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COMT says don't take methyl MTRR says DO take.....

Discussion in 'Genetic Testing and SNPs' started by Al Klein, Jul 29, 2013.

  1. Al Klein

    Al Klein Senior Member

    I currently take methyl cobalamin and methyl folate - feel OKish

    Do I follow COMT guidelines or MTRR?
  2. caledonia


    OH, USA
    Can you post your COMT and VDR SNPs?
  3. Al Klein

    Al Klein Senior Member

    COMT V158M ++
    COMT H62H ++
    vDR taq ++

    All others --
  4. caledonia


    OH, USA
    Yasko suggests hydroxycobalamin and adenosylcobalamin for that combination. Your body is supposed to be able to convert the hydroxycobalamin to methylcobalamin for use by MTRR, etc.

    So it's sort of like eating a complex carb instead of pure sugar. You still get the sugar, it just goes in slower so you don't get a spike.
  5. Valentijn

    Valentijn Senior Member

    You can avoid most of the methyl problem by taking hydroxoB12 instead of methylB12. Methylfolate is still required if you have a MTHFR C677T mutation, but doses of methylfolate should be pretty effective at much lower doses than B12. So a normal dose of methylfolate, and then with hydroxoB12 you can go pretty high if you tolerate it.
  6. Helen

    Helen Senior Member


    Sorry, I donĀ“t know what you mean by OKish. If your methylation capacity is decreased, hydroxycobalamin might not be methylated to methylcobalamin. So there can be a viscious circle whatever your COMT mutations are. I tried hydroxycobalamin after many years of methylcobalamin and got all my deficiency symptoms back. It took 3 months to reach the bottom and 3 months to be back to "normal" on methylcobalamin again. I am +/+ for two of the COMTs and +/- for one of the 3 tested.

    My , (and many others who I know about) experience is :follow MTRR. And your symptoms. Best of luck to you!


    PS Rich Van Konynenburg realized this fact and wrote about it during the first part of 2012.
  7. Al Klein

    Al Klein Senior Member

    Earlier this year I felt really bad, I have Hashimotos, and take 2.5 grains Armour. GP finally also diagnosed Pernicious Anemia (B12 deficiency) For th past 4 months I have had 8 weekly hydroxocobalamin shots (from the GP) and have been myself taking Jarrows 5000 (I seem to need daily B12) plus a general B (Bio Minerals) and Metafolin (now up to 800mcgc) (also general vits and minerals e.g magnesium, C etc etc)

    I am feeling much better - leg pains all gone, fatigue much lifted, but still feel the is more needed on the energy levels, plus I have not lost a single pound in weight, despite a relatively normal diet.

    I attach my genetic genie results, plus any other methylation results from livewello. I have 2 main questions :
    1) I started taking metafolin rather than folic acid after reading about MTHFR (which I dont seem to have) is this better for me?
    2) Is swapping say every other day methylB12 with a HydroxoB12 spray (limited choice in UK) a better idea? or try and convince my GP to more frequent jabs / start self injecting (as these are hydroxo)


    Gene & Variation rsID Alleles Result
    COMT V158M rs4680 AA +/+
    COMT H62H rs4633 TT +/+
    VDR Bsm rs1544410 CC -/-
    VDR Taq rs731236 AA +/+
    MAO-A R297R rs6323 TT +/+
    MTRR A66G rs1801394 GG +/+
    MTRR A664A rs1802059 AG +/-
    BHMT-02 rs567754 CT +/-
    BHMT-04 rs617219 AC +/-
    AHCY-01 rs819147 CT +/-
    AHCY-02 rs819134 AG +/-
    AHCY-19 rs819171 CT +/-
    CBS C699T rs234706 AA +/+
    AGT M235T/C4072T rs699 AA +/+
    CBS A13637G rs2851391 TT +/+
    CBS C19150T rs4920037 AA +/+
    DHFR rs1643649 CT +/-
    FOLR2 rs651933 AG +/-
    FUT2 rs492602 GG +/+
    FUT2 rs601338 AA +/+
    FUT2 rs602662 AA +/+
    GAD1 rs3749034 AG +/-
    GAD1 rs2241165 CT +/-
    GAD1 rs2058725 CT +/-
    GAD1 rs3791850 AG +/-
    GAD1 rs10432420 AG +/-
    GAD1 rs701492 CT +/-
    GIF (TCN3) rs558660 AA +/+
    MAO A R297R rs6323 TT -/-
    MTHFD1 C105T rs1076991 TT +/+
    MTRR A66G rs1801394 GG +/+
    MTRR-11 A664A rs1802059 AG +/-
    NOS2 rs2274894 GT +/-
    NOS2 rs2248814 AG +/-
    NOS3 rs1800783 AT +/-
    NOS3 rs1800779 AG +/-
    NOS3 rs3918188 AC +/-
    NOS3 G10T rs7830 GT +/-
    NOS3 T786C rs2070744 CT +/-
    SLC19A1 rs3788200 AG +/-
    SOD2 rs2855262 CT +/-
    TCN2 C766G rs1801198 CG +/-
    TYMS rs502396 CT +/-
    DAO rs2070586 AG +/-
    DAO rs2111902 GT +/-
    DAO rs3741775 AC +/-
    GAMT rs17851582 AG +/-
    GAMT rs55776826 CT +/-
    MTHFD1L rs11754661 AG +/-
    MTHFD1L rs17349743 CT +/-
    MTHFD1L rs6922269 AG +/-
    MTHFD1L rs803422 AG +/-
    MTHFR rs6495446 CC +/+
    PEMT rs4244593 GT +/-
    PEMT rs4646406 AT +/-
  8. Sea

    Sea Senior Member

    NSW Australia
    Have you looked at Valentijn's threads on interesting snps? So far there are ones for MTHFR, CBS, MTRR, VDR and probably more.
    There's more info in your 23andme data than what Yasko/Genetic Genie shows.

    By the way rs6495446 is in the MTHFS gene not MTHFR
  9. Al Klein

    Al Klein Senior Member

    Then that is a mistake in the Livewello report, as I copied and pasted from there!!!!
  10. Al Klein

    Al Klein Senior Member

    I have been reading those today, but am still confused, sorry for asking - for me it's understanding the effect that each of the homo/hetero's have - some cancel each other out, and I am trying to understand wether methyl groups are a prob;em for me or not!
  11. Crux

    Crux Senior Member

    Hi Al Klein;

    I see you have a couple of polymorphisms that are a big reason for pernicious anaemia. GIF is one, and TCN is another.

    I don't know much about genetics, but I've come across these when reading about B12 deficiency.

    The above is a good link, but I had trouble printing it, ( ? ), so I'll try to get some more links for you to show to the doc.
    Helen likes this.
  12. Al Klein

    Al Klein Senior Member

    Thank you - that is the first time I've seen a link between my data and PA - lots for me to read :)
  13. Al Klein

    Al Klein Senior Member

  14. Crux

    Crux Senior Member

    Here's one that discusses MTR and MTRR, etc. With a bit about transcobalamin deficiency.
    It's a bit of a slog to read, but it may make for 'fun' for the doctor.

    I see you've struck gold, good on you!
  15. Crux

    Crux Senior Member

  16. Al Klein

    Al Klein Senior Member

    I re-read lots here and decided to add some adenosycobalamin - Source Naturals, half a tablet 5mg per day, sublingually at the same time as methylcobalamin, within a week fatigue and nerve pains in my legs returned, almost as though the methylcobalamin wasnt working - am I missing another co-factor?

    I take 99mg Potassium gluconate, various minerals, 800mcg metafolin.

    dont like this at all :(
  17. misskatblack


    I have a similar conundrum. I am heterozygous for MTRR and COMT, so I am not really sure which are expressing. I have a lot of problems with anxiety and fatigue.
    What are the clues to find out which genes are expressing? After reading your post, I am experimenting today with some high dose sublingual Methyl B12 after having Hydroxy B12 for the last week and feeling worse. Not sure if the Hydroxy B12 has anything to do with the return of my intense fatigue this week. Still haven't got my hands on any Adenosyl B12.
    I spoke with Sterling Hill about 2 weeks ago and she said Hydroxy 12 drains more quickly than other B12s.
    I also am homozygous for FUT2 which is also related to B12 deficiency. Oddly enough, I am sitting here and over the course of 20mins can feel something happening after taking the sublingual methyl B12...We'll see...

    Gene Mutations:
    CYP1A2 +/-

    CYP1B1 +/+

    CYP2C19*17 +/-

    CYP2D6 +/-

    GSTP1 +/-

    NAT2 +/+

    SOD2 +/-

    HLA +/-

    C3 +/+

    FCER1A / OR10J2P +/-

    GSTM3 +/-

    IRF5 +/+

    IGF1R +/-

    HLA +/-

    HLA-DQA2 +/-

    MTC03P1 +/-

    ACE Del16 AG +/-

    AGT M235T/C4072T +/-

    AHCY-01 +/-

    AHCY-02 +/-

    AHCY-19 +/-

    BHMT-08 +/-

    BHMT R239Q +/-

    CBS A13637G +/-

    COMT H62H +/-

    COMT V158M +/-

    DAO +/-

    DHFR +/-

    FUT2 G AG +/-

    FUT2 A AG +/-

    GAD1C CG +/-

    GAD1 C CT +/-

    GAD1 T TT +/+

    GAD1 T CT +/-

    GAD1 G AG +/-

    MAO A R297R T GT +/-

    MTHFD1 G1958A A AG +/-

    MTHFD1L A AG +/-

    MTHFR T CT +/-

    MTHFS C CC +/+

    MTRR A66G G AG +/-

    MTRR H595Y T CT +/-

    MTRR K350A G AG +/-

    MTRR-11 A664A A AG +/-

    MTRR T CT +/-

    MTRR G AG +/-

    MTRR A AG +/-

    NOS2 T GT +/-

    NOS2 A AG +/-

    NOS3 A AT +/-

    NOS3 G AG +/-

    NOS3 A AC +/-

    NOS3 G10T T GT +/-

    NOS3 T786C C CT +/-

    PEMT A AT +/-

    PEMT C CT +/-

    SHMT1 C1420T A AG +/

    SHMT1 C CT +/-

    SHMT2 A AG +/-

    TYMS C CC +/+

    VDR Bsm T CT +/-

    VDR Taq +/-

    HLA G AG +/-

    CTLA4 G AG +/-

    BCMO1 A379V T TT +/+

    ATP5c1 T CT +/-

    ATP5c1 T CT +/-

    ATP5c1 C CT +/-

    COX5A G AG +/-

    NDUFS7 A AA +/+

    NDUFS7 T TT +/+

    NDUFS8 A AG +/-

    NDUFS8 C CT +/-

    UQCRC2 C CT +/-

    UQCRC2 2 A AC +/-

    ATG16L1 C CC +/+

    GSDMB T TT +/+

    IL5 A AG +/-
  18. Al Klein

    Al Klein Senior Member

    I have temporarily stopped the methyl and adenosyl and am doing every other day B12 hydroxocobalamin injections ( I DO have pernicious anemia meaning no IF) I will work towards doing weekly injections, topping up with methyl in between if I need. Still not sure wether it was th asenosyl that made me feel bad, or just the build up of methyl, but methyl overload symptoms seem to be anxiety whereas I just had a return of fatigue and to some extent brain fog.
    Feeling a bit better already, had 3 injections
    Valentijn likes this.
  19. misskatblack


    Glad to hear you are feeling better :) I definitely got a small spike in energy just before from the methyl -b12 despite taking the hydroxyl b12 all this week. I am still confused about whether I can tolerate methyl donors. Seem to have trouble with methyl folate when I have taken it in the past but I haven't really noticed too much of an issue with the Methyl B12. I am still on the fence about SaMe also... I don't really have the MTHFR gene mutation, well...I have one hetero minor one but not the main ones most people have trouble with.
  20. picante

    picante Senior Member

    Helena, MT USA
    My husband is having the same confusion about taking methyl-whatever. He has snps similar to @Al Klein.
    But with the additional complication of:
    MTHFR A1298C +/+
    As well as +/+ for all these MTHFRs: rs1476413, rs3737964, rs4846048, rs4846049

    These are like Al's, only the VDR genes are the reverse of his:
    COMT V158M rs4680 AA +/+
    COMT H62H rs4633 TT +/+
    VDR Bsm rs1544410 CC +/+
    VDR Taq rs731236 AA -/-
    MAO-A R297R rs6323 TT +
    MTRR A66G rs1801394 GG +/+
    MTHFS rs6495446 +/+

    Before we saw his snp results, he was taking MeB12 and AdB12 and Mefolate, and doing better -- until he raised his dose and crashed a couple of days later (horrid mental exhaustion, low mood, low energy -- a bump on a log). We were waiting for his 23andme results, and at that point I went and found the notice from 23andme in his junk mail.

    He immediately took niacin and got relief, then switched to HydroxyB12 + AdB12 the next day, which worked really well for 5 days. Now it's a week later, and he crashed again. We wondered if he needed MeB12, so he tried it today and felt worse. Took niacin and felt better.

    QUESTION: With those MTHFR snps (and MTRR), would you think he might need either some methylfolate or some methylB12 occasionally? Or should he stop experimenting with those?

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