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My Blood Test Results [20 years old, ApoE-ε4] - Recommendations?

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#1 Elus

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Posted 05 January 2012 - 11:47 PM


Hi everyone,

After browsing Imminst and reading posts here, I decided that it would be wise to examine my current state of health. Therefore, I had some blood tests done. I also had my SNPs sequenced by 23andme. Any comments or recommendations regarding diet and supplements would be greatly appreciated. Below you'll find my blood test results and extra information that may be relevant:

Blood Test Results (Apologies in advance if I incorrectly copied something from the report)

Google Docs Spreadsheet: Link Here

Excel spreadsheet attachment here: Attached File  2012_Blood_Work.xls   15KB   45 downloads

Extra information:

Age: 20
Gender: Male
Weight: 132 lbs.
Height: 6 ft
BMI: 17.9
Genes: I carry both the ApoE-ε4 and ApoE-ε3 alleles.


Diet: I was experimenting with a high-fat paleo diet for 2-3 weeks prior to these blood tests. I found out about my ApoE-ε4 status a few days ago. Therefore, I am switching to a low-fat paleo diet (Advice niner was kind enough to give me - thanks niner). My aim is to avoid processed carbs, avoid sugar, increase nutrient dense vegetable intake, consume lean meat, and avoid alcohol. Meat intake would include fish and chicken (Though I can't be sure of the quality of either since I am at college and they tend to cut corners on organic food). This chart may also lend some insight to my decisions (Also courtesy niner):

Posted Image




Supplements:
  • 2x-3x Vimmortal multivitamin caps
  • 10,000 IU Vitamin D (This one) until recently, now cutting back to 5,000 IU because I think my Vitamin D level is too high (Aiming for 50 ng/mL).
  • 2 mg sublingual vitamin B12 (This one)
  • 2 grams fish oil (This one) (I'm not too sure if this will help or hurt given my ApoE status)
  • Occasional adrafinil and modafinil usage
  • Occasional cup of coffee
  • I'm also planning to order potassium iodide and green tea extract.
Issues: For the past year, I have been struggling with motivation (Currently working on a degree in biology or biochemistry) and procrastination. It started during second semester of freshman year in college (I'm currently beginning 2nd semester of sophomore year). I also have some lethargy, but it may just be in my head. I generally try to keep a positive attitude despite numerous academic failures I've had in the past year, though. This is partly what has lead me to carefully analyze my health.

Thanks, and happy new year!
-Elus

Edited by Elus, 05 January 2012 - 11:50 PM.

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#2 AgeVivo

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Posted 07 January 2012 - 11:56 AM

thinking of the future: when gene therapy becomes available and safe for apoe, wouldn't it be healthier to "simply" become 3/3?
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#3 niner

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Posted 07 January 2012 - 01:34 PM

Elus, things actually look pretty good in your blood tests, all things considered. The small dense LDL is probably the most worrisome, while the LDL really isn't that bad. The changes in your diet (reducing fat, alcohol, etc) will probably clean this up a lot. I'd stay with the fish oil, since it looks like s.d. ldl is more of an issue that total LDL. I like the iodine idea, along with the GTE. Both of those had positive effects on my mood and motivation, FWIW. You could knock your high iron down some by donating blood.

After a few months of the new regimen, you could repeat the tests that were abnormal. I'd be surprised if your doctor/insurer wouldn't go for that. I think you are going to be in great shape. You are super lucky to have figured this out at such a young age.
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#4 smithx

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Posted 07 January 2012 - 09:04 PM

I believe your HDL and LDL levels are definitely cause for concern.

The latest guidelines discussed by multiple researchers at the Lipid Summit last year (12/3/2011) were:

- LDL < 70
- HDL around 60

Increased LDL is is closely associated with atherosclerosis and increased risk, increased HDL is loosely associated with decreased risk. So getting the LDL down is probably more important than getting the HDL up.

For HDL, the story is a bit more confused: there seems to be a decreased risk around 60, then risk goes up again after that. However, the effectiveness of HDL depends on the person's genotype, so for some individuals very high HDL is protective, for others it's an indication of something going wrong.

A patient with levels like yours was discussed in one lecture as someone who appeared to be fine and was doing all the right things, but still got a heart attack at the age of 38.

From what I've read I'd suggest that you try niacin. It decreases LDL and raises HDL. 500mg to start once a day. Do not use time released niacin because it can cause liver damage.

Vitamin K2 will help keep the calcium out of your blood vessels.

Avoid wheat in particular and carbs in general.

Intense exercise 4x a week is also a must.

Edited by smithx, 07 January 2012 - 09:11 PM.

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#5 Michael

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Posted 07 January 2012 - 09:24 PM

Vitamin D: suggest targeting more like 30-40 ng/dL 25(OH)D3.

The iron: you will want to get this down, surely. I might suggest cutting down on the meat, in favor of vegetable protein if you want to keep your pro up: a better path on multiple fronts than (more than normal) blood donation.

Elus, things actually look pretty good in your blood tests, all things considered. The small dense LDL is probably the most worrisome, while the LDL really isn't that bad.


This is an idea that has some support in case-control studies, and has become widely believed because it has been advanced vigorously by paleo and strong low-carb advocates (esp when it touches on sat fat concerns), but there is little support for the idea in prospective studies, and the overall evidence doesn't support it.((1) -- and see more recently (2), published after this meta-analysis. And (3), again more recent, finds it in women but not men). Certainly your (Elus') levels are remarkably high. It looks to me like it's a surrogate marker for insulin resistance and central obesity, with no independent predictive power or etiological significance. No glycemia aside from fasting glucose, Elus ...?

IAC, it's total and LDL cholesterol that has been thus linked to risk of AD per se (rather than CVD) which is surely Elus' concern: I know of no studies looking specifically at small, dense LDL as a risk factor in AD.

Genotyping: an overall review finds the evidence on this lacking,(4,5) tho' this can't be considerede definitive as there are so few studies and no proper meta-analysis.


References
1: Ip S, Lichtenstein AH, Chung M, Lau J, Balk EM. Systematic review: association
of low-density lipoprotein subfractions with cardiovascular outcomes. Ann Intern
Med. 2009 Apr 7;150(7):474-84. Review. PubMed PMID: 19349632.

(AHRQ version here)


2: Toft-Petersen AP, Tilsted HH, Aarøe J, Rasmussen K, Christensen T, Griffin BA,
Aardestrup IV, Andreasen A, Schmidt EB. Small dense LDL particles--a predictor of
coronary artery disease evaluated by invasive and CT-based techniques: a
case-control study
. Lipids Health Dis. 2011 Jan 25;10:21. PubMed PMID: 21262005;
PubMed Central PMCID: PMC3038964.


3: Ai M, Otokozawa S, Asztalos BF, Ito Y, Nakajima K, White CC, Cupples LA,
Wilson PW, Schaefer EJ. Small dense LDL cholesterol and coronary heart disease:
results from the Framingham Offspring Study
. Clin Chem. 2010 Jun;56(6):967-76.
Epub 2010 Apr 29. PubMed PMID: 20431054.

4: Masson LF, McNeill G. The effect of genetic variation on the lipid response to
dietary change: recent findings. Curr Opin Lipidol. 2005 Feb;16(1):61-7. Review.
PubMed PMID: 15650565.

5: Masson LF, McNeill G, Avenell A. Genetic variation and the lipid response to
dietary intervention: a systematic review
. Am J Clin Nutr. 2003
May;77(5):1098-111. Review. PubMed PMID: 12716659.

Edited by Michael, 07 January 2012 - 09:28 PM.

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#6 Elus

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Posted 08 January 2012 - 07:51 PM

thinking of the future: when gene therapy becomes available and safe for apoe, wouldn't it be healthier to "simply" become 3/3?


Yeah, maybe one day. But for now I think that dietary modulation can do a lot to help overcome the downsides of this particular allele.

Elus, things actually look pretty good in your blood tests, all things considered. The small dense LDL is probably the most worrisome, while the LDL really isn't that bad. The changes in your diet (reducing fat, alcohol, etc) will probably clean this up a lot. I'd stay with the fish oil, since it looks like s.d. ldl is more of an issue that total LDL. I like the iodine idea, along with the GTE. Both of those had positive effects on my mood and motivation, FWIW. You could knock your high iron down some by donating blood.

After a few months of the new regimen, you could repeat the tests that were abnormal. I'd be surprised if your doctor/insurer wouldn't go for that. I think you are going to be in great shape. You are super lucky to have figured this out at such a young age.


Thanks, niner. Yes, I plan on repeating the tests for sure in the coming months. I will post an updated bloodwork here when I do. I could reduce iron by reducing meat intake as well, because I'm a little squeemish when it comes to needles and my arm ;). But yeah, if push comes to shove I could do that as well. I'll stick with fish oil for now but I'll see what the studies say when it comes to total LDL...

I believe your HDL and LDL levels are definitely cause for concern.

The latest guidelines discussed by multiple researchers at the Lipid Summit last year (12/3/2011) were:

- LDL < 70
- HDL around 60

Increased LDL is is closely associated with atherosclerosis and increased risk, increased HDL is loosely associated with decreased risk. So getting the LDL down is probably more important than getting the HDL up.

For HDL, the story is a bit more confused: there seems to be a decreased risk around 60, then risk goes up again after that. However, the effectiveness of HDL depends on the person's genotype, so for some individuals very high HDL is protective, for others it's an indication of something going wrong.

A patient with levels like yours was discussed in one lecture as someone who appeared to be fine and was doing all the right things, but still got a heart attack at the age of 38.

From what I've read I'd suggest that you try niacin. It decreases LDL and raises HDL. 500mg to start once a day. Do not use time released niacin because it can cause liver damage.

Vitamin K2 will help keep the calcium out of your blood vessels.

Avoid wheat in particular and carbs in general.

Intense exercise 4x a week is also a must.


Thanks for the niacin tip. I'll definitely look into that. Could you possibly link the lecture with the 38 year old heart attack victim? I'd love to compare my stats to his just for kicks (Though differing genetics would make such a comparison questionable).

Is my calcium high in my blood, do you think?

Also, I plan to up my exercise, but I will keep it fairly mild (Some biking, jogging, lifting probably). I'm a very skinny guy (as you can probably surmise from my posted BMI).

Vitamin D: suggest targeting more like 30-40 ng/dL 25(OH)D3.

The iron: you will want to get this down, surely. I might suggest cutting down on the meat, in favor of vegetable protein if you want to keep your pro up: a better path on multiple fronts than (more than normal) blood donation.
...
This is an idea that has some support in case-control studies, and has become widely believed because it has been advanced vigorously by paleo and strong low-carb advocates (esp when it touches on sat fat concerns), but there is little support for the idea in prospective studies, and the overall evidence doesn't support it.((1) -- and see more recently (2), published after this meta-analysis. And (3), again more recent, finds it in women but not men). Certainly your (Elus') levels are remarkably high. It looks to me like it's a surrogate marker for insulin resistance and central obesity, with no independent predictive power or etiological significance. No glycemia aside from fasting glucose, Elus ...?

IAC, it's total and LDL cholesterol that has been thus linked to risk of AD per se (rather than CVD) which is surely Elus' concern: I know of no studies looking specifically at small, dense LDL as a risk factor in AD.

Genotyping: an overall review finds the evidence on this lacking,(4,5) tho' this can't be considerede definitive as there are so few studies and no proper meta-analysis.


References
1: Ip S, Lichtenstein AH, Chung M, Lau J, Balk EM. Systematic review: association
of low-density lipoprotein subfractions with cardiovascular outcomes. Ann Intern
Med. 2009 Apr 7;150(7):474-84. Review. PubMed PMID: 19349632.

(AHRQ version here)


2: Toft-Petersen AP, Tilsted HH, Aarøe J, Rasmussen K, Christensen T, Griffin BA,
Aardestrup IV, Andreasen A, Schmidt EB. Small dense LDL particles--a predictor of
coronary artery disease evaluated by invasive and CT-based techniques: a
case-control study
. Lipids Health Dis. 2011 Jan 25;10:21. PubMed PMID: 21262005;
PubMed Central PMCID: PMC3038964.


3: Ai M, Otokozawa S, Asztalos BF, Ito Y, Nakajima K, White CC, Cupples LA,
Wilson PW, Schaefer EJ. Small dense LDL cholesterol and coronary heart disease:
results from the Framingham Offspring Study
. Clin Chem. 2010 Jun;56(6):967-76.
Epub 2010 Apr 29. PubMed PMID: 20431054.

4: Masson LF, McNeill G. The effect of genetic variation on the lipid response to
dietary change: recent findings. Curr Opin Lipidol. 2005 Feb;16(1):61-7. Review.
PubMed PMID: 15650565.

5: Masson LF, McNeill G, Avenell A. Genetic variation and the lipid response to
dietary intervention: a systematic review
. Am J Clin Nutr. 2003
May;77(5):1098-111. Review. PubMed PMID: 12716659.


Hey Michael, I definitely am planning to get my iron down (as it promotes oxidation, right). As for my primary concern, I don't want either CVD or AD, obviously, so I want to minimize my risk of both (23andme says I have a lowered risk of CVD, but I haven't actually read the studies that these claims are founded on, so I can't be sure).

No one in my family has had diabetes, and the blood glucose level you see in my tests is fasting glucose (didn't eat anything 12 hours prior to the test). I haven't measured my non-fasting blood glucose.... should I?

EDIT: Thank you for those studies! Will definitely read up...

Edited by Elus, 08 January 2012 - 07:58 PM.

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#7 smithx

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Posted 08 January 2012 - 11:32 PM

Mild exercise probably won't do what you need.

The lectures are on Medscape, but I can't link them because it's a registration only site for medical professionals.
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#8 Elus

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Posted 09 January 2012 - 04:08 AM

Mild exercise probably won't do what you need.

The lectures are on Medscape, but I can't link them because it's a registration only site for medical professionals.


Okay, so did you mean short duration high intensity exercise?
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#9 smithx

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Posted 09 January 2012 - 10:55 AM

Okay, so did you mean short duration high intensity exercise?


Yes, if by short you mean 1/2 hour per day, 4-5 days a week.
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#10 niner

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Posted 09 January 2012 - 02:08 PM

How would I know if my exercise was intense enough? Heart rate? Number of reps I could do when lifting? What sort of number would I need?
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#11 smithx

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Posted 09 January 2012 - 08:32 PM

It should be at least 75% of your maximum heart rate for at least 20-30 minutes.

BTW, here's the link for the lipid summit, if you can get access:
http://www.medscape....rc=0_mp_cmenl_0
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#12 The Immortalist

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Posted 10 January 2012 - 03:19 AM

A patient with levels like yours was discussed in one lecture as someone who appeared to be fine and was doing all the right things, but still got a heart attack at the age of 38.


Did the patient have a congenital heart defect?
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#13 The Immortalist

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Posted 10 January 2012 - 04:06 AM

Also, I plan to up my exercise, but I will keep it fairly mild (Some biking, jogging, lifting probably). I'm a very skinny guy (as you can probably surmise from my posted BMI).


I don't know if this will add to the discussion but....

Are you doing hardcore cr? If not how do you stay at that weight normally? I remember being 135lbs when I was 13 and I was 5ft7/5ft8(I was very lean and had a low bf% then. I could actually see my rib cage and my pelvis bones were popping out lol.). My lowest weight I remember in the last 2 years is 150lbs at 5ft10. People thought I was very skinny then! I am now currently 6ft and the lowest weight I've been at this height is 165lbs and I still looked skinny at that weight. I personally feel better now at 196lbs then I was at any other weight.

Maybe you're too skinny? I've personally had problems with fatigue when dieting and being at a low bodyweight.
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#14 Elus

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Posted 10 January 2012 - 06:24 AM


Also, I plan to up my exercise, but I will keep it fairly mild (Some biking, jogging, lifting probably). I'm a very skinny guy (as you can probably surmise from my posted BMI).


I don't know if this will add to the discussion but....

Are you doing hardcore cr? If not how do you stay at that weight normally? I remember being 135lbs when I was 13 and I was 5ft7/5ft8(I was very lean and had a low bf% then. I could actually see my rib cage and my pelvis bones were popping out lol.). My lowest weight I remember in the last 2 years is 150lbs at 5ft10. People thought I was very skinny then! I am now currently 6ft and the lowest weight I've been at this height is 165lbs and I still looked skinny at that weight. I personally feel better now at 196lbs then I was at any other weight.

Maybe you're too skinny? I've personally had problems with fatigue when dieting and being at a low bodyweight.


I'm not doing CR, I just have a fast metabolism. I eat pretty much anything I want and stay the same weight. I think I just have some genes that are responsible for this. I don't really like the feeling of being hungry so much as is the case with CR.

Edited by Elus, 10 January 2012 - 06:25 AM.

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#15 Elus

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Posted 11 January 2012 - 07:42 PM

I have a question regarding my supplements (Which I listed) in the original post.

Can I take all the supplements together? Will they be just as effective as taking them over a longer period of time?
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#16 niner

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Posted 11 January 2012 - 08:20 PM

I'm not doing CR, I just have a fast metabolism. I eat pretty much anything I want and stay the same weight.


I've often wondered about the fast metabolism concept. Can people really have metabolic rates that are substantially different, such that we'd burn way more or less calories than normal? Maybe you're very active, so you're just moving around more than average? Is there any chance that you have a malabsorption problem, like a celiac condition?

Can I take all the supplements together? Will they be just as effective as taking them over a longer period of time?


There are a couple things that impact the timing of supplement consumption. One is the half life of the substance. Vitamin D hangs around forever, so you could take a week's worth on Sunday if you wanted to. There are some things that the body maintains stores of, so even though the half life of the compound in plasma might be relatively short, it isn't important to take it multiple times a day. Most vitamins and essential minerals would fall into this category, unless you are taking large doses of them for a pharmaceutical effect. Compounds that are lipid soluble are best taken when already dissolved in oil. If that can't be arranged, then they should be taken with a high fat meal. Things with poor bioavailability are often better when taken on an empty stomach. This varies from compound to compound. I like to take anti-glycation agents at whatever time best matches their plasma concentration to the post-prandial glucose spike. I'm not exactly sure when that is, but my guess is that they'd be best with a meal, or somewhat before if it's high-GI.

As far as the supps you listed, D and sublingual B12 don't matter much. I'd spread out the vimmortal, and split the fish oil into two doses, like breakfast and dinner. Someone looked at fish oil (I forget where I read it) and found it to work better against dyslipidemias if the dose was split. Noots should be whatever works best for you. KI doesn't matter, and GTE might be better early in the day, since it might possibly keep you awake. Unless I have reason to do otherwise, I take most things in the morning, a while before I eat. If you have digestive issues, it might be better to take things with food. Large doses of GTE should be split or taken after eating, based on a report of someone who showed a liver toxicity from high dose GTE.
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#17 Elus

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Posted 12 January 2012 - 08:04 PM

I've often wondered about the fast metabolism concept. Can people really have metabolic rates that are substantially different, such that we'd burn way more or less calories than normal? Maybe you're very active, so you're just moving around more than average? Is there any chance that you have a malabsorption problem, like a celiac condition?


Hmm, not that I know of... Would my blood results hint at that?

Also, I'm far from active (Hoping to change this). I sit on the computer most of the time.


There are a couple things that impact the timing of supplement consumption. One is the half life of the substance. Vitamin D hangs around forever, so you could take a week's worth on Sunday if you wanted to. There are some things that the body maintains stores of, so even though the half life of the compound in plasma might be relatively short, it isn't important to take it multiple times a day. Most vitamins and essential minerals would fall into this category, unless you are taking large doses of them for a pharmaceutical effect. Compounds that are lipid soluble are best taken when already dissolved in oil. If that can't be arranged, then they should be taken with a high fat meal. Things with poor bioavailability are often better when taken on an empty stomach. This varies from compound to compound. I like to take anti-glycation agents at whatever time best matches their plasma concentration to the post-prandial glucose spike. I'm not exactly sure when that is, but my guess is that they'd be best with a meal, or somewhat before if it's high-GI.

As far as the supps you listed, D and sublingual B12 don't matter much. I'd spread out the vimmortal, and split the fish oil into two doses, like breakfast and dinner. Someone looked at fish oil (I forget where I read it) and found it to work better against dyslipidemias if the dose was split. Noots should be whatever works best for you. KI doesn't matter, and GTE might be better early in the day, since it might possibly keep you awake. Unless I have reason to do otherwise, I take most things in the morning, a while before I eat. If you have digestive issues, it might be better to take things with food. Large doses of GTE should be split or taken after eating, based on a report of someone who showed a liver toxicity from high dose GTE.


Thanks for that, niner. The vitamin D fact was pretty surprising - didn't know about that. I guess spreading the multi out would allow me to get a more even vitamin/nutrient distribution throughout the day. Was that the rationale? Also, I agree with the GTE - I wanna start my day having more energy and a brighter mood.
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#18 smithx

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Posted 12 January 2012 - 08:21 PM


A patient with levels like yours was discussed in one lecture as someone who appeared to be fine and was doing all the right things, but still got a heart attack at the age of 38.


Did the patient have a congenital heart defect?


No. Just fast accumulating atherosclerosis.

Edited by smithx, 12 January 2012 - 08:22 PM.

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#19 niner

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Posted 12 January 2012 - 09:10 PM



A patient with levels like yours was discussed in one lecture as someone who appeared to be fine and was doing all the right things, but still got a heart attack at the age of 38.


Did the patient have a congenital heart defect?


No. Just fast accumulating atherosclerosis.


Was his ApoE genotype known?
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#20 AgeVivo

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Posted 12 January 2012 - 10:04 PM

very likely 4/4 ....
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#21 Elus

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Posted 17 January 2012 - 01:31 AM

Hi all,

Any thoughts on reducing (But not eliminating) meat intake and using whey protein to make up for it? At University I don't really have a reliable source of organic meat, so what I am eating might be full of hormones and other potentially harmful substances.

Also, what about wraps from blimpies (i.e. veggy or wheat wrap with chicken, lettuce, tomato, onion, pickles, and mustard)? Is that amount of carbohydrate okay or should I stay away from wraps altogether?
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#22 niner

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Posted 17 January 2012 - 05:01 AM

Any thoughts on reducing (But not eliminating) meat intake and using whey protein to make up for it? At University I don't really have a reliable source of organic meat, so what I am eating might be full of hormones and other potentially harmful substances.

Also, what about wraps from blimpies (i.e. veggy or wheat wrap with chicken, lettuce, tomato, onion, pickles, and mustard)? Is that amount of carbohydrate okay or should I stay away from wraps altogether?


Reducing meat and replacing the lost protein with whey would probably reduce dietary AGEs, arachadonic acid, and fat, so yeah, I think that would be helpful for you. I worry a lot more about the natural ingredients of most foods than the possible low level contaminants. Milligrams of arachidonic acid are worse than picograms of pesticide.

I wouldn't worry too much about the carbs. Since you're ApoE 4, going super low carb is probably not a good idea. I would worry more about what else is in the wrap besides carbs. Omega 6 level, in particular.
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#23 Elus

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Posted 18 January 2012 - 12:09 AM

Thanks, niner. I'm getting back to uni soon, so I'll have a shot at these dietary changes. I'll keep you guys posted on how I feel (in terms of energy and mental clarity). Perhaps I can even post what sorts of things I'm trying outside of diet/supplements in order to improve my wellbeing, stress tolerance, and academic performance. This semester I'll be taking classes on computer science, calculus, logic, and writing (Putting biology on hold for a moment so that I can explore more subjects in the sciences and fulfill general requirements).

Edited by Elus, 18 January 2012 - 12:13 AM.

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#24 Elus

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Posted 03 February 2012 - 06:17 PM

Hmm, interesting. Perhaps ApoE4 isn't all bad?

Better Memory and Neural Efficiency in Young Apolipoprotein E ε4 Carriers

Abstract:

The apolipoprotein E (APOE) ε4 allele is the major genetic risk factor for Alzheimer's disease, but an APOE effect on memory performance and memory-related neurophysiology in young, healthy subjects is unknown. We found an association of APOE ε4 with better episodic memory compared with APOE ε2 andε3 in 340 young, healthy persons. Neuroimaging was performed in a subset of 34 memory-matched individuals to study genetic effects on memory-related brain activity independently of differential performance. E4 carriers decreased brain activity over 3 learning runs, whereas ε2 and ε3 carriers increased activity. This smaller neural investment of ε4 carriers into learning reappeared during retrieval: ε4 carriers exhibited reduced retrieval-related activity with equal retrieval performance. APOE isoforms had no differential effects on cognitive measures other than memory, brain volumes, and brain activity related to working memory. We suggest that APOE ε4 is associated with good episodic memory and an economic use of memory-related neural resources in young, healthy humans.


Intro:

Although the frequency of the APOE4 allele is low in humans (15% in Caucasians), studies in primates suggest that it is the ancestral allele (Finch and Sapolsky 1999). The common (75% in Caucasians) and uniquely human APOE3 allele appeared as a mutation, and its frequency increased during human evolution (Finch and Sapolsky 1999). Because the APOE4 allele has been related to several deleterious biological effects, the question arises why it existed in the first place (Finch and Sapolsky 1999). From an evolutionary point of view, a possible advantageous effect of the APOE4 allele in childhood and early adulthood could explain its existence and further persistence in humans. Support for this notion comes from studies where APOE4 has been associated with higher IQ scores (Yu et al. 2000), a higher educational level (Hubacek et al. 2001), a reduced cardiovascular response to experimentally induced stress (Ravaja et al. 1997), and a protective effect against spontaneous abortion during embryogenesis (Zetterberg et al. 2002) and against perinatal death (Becher et al. 2006). Advantageous effects of the APOE4 allele have also been found for memory-related functions in young animals. Hippocampal long-term potentiation (LTP) was enhanced at a young age in knock-in mice lacking mouseAPOE but instead expressing human APOE4 (Kitamura et al. 2004). This LTP enhancement was age dependent and disappeared in adult knock-in mice. Moreover, APOE4, but not APOE3, stimulated the transcriptional activity of cyclic adenosine 3′,5′-monophosphate response element-binding protein (CREB) by activating the extracellular signal-regulated kinase (ERK) cascade in rat primary hippocampal neurons (Ohkubo et al. 2001).
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#25 AgeVivo

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Posted 03 February 2012 - 08:48 PM

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

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Posted 04 February 2012 - 03:36 AM

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.
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#27 Elus

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Posted 04 February 2012 - 05:28 AM

Wasn't Animal our resident gene therapy expert? He might be able to answer that.
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#28 nowayout

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Posted 07 February 2012 - 04:44 PM

Avoid wheat in particular and carbs in general.


I don't see anything about the effect of carbs in the OP table. Do you know of studies linking APOE and carbs?

It may be premature basing dietary interventions on that table at this point. From the review quoted by Michael:

There is evidence to suggest that variation in the genes for apolipoprotein (apo) A-I, apo A-IV, apo B, and apo E contributes to the heterogeneity in the lipid response to dietary intervention. However, the effects of genetic variation are not consistently seen and are sometimes conflicting. Future studies need to have much larger sample sizes based on power calculations and carefully controlled dietary interventions and should investigate the effects of polymorphisms in multiple genes instead of the effects of polymorphisms in single genes.


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#29 Elus

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Posted 07 February 2012 - 05:57 PM

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).

Edited by Elus, 07 February 2012 - 06:02 PM.

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#30 rg8032

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Posted 07 February 2012 - 06:20 PM

Unfortunately, there is only a small window during which you can edit your post. It is a major gripe of mine. I am ApoE 3/4 and I am following this with interest.

Edited by rg8032, 07 February 2012 - 06:21 PM.

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