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High Methionine, yet blocked Methylation cycle

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by droit, Jun 15, 2013.

  1. droit



    Hello all, this is my first post, though I've been around for a while.

    I've had two Methylation Pathway Panels, 4 months apart. The second one showed good improvement just from the classic Simplified Protocol, but there is still clear methylation cycle dysfunction per Dr. Van Konynenburg's typical characterization of a Methylation block.

    Here is data from the first one. Everything in the second one is still out of range but slightly moved in the right direction.

    glutathione (oxidized) 0.56 (0.16-0.50)
    glutathione (reduced) 3.0 (3.8-5.5)
    S-adenosymethionine 216 (221-256)
    S-adenosylhomocysteine 55.3 (38.0-49.0)
    Folic Acid, active (RBC) 332 (400-1500)

    Mutations of note:

    MTHFR C677T +/-
    CBS C699T +/+
    MTRR H595Y, K360A, A664A all +/-

    The strange thing is, per my blood amino acid test, I have very high Methionine. I tested at 40 micromol/L (range of 10-33).

    I would expect that raw material to go around the cycle to SAMe, but from my low SAMe numbers it appears as though I am throttled at conversion of Methionine to SAMe.

    The s-adenosylmethionine synthase enzyme (MAT) is not typically talked about in detail in terms of mutations or cofactors to this enzyme that I may need to optimize.

    I wonder if anyone else is in this state or has any advice.
  2. triffid113

    triffid113 Day of the Square Peg

    My guess...I can't take the time to look this up for you but I believe the ONLY THING needed on the path from methionine to SAMe is ATP. But I recall stated in the old B12 conference by others that in order to use ATP you need magnesium. So my guess is you need to take magnesium. It's the only clue I can think of.
  3. DREBS


    Hey droit I think I am in the exact same state, as your lab’s and mutations are very similar to mine. My numbers are almost identical to yours on the methylation pathway and I have high methionine, low SAM-E, high SAH and Adenosine, with high oxidized glutathione and lower reduced… I sure wish Rich was still around to give us his 2 cents. My mutation’s are also the same as your CBS +/+ MTHFR +/-. I have had post viral fatigue for over a year now. Yet I have higher Methionine and a blocked methylation cycle as well and am a bit puzzled but have a few theories.

    Something I’ve been reading a lot about recently is NADHP it is the enzyme needed to convert oxidized glutathione back into reduced glutathione. It is also what is needed to convert folic acid to methylfolate and aid's on the production of Nitric Oxide, which mine has been tested and is very low as opposed to high in most PWC’S.... leading to my always cold hands and feet. I’ve noticed when I take D-Ribose(5g) which is the “bridge” in ATP from adenosine to tri-phosphate it give me an energy rush( too much). If you look at the biosynthesis of the Methylation cycle ATP is what converts Methionine to SAM-E so if you have low mitochondria production via ATP, which, low reduced Glutathione/ High Oxidized will already put you at more disadvantage for ATP production. Im still wrapping my head around a lot of the NADHP material but from my understanding the supplement NADH and FMN (coenzyme b2) along with adequate phosphorus (mine is low on OAT’S and Hair Essential/toxic elements). Will help convert the Oxidized glutathione back into the needed and useable reduced glutathione to help with ATP protection and production thus higher ATP content helping to convert Methionine into SAM-E. But now if you get your SAM-E back up higher it will just go to your SAH which is already high, so now you have to address this, I think with our CBS mutations the block in in the homocystine ( yet this is counter intuitive because of normal ammonia level) but it is my best guess. In which TMG, methylfolate, methyl/hydrxo/hydroxyl/adensyl b-12, P-5-P (B6) along with B2 needed to use the b6 as rich points out, Will all work on both sides of the cycle to get you methylating again. Im still looking into some things like p450 and other enzymes but this is the best I can make of it now.

    I think the block could be in multiple places I still can’t pinpoint why everything is high but SAM-E. Are you sensitive to overstimulation when you take supplements esp. methyl donors? I am and my theory is that where “ all the methyl donors are getting off the highway” at SAM-E because everything else is blocked up. While I have the CBS mutation my Transulfuration flow is low which is a little uncharacteristic of CBS +/+… Yes magnesium is important but it’s only a tiny piece of this puzzle.

    The frustrating part is methylation issues are so individualistic,. While one person may flourish on a mixture of supplements another may get worse. One thing I had found very helpful is typing in phoenix rising along with the keywords of what I’m looking for and look for Rich’s post’s he was truly a brilliant man. But there is so much good information out there if you know where to look. If anyone had any ideas or knowledge please share.

    My mutations are as follows…

    MAO A +/+


    CBS (C699T) +/+


    SHMT +/+


    ACAT +/-


    MTHFR (C677T) +/-


    MTR (A2756G) +/_


    MTRR (A66G) +/-


    MTRR(11) +/-


    BHMT 2 +/-


    BHMT 4 +/-

    BHMT 8 +/-

    CBS (A360A) +/-

    Methylation Pathway Panel

    Glutathione (oxidized) 0.58 (.16-0.50)

    Glutathione (reduced) 3.8 (3.8-5.5)


    SAM-E….................. 223 (221-256)

    SAH……................... 56.4 (38-49)


    5-CH3-THF …….….14.3 (8.4-72.6)

    10-Formyl-THF…. ....8.5 (1.5-8.2)

    5-Formyl-THF……....2.0 (1.20-11.7)


    Folic Acid…………...16.6 (8.9-24.6)

    Folinic Acid (WB).......10.2 (9.0-35.5)

    Active Folate…… 361 (400-1500)


    Adenosine ……….26.9 (16.8-21.4)

    Borderline high Methionine 3.3 (1.6-3.6) per Amino Acid Plasma

    Borderline High Homocystine .41 (<.50)

    However my Ammonia isn’t bad 18 (<30)
  4. 1Charles


    Some interesting comments there and some stuff I would like to try. My panel is quite similar. I have bolded a section that I do not understand why you think that. The reaction SAH <-> homocysteine + adenosine is reversible. Your homocysteine is within range yet the adenosine is clearly high. Surely it is the adenosine that is pushing this reaction back to SAH.

    I am not sure what to do about high adenosine. Apparently zinc is a co-factor for adenosine deanimase so perhaps more zinc. I am already taking 25mg/day although my serum zinc is low normal. The NIH safe upper limit for zinc is 40mg. The only other suggestion I have seen is caffeine and I already drink a fair bit of coffee. While my views are not as firmly based I wonder whether trying to raise SAM is likely to be productive given supplementation with SAM doesn't seem often effective. Any thoughts?

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