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Just discovered I'm APOE4. Now what?

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#1 game6

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Posted 11 May 2012 - 12:53 AM


Basically, my question is . . . what supplements/lifestyle choices would you consider critical if you were APO E3/E4?

I’m a 35 year old male, 5’11” and 190lbs. For close to a decade I’ve followed a low-carb, high-fat diet, only to see my total cholesterol gradually get higher. A decade ago, it was just under 200, so I didn’t worry about it too much, but now it is around 260. After some research, I began to wonder whether I carried the APOE4 gene. I just got my 23andme results back and, sure enough, I’m E3/E4.

This has caused me to question everything I thought I knew about nutrition and lifestyle. Based on my reading here and other places, I’ve begun the process of eliminating saturated fat and cholesterol from my diet, which sucks because I love red meat and cheese. And I’m trying to drop alcohol altogether, which is even harder than giving up meat (an evening cocktail is/was one of the highlights of my day). I’ve also added daily flush niacin to my supplement regimen to try to bring cholesterol down some.

I think the moves above are probably necessary, even though they have taken much of the fun out of life. The problem is, beyond these things, I’m kind of at a loss for what else I should be doing to lower the risk of CVD and AD that comes with APOE4. Some of my questions:
  • Historically, I tend to prefer a mix of weight training and HIIT (and sometimes P90X), as opposed to steady cardio. Should I instead start doing more sustained cardio?
  • Can I still eat fats that aren’t saturated, like nuts and avocado? Or should I try to limit all forms of fat?
  • Due to the APOE4 gene, are there certain supplements I should be adding/subtracting from my regimen (listed below)? I also know there are studies that suggest certain vitamins negate the effects of exercise. Since I’ll be renewing my focus on exercise, as it is apparently important for APOE4 individuals, are there supplements I should be dropping from my regimen?
Thanks all for your thoughts/suggestions. This genetic discovery has really turned my world upside down.

SUPPLEMENT REGIMEN

On an empty stomach:
ALC 1g x 3 times
ALA 300mg x 3 times
Benfotiamine 80mg x 3 times
Taurine 1g x 3 times
NAC 600mg x 2 times
Ecklonia cava extract 400mg x 2 times
Navitas Cacao Powder 2 tbsp
Magnesium 400mg
Ashwagandha extract 225mg
Selenium 200mcg
ZMA (bed)
Melatonin (bed)

With meals:
Vimmortal 2 capsules x 3 times
Fish Oil 1.2g total EPA/DHA x 3 times
GliSODin 100mg x 2 times
Niacin 500mg
Vitamin D3 2400IU
Jarrow Curcumin 500mg
Resveratrol 200mg
Blueberry Extract 1 capsule
Green Tea Phytosome 1 capsule
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#2 nameless

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Posted 11 May 2012 - 01:13 AM

I'm also APO E3/E4. The main thing I guess I'd recommend would be to restrict saturated fats, and not go crazy on other fats, like you plan to do. Some nut fats + olive oil should be okay, but that may vary per person.

The fact that a decent percentage of people do have the E4 allele makes me cringe every time I see people promoting high fat diets, without taking into account that for some people, it's a real bad idea. I lost some faith in Dr. Davis' blog, after seeing him repeatedly lean pro-paleo, pro-fat... and then one day he threw out a post about E4 people not doing well on such diets... sort of contradicting what he had been saying all along. Pro-fat people should put an asterisk next to their recommendations -- only okay for non-E4 people.

Anyway, lower inflammation, reduce fats, and reduce that fish oil too. There isn't a need for that much fish oil. I'd drop or lower selenium, drop NAC, drop Benfotiamine, and probably drop a lot of those other things too, but that's just a general recommendation, nothing to do with being A3/A4.
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#3 game6

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Posted 11 May 2012 - 01:35 AM

The fact that a decent percentage of people do have the E4 allele makes me cringe every time I see people promoting high fat diets, without taking into account that for some people, it's a real bad idea.


Seriously, it's really depressing to think about the damage I've done to my body by trying to eat "healthy" over the last decade. Do you completely abstain from alcohol? I feel like this gene is death sentence to my social life.
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#4 nameless

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Posted 11 May 2012 - 01:42 AM

You are still young-ish, so you may have not done that much damage. If your c-reactive protein has been low, and your LDL not insanely high, you are probably okay. It's when people go high fat with A4, or especially A4/A4, and ignore their LDL of 160+, thinking it's not important or miscalculated, that I'd worry.

In a weird way, being A4 didn't change my diet a whole lot. I never ate tons of fat to begin with. And not out of health reasons, but simply because I didn't like the taste of most fatty foods. I reduced saturated fats some, increased olive oil some, since finding out, but no idea if it made a difference as to my health.

And I've never been a big drinker either. I sort of felt cheated as to alcohol. I was never was one to get drunk. I went straight from feeling normal, to feeling sick... so I never really drank very often. I can't drink now anyway, due to another health issue. But for me, that was no biggie.

Edited by nameless, 11 May 2012 - 01:43 AM.

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#5 Junk Master

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Posted 11 May 2012 - 03:18 AM

You don't have to abstain from a couple glasses of red wine per day, but a couple bottles might not be the best idea for your brain, or cardiac health.

Bottom line is can you stop at two?
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#6 Luminosity

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Posted 11 May 2012 - 04:37 AM

What is this APO thing? What are the other abbreviations about?
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#7 game6

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Posted 11 May 2012 - 04:55 AM

What is this APO thing? What are the other abbreviations about?


Apolipoprotein E, or APOE. There are different variants of the gene, mapped to chromosome 19. Most people have APOE3, which has a neutral effect on lipids and a normal likelihood of Alzheimer's. About 20% of people have one copy of the variant APOE4, which doubles the chances of AD and increases the risk of CVD. For people who have two copies of APOE4 (about 2% of the population), they have maybe a 20x chance of getting AD.

People with an APOE4 gene tend to have the opposite reaction that APOE3 people have to a low-carb diet--that is, it increases LDL.
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#8 smithx

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Posted 11 May 2012 - 10:07 AM

I just recently found out I'm A3/A4 too. And there's a history of heart attacks in my family. And I just had a VAP test and it was not good: HDL 30, lots of small dense LDL, high trigs.

I've started taking niacin 500mg 2x/day. I don't want to go higher because it raises homocystine, and can cause liver damage, but the "therapeutic dose" is about 2G. OTOH, I haven't found data on whether niacin is beneficial for APO E4 or not. This very interesting document says statins are not beneficial, but doesn't mention niacin:
http://www.bhlinc.co....php?chapter=19

I also started taking three of these with each meal, because they contain plant sterols and oat beta glucan:
http://www.futurebio...lesterolbalance

To try to minimize the artery clogging effects, I've been taking 5000 IU of vitamin D and 15mg of vitamin K2.

I'm exercising too, but wonder what else would be helpful.

The other thing is, I haven't come across many studies which resulted in specific recommendaitons for APO E4 people. If anyone has good references, they'd be very much appreciated.
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#9 game6

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Posted 11 May 2012 - 01:30 PM

I also started taking three of these with each meal, because they contain plant sterols . . .


Again, I'm not sure what to believe anymore (hence, this post), but Dr. Davis thinks that sterols should be avoided by people with Apo E4. Just FYI, in case you hadn't seen it.

http://www.wellspher...ination/1354404
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#10 maxwatt

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Posted 11 May 2012 - 02:10 PM

The niacin/homocystine angle has another complication: if you have are heterozygous or homozygous for the MTHFR SNP, you cannot use folic acid efficiently. Since folate is necessary to keep homocystine low you will have to eat tons of leafy greens to compensate, more than most people can or do. But one can supplement with the active form of folate, methyl-tetrahydro-folate which is sold by an increasing number of supplement makers under various names. Solgar, Thorne and others are selling it.

23andme does not report this directly. You will have to download your raw data from the 23andme site to a spreadsheet, then go to promethase
( http://www.snpedia.c...php/Promethease ) and create a report from the data. The free version takes a couple of hours to parse the file, but for about two dollars you can get the results in two minutes, plus more data analysis on your SNPs.

You will have to search through the results to find if you have the MTHFR snp. If you do, I think supplementing 5-MTHF can alleviate much of the cardiovascular risk.
I found 23andme's reporting to be vague, where promethease drills down to a lot more information.

Some months ago 23andme reported on three different SNP combinations; the upshot was three types:
One does well with high saturated fat (>30%), keeping a stable weight on such a diet. Paleo.
A second does will with a high mono-unsaturated fat diet, i.e. Mediteranean, keeping a stable weight with a high percentage (>30) of calories from such fats.
The third group, alas mine, will gain weight and develop bad lipid profiles if any fat calories exceed about 30% of the diet. I guess you can call this the Chinese subsistence farmer's diet.

This is why I get fat on paleo, but my lipid profile is excellent if I go semi-vegan, very little cheese, most days no meat at all. As many carbs as I want as long as they are not from sucrose or fructose; fruit is OK in moderation. My HDL is a bit lower than I'd like to see, promethease indicates I have a gene resulting in large particle size for all my lipoproteins, though I've not had it tested . Such means lower risk for heart attacks or dementia.

I'd post links but I have a project due, and little time to look them up. Coffee break over.
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#11 game6

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Posted 11 May 2012 - 04:11 PM

maxwatt, many thanks for your post, this is fascinating. I just ran promethase and this is what I got related to the (apparently aptly named) MTHFR:

rs1801133 is a SNP that is relatively common and has been studied for (relatively) a long time. Also known as C677T, Ala222Val, and A222V, it encodes a variant in the MTHFR gene, which encodes an enzyme involved in folate metabolism. Homozygous rs1801133(T;T) individuals have ~30% of the expected MTHFR enzyme activity, and rs1801133(C;T) heterozygotes have ~65% activity, compared to the most common genotype, rs1801133(C;C). This reduced activity (i.e. this SNP) has been linked at least once to each of the following disorders (though not necessarily reproducibly): * autism * cancer, including ** gastric cancer ** lung cancer ** head and neck cancer * cleft lip and cleft palate * coronary artery disease * depression * hyperhomocysteinemia * migraine * neural tube defects * pre-eclampsia (ges...


Also, this:




gs192
3 Magnitude 20100613 Geno time

75]
MTHFR polymorphisms affecting homocystine You have 2 variations in MTHFR which influence homocystine levels. people with gs193 are more strongly affected.







So, I'm assuming from this that I should be supplementing as you suggested? If I do, need I worry about the amount of niacin I take?

Edited by game6, 11 May 2012 - 04:12 PM.

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#12 scottknl

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Posted 11 May 2012 - 07:28 PM

Basically, my question is . . . what supplements/lifestyle choices would you consider critical if you were APO E3/E4?

I’m a 35 year old male, 5’11” and 190lbs. For close to a decade I’ve followed a low-carb, high-fat diet, only to see my total cholesterol gradually get higher. A decade ago, it was just under 200, so I didn’t worry about it too much, but now it is around 260. After some research, I began to wonder whether I carried the APOE4 gene. I just got my 23andme results back and, sure enough, I’m E3/E4.

This has caused me to question everything I thought I knew about nutrition and lifestyle. Based on my reading here and other places, I’ve begun the process of eliminating saturated fat and cholesterol from my diet, which sucks because I love red meat and cheese. And I’m trying to drop alcohol altogether, which is even harder than giving up meat (an evening cocktail is/was one of the highlights of my day). I’ve also added daily flush niacin to my supplement regimen to try to bring cholesterol down some.

I think the moves above are probably necessary, even though they have taken much of the fun out of life. The problem is, beyond these things, I’m kind of at a loss for what else I should be doing to lower the risk of CVD and AD that comes with APOE4. Some of my questions:

  • Historically, I tend to prefer a mix of weight training and HIIT (and sometimes P90X), as opposed to steady cardio. Should I instead start doing more sustained cardio?
  • Can I still eat fats that aren’t saturated, like nuts and avocado? Or should I try to limit all forms of fat?
  • Due to the APOE4 gene, are there certain supplements I should be adding/subtracting from my regimen (listed below)? I also know there are studies that suggest certain vitamins negate the effects of exercise. Since I’ll be renewing my focus on exercise, as it is apparently important for APOE4 individuals, are there supplements I should be dropping from my regimen?
Thanks all for your thoughts/suggestions. This genetic discovery has really turned my world upside down.

SUPPLEMENT REGIMEN

On an empty stomach:
ALC 1g x 3 times
ALA 300mg x 3 times
Benfotiamine 80mg x 3 times
Taurine 1g x 3 times
NAC 600mg x 2 times
Ecklonia cava extract 400mg x 2 times
Navitas Cacao Powder 2 tbsp
Magnesium 400mg
Ashwagandha extract 225mg
Selenium 200mcg
ZMA (bed)
Melatonin (bed)

With meals:
Vimmortal 2 capsules x 3 times
Fish Oil 1.2g total EPA/DHA x 3 times
GliSODin 100mg x 2 times
Niacin 500mg
Vitamin D3 2400IU
Jarrow Curcumin 500mg
Resveratrol 200mg
Blueberry Extract 1 capsule
Green Tea Phytosome 1 capsule

Yeah, so I was in the same boat as you with APOE3/4 (via 23andme) and 6'2" 190 lbs with high cholesterol. Everything else I tried didn't make a lot of progress, but when I implemented a vegetarian CRON diet my lipid numbers went from bad to perfect. You can see my diet in the Vegetarian CRON posting in the Calorie Restriction section if you want. Yes, it can be done. I never had any social life to begin with (**geek**) so no loss there, but I did retain a little bit of red wine each day with my resveratrol. My physical performance for long distance running improved dramatically, but I gave up some muscle strength but added the benefit of getting a ripped muscular look (but not big). I like the trade offs. No big sexual side effects that I noticed either.

Cheers.
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#13 smithx

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Posted 11 May 2012 - 10:08 PM

Wow, this Promethease report is depressing, at least in my case. I wonder if it was counter productive to look at, since the mind influences health.

According to the report, I am much more likely to get cancers, heart disease, macular degradation, liver disease, diabetes and baldness. I'm already bald, which makes me wonder about the rest. Until recently I thought I had really good genes, but if I believe I'm likely to get sick, the chances I will increase. So... more supplements and exercise...

Maxwatt: I do have rs1801133 C:T which gives me only 65% folate metabolism, but I am supplementing methylfolate, and my homocystine levels have always been fairly low.

The article about sterols possibly being very bad for APO E4 people is worrisome, but he doesn't link any study indicating that sterols are actually absorbed differently by APO E4 people. http://www.wellspher...ination/1354404 Are there any studies indicating that?

I'm rather shocked at the dearth of information and advice specific to people with different genotypes, since they seem to make such a difference.

So I should get off low carb and go on a low fat diet instead? I did lose quite a lot of weight on low carb, so that idea is confusing. And since I apparently have such a predisposition to diabetes, staying low carb would seen to be a good idea from that perspective.

Anyone with thoughts/references?
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#14 nameless

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Posted 11 May 2012 - 11:51 PM

@smithx

I'd recommend probably dropping the sterols. There is no data (that I am aware of) that they lower heart disease. And just moving cholesterol numbers around -- lower LDL or higher HDL -- doesn't always work, as seen by several failed drug therapies. It may result in a better result on a cholesterol test, but if it doesn't improve CVD risk, it's a waste... or possibly harmful.

And the lack of data or dietary advice on APO genotypes is annoying, and surprising. I've also wondered what the avg. genotype is for populations with low risk of CVD. -- ie:
A racial difference in apolipoprotein E allele frequencies between the Japanese and Caucasian populations.

http://www.ncbi.nlm.nih.gov/pubmed/3802561


What are your lipid numbers? Did you get a VAP done? I'd also recommend a VAP for game6 too... total cholesterol is sort of a meaningless number. It may take some trial and error to find a diet that seems best.
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#15 game6

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Posted 12 May 2012 - 12:26 AM

@scottknl -- If you don't mind me asking, how much do you weigh now after doing CRON? And how long have you been doing it?

@smithx -- Yeah, this whole thing is unbelievably depressing. I'd feel better if I just knew what I should be doing to balance it (and better yet if that didn't require me to give up meat and alcohol entirely).

@nameless -- When I had my lipid panel directly measured two years ago, these were the results. Based on my recent non-directly measured results, I would guess that all are slightly higher now.

Total LDL-C 159
Total HDL-C 60
Total VLDL-C 24
Total Cholesterol 243
Triglyceride 117
Lp(a) 6
IDL 16
Real LDL 137
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#16 smithx

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Posted 12 May 2012 - 12:40 AM

Here's my VAP:

LDL Density Pattern B Abnormal
LDL4 Pattern B 22.5 mg/dL
LDL3 Pattern B 47.4 mg/dL
LDL2 Pattern A 4.8 mg/dL
LDL1 Pattern A 19.3 mg/dL
VLDL-3 (Small Remnant) 16 High mg/dL <10
HDL-3 (Less Protective) 28 Low mg/dL >30
HDL-2 (Most Protective) 7 Low mg/dL >10
Probable Metabolic Syndrome Yes
Remnant Lipo. (IDL+VLDL3) 34 High mg/dL <30
IDL Cholesterol 18 mg/dL <20
Lp(a) Cholesterol 1.0 mg/dL <10
LDL-R (Real)-C 94 mg/dL <100
apoB100-calc 100 mg/dL <109
Non HDL Chol. (LDL+VLDL) 146 mg/dL <160
Triglycerides 153 High mg/dL <150
Cholesterol, Total 181 mg/dL <200
VLDL Cholesterol 33 High mg/dL <30
HDL Cholesterol 35 Low mg/dL >=40
LDL Cholesterol 113 mg/dL <130

The numbers after <>= are desired numbers. The numbers to the left are my measured numbers.

It could be a lot worse, but it's definitely not great.
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#17 scottknl

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Posted 12 May 2012 - 01:38 AM

@scottknl -- If you don't mind me asking, how much do you weigh now after doing CRON? And how long have you been doing it?

...snip...

This morning I was 157 lbs. I started CRON in June of 2009. My numbers have been very steady since September 2009. So a really good diet and some exercise really helps. FYI my max weight was 203 lbs in 2001.
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#18 maxwatt

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Posted 12 May 2012 - 02:38 PM

Wow, this Promethease report is depressing, at least in my case. I wonder if it was counter productive to look at, since the mind influences health.

According to the report, I am much more likely to get cancers, heart disease, macular degradation, liver disease, diabetes and baldness. I'm already bald, which makes me wonder about the rest. Until recently I thought I had really good genes, but if I believe I'm likely to get sick, the chances I will increase. So... more supplements and exercise...

Maxwatt: I do have rs1801133 C:T which gives me only 65% folate metabolism, but I am supplementing methylfolate, and my homocystine levels have always been fairly low.

The article about sterols possibly being very bad for APO E4 people is worrisome, but he doesn't link any study indicating that sterols are actually absorbed differently by APO E4 people. http://www.wellspher...ination/1354404 Are there any studies indicating that?

I'm rather shocked at the dearth of information and advice specific to people with different genotypes, since they seem to make such a difference.

So I should get off low carb and go on a low fat diet instead? I did lose quite a lot of weight on low carb, so that idea is confusing. And since I apparently have such a predisposition to diabetes, staying low carb would seen to be a good idea from that perspective.

Anyone with thoughts/references?


If your lipids are good on low carb, and you're not getting fat, then it works for you. But test the lipids. I was skinny-fat.
By the promethease analysis I'd think a low fat diet would be better for you but the carbs cannot be from sucrose or fructose. Complex carbs are key. Lots of greens, nuts, mushrooms. More fish than meat, meat as an occasional indulgence.
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#19 nameless

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Posted 12 May 2012 - 07:16 PM

@smithx

Your numbers sort of remind me of my own. My particle sizes and trig numbers are a little better, while your ldl is a little lower than mine. Your lp(a) is quite good. But my HDL sort of stinks, like yours does too ... mine tends to vary between 30-40. I think once or twice I got it a tad over 40, but it's hardly ideal.

They are basically numbers that will get your family doctor to say, 'Good enough'... but to a cardio, they'll look somewhat lousy. The niacin should help you some -- for myself, I unfortunately cannot tolerate it. As Maxwatt mentioned, reduce or eliminate simple carbs.

I also recommend getting your c-reactive protein checked, and get HbA1c tested too. The latter will test your glycated hemoglobin, or glucose levels for the past several months.

@game6

I'd love to have your HDL numbers. But yeah, your LDL needs some work there. Dietary changes + niacin should help.

Edited by nameless, 12 May 2012 - 07:18 PM.

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#20 smithx

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Posted 12 May 2012 - 07:51 PM

It's confusing: eliminate carbs but also fat? Then what are APO E4 people supposed to eat? I have been low carb intermittently for a while, but that involves lots of nuts, fatty meats, etc.

BTW, here are those other test results.
C-Reactive Protein, Cardiac 1.58 mg/L (Range 0.00-3.00)
HbA1c 4.5% (Range 4.8% to 5.9%)

That last figure has everyone baffled because my fasting blood glucose is consistently measured at 99 or 100, which isn't that low. It's been retested twice and comes up the same every time.
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#21 nameless

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Posted 12 May 2012 - 08:32 PM

Yeah, I know... it's difficult to know what to eat. For myself, it was more a reduction in simple carbs, rather than all carbs. Unless you just chew on low fat protein all day, I don't think you can go super low carb and low fat at the same time. Restrict wheat/breads, restrict dessert-type foods, restrict sugar, etc. I'd recommend more veggies over meat.

Your c-reactive protein and HbA1c are also very similar to mine. I think you have my blood.

One weirdness is that with such a decent HbA1c, you'd think our trigs would be super low. Or at least I had assumed such. My fasting glucose is lower, however -- not sure if there is any significance to your number or not.
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#22 niner

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Posted 12 May 2012 - 09:34 PM

It's confusing: eliminate carbs but also fat? Then what are APO E4 people supposed to eat? I have been low carb intermittently for a while, but that involves lots of nuts, fatty meats, etc.

BTW, here are those other test results.
C-Reactive Protein, Cardiac 1.58 mg/L (Range 0.00-3.00)
HbA1c 4.5% (Range 4.8% to 5.9%)

That last figure has everyone baffled because my fasting blood glucose is consistently measured at 99 or 100, which isn't that low. It's been retested twice and comes up the same every time.


That's a great HbA1C. You probably have very low post-prandial glucose spikes. In non-diabetics, HbA1C is dominated by the post-prandial values. In diabetics, high fasting glucose tends to be a bigger part of HbA1C.

For an ApoE 4 diet, you'll want to do what nameless said; avoid sugar and refined grains. Eat lots of non-starchy vegetables. At the bottom of this thread are other threads that have the tag 'apoe4'. A couple of those are pretty good. It's probably not necessary to go crazy low with either fat or alcohol, though you'll want to be kind of low on both. You're lucky that you at least know your status, because now you can start to do something about it, and will know what to monitor. I'm not happy about my lp(a), but at least now I'm doing something about it.
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#23 Elus

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Posted 12 May 2012 - 11:01 PM

I am E3/E4 too. Made a thread about my results if you want to check that out Q_Q

http://www.longecity...ecommendations/
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#24 game6

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Posted 13 May 2012 - 06:02 PM

You will have to search through the results to find if you have the MTHFR snp. If you do, I think supplementing 5-MTHF can alleviate much of the cardiovascular risk.


What is the recommended dosage of 5-MTHF for people who are heterozygous rs1801133(C;T)? I notice that they sell it in 1mg, 5mg, and even 10 mg doses.
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#25 game6

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Posted 13 May 2012 - 06:11 PM

I'd love to have your HDL numbers. But yeah, your LDL needs some work there. Dietary changes + niacin should help.


I ate a lot of coconut oil, which I think contributed to the good HDL levels. Of course, now I know it might have also been contributing to high LDL. I worry that my HDL will drop along with my LDL as a result of this switch to low fat. I guess we'll see. Which brings me to a question I had...how long should I give a low-fat diet before checking my lipids again? I know I have to give it some time to work, but I'd kind of like to know sooner rather than later if its working. I'm a little on edge about CVD right now...my girlfriend's father (a very slight, fit man in his early 60's) just had quadruple bypass surgery.


It's probably not necessary to go crazy low with either fat or alcohol, though you'll want to be kind of low on both.



niner: I hope you are right that it's not necessary to be a teetotaler, as I really do enjoy a drink here and there. But I'm a bit scared by this: http://blog.cognitiv...s-risk-for.html

The key quote:

"Persons who had the apoE4 and drank infrequently had a four times higher risk of developing dementia compared with people who never drank," Kivipelto said. Frequent drinkers with the apoE4 gene had seven times the risk compared with people who never drank, she added.

Frequent drinking was defined as drinking several times a month. Infrequent drinking was drinking less than once a month, according to the report in the Sept. 4 issue of the British Medical Journal.


Edited by game6, 13 May 2012 - 06:48 PM.

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#26 maxwatt

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Posted 13 May 2012 - 06:49 PM


You will have to search through the results to find if you have the MTHFR snp. If you do, I think supplementing 5-MTHF can alleviate much of the cardiovascular risk.


What is the recommended dosage of 5-MTHF for people who are heterozygous rs1801133(C;T)? I notice that they sell it in 1mg, 5mg, and even 10 mg doses.


That is a very good question, whose answer I can but guess. I think that bypassing the limiting enzyme is good enough, and going with the maximum recommended dose for folic acid is a starting point -- that would be 400 mcg or twice that - 800 mcg - if you are pregnant ;). I am homozygous for MTHFR, and take 1000 mcg ( 1 mg). I hope it's enough. Perhaps the only way to tell is to look at your homocystine levels before and after supplementing. The combination of APOe4 and MTHFR would be bad, but I think the right form of folate can reduce one's risk.
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#27 scottknl

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Posted 13 May 2012 - 07:16 PM

@game6:

I thought that study was a bit old, so I looked for a newer summary of alcohol consumption vs alz. I found this:
http://www.ncbi.nlm....90/?tool=pubmed

Neuropsychiatr Dis Treat.

2011;7:465-84. Epub 2011 Aug 11.


Moderate alcohol consumption and cognitive risk.


Neafsey EJ, Collins MA.



Source

Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago, Stritch School of Medicine, Maywood, IL, USA.



Abstract


We reviewed 143 papers that described the relationship between moderate drinking of

alcohol

and some aspect of cognition. Two types of papers were found: (1) those that provided ratios of risk between drinkers and nondrinkers (74 papers in total) and (2) those that, although they did not provide such ratios, allowed cognition in drinkers to be rated as "better," "no different," or "worse" than cognition in nondrinkers (69 papers in total). The history of research on moderate drinking and cognition can be divided into two eras: 1977-1997 and 1998-present. Phase I (1977-1997) was the era of neuropsychological evaluation involving mostly young to middle-aged (18-50 years old) subjects. Although initial studies indicated moderate drinking impaired cognition, many later studies failed to confirm this, instead finding no difference in cognition between drinkers and nondrinkers. Phase II (1998-present) was and is the era of mental status exam evaluation involving mostly older (≥55 years old) subjects. These studies overwhelmingly found that moderate drinking either reduced or had no effect on the risk of dementia or cognitive impairment. When all the ratios of risk from all the studies in phase II providing such ratios are entered into a comprehensive meta-analysis, the average ratio of risk for cognitive risk (dementia or cognitive impairment/decline) associated with moderate "social" (not alcoholic) drinking of alcohol is 0.77, with nondrinkers as the reference group. The benefit of moderate drinking applied to all forms of dementia (dementia unspecified, Alzheimer's disease, and vascular dementia) and to cognitive impairment (low test scores), but no significant benefit against cognitive decline (rate of decline in test scores) was found. Both light and moderate drinking provided a similar benefit, but heavy drinking was associated with nonsignificantly higher cognitive risk for dementia and cognitive impairment. Although the meta-analysis also indicated that wine was better than beer or spirits, this was based on a relatively small number of studies because most studies did not distinguish among these different types of alcohol. Furthermore, a number of the studies that did make the distinction reported no difference among the effects of these different types of alcohol. Therefore, at present this question remains unanswered. Analysis also showed that the presence of the apolipoprotein E epsilon 4 allele eliminated the benefit of moderate drinking. However, this was based on a relatively small number of studies and several other studies have found a beneficial effect of the epsilon e4 allele. Further studies are necessary to settle this question. The benefit of moderate

alcohol for cognition was seen in both men and women, although the amount and pattern of drinking is very different between the two sexes. Lastly, the finding of unaffected or significantly reduced cognitive risk in light to moderate drinkers was seen in 14/19 countries for which country-specific ratio data were available, with three of the five remaining countries showing nonsignificant reductions as well. Overall, light to moderate drinking does not appear to impair cognition in younger subjects and actually seems to reduce the risk of dementia and cognitive decline in older subjects.

edit: formatting, bold

Edited by scottknl, 13 May 2012 - 07:20 PM.

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#28 game6

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Posted 13 May 2012 - 08:30 PM

@scottknl: Thanks for that summary of studies, it just made my entire weekend! I had been a relatively heavy drinker (approximately 3-4 drinks per day), so the thought of total abstinence was very unappealing. Based on what you sent, it sounds like it probably isn't necessary. I do think I need to reduce my drinking, probably to no more than 1-2 per day.

Based on what I'm reading, I'm starting to think that to the extent alcohol consumption is correlated with increased AD risk in ApoE4 carriers, the correlation may be entirely due to the unusually negative effect that drinking can have on an ApoE4's HDL/LDL. If that's true, then light to moderate drinking might not be harmful, so long as lipid numbers remain in good shape.

That is a very good question, whose answer I can but guess. I think that bypassing the limiting enzyme is good enough, and going with the maximum recommended dose for folic acid is a starting point -- that would be 400 mcg or twice that - 800 mcg - if you are pregnant ;). I am homozygous for MTHFR, and take 1000 mcg ( 1 mg).


Thanks, that's very helpful. I think I'll avoid the expensive high-dose varieties, at least to start.

Edited by game6, 13 May 2012 - 08:52 PM.

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#29 James Cain

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Posted 13 May 2012 - 08:47 PM

A few weeks ago I pulled together the most relevant 5-6 papers on ApoE and alcohol consumption for my personal collection, and I think one or two had some decent mechanistic reasoning for why alcohol wouldn't be either negative or at best neutral, but that it could potentially be irrelevant with an overall healthy lifestyle. I may have time to go through them tonight and post them, along with commenting quite a bit on stuff that was already said about ApoE4, but between celebrating my wife's birthday and my prelim exams next week I've been super busy.
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#30 buckwheats

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Posted 14 May 2012 - 01:30 AM

I think the answers on PaleoHacks to a similar question may be worth reading.

http://paleohacks.co...o#axzz1usyyyto4

especially the first one which points to a study that shows that apoe4 carriers' ldl particle size is greater on a high-fat diet compared to a low-fat one.

Edited by buckwheats, 14 May 2012 - 01:33 AM.

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