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Genotypes (SNPs) to help determine Vitamin E supplementation - Relation to Inflammatory Cytokines

Discussion in 'Genetic Testing and SNPs' started by nandixon, Sep 16, 2012.

  1. nandixon

    nandixon Senior Member

    Interesting article here that may have application to vitamin E supplementation in Chronic Fatigue Syndrome (CFS/ME):

    "In healthy control subjects, the effect of α-tocopherol supplementation on the production of inflammatory cytokines appears to be dependent on an individual's genotype. These genotype-specific differences may help explain some of the discordant results in studies that used vitamin E."

    A related published U.S. patent application is here (METHODS FOR DETERMINING GENE-ALPHA TOCOPHEROL INTERACTIONS):

    The authors found in a study of healthy males that alpha-tocopherol could have either anti-inflammatory OR pro-inflammatory cytokine activity based on a person's genotype. The SNPs used are available through 23andMe testing.

    The most important SNP, among those looked at, seems to be glutathione-S-transferase pi, GSTP1 A316G (rs1695 in 23andMe). Persons having the alleles AA or AG had an increase in interleukin-6 (IL-6) upon supplementing alpha-tocopherol while those with GG saw a decrease (see Fig. 3A in the patent app; note that in the text of the app there is a typographical error in multiple places where GG should be AA).

    (See here for more on IL-6:

    I found the article while trying to figure out why supplementing with 400iu of alpha-tocopherol (succinate form) worsened my fatigue. This might possibly explain it. To make it easier for others to determine their own status, here are my personal results for the above SNP and two others. Bottom line is - assuming I follow the pattern of the healthy test cases - all of my SNPs would seemingly dictate an increase in pro-inflammatory cytokines upon supplementing alpha-tocopherol - which I guess would be a bad thing:

    GSTP1 A313G -/- AA (AA) rs1695
    (See Fig. 3A for the changes in IL-6 levels for each SNP variant in response to alpha-tocopherol supplementation; Fig. 4A for IL-1)

    TNF G(-238)A -/- GG (GG) rs361525
    (Fig. 2B for TNF-alpha)

    IL10 A(-1082)G +/- CT (TT) rs1800896
    (Fig. 2* for TNF-alpha; Fig. 4D for IL-1)

    *Figure "2" seems to be missing . . . the text says the "AG" (= CT for 23andMe) and "AA" (= TT) genotypes were associated with an increase in TNF-alpha levels.

    I also feel almost as bad supplementing the gamma form of vitamin E. I always thought in either case it might be due to a blood pressure lowering effect. Now I'm not so sure, and am just going to stick to the amount in my multivitamin from now on. On the other hand, it seems people with the GG genotype for GSTP1, and/or the AG for TNF (and/or maybe CC for IL10), for example, might benefit from extra alpha-tocopherol, since those genotypes may have a decrease in their pro-inflammatory cytokine levels.
    ebethc, aaron_c, Gondwanaland and 3 others like this.
  2. Thera


    That is very interesting. I am also AA for rs1695 and have always felt worse after taking vitamin E. Thanks for sharing.
  3. triffid113

    triffid113 Day of the Square Peg

    This is really interesting. I take 1 d alpha-tocopherol and have for 35 years (b4 that 600mg for all the early years of my life). I have always felt it was a very important part of my health protocol along with 2g mineral ascorbates (and apparently / potentially calcium and magnesium citrates - someone sent me an article recently which seemed to think that keeping ones citrate level up was important to avoiding kidney stones...the kidney doctors are saying that >500mg C can cause kidney stones, but I have had no issue, perhaps because I take citrates...and I have always felt better with citrate forms that asporotate forms but could never really explain why).

    I believe I am autistic but the lifelong high antioxidant dosage as well as wide ranging supplementation (such as lifelong multi and extra B100, etc) has saved me from the worst of it as a youngster. I wish I knew where to get such genes as above tested. In particular I have reason to suspect I have trouble breaking down B6 (I get short of breath if I stop my 50mg P5P) and also Vitamin A (despite taking beta carotene). I would like to be able to look at more of my genes. I have had the Yasko test and have 18 genetic defects out of 30. If anyone runs across any other good genetic panels I hope you will share!
  4. roxie60

    roxie60 Senior Member

    Central Illinois, USA
    Maybe 23andme???
  5. triffid113

    triffid113 Day of the Square Peg

    Isn't 23andme the same as the Yasko panel but with fewer genes covered? I want to see genes governing breakdown of B6 to active P5P and breakdown of beta-carotene to active Vitamin A, for example, and I know these are not in that panel. It is disappointing how slowly genetic panels of wide scope are becoming available. The Yasko and 23andme panels have been available for 4 or more years and there have been no new wide scope panels developed since. Why??! Just when we have the tools to start making headway, science...stalls?!!
  6. adreno

    adreno Learned helplessness

    Bump. I somehow missed this before - good information here.

    I wish I knew more about the effects of SNPs on gamma-tocopherol.
    Last edited: Feb 10, 2015
    Gondwanaland likes this.
  7. nandixon

    nandixon Senior Member

    (My original post was a bit dense, so here is a simplification.)

    Effect of supplementing alpha-tocopherol based on the following 23andMe SNPs*:

    GSTP1 rs1695
    AA or AG = pro-inflammatory (increases IL-6)
    GG = anti-inflammatory (decreases IL-6)

    TNF rs361525
    GG = pro-inflammatory (increases TNF-α)
    AG = anti-inflammatory (decreases TNF-α)
    (AA is rare)

    IL10 rs1800896
    TT or CT = pro-inflammatory (increases IL-1β)
    CC = anti-inflammatory (decreases IL-1β)

    *Taken from Figure 1 (A, B & D) here.

    (Note that only men were studied.)
    Sidereal, aaron_c, Valentijn and 2 others like this.
  8. aaron_c

    aaron_c Senior Member

    Thanks for the work you put into this @nandixon. I was curious about how common these genotypes were. Here is what I found:

    AA:AG:GG = 43:43:13
    EDIT: The PRO-inflammatory snps seem to be much more common.

    could not find data

    TT:CT:CC = 58:37:9
    Edit: Here too the PRO-inflammatory snps seem to be much more common.

    (Assuming my dyslexia hasn't fooled me again) It seems like most people will react poorly to alpha tocopherol. I'm not sure what conclusion to draw, other than "huh."
    Last edited: May 27, 2015
    nandixon likes this.
  9. Sidereal

    Sidereal Senior Member

    Alpha tocopherol succinate made me feel more fatigued. Red palm oil extract made me feel great for a week followed by a severe inflammatory reaction in the joints lasting months.




    Well, that explains that mystery!

    As always, fantastic information, @nandixon. Thanks.
    nandixon likes this.
  10. Gondwanaland

    Gondwanaland Senior Member

    I am TT and DH is CC

    I took Gamma E continuously for 1.5 years, after taking warfarin for 1.5 years...

    Now I know it worsened my K2 deficiency, in addition to my pro-inflammatory SNPs :ill:

    Hopefully taking mixed tocopherols + mixed tocotrienols lessened the detrimental effects... At least no one beats my HDL -- it raised from the 70-80 range to 90-104, which is a good thing b/c the ratio total cholesterol/HDL has been between 2.5 and 3 (desirable <5).

    Although it is good to know that my husband will better benefit from it than myself. In fact I started giving him Gamma E earlier this year when I first saw this thread (thanks @nandixon ).

    Soon we are going to have his cholesterol retested, but he has been having so many other problems lately that I doubt this supplement had any significative positive outcome...
    nandixon likes this.
  11. nandixon

    nandixon Senior Member

    Yes, the authors of the study indicate that it may be counterintuitive. As a general matter, you would seemingly want to have the SNPs that cause the pro-inflammatory response (from taking vitamin E), because those SNPs are apparently found in individuals with a higher antioxidant capacity.

    As the authors state in the Discussion:

    However, having ME/CFS may mess things up: Because our disease is associated with high levels of oxidative stress, it would seemingly be desirable to be able to supplement with vitamin E. But having those SNPs that are pro-inflammatory with respect to vitamin E (and which are actually normally the good SNPs) then becomes a problem for us. Because in the process of trying to lower the oxidative stress, the levels of the cytokines mentioned are being increased, and that increase (or change) may make us feel worse.

    That's what I'm theorizing, anyway. Someone else may have a better idea.
    Sidereal and Gondwanaland like this.

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