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Any help with my 23andme methylation and detox results most appreciated

Discussion in 'Genetic Testing and SNPs' started by anniekim, Feb 23, 2014.

  1. anniekim

    anniekim Senior Member

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    Sorry I am another one seeking help with interpreting my SNP's for methylation and detox. If any one can make any suggestions on any of the results it would be truly appreciated. Huge thanks in advance

    My results are:

    Methylation

    ++
    Bhmt 08
    Bhmt 02
    VDR taq

    + -

    MTHFR 03 P39P
    MTHFR A1298C
    COMT V158
    COMT H62H
    MAO-A R297R
    MTR A2756G
    MTRR A66G
    MTRR K350A
    CBS A360A

    Detox profile

    ++

    SOD2 A16V

    + -

    CYP1B1 L432V
    CYP1B1 R48G
    CYO2C9*3 A1075C
    GSTP1 1105V
    NAT2 I114T
    NAT2 R197Q
    NAT k268R

    I read this on the genetic genie report, 'With a COMT + status, it has been clinically observed by physicians that people may have trouble with methyl donors'. Can anyone explain what this means? Does this mean all methyl supps?
     
    Last edited: Feb 23, 2014
  2. Critterina

    Critterina Senior Member

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    Hi @anniekim ,

    I don't think that the COMT + status means all things methyl, and not all COMT + people have trouble with methyl donors.

    Your ++ (homozygous) VDR Taq suggests that you should keep your vitamin D levels up, probably in the upper half of the normal range, because your receptor sites aren't as good at binding as VDR Taq negative people. You will need blood tests to verify that you're at a good level.

    The BHMT 08 ++ means your secondary methyl pathway is inefficient; it could be helped by TMG, but that is tri-methyl-glycine. It's normally written without the hyphens, but I wanted to emphasize that it has three methyl groups - not a good place to start if you may be sensitive to them! So let's forget about that for now.

    You have MTR A2756G, which means you are more efficient at using up methylfolate for the primary pathway of the methyl cycle (also meaning that you're probably OK ignoring your BHMT mutation in your secondary pathway.) There's nothing wrong with that. But, you have MTHFR A1298C, which means you're not so efficient at using methylfolate for the biopterin cycle. So most of your methylfolate gets used for one thing and not another.

    The biopterin cycle makes neurotransmitters serotonin and dopamine, which then turn into other important things. A lot of symptoms and conditions are identified with lower biopterin function: migraines, anxiety, depression, autism, bipolar, fibromyalgia, chronic fatigue, Parkinson's, irritable bowel, ADHD, etc. If you have absolutely no problems with these, you're lucky. If you want to supplement, use methylfolate. Many people on this site like Solgar brand.

    Start with a small amount if your sensitive to supplements - some people just crush up a tablet and put a little powder on their tongue. Then if you're OK, a little more. Me, I just took the whole pill and had no ill effects. You need to learn enough to choose for yourself. Hope that what I've said gives you a start on what to look into.

    I'm not sure, but I think that COMT individuals who react to methyl donors react to methylcobalamin (b12), TMG, SAMe, and others, but not methylfolate.

    One thing for consideration further down the road, is that if you find a methylfolate dose that is good for you, you might - well, you might leave well enough alone, but you also might consider trying folinic acid instead (folinic, not folic acid). You should have no trouble converting folinic to methylfolate, so in theory, it should be about the same. The main reason for the switch is that folinic acid is quite a bit cheaper. I don't remember the price difference, but it may be $15-$20/month if you take 1 mg/day. Please let me know if you decide to do this and whether it works. I'm going to try it myself, but I'm not out of methylfolate yet.

    Good luck.
     
  3. anniekim

    anniekim Senior Member

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    Critterina, a huge thanks for this very helpful reply.

    Is the MTHFR A1298 the only one associated with the biopterin cycle? Ie is the other one C677T not involved? Sorry if this is a daft question, I am very new to this.

    I take it if I take methyl folate I should also be taking B12 but not methyl B12?

    Thank you for the suggestion of folinic acid instead of methylfolate. I will consider it after trying methylfolate and I will let you know how it goes if I do. I hope you are right that methyl folate will be ok even though I apparently don't respond well to methyl donors. I took a supplement once with TMG and it knocked me out for six. I just couldn't stay awake. I wonder if this is due to the comt mutation.

    I did read online a doctor who says +- A1298C is quite common and shouldn't cause so many problems. I take if you would disagree with that and would say methylfolafe js still necessary?

    Once again thank you so much for taking the time to reply
     
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  4. anniekim

    anniekim Senior Member

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    @Critterina I read today on the heart fixer website a claim that COMT (+/-) and VDR (+/+) behaves like COMT (-/-) and the information they give for COMT - - says, '1. Here you are draining SAMe and methyl groups in general, so supplement liberally with methyl donors, such as those listed above.
    2. SAH (S-adenosyl homocysteine) puts a break on COMT, and will be generated from the SAMe that you are taking to provide methyl groups,
    3. Support dopamine with agents such as Mood D (1/4 dropper 1-2 times a day), Mood Focus (1/8-1/4 dropper daily), quercetin, ginko, and macuna puriens. No need to avoid high dopamine foods. Dopamine protects nerve cells from metal toxicity, especially if glutathione is lacking.

    Do you have any thoughts on this? Many thanks
     
  5. Critterina

    Critterina Senior Member

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    My thought is that I haven't followed the pathways closely enough to see why, theoretically, all this would be so. If you send this to me in a conversation, I'll be able to find it again when I have some time.
     
  6. anniekim

    anniekim Senior Member

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    @Critterina that's very appreciated and I will copy and paste it into a conversation. I appreciate this all takes up I your time so no rush whatsoever. Many thanks
     
  7. Critterina

    Critterina Senior Member

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    Annie,
    The MTHFR enzyme converts folinic acid (or is it another precursor? I'd have to check) to methylfolate. It also converts methylfolate back to what it started with. When it does the second part of the reaction, it converts biopterin into the active form (dihydro to tetrahydro). I think that whether the A1298C +/- may or may not be important depending on whether another enzyme is working well, I think it's called IDHP but I'd have to look it up. I have not investigated whether there is research on the SNPs that may make IDPH more or less active, so for me and for you, we don't know.

    For me, when I started using methylfolate, my tryptophan levels dropped, meaning to me that I was using it to make serotonin. I did feel better.

    Here's a link. Check out the A1298C arm. I think that a lot has been refined in medical understanding since this, but I like it to get my head around the idea. http://www.mindmeister.com/12694596/mthfr-related-health-problems
     
  8. anniekim

    anniekim Senior Member

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    Thank you for this. I know the MTHFR gene codes for an enzyme to convert folic acid or folinic acid into methyfolate what I haven't worked out is how this is further divided up with the A 1298C and the C677 Do they both produce different enzymes, or is it all the same enzymes? Many thanks
     
  9. Valentijn

    Valentijn Activity Level: 3

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    They're SNPs on the same gene (MTHFR) which always produces the same enzyme. Hence any problems with the gene should have the same type of impact. One is more severe (C677T) in reducing enzyme activity, but they shouldn't be causing different problems.
     
  10. anniekim

    anniekim Senior Member

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    Thanks @Valentijn for explaining that. As you can see, I am clueless about this all. If I have understood it correctly it is accepted that the C677T will reduce activity but science is still disputing how much an effect -/+ A198 has?

    Do you have any thoughts on the claim that a vdr taq +/+ and a COMT +/- combo causes the same situation as a COMT -/-? Many thanks
     
  11. Valentijn

    Valentijn Activity Level: 3

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    +/- C677T will reduce MTHFR enzyme activity to about 65% of normal. +/+ will reduce it to 30% of normal.

    +/+ A1298C combined with +/- C677T will reduce MTHFR enzyme activity to 30% of normal. +/- A1298C combined with C677T +/- has a 50% chance of reducing MTHFR activity to 30% of normal, if the + for each is on a different strand - this can't be determined based on 23andMe results. If each + is on the same strand, activity is just 65% of normal.

    As far as I have seen in the research, a +/- A1298C should have little or no impact, if C677T is -/-. It also sounds like +/+ A1298C doesn't have a sizable impact on it's own. The primary effect of A1298C is to aggravate the serious MTHFR mutations.
    I haven't looked into that claim specifically, but it sounds pretty implausible to me. I'd be interested to see any real research supporting that claim, if it exists. I also don't know what the logic behind that claim could possibly be.
     
  12. anniekim

    anniekim Senior Member

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    Thanks @Valentijn appreciated. If +/- A1298C doesn't have much of an impact, is it really necessary to take methyl folate? EDIT: I've just seen elsewhere that it is stillrecommended as needed for help when methylfolate converted to something else, can't remember now.

    I asked on a MTHFR Facebook page about VDR ++ making a +/- COMT -/- and one person said 'VDR -- exacerbates COMT downregulations, as does a build-up of SAH'. I admit I don't understand all of this would that explanation throw any light no the COMT claim? It was heart fixer who made the claim by the way. Is he any good? Many thanks
     
    Last edited: Feb 26, 2014
  13. anniekim

    anniekim Senior Member

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    @Critterina you explained above ' you have MTHFR A1298C, which means you're not so efficient at using methylfolate for the biopterin cycle. So most of your methylfolate gets used for one thing and not another.' If my A1298C mutation means I don't convert methylfolate into biopterin well, how does taking more methylfolate help? Is it because I just need a lot more methyl folate to produce the biopterin as it's not very efficient in making biopterin? Many thanks and as always no rush for a reply
     
  14. Critterina

    Critterina Senior Member

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    It doesn't actually turn methylfolate into biopterin. Let me get a layer deeper: Methylenetetrahydrofolate reductase (MTHFR) turns 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate (a.k.a methylfolate). It also turns it back. The C677T mutation slows down the forward reaction; the A1298C mutation slows down the backward reaction. So, if you take methylfolate, you have more substrate for the backward reaction, and since chemical systems tend to equilibrium, it will encourage the backward reaction to happen more.

    When the backward reaction occurs, it also turns dihydrobiopterin (BH2) into tetrahydrobiopterin (BH4). BH4 is used for a lot of things, including detox and neurotransmitter synthesis (dopamine from tyrosine and serotonin from tryptophan via 5-htp).

    I believe there is another enzyme, IDHPR, that catalyzes this same conversion of BH2 to BH4. Pure speculation on my part, but I bet that some of us have more efficient IDHPR than others, maybe because of an SNP, and that those who have both BH4 pathways not working so well, even if the only SNP we know is A1298C +/-, are the ones who have the problems associated with A1298C (or biopterin problems), and those who have a good secondary pathway do not. Maybe one day I'll do some literature search on IDHPR.
     
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  15. Valentijn

    Valentijn Activity Level: 3

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    Okay, that makes a little more sense. They're probably referring to the effect VDR and COMT can have on neurotransmitter levels, as VDR goes toward creating some neurotransmitters and COMT goes toward breaking down some neurotransmitters. +/+ is basically the slower version of each, so they seem to be saying that having slower formation of neurotransmitters and medium-speed breakdown of those neurotransmitters is about the same as having slow breakdown of those neurotransmitters. The (unsubstantiated?) theory is that this might be problematic, as the slowly produced neurotransmitters are broken down too quickly to be replaced, and neurotransmitters are too low and/or unbalanced as a result.

    In regards to methylation, +/+ COMT or VDR indicates slower use (and potentially less tolerance) of methyl groups. What they're talking about is not in reference to methylation, however, and probably largely irrelevant especially if you don't have mood issues. It's possible that they think that VDR +/+ somehow effects COMT-dependent methyl group tolerance, but that wouldn't make any sense, as there's no plausible way for VDR +/+ to make COMT +/- methyl group use any faster or slower.
     
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  16. anniekim

    anniekim Senior Member

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    @Critterina and @Valentijn thanks so much for both of your very helpful answers. You explained it very clearly for a novice like me on all of this - and thanks too for your patience with someone so clueless :)

    Just to confirm I have understood one point correctly, are you saying VDR +/+ indicates slower use? Many thanks
     
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  17. Valentijn

    Valentijn Activity Level: 3

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  18. anniekim

    anniekim Senior Member

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    Thanks @Valentijn

    Another question if that is ok. I would say I have often struggled with low mood over the years. I take anti d's now and definitely feel so much better on them, even though I worry when I read they are not good for you. Are my VDR taq ++ and BH2 ++ and BH4 ++ probably responsible for my low mood? Many thanks

    There is another issue I don't understand. I have COMT V158M +/- and COMT H62H +/- would I add the two together to say I am +/+ COMT overall?

    I somehow thought that for each gene, such as MTHFR, COMT etc you could only have two in total of all the variations but I noticed in another thread that someone had COMT +/- with three different variations so I think I may have understood that wrongly? Many thanks
     
  19. Critterina

    Critterina Senior Member

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    Really? VDR Taq ++ can mean less tolerance of methyl groups? I can take methylB12 like candy, and I've been using methionine (SAMe for a while instead) and TMG, no problem. Huh. Go figure.
     
  20. Valentijn

    Valentijn Activity Level: 3

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    If + is the "G" allele, then yes, it's a mild down-regulation. Personally I doubt it has enough impact to do much of anything noticeable, but the Yasko/Heartfixer theory is that it causes a reduced tolerance to methyl groups due to slower VDR using less methyl groups.

    Additional VDR mutations tested by 23andMe, many of which can have a much more significant impact, are listed at http://forums.phoenixrising.me/index.php?threads/interesting-vdr-variations.24480/
     
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