man. We should track our blood numbers from year to year, and see what diet works best. As for the mouse study, that is indeed worrisome. Were the mice engineered before birth or was it gene therapy?

I would be interested in a way to scan for plaques using some sort of modern technology. I should look into that..

Edited by Elus, 08 February 2012 - 08:05 PM.

[James Cain]

With regards to the interaction between ApoE isoform and other mediators of lipids and athersclerosis, I think this is a good summary of human vs. animal models. The whole paper is pretty good, but here's the relevant section:




http://www.jlr.org/c...ement/S178.full

MICE WITH HUMAN APOE ISOFORMS

While the apoEKO mouse has been established as an excellent model of atherosclerosis, the lack of apoE is extremely rare in the human population. However, apoE is polymorphic in humans, and plasma LDL cholesterol levels and atherosclerosis risk are both strongly associated with the three common apoE isoforms in the order of apoE4 > apoE3 > apoE2. This association is rather counterintuitive because apoE4 (Arg-112 and Arg-158) binds to LDLR with a slightly higher affinity than apoE3 (Cys-112 and Arg-158), while apoE2 (Cys-112 and Cys-158) binds to the receptor with much reduced affinity (15).

Unlike in humans, the plasma lipoprotein profiles in apoE knockin mice expressing the human apoE proteins in place of mouse apoE are reflective of their different LDLR affinities. Thus, mice with apoE3 and apoE4 are normolipidemic and do not develop atherosclerosis even on a Western-type diet (15). In contrast, mice with human apoE2, which binds to LDLR with less affinity, accumulate plasma remnants with high cholesterol and triglycerides (TG) and develop atherosclerosis (16).

Surprisingly, however, mice with human apoE2, E3, or E4 recapitulate the lipoprotein profiles of their human counterparts when they also express a high amount of the human LDLR and are fed a Western-type diet (17). Thus, an increased expression of LDLR in mice with human apoE4 causes an accumulation of cholesterol-rich, apoE-poor remnants in plasma, a reduction of HDL, and severe atherosclerosis. In marked contrast, the same increase in LDLR in apoE2 mice ameliorates their hyperlipidemia and diet-induced atherosclerosis. These results raise the possibility that apoE4, by binding strongly to excess LDLR, is prevented from transferring to nascent lipoproteins, a step necessary for their subsequent clearance. This in turn leads to an increase in the plasma concentration of apoE-poor remnants. Indeed, we found that primary hepatocytes from apoE4 mice secrete less apoE into the medium than hepatocytes from apoE2 mice. Increased LDLR expression leads to a localization of apoE4 on the hepatocyte surface and enhances sequestration of apoE-deficient VLDL remnants injected into apoE4 mice. However, these surface-bound VLDL were poorly internalized compared with apoE2 mice (18).

ApoE isoform-dependent changes in cholesterol uptake and efflux from macrophages have been reported (19, 20). Cholesterol delivery to macrophages in culture increases as LDLR expression increases, and the effect was more prominent in apoE4 macrophages than those with apoE3 (21). Conversely, increased LDLR expression reduces cholesterol efflux from macrophages expressing apoE4 but not apoE3 (22). Consequently, in mice with human apoE4 that lack the LDLR (LDLRKO), the replacement of bone marrow cells with cells expressing LDLR increased atherosclerosis in a dose-dependent manner compared with mice transplanted with LDLRKO cells. In contrast, atherosclerosis in LDLRKO mice expressing human apoE3 was not affected by the bone marrow with varying levels of LDLR expression (22). Although further tests are required to extrapolate these findings in mice to humans, interactions between apoE isoforms and LDLR in macrophages likely contribute to the association of apoE4 with an increased cardiovascular risk in humans.

Edited by James Cain, 08 February 2012 - 08:18 PM.

[niner]

Would it be possible for you to give me editing privileges on my post? I'd like to edit my additional supplements in.

Mods can't do that, although it might be possible for an admin to do it. The easiest solution is just to repost an update, which has the advantage of keeping the thread logic right, if the earlier regimen had been discussed.

[nowayout]

Would it be possible for you to give me editing privileges on my post? I'd like to edit my additional supplements in.

Mods can't do that, although it might be possible for an admin to do it. The easiest solution is just to repost an update, which has the advantage of keeping the thread logic right, if the earlier regimen had been discussed.

I agree. It is better to post a new message to the thread witth the updates. I have in the past been mightily confused on other forums where people cold update the first post, thereby turning much of the subsequent discussion into non sequiturs.

Edited by viveutvivas, 08 February 2012 - 10:37 PM.

[Elus]

WTF...

http://www.cbsnews.c...ope-for-humans/


Cancer drug reverses Alzheimer's disease in mice: Hope for humans?

The drug, bexarotene, reversed signs of Alzheimer's in mice brains and also improved their memory in as little as 72 hours, according to the study.

"This is an unprecedented finding," study author Paige Cramer, a PhD candidate at Case Western Reserve School of Medicine, said in a university written statement. "Previously, the best existing treatment for Alzheimer's disease in mice required several months to reduce plaque in the brain."

...

Dr. Landreth and his grad student, Cramer, thought if they could use this drug to increase ApoE, then maybe they could reduce some of the plaques in mice that were genetically bred to have Alzheimer's. The researchers found that the drug caused a 50 percent reduction in the amount of amyloid plaques within only three days, and after 14 days, they saw a 75 percent reduction. The drug essentially "reprogrammed" the brain's immune cells to "eat" the amyloid plaques.

Edited by Elus, 10 February 2012 - 06:00 PM.

[Elus]

Thought I would give a quick update... I've been having some success with following my diet. I've been making salads for lunch and dinner, and I try to have a piece of fruit or two for breakfast (a banana or orange usually). My rationale for fruit is that the sugar helps me wake up a bit more easily (I have a hard time waking up). I also tried .5 mg of melatonin before bed to help bring my sleeping schedule back to its baseline time (Usually that's 11pm-1am, but sometimes I stay up a bit later and the melatonin helps).

I've been having some success with exercising. I am managing to go to the gym 2-3 times per week (ideally it should be 4-5, but I'm working on it...kinda new to the whole gym thing). I've been running 2-3 miles at 6.0-6.5 mph. After that, I do some inverted situps, some pullups, and some chest exercises on the machines.. In all it's about an hour at the gym (yeah, not impressive but hopefully I can improve). I consume whey protein mixed with water before workouts.

Other than that, I've been sticking to some wraps from blimpies, vegetable soups, grilled chicken, tuna, a little bit of pasta (less than handful), and the occasional omelet with vegetables.

My motivation is good, my classes are interesting, and I'm doing alright, I think. Anyway, here's picture of a nice salad I made, and one of me at the current age of 20 ^^.

[Next]

Start APOE4, become APOE3 when such gene therapy is available?

I'd be interested in your estimation of the difficulty of such a procedure, or an estimate of when such a thing might be possible.

Gene therapy in the organ that gives rise to consciousness is not going to be taken lightly when the time comes to try it out clinically (in maybe 20 years)