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  • Apoe 2/3/4 variants and diet

    So I've been reading about apoe variants and how this may have a strong effect on what we should eat.

    Stuff I've gleaned that may or may not be right
    1) People have two copies of the genes, so you can be 2/2, 3/3, 3/4, 2/3, 2/4, etc.
    2) 75% of the population have no 4 allele, and 2% have the 4/4 variant. Most people are 3/3. (This is specific to Europeans)
    3) 4 is the most ancestral gene, 2 is the newest gene. There are claims that the 4/4 is much rarer now because our switch to a grain-based diet killed off most of the 4/4s. However, I have also read that the 4/4 genotype is actually even more ancient than paleo, and the diet would be more similar to other primates.
    4) People are afraid of having 4/4 because that means a significantly higher risk of Alzheimer's, and the associated implications with insurance coverage and so forth
    5) Having the 4 variant is associated with higher LDL, and I think especially the bad dense kind
    6) However, this is because 4 variants have a harder time getting enough saturated fats in the brain, which is why the body needs to increase the LDL, however, this also increases plaque formation

    From those points, are the following questions/comments
    1) I have heard people comment that if you have the 4/4 variation you should lower your saturated fat intake because it'll be bad for your LDL numbers, but that doesn't make sense to me for the following reasons:
    a) Given the general paleo/primal framework, it would seem to me that having the ancestral allele would make it even more important to be eating a non-grain diet, which means more protein and fat in general
    b) If your brain is already not getting enough saturated fat, wouldn't reducing saturated fats just make it worse?
    2) However, what does the additional plaque formation mean in regards to heart disease?
    3) Apoe4 isn't the be-all-end-all, as there are those who were 4/4 or 4/3 (I forget which) who said their health/numbers improved going on a high fat diet and things sucked on a low-fat diet, but at the same time, there are those who found their numbers better going on a low-fat (esp. sat fat) diet.
    4) As such, what should be the recommended diets for people of the various variations of the alleles (or if there should be any variations)? Not enough information is also a probable answer.

  • #2
    Been taking a bit of an interest in this lately as my LDL numbers have skyrocketed. Haven't had the ApoE genotype test yet because I'm not sure what to do with the results. There is a lot of contradictory information out there, little of it concrete.

    Do you have any evidence that high LDL resulting from the ApoE4 genotypes is necessarily artherogenic? Some of the reading that I've done points to ApoE4 inducing high LDL and high Triglycerides. Very easy to see this as being artherogenic. But if Trigs are low is there solid evidence of a danger?
    Four years Primal with influences from Jaminet & Shanahan and a focus on being anti-inflammatory. Using Primal to treat CVD and prevent stents from blocking free of drugs.

    Eat creatures nose-to-tail (animal, fowl, fish, crustacea, molluscs), a large variety of vegetables (raw, cooked and fermented, including safe starches), dairy (cheese & yoghurt), occasional fruit, cocoa, turmeric & red wine

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    • #3
      It mainly seems to be Dr. Davis who feels that those with Apoe4 should reduce their saturated fat intakes: e.g. The exception to low-carb | The Heart Scan Blog and http://www.trackyourplaque.com/blog/...t-fit-all.html

      Others (I think Kruse?) have different opinions.

      Comment


      • #4
        What is the bottom line here? My mother has Alzheimer's as do her sisters and her mother had it also. I'm a bit concerned right now as to what my dietary strategy should be to avoid it myself, given that I have already been displaying symptoms of memory loss. Is this test something that doctors perform routinely, or do I need to ask for it myself? Is the paleo diet protective for the Apoe4 gene or do I need to undertake a special diet if I am gene positive?

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        • #5
          Originally posted by Dig62 View Post
          What is the bottom line here? My mother has Alzheimer's as do her sisters and her mother had it also. I'm a bit concerned right now as to what my dietary strategy should be to avoid it myself, given that I have already been displaying symptoms of memory loss. Is this test something that doctors perform routinely, or do I need to ask for it myself? Is the paleo diet protective for the Apoe4 gene or do I need to undertake a special diet if I am gene positive?
          At this point, I wouldn't base any particular dietary strategy on ApoE allele status. Not nearly enough evidence.

          Remember that Alzheimer's is virtually absent amongst HGs, which is way it's included under the diseases of civilization umbrella. Nobody in dementia-free traditional cultures was deciding what they should eat based on genetic polymorphisms.

          If you're already following a primal diet, then you're already doing all you can nutritionally to minimize your risk of AD. I wrote a couple posts recently about Alzheimer's and nutrition recently, if you're interested (I do Alzheimer's research for a living).
          sigpic

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          • #6
            I seem to recall that some HGs (Inuits?) did have plaque formations though. Supposedly the problem is if you have the variation, high-fat = plaques, and low-fat = Alzheimer's. But HGs were generally high-fat, so hence the first problem. However, despite the plaques, I think they didn't actually have any/more heart attacks, I think because they weren't getting a lot of inflammation.

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            • #7
              This seems to give rise to a number of issues. One that really strikes me is this. Is it not medical malpractice to prescribe statins to someone with the ApoE4 allele? Or to someone whose ApoE genotype hasn't been established?
              Four years Primal with influences from Jaminet & Shanahan and a focus on being anti-inflammatory. Using Primal to treat CVD and prevent stents from blocking free of drugs.

              Eat creatures nose-to-tail (animal, fowl, fish, crustacea, molluscs), a large variety of vegetables (raw, cooked and fermented, including safe starches), dairy (cheese & yoghurt), occasional fruit, cocoa, turmeric & red wine

              Comment


              • #8
                Peril, my mother was put on Lipitor four years ago and she didn't even have high cholesterol! Her doctor put her on it strictly as a 'preventative measure'. After being on it for two years she started to develop memory problems and now has Alzheimers, though I admit that it may be pure coincidence. Nonetheless I've gotten her off the Lipitor with her doctor's consent, and her cholesterol profile has remained good. Even if it doesn't help I figure it's one less pill for her to take and I'm all for that.

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                • #9
                  Studies on APOE4 and high fat poorly constructed

                  Originally posted by Dig62 View Post
                  Peril, my mother was put on Lipitor four years ago and she didn't even have high cholesterol! Her doctor put her on it strictly as a 'preventative measure'. After being on it for two years she started to develop memory problems and now has Alzheimers, though I admit that it may be pure coincidence. Nonetheless I've gotten her off the Lipitor with her doctor's consent, and her cholesterol profile has remained good. Even if it doesn't help I figure it's one less pill for her to take and I'm all for that.
                  The studies on APOE4 and high fat/cholesterol are not done in the context of a low carb diet. High fat + high carb may jack up cholesterol but not high fat alone.

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                  • #10
                    Originally posted by jturk View Post
                    At this point, I wouldn't base any particular dietary strategy on ApoE allele status. Not nearly enough evidence.

                    Remember that Alzheimer's is virtually absent amongst HGs, which is way it's included under the diseases of civilization umbrella. Nobody in dementia-free traditional cultures was deciding what they should eat based on genetic polymorphisms.

                    If you're already following a primal diet, then you're already doing all you can nutritionally to minimize your risk of AD. I wrote a couple posts recently about Alzheimer's and nutrition recently, if you're interested (I do Alzheimer's research for a living).
                    Good stuff! I wish to avoid AD and find all the above very interesting.

                    Comment


                    • #11
                      Originally posted by Dig62 View Post
                      What is the bottom line here? My mother has Alzheimer's as do her sisters and her mother had it also. I'm a bit concerned right now as to what my dietary strategy should be to avoid it myself, given that I have already been displaying symptoms of memory loss. Is this test something that doctors perform routinely, or do I need to ask for it myself? Is the paleo diet protective for the Apoe4 gene or do I need to undertake a special diet if I am gene positive?
                      Emphasis added. I suggest you watch this video - Low Carb Explained - YouTube - and notice what she said about LCHF and her brain function. I notice I'm sharper, and more emotionally steady with reduced protein (less than I thought I needed - holding at just about the magic .7g/kg weight/day) and keeping my carbs as low as I can manage without worrying too much (generally <20g). The rest of my energy is from fat. And as Peter (Hyperlipid) once said, it can be from butter or your butt!

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                      • #12
                        Heart Brain dilemma indeed seems the nub of it

                        Originally posted by Dracil View Post
                        b) If your brain is already not getting enough saturated fat, wouldn't reducing saturated fats just make it worse?
                        I agree this is the nub of it. I posted an inquiring thread over at Paleohacks that led to some very interesting discussion which you might find educational.

                        FWIW, don't know that I can prove it (yet), but I continue to move forward with hypothesis that APOE4's need to keep cholesterol and sat fats high, but inflammation & oxidation low.

                        Comment


                        • #13
                          Originally posted by peril View Post
                          This seems to give rise to a number of issues. One that really strikes me is this. Is it not medical malpractice to prescribe statins to someone with the ApoE4 allele? Or to someone whose ApoE genotype hasn't been established?
                          My Dad just lost his battle which I strongly believe the evidence indicates precisely this causative relationship. However, I don't see how we can charge malpractice to professionals following best current practice. I do hope that one day this is indeed the case. I do think there's a stronger case against those that make and promote statins as this line of inquiry is not only supported by evidence, but some pretty good first-principle logic.

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                          • #14
                            Dr. Steven Gundry Podcast of interest

                            Originally posted by Dig62 View Post
                            What is the bottom line here? My mother has Alzheimer's as do her sisters and her mother had it also. I'm a bit concerned right now as to what my dietary strategy should be to avoid it myself, given that I have already been displaying symptoms of memory loss. Is this test something that doctors perform routinely, or do I need to ask for it myself? Is the paleo diet protective for the Apoe4 gene or do I need to undertake a special diet if I am gene positive?
                            35: Dr. Steven Gundry | High-Fat Diets: Good vs. Bad | Jimmy Moore Presents: Ask The Low-Carb Experts

                            According to Gundry which was touted as an expert on fats...a 3/4 or 4/4 means animal fats in particular may be a bad idea.

                            BRAIN GUT 6: EPI-PALEO Rx | Living an Optimized Life

                            This without the animal foods or with less of them might be a good idea if you have a 3/4 or 4/4. Fish because of the limited saturated fat is still a good choice. Also saturated fats from coconut and red palm would be good choices.

                            Plant sources of saturated fat seem to be the preferred fats if he is correct. I haven't read the whole thread...so many someone already mentioned it if this is all old news sorry :P.
                            Age: 28
                            Height: 6'1"
                            Primal start date: July 1st 2011
                            Start Weight: 275
                            Current Weight: 248
                            Stats below as of September 1st 2011 Tested via BodPod
                            Body Fat 25.4%
                            Fat Mass 63.721
                            Fat Free Mass 74.6%
                            Fat Free Mass 187.087
                            Goal weight: 180-200 lbs(Recommended weight is around 180 for my height but that sounds low)
                            Total lost so far: 27 lbs

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                            • #15
                              I just got my results from 23andme. I'm ApoE 2/3. From what I've read, we take longer to clear fat from the blood but we are also slow to convert IDL to LDL. We have more protection from Alzheimer's.

                              In apo E2 patients, LDL-C levels do not decrease significantly in response to a low fat diet, whereas, paradoxically, the distribution of small dense LDL subclasses tends to increase. At the same time, apo E2 subjects seem to respond well to relative carbohydrate restriction.
                              Berkeley HeartLab

                              If this is the case, LDL-P would also be going up on a low fat diet.

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