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Very Confused on Methyl Donors for COMT & MTHFR Mutations..

Discussion in 'Genetic Testing and SNPs' started by geneticmysteries, Sep 13, 2016.

  1. geneticmysteries


    Hi All -

    I’m new to this community as a poster, but been researching and reading for months and months to try to find the right mix for me along with working with my integrative doctor on any research/reading I find..

    I’m still a bit confused on my status as I get conflicting information/posts and am still struggling to find the right mix of vitamins/supps for me.

    I wanted to see if this fabulous community could help with my jigsaw puzzle, based on your own experience and understanding.

    • Compound Heterozygous for MTHFR (MTHFR C677T +/- and MTHFR A1298C +/-)
    • Heterozygous for COMT V158M and H62H
    • Homozygous for MAO A R297R
    • Several more. not sure if they are relevant. if so, let me know which ones!

    What I just removed a week ago as symptoms were getting slowly worse for a while. :
    • took for 6 months - NAC (felt fine, just can’t keep track of a gazillion supps!) can add back in if needed, had no averse reaction
    • took for 4 months - Rhodiola – for adrenal support. found out this was an MAO A inhibitor. been taking for 5 months and symptoms have slowly gotten worse. I think this may be the culprit due to my MAO A status
    • just removed.. Coffee – was drinking 3-4 cups a day, went cold turkey 4 days ago. this is tough to withdrawal for me. but I've read in several places this can affect catecholamines and is an MAO A inhibitor. .
    What I’m taking (notation with how long)
    • 10 months - Hydroxy B12 4000mg/day (MTHFR Support) (taking hydroxyl version due to COMT and intolerance of Methyl b12)
    • 3 weeks - Methyl B12 65mg.. as I am avoiding taking more due to overmethylation in the past. Slowly trying this again.. this is from a multivitamin, seeking health
    • 3 weeks - Methylfolate 200mcg.. as I am avoiding taking more due to overmethylation in the past. Slowly trying this again. this is from a multivitamin.. seeking health
    • 10 months - Progesterone cream (MAO A support)
    • 1 week - Riboflavin 400mg (MAO A support)
    • 1 week - B6 – 50mg
    • 1 week - Inositol 2000 mg
    • 8 months - Taurine ( I have very low Taurine levels) – 1000mg
    • 4 years - Probiotics
    • 1 week - Magnesium – 800mg


    Thoughts on what I'm missing or anything I should just remove from my list I'm taking, or am I right on for now and see how it goes?

    I clearly need methylfolate to help with homocysteine reduction right? I have high blood homocysteine levels. I have had severe over methylation with not much dosage from Methylfolate in the past. Starting small again. At 200/day. .. I do need this right - even though everything I’ve read says because of COMT to avoid it. it's contradicting and confusing.

    Do I need methyl B12 even though I take Hydroxy B12? Due to COMT I’ve read methyl B12 is to be avoided and I had averse reactions to it when trying it last year.. but don't i need it to help support methylfolate? .. again, contradicting and confusing for me.

    Is it worth addressing the lower catacholamines? (serotonin, dopamine, epinephrine, norepinephrine with amino acid supplementation? i.e. tryptophan, tyrosine etc? or do these solve for themselves as everything else is addressed?

    Curious on thoughts, I’ve learned so much reading etc. on here I thought I’d finally reach out and ask.. as I'm still confused on some of this :cool:

  2. alicec

    alicec Senior Member

    You may or may not be compound heterozygous for MTHFR. 23and me doesn't say which SNP is on which strand.

    Even if you are, the slowing of the enzyme is not dramatic. Stimulation with its cofactor B2 and its product methylfolate may be helpful.

    COMT V158M does slow the enzyme but +/- has a modest effect. Supplementation with the cofactor magnesium may be helpful.

    The other COMT SNP and the MAO A SNP have no effect. The enzyme produced by the variant is identical to that produced by the ancestral gene.

    Here is a post about that MAO A SNP.

    The claim that COMT +/+ means you are sensitive to methyl groups is just an assumption which is not based on any evidence. Plenty of people on PR who are COMT +/+ (including myself) have no problem with methyl groups.

    You may be sensitive to methyl groups but it has nothing to do with COMT.

    Here is a thread which discusses some resources that can be helpful in evaluating SNPs.

    Here is a post about useful programs for analysing 23andme results.

    Here is a post about supplementing with active folate and B12.
    geneticmysteries and Valentijn like this.

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