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Methylation Pathway Analysis results

Discussion in 'Genetic Testing and SNPs' started by doors68, Mar 9, 2014.

  1. doors68

    doors68

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    Hello, this is my first post to Phoenix Rising. I do not have CFS (at least as far as I know) but have suffered from a variety of health problems, which really became noticeable in 2004 or 2005 when I was about 25. I would be interested in any information you can give me, and if anyone else thinks or knows if they have Ehler Danlos, or anhedonia, or any of the other issues I have, or if we share common methylation genes. I was tested through Dr. Amy Yasko and plan on following her protocol. Thank you guys!


    Background: 34 year old male. Developed Ulcerative Colitis at age 26, no family history. Discovered gluten free greatly helped bowel symptoms, went gluten free 1/2012. Chronic joint pains and subluxations started the same time as colitis, now I suspect something related to Ehler Danlos. Ahnedonia/nerve issues started then and have worsened. Poor libido, limited sensation and sexual function. I do have a bit of a family history with difficulty sleeping, and my sleep problem started when I got sick as well. I suspect that I got sick with everything then because my crappy genes kicked in. For the anhedonia, I suspect nerve issues/demyelination, neurotransmitter problems or neuropathy, for instance from b12 deficiency. For years I took 800 mcg of regular Folic acid at the advice of my GI, but my folate levels on blood tests are always greater than 20, while my b12 level would should in the 2 or 300 level.

    For those kind enough to read this, thank you. I am really hoping that you can help guide me in terms of my plan for starting the program. First let me tell you that I did a trial run before I received my results, of taking methylcobalamin 1mg. It made me feel a little spacy, but I immediately noticed my anhedonia beginning to go away and normal healthy male gender coming back to me, including normal sensation. My face looked better, and there was some sign of life coming back to my eyes that had been missing since I got sick with ulcerative colitis at age 26. Then, on the 3rd or 4th night I developed insomnia. It lasted for another day after I stopped taking it, and from reading on mthfr.net, I ended up taking 500mg of Niacin to try to soak up the methyl groups, and this did seem to help me start sleeping, but the whole ordeal scared me. I now know that based on my COMT/VDR status, I should use the hydroxyl/adeno versions of b12.

    I ordered the Methylation Pathway Analysis through Dr. Amy Yasko, and am intending on following her protocol, as I have no reason not to. Accordingly, my planned steps to start on the protocol are: purchase some GABA and maybe becalm spray for my GABA/Glutamate balance. Order a UTM/UEE(toxic metals, essential elements) and HTM analysis (hair analysis) I guess this will give me a baseline for metal detox later and for lithium levels now?
    I also believe based on my results I may need to watch my ammonia levels, but I am thinking it would be best to run a UAA(urinary amino acids) after I begin treatment, in order for my CBS mutation to act up, as it is costly. I guess I will then need to look at the shortcut through the methylation cycle, and the b12, before getting into adding the 5MTHF which is where I imagine the detox can get interesting? Does anyone have any feedback on my situation or on my planned steps? Thank you so much!
    Chief Complaints
    1. Intermittent severe problems falling asleep, lack of dreams (I suspect b6 insufficiency for the dreams and neurotransmitter for sleep onset)
    2. Severe loss of libido and sexual function, including basic physiological sensation, ejaculatory anhedonia. (I did a 3 day trial of methyl b12 and sensation came back but it caused me insomnia. Now I know based on my COMT/VDR I should use hydroxy, but I'm hoping that it has the same benefit. This makes me wonder if I have nerve damage, and is making me want to take b12 immediately and skip over STEP ONE).
    3. Chronic subluxation and joint pain in upper back and neck. (I now believe this may be related to Ehler Danlos Syndrome, due to excessive joint laxity)
    4. Lack of muscle tone and exercise intolerance (I suspect something mitochondrial or kreb's cycle as the fatigue manifests immediately after exertion)
    5. Brain fog/cognitive decline (though this has improved with gluten free)




    Recent Blood Work (prior to starting any methylation supplements)
    Histamine 132ng/mL (HIGH)
    Homocysteine plasma 7.7umol/L (reference range 0-15)
    I tested as mildly positive for pyroluria based on a urine test (I wonder if pyroluria is just an aspect contained within the methylation cycle)
    I am betting my CBS mutation explains the high histamine and low homocysteine?

    *I always have high serum folate - over 20 and b12 in the 200-300 range.
    Other Genetic Tests
    HLA-DQ2 positive (related to celiac disease)

    Methylation Pathway
    homozygous
    MTR/A2756G +/+ G
    MTRR/A66G +/+ G
    MTRR/11 +/+ A
    CBS/C699T +/+ T
    MAO A/R297R +/+ T

    heterozygous
    MTHFR/C677T +/- Hetero
    MTHFR/A1298C +/- Hetero
    BHMT/1 +/- Hetero
    BHMT/8 +/- Hetero
    COMT/V158M +/- Hetero
    COMT/H62H +/- Hetero
    VDR/Taq1 +/- Hetero
    VDR/Fok1 +/- Hetero
    NOS/D298E +/- Hetero


    full methylation profile
    SHMT/C1420T -/- G
    AHCY/1 -/- A
    AHCY/2 -/- T
    AHCY/19 -/- A
    MTHFR/C677T +/- Hetero
    MTHFR/A1298C +/- Hetero
    MTHFR/3 -/- C
    MTR/A2756G +/+ G
    MTRR/A66G +/+ G
    MTRR/H595Y -/- C
    MTRR/K350A -/- A
    MTRR/R415T -/- C
    MTRR/S257T -/- T
    MTRR/11 +/+ A
    BHMT/1 +/- Hetero
    BHMT/2 -/- C
    BHMT/4 -/- A
    BHMT/8 +/- Hetero
    CBS/C699T +/+ T
    CBS/A360A -/- C
    CBS/N212N -/- C
    COMT/V158M +/- Hetero
    COMT/H62H +/- Hetero
    COMT/61 -/- G
    SUOX/S370S -/- C
    VDR/Taq1 +/- Hetero
    VDR/Fok1 +/- Hetero
    MAO A/R297R +/+ T
    NOS/D298E +/- Hetero
    ACAT/1-02 -/- G
     
  2. Valentijn

    Valentijn Activity Level: 3

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    The CBS SNPs have very little impact. They are beneficial and aren't going to cause ammonia problems.

    Homozygous MTRR A66G means you are very ineffecient (around 30% of normal) at recycling methylB12. Supplementing B12 is probably a very very good idea. Since the methylB12 made you feel a bit off, hydroxoB12 does sound like a better option. Adreno12 might not be necessary, as you should be able to convert hydroxoB12 to adrenoB12 or methylB12 as needed.

    Heterozygous MTHFR C677T combined with heterozygous MTHFR A1298C means that you are producing methylfolate at either 65% or 30% of the normal rate, depending on whether the + alleles are on the same strand or opposite strands. Either way, you probably need to supplement methyfolate, not folic acid.
     
  3. Helen

    Helen Senior Member

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    Interesting. Do you have a reference to the fact about the decrease in recycling MeCbl when homozygous?
     
  4. Valentijn

    Valentijn Activity Level: 3

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    Helen likes this.
  5. Helen

    Helen Senior Member

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  6. doors68

    doors68

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    Thank you for the response - but I'm confused - Dr. Amy Yasko sure seems to think that CBS upregulation is a major issue that needs to be addressed, and I was wondering specifically WHY I had a bad reaction to the methylcobalamin (low lithium or high ammonia) or perhaps due to detox?

    You are the second person I've talked to who has mentioned that they don't really care about the CBS SNP. Can you elaborate a little bit on why? I agree that my compound heterozygous MTHFR and MTR/MTRR probably mean methylfolate is needed...hopefully I can tolerate that to! I would liked to have continued on with the methyl b12, but I have no indication of whether the insomnia would let up...I guess if the hydroxy b12 has the same or better subjective benefits I will be ok with that...otherwise I'm sure I will end up revisiting the methylb12. I wonder if anyone else has been down that road. I was checking a guys blog who posts here with CFS and it looked like he was going through detox and had used the methyl b12.

    Thanks again for your reply!
     
  7. Valentijn

    Valentijn Activity Level: 3

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    Because the published research contradicts Yasko's theory. Her theory seems to be based on very badly misinterpreting a study involving a lab yeast with half of the entire CBS gene removed. That study doesn't involve the Yasko-tested CBS SNPs at all, hence her conclusions regarding it are completely unfounded. Furthermore, the research which does involve those SNPs shows that 1) they have little or no impact, and 2) any impact they have is purely beneficial.

    This is not to say that the CBS gene cannot be a problem, or that whatever treatment someone has designed for it necessary won't be helpful. But that problem and that "treatment" have nothing whatsoever to do with your CBS SNP results, hence it seems unlikely that a treatment designed for treating a non-existent problem will be helpful.
     
  8. trev343

    trev343

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    Wilmington, North Carolina
    Valentijn I was also from the Netherlands.. raised in Leeuwarden! Anyway you can check my thread and help me out as well?
     
    Valentijn likes this.

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