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Why am I unable to tolerate methylfolate?

Discussion in 'Genetic Testing and SNPs' started by Tonya, Sep 9, 2013.

  1. Tonya

    Tonya

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    Hi all,

    I decided to do the 23andme test to see if it would tell me why I cannot tolerate methylfolate. I take methyl b12 in high doses without issue and that has cleared my hyperhomocystinemia. I have depression and lethargy and was hoping to take higher dose of 5mthf. When I first took 5mthf I felt really good but then dissolved into rage and tears. I am having trouble trying to figure out what is going on. I had a hair test (I know not reliable) a while back that showed really high phenylalanine and really low taurine. If anyone has any guidance to offer I would really appreciate it.

    COMT V158M rs4680 AA +/+
    COMT H62H rs4633 TT +/+
    COMT P199P rs769224 AG +/-
    VDR Bsm rs1544410 TT +/+
    VDR Taq rs731236 GG -/-
    MAO-A R297R rs6323 GT +/-
    ACAT1-02 rs3741049 AG +/-
    MTHFR C677T rs1801133 AG +/-
    MTHFR 03 P39P rs2066470 GG -/-
    MTHFR A1298C rs1801131 GT +/-
    MTR A2756G rs1805087 AA -/-
    MTRR A66G rs1801394 AG +/-
    MTRR H595Y rs10380 CT +/-
    MTRR K350A rs162036 AG +/-
    MTRR R415T rs2287780 CC -/-
    MTRR A664A rs1802059 AG +/-
    BHMT-02 rs567754 CC -/-
    BHMT-04 rs617219 AA -/-
    BHMT-08 rs651852 CC -/-
    AHCY-01 rs819147 CT +/-
    AHCY-02 rs819134 AG +/-
    AHCY-19 rs819171 CT +/-
    CBS C699T rs234706 AG +/-
    CBS A360A rs1801181 AG +/-
    CBS N212N rs2298758 GG -/-
    SHMT1 C1420T rs1979277 AG +/-
     
  2. Valentijn

    Valentijn Activity Level: 3

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    I've deleted the -/- results and crossed out the SNPs which aren't relevant to gene functioning.

    Heterozygous MTHFR C677T reduces methylfolate production to 65% of normal. If the heterozygous MTHFR A1298C is on the opposite strand, methylfolate production is 30% of normal. SHMT1 can also aggravate the problem. Hence methylfolate supplementation is probably needed.

    All of the MTRR indicates some need for B12. Because it's all heterozygous, it's not as bad as it could be, but might still be pretty bad.

    Your CBS might be running a little slow, which could result in homocysteine getting a bit high. If so, B6 can help with that.

    Due to all of the COMT, MAOA, and VDR being slow versions, you likely have too many methyl groups floating around already, and don't need more. This might partially explain your inability to tolerate methylfolate. It might be worthwhile to try hydroxoB12 instead, to see if that allows you some extra leeway regarding methyl groups so that you can try methylfolate again.

    It's also possible that methylfolate is getting things going, and causing unpleasant side effects in the process. Have you tried a normal dose of methylfolate, especially without taking methylB12 at the same time?

    SUMMARY:
    Methylfolate supplementation is strongly indicated, and hydroxoB12 is probably needed too. B6 also might be helpful. To determine where the problem is, it might be good to try a small or normal dose of methylfolate first, with little or no B12 at the same time, then add in B12 slowly until you're at your usual dose. If it's still causing problems, it might be worth trying B6 before the methylfolate.
     
    helen1 likes this.
  3. Tonya

    Tonya

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    Hugs and Thanks to you!

    I forgot to mention I tested deficient in b12 my level was 191 (211-946). This is the 2nd time in 6 years it went that low. The 1st time I did not continue to take methyl b12 after my levels came up...I thought it was transient. So I am a little fearful of not taking it. I thought we had to take b12 first and then add 5mthf? On second thought I think I will try it. Any idea how long I need to be off of b12 before I start?
     
  4. Valentijn

    Valentijn Activity Level: 3

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    A day or so might be sufficient. And with your confirmed B12 deficiency, you really should look into getting hydroxoB12. It's harder to find than methylB12, but with your COMT, VDR, and MAOA, and problems with methylfolate, it may make things much more manageable.
     
  5. Gandalf

    Gandalf

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    If you take folate with low b12, this can result in serious, irreversible neurological issues. You might want to consider shots. You should talk to your doctor.
     
  6. Kimsie

    Kimsie Senior Member

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    My guess would be, you need more niacin or niacinamide. It is required in order to degrade the catecholamines such as dopamine an nor-epinephrine. You felt good at first because most likely your depression and lethargy is caused by excess histamine and the SAMe was able to degrade the excess histamine. If you take niacinamide you will be able to tolerate the methylfolate, but it may only make you feel good for a couple of days before it stops working as well because if your histamine levels fluctuate much between day and night, the SAMe levels will readjust but this can be overcome by taking more niacin or niacinamide, plus B6, vitamin C, and magnesium in addition to B12 and methylfolate in order to support the DAO pathway to get rid of histamine.

    It sounds like you have the exact same problem as one of our sons - he gets depression and lethargy (and apathy) from histamine that is being produced by gut bacteria after having had antibiotics over 2 years ago. We find the above vitamins are very helpful.
     
  7. Gandalf

    Gandalf

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    Your serotonin is disintegrating at a lower rate than your dopamine. If you tackle it via methylfolate, one will be low, the other will be high. So you will have depression with no mood swings OR no depression with massive mood swings. I'm not a huge fan of SSRIs but they might be worth trying in your case in a very low dose. If you want some natural antidepressant you might want to have a look at Hypericum perforatum.

    Edit: I just had a better idea. Maybe you should stop methylfolate and take 5-HTP. Dont stop the mb12 though.
     
  8. caledonia

    caledonia

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    The question might actually be, when I add methylfolate to the methylcobalamin why am I having problems? The reason is it takes both folate and B12 to create methyl groups. It's like mixing baking soda with vinegar. If you just have baking soda, nothing much happens. If you just have vinegar, same thing. If you add them both together - you get a huge fizzing reaction.

    With MTRR, you probably do need a constant infusion of B12. According to Yasko, you have the most sensitive combination of COMT/VDR and will be prone to mood swings if not careful. Yasko suggests taking mostly hydroxycobalamin.

    My suggestion would be to try switching to hydroxycobalmin first, and if that goes well, then add a teeny tiny amount of methylfolate. Wait about 3-4 days to see how it goes before adding more. I'm currently only dosing folate twice a week and that works better for me than dosing every day, due to metal detox.

    The ratio of B12 to folate should be about 5:1 or 5:3. If it was me, I would drop back on the amount of B12 relative to the folate, then gradually increase both, maintaining the same ratio.

    The reason is that too much B12 or folate relative to the other can cause a methyl trapping situation.
     
  9. Gandalf

    Gandalf

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    @caledonia I'll have to disagree with you.

    The goal of B12 and methylfolate is to create methylcobalamin in order to provide methyl groups. But this B12 (you are refering to) is HB12 or CB12. Methyl-B12 is the finished product. Tonya should be greatful that she tolerates it so well.

    Definetly not with only +/- mutations. Most healthy people have heterozygous alleles and they mostly have normal b12 levels. The MB12 she is taking should already do the job.

    Yes it was obvious like I already pointed out. Again, Methyl-B12 is better, if tolerated.

    No
     
  10. Valentijn

    Valentijn Activity Level: 3

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    Actually the one and only use for methylB12 is in creating methionine. And the methionine synthase reductase takes plain cobalamin (B12) to do this, meaning that supplemented methylB12 is first broken down into cobalamin and methyl groups, and then reassembled by MTRR.

    Hence it seems that methylB12 is only advantageous as a supplement when the extra methyl groups are actually needed. And I wouldn't say that the methylB12 being ingested is the finished product.
     
  11. Gandalf

    Gandalf

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    @Valentijn
    I don't think you can make that statement.
    Thats like saying that the one and only use of alkohol is for disinfection.

    MTRR is important to recycle oxidized cobalamin and is not part of the conversation. What you are trying to refer to is Methionine-Synthase(MTR). It uses Methyl-B12 to create Methionine from Homocystein.

    We are assuming this because of Tonyas hyperhomocystinemia.

    In the context of hydroxy-B12, methylfolate and Methyl-B12 it is indeed the finished product.(of the 3)

    Im very sad that, seemingly, so many people have difficulties understanding methylation.
     
  12. Valentijn

    Valentijn Activity Level: 3

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    So you know of another biological need specifically for methylcobalamin?
    MTRR is the substance which is responsible for converting methionine synthase-cobalamin into methionine synthase-methylcobalamin. Hence I think it is very much what we are talking about.
     
  13. Gandalf

    Gandalf

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    @Valentijn
    I dont know another need but if I now assume that there isnt another need, then I am implying that I know everything about the human body, which I dont and neither does science.

    You aren't thinking correctly then. I have nothing more to say.
     
  14. caledonia

    caledonia

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    Suggestions from Ben Lynch on methylfolate side effects:http://mthfr.net/methylfolate-side-effects/

    He also has other suggestions in his Clinical Breakthroughs 2013 video #2 (Q&A) in my links. About 15 minutes in.
     

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