16

votes

Should everybody be tested for ApoE4 before going high fat Paleo?

Answered on September 12, 2014
Created January 02, 2012 at 4:20 PM

First of all, I'm assuming the hypothesis that ApoE4 carriers (one or two alleles) face the problem of high LDL Cholesterol and TC, probably due to a diet high in saturated fat.

If that holds true, and according to various blogs (Dr. Davis, Paul Jaminet and Paleo Hacks to name a few), around 15-25% of the populations will be ApoE4 carriers (source), with 2% being double carrier (worst scenario).

Moreover, this condition (in various degrees related to ApoE combinations) could be a problem for newcomers to a high fat paleo diet. Since 1 out 4 is a high proportion it seems to me a safe bet to be tested against ApoE4 before going into a high fat paleo diet.

What do you think? Where and how can one be tested about Apoe4?

PS.: In my case, although I'm from Spain, I'm pretty sure that I could be an ApoE4 carrier, since my ancestors were from Scotland and the prevalence of this gene seems to be higher there.

More Info about ApoE4:

5dd50f78f47b8848d93724d6eb38d4c1

(907)

on January 22, 2013
at 05:35 AM

You're advice is based on the old "large fluffy ldl is non athrogenic". Which is way off target.

A1081af52b61372dbb3ed572d88968f4

(425)

on January 06, 2012
at 02:27 PM

Nirgal, Whereas I'm currently interpreting the collected insights one way, I fully agree that what optimal looks like for APOE4's is an open question, so will be very interested to hear from you again to know what you learn.

77877f762c40637911396daa19b53094

(78467)

on January 04, 2012
at 01:09 AM

Nirgal, I think you are going to have to just jump in and see. I would start with your ancestral diet, if you can figure it out. That would be the foods that your ancestors had available to them before the agricultural revolution. It's easy for me, because I am Irish and Northern European, and they were the last to switch to farming.

9de28a80b0dea81e50495aa5bf28184b

(180)

on January 03, 2012
at 10:53 AM

Ok, thak you guys. Now I think I have a clear picture of the situation. My intention was not to leave paleo, only to be sure what kind of paleo diet would be better for me. It seems that Cordain and to some extent, Robb Wolf suggest a moderate saturated fat intake.

9de28a80b0dea81e50495aa5bf28184b

(180)

on January 03, 2012
at 10:48 AM

Great explanation Ambimorph. Thank you!

A1081af52b61372dbb3ed572d88968f4

(425)

on January 03, 2012
at 01:54 AM

Quilt - glad you think I'm on the right track. Still much to learn...

4781cf8ae1bfcb558dfb056af17bea94

(4359)

on January 03, 2012
at 01:05 AM

The problem, as you put it yourself, is that you "assumed the hypothesis." As far as I know, the evidence suggests that the hypothesis is false...

4781cf8ae1bfcb558dfb056af17bea94

(4359)

on January 03, 2012
at 01:03 AM

The problem, as you put it yourself, is that you "assumed the hypothesis."

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on January 02, 2012
at 11:49 PM

smart move Russ. Plus one.

100fd85230060e754fc13394eee6d6f1

(18696)

on January 02, 2012
at 06:36 PM

Nice post, Cody. You are way faster and more succinct than I am. :-)

77877f762c40637911396daa19b53094

(78467)

on January 02, 2012
at 05:28 PM

Small dense LDL is made in the liver from carbohydrates.

77877f762c40637911396daa19b53094

(78467)

on January 02, 2012
at 05:28 PM

Small dense LDL is driven by carbs NOT saturated fat.

9de28a80b0dea81e50495aa5bf28184b

(180)

on January 02, 2012
at 05:23 PM

Yes the one you mention said that but, have you read Dr. Davis and Paul Jaminet's posts? Here in Paleo Hacks are some more questions about that: http://paleohacks.com/questions/50789/why-does-ldl-skyrocket-when-doing-paleo-it-could-be-apoe#axzz1iJkmMdxu Evolutionary Psychiatry says that the higher the LDL when older the better since it seems to play a role in the transportation of cholesterol to the brain. However is the type of LDL which matters and it seems to me that ApoE4 carriers have the worst profile (small dense and prone to oxidation).

6498694060d879a7960b35913539b75f

(1307)

on January 02, 2012
at 05:08 PM

I agree with Cody. I think you need to read these articles again. You seem to be missing the point.

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6 Answers

18
100fd85230060e754fc13394eee6d6f1

(18696)

on January 02, 2012
at 06:20 PM

23and me gives the following statistics for APO E4. Like you said, although about 20% of people have 1 E4, 2 is much less common.

APOE variant frequencies in Europeans

Genotype Frequency

  • ??2/??2 0.4%
  • ??2/??3 13.7%
  • ??3/??3 63.9%
  • ??2/??4 1.3%
  • ??3/??4 19.0%
  • ??4/??4 1.7%

Data from Lahoz et al (2001).

They also say that

while there is evidence that the APOE ??4 variant may associate with higher LDL cholesterol levels, consistent associations have not been demonstrated for coronary heart disease or response to statins.

The connection to LDL is complicated. The biggest effect is seen in people with 2 ApoE4s.

This study suggests that it only makes a difference if you drink alcohol, for example.

This paper, shows a table with the different values of lipid panels associated with the different Apo E combinations. They show, for example that a typical someone with 2 E4's had LDL of 157, a 3 and a 4 with 143, a 4 and a 2 (which was the lowest!) with 101.

Here is a paper that acknowledges some of the complexity of the problem:

Interestingly, even though both apoE phenotype and diet modify LDL size, studies showing the interaction between these 2 factors are scarce or discrepant. Thus, a higher saturated fat intake was associated with smaller LDL particles in apoE2 subjects, and larger LDL particles in apoE4 subjects (31). However, another study showed that when subjects changed from a high- to a low-fat diet, there was a shift from large, buoyant, cholesterol-rich particles, to smaller, denser LDL particles, with progressively greater reductions in levels of larger LDL from apoE3/2 to apoE3/3 to apoE3/4 (32).

These two points strongly suggests that people with Apo E4 should not lower their fat / saturated fat intake!

The rest of that study is even more complex, in part because they compare only two conditions (which in my opinion aren't very comparable -- moderately high CHO with moderately high MUFA), and it's really unclear what conclusions to draw. The resulting discussion section is interesting to read, if only to show how little is understood. The authors do conclude something related to your suggestion: that there are many factors which make optimal diet individual.

My opinion is that LDL doesn't really matter very much. It has been shown that a diet with plenty of saturated fat often increases LDL, but it also increases the particle size. So it really isn't clear that high LDL in this scenario is dangerous. In fact, if the diet is low in carbs, the larger particle size, combined with the lowered triglycerides, and raised HDL, suggests to me that the perceived risk of higher LDL is more than compensated for. The problem in answering your question is that most studies that compare the cholesterol outcomes of people based on their Apo E variant and fat intake do not have a low carbohydrate intake in mind, and don't test the conditions that would make that part of the picture come into focus.

9de28a80b0dea81e50495aa5bf28184b

(180)

on January 03, 2012
at 10:48 AM

Great explanation Ambimorph. Thank you!

5dd50f78f47b8848d93724d6eb38d4c1

(907)

on January 22, 2013
at 05:35 AM

You're advice is based on the old "large fluffy ldl is non athrogenic". Which is way off target.

12
77877f762c40637911396daa19b53094

(78467)

on January 02, 2012
at 04:56 PM

Why would a high fat diet be a problem? Not sure you understood the article. The one you linked to on Animal Pharm said this:

The density of the LDL determines its function. Small dense is damaging. For E4, dietary carbohydrates and dietary deficiencies of saturated fat dramatically shape and create small, dense, harmful LDL particles. The only rare cases of coronary calcification improvement on EBCT at a coronary heart website were the uncommon participant on a lower carb, HIGH SATURATED FAT intake. E4 appear exquisitely more sensitive to diet, exercise, fats/carbs and environmental toxicant

Saturated fat is not bad, and it is especially good for people ApoE4.That is what these articles are saying. Yet your question seems to imply that Saturated fat is bad for people with ApoE4???

The title of the Evolutionary Psychiatry article even says it!!!

What the Heck Is an ApoE and Other Stories of How Cholesterol Is Good for You

77877f762c40637911396daa19b53094

(78467)

on January 02, 2012
at 05:28 PM

Small dense LDL is made in the liver from carbohydrates.

77877f762c40637911396daa19b53094

(78467)

on January 02, 2012
at 05:28 PM

Small dense LDL is driven by carbs NOT saturated fat.

9de28a80b0dea81e50495aa5bf28184b

(180)

on January 02, 2012
at 05:23 PM

Yes the one you mention said that but, have you read Dr. Davis and Paul Jaminet's posts? Here in Paleo Hacks are some more questions about that: http://paleohacks.com/questions/50789/why-does-ldl-skyrocket-when-doing-paleo-it-could-be-apoe#axzz1iJkmMdxu Evolutionary Psychiatry says that the higher the LDL when older the better since it seems to play a role in the transportation of cholesterol to the brain. However is the type of LDL which matters and it seems to me that ApoE4 carriers have the worst profile (small dense and prone to oxidation).

100fd85230060e754fc13394eee6d6f1

(18696)

on January 02, 2012
at 06:36 PM

Nice post, Cody. You are way faster and more succinct than I am. :-)

8
A1081af52b61372dbb3ed572d88968f4

(425)

on January 02, 2012
at 07:44 PM

Yes, absolutely... but not for the reasons you imply. APOE4 is not a reason to avoid paleo, but I do think you can use the knowledge that you are APOE4 to find optimums for you.

I recently found my way to paleo precisely because I am APOE4. I support answers above from Cody and ambimorph. See my own question and particularly the long discussion in comments here. I particularly draw your attention to the exchange between @Hans and @Grace in the Answers/comments.

As you'll see there, my synthesis of all the research I've read to far is that as an APOE4 I actually want higher LDL (for brain health), but that I want to shape the average size to be the large and fluffy type. Notwithstanding measurement uncertainties pointed out by Masterjohn and others, I have gone from 25% to 40% larger LDL on my first 2 VAPs 30 days apart.

But I find wisdom in Quilt's post on using VAP tests for broader view of brain/gut health here, although what this means for me is not yet clear. I am currently focusing on raising HDL (stable at 47 mg/dl) using coconut oil, Vitamin D and probiotics (answer from Quilt on another paleohacks Q). Will update my earlier post with results +/- as I go.

Bottom line - test for APOE4 for sure, but use this information to find optimal, not to stay away from paleo. So far for me, after ~4 months paleo, I feel better than I have in 20 years, so that's telling me something that for now I take as a net positive. In the end, I won't be surprised that APOE4's, as carriers of the truly ancestral allele of APOE, need paleo even more than others :-)

A1081af52b61372dbb3ed572d88968f4

(425)

on January 03, 2012
at 01:54 AM

Quilt - glad you think I'm on the right track. Still much to learn...

Ed71ab1c75c6a9bd217a599db0a3e117

(25477)

on January 02, 2012
at 11:49 PM

smart move Russ. Plus one.

3
F694b3d8c620c7717287b32b6cac7f7e

on August 26, 2012
at 03:57 PM

Great Study on the link between Alzheimers and High carb low fat diet.

http://www.lizscript.co.uk/Glyn/EJIM01.pdf

3
77877f762c40637911396daa19b53094

(78467)

on June 29, 2012
at 12:56 AM

In my view finding out you are an APOe4 carrier should provide additional incentive to go Paleo - as well as getting an understanding of cholesterol metabolism and how it is influenced by a Western diet versus a Paleo diet.

3
6120c989fd5b69f42a0834b69b87955b

(24553)

on January 03, 2012
at 04:58 AM

I've tried a lot of different diets on in my time as directed by doctors here and there in response to being an ApoE4 carrier, and my health only improved (including an improvement in lipid panels) after I chucked all of the low fat recommendations made by my well-intentioned docs, and adopted a high fat version of paleo. In my mind ApoE4 equals needing more saturated fat than your average Joe.

So, yes, testing could help, but I think in a way inverse to the intention of your question.

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