A New Decade of ME Research: The 11th Invest in ME International ME Conference 2016
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Some Confusion?! :( - MethylB12 and VDR taq & COMT

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by ryane, Feb 28, 2016.

  1. ryane

    ryane

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    Hey Guys,

    I'm new here and haven't been diagnosed with ME/CFS, however I believe that forum has incredible knowledge around the Methylation protocols - and would really appreciate some input on the below. I see this as a preventative query (or at least limiting worsening) based on the various issues that can materialize due to MRHFR mutations. While I am only heterozygous, i feel things are compounding a bit as I seem to be having difficulty getting b12 from my diet.
    Due to living in South Africa, unfortunately a lot of my work is self exploration as there are limited experts here.

    I had my genetic test done and I have MTHFR C677T+-, VDR Taq+- and COMT ++ (Both V158M & H62H) - amongst other mutations, but the question is based on these.

    While I am functioning pretty well, through the process I realized that I am very likely to have a b12 deficiency (swollen tongue, brain fog, low energy etc) - even though I have a very healthy lifestyle and diet.

    Now during my MTHFR research, i got it in my head that i should use Adenosylb12 and HydroxyB12 due to Dr Amy Yasko's research stating that one with COMT and VDR Taq mutations should avoid Methylb12 due to having to avoid methyl-donors. However, a couple of days i revisited my researching and came across this thread - http://howirecovered.com/active-b12-therapy-faq/ - which is heavily based on information from this forum. What i got from this page is that you actually need both types of b12 (Methyl and Adeno), as they serve very different purposes, and one (Adeno) cannot simply be supplemented for everything.

    So, having just purchased a bunch of Adenosylb12. What is the general consensus? Should i supplement both forms, or do i stick with Yasko - and only supplement Adenosylb12?
    I've heard that HydroxyB12 is a waste of time, which further makes me question her protocol?
    I bought one bottle of HydroxyB12 which is on route - should i just bin it?

    I also saw the following statement on the howirecovered website:
    "The methylb12 has only a tiny fraction “methyl” which is CH3. That is a total of only 18 out of more than 1335 total molecular weight. Compared to methylfolate or SAM-e or other methylators, Mb12 is very weak and has very little methyl to contribute."

    Any help would be appreciated immensely - seems there is a lot of conflicting information, and would really like to start supplementing this week. [Might need to change my current course of action and hunt for some MethylB12!)

    Thanks all, glad i found this community. :)
    Ryan
     
    Last edited: Feb 28, 2016
  2. ahmo

    ahmo Senior Member

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    There is a lot of conflicting info. I've done very well with Freddd Protocol, 3 versions of info about this in my signature. Also, caledonia has methylation guides in her signature.

    Adeno and methyl B12 do 2 different things. Hydroxy did nothing for me.
     
  3. alicec

    alicec Senior Member

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    Yasko is not a reliable source of information. She has made serious errors about a number of snps, focusses on many which do little or nothing or for which no research is available and promotes myths based on dubious assumptions.

    Of the snps you mention, VDRTaq is one of the inexplicable ones which do very little (there is a thread about VDR here). It and COMT have become part of the mythology about not tolerating methyl groups. Some people do indeed have trouble with methyl groups but it has nothing to do with COMT and VDR.

    The MTHFR snp you list does cause a small slowing of the enzyme, as does the COMT V158M. The other COMT snp has no effect. There are threads here and here

    These and various other methylation snps are discussed over and over again on PR - for example there has been a recent thread that may help you understand more about them here. There are many others - just search around.

    You do need both methyl and adenosylB12. Theoretically in a healthy person the forms should interconvert but we are not healthy and many of us find benefit from supplementing both.

    Howirecovered is based on a protocol you can read about in great detail on PR from Freddd. There are four central ingredients (the so-called deadlock quartet), methylfolate and carnitine in addition to the two forms of B12. Some people have benefitted from it (including myself) but others have not. It is not a straightforward protocol I must warn you.
     
    Valentijn likes this.
  4. JES

    JES Senior Member

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    I have similar snps (COMT++, MTHFR C677T +/-, VDR Taq++) on my genetic test, however, I think these results can only be used as a guideline at best. I react badly to any methylation enhancing supplements, they all produce bad anxiety for me. This anxiety reaction is supposedly something that comes with COMT++ snps.

    MB12 is one of the milder ones among the methylation protocol supplements, so that or hydroxocobalamin (if you can find it) is probably a good starting point.
     
  5. Critterina

    Critterina Senior Member

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    Whoever wrote this has no concept of chemistry. That's like saying the warhead is a very small part of the missile, so it has very little contribute. You can't compare the weight of a functional group to it's importance or effectiveness; it just doesn't work like that.

    One molecule of mb12 can only have one methyl group. And what's more, the MTRR enzyme needs Mb12 in order to make the methyl cycle turn; it's not even a case of donating it.
     
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  6. zelda

    zelda

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    I don't mean to hijack this thread, but do have a related question. I have been following PR for literally years and read all the posts on methylation, Rich's theories, Freddd Protocol, opinions on Yasko and everything else.

    I have been hesitant to post, not sure why really, but probably mostly because I don't have a CFS/ME diagnosis. I have had periods of being bedridden and have been chronically ill for about a decade. To make it short, I have gotten sicker with doctors and managed to heal myself to much better function on my own by addressing methylation and gut health but in a very individual way.

    My question is about Adeno B12 and my reaction to it. I am +/+ for MTHFR 677, MTHFS, MTRR (2 variants). TCN1, TYMS, SLC, so I am fairly certain I have a high need for both Mfolate and B12. Right now I take 6mg MFol daily, along with 20mg Mb12 and a low dose, active B complex. Last week I realized I have had some Adeno B12 in the cupboard and have forgotten to take it for about 6 months or so, so I popped a 10mg sublingual. (Source Naturals).

    Later that day became really fatigued and foggy and have repeated this reaction upon taking the adeno B12 each day. It does not disable me, but definitely weighs me down heavily.

    My question is, does this happen to anyone else? When I first started MB12 it did this to me also, but it makes less sense to me that the adeno would do this. Just trying to figure out if this means I should back off, as it is not helping me, or if it is more likely a sign that I have turned something on and found a missing piece. ( I do still have a bit of healing to do).

    Anyone had a similar reaction? And as it relates to part of the initial post here, what specifically could the adeno be doing that the methyl B12 was unable to and that would trigger this type of fatigue and fogginess?

    thanks!
     
  7. alicec

    alicec Senior Member

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    The two forms of B12 act differently. MeB12 is part of the methylation cycle while adoB12 helps to feed fatty acids into the Kreb's cycle for energy production.

    I suspect your problem is that 10 mg adoB12 straight off is just too much. Like the MeB12, it is something you need to build up slowly.

    You might like to think about the role of carnitine also. It is part of the same pathway that adoB12 affects in that it is necessary to transport fatty acids into mitochondria. In Freddd's protocol, carnitine forms the 4th part of the deadlock quartet.
     
  8. PointsNorth

    PointsNorth Paulo

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    Welcome Zelda, this is completely off-topic but have you tried LDI low-dose immunotherapy? I have multiple sclerosis with the VDR Taq and COMPT. LDI Lyme gave me momentary relief from my fatigue and increased leg strength. Your local Naturopath Will be familiar with LDI for CFS/ME. I have MS myself.
     
    Last edited: Apr 5, 2016
  9. zelda

    zelda

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    Thanks for your replies @alicec and @PointsNorth. I do understand the different actions of MB12 and Adeno, but maybe need to do more research.

    I also agree I likely just took too much at the get go, but still just a bit confused as to why it would make me tired and drained and not stimulate instead, however I do understand that getting pathways working can cause all sorts of various symptoms, especially at first.

    I have tried carnitine in the past and found it just too intolerable gut wise, in various forms. Other than that, it really did nothing for me.

    But perhaps it might be time to revisit it. I had gotten to the point with my other supps (MB12 and MFol and B complex) that my energy has been good, pretty darn functional. I just hate to add something that now wipes me out (the adeno) unless I can kind of figure out that it is for a good cause and helping move me further into healing. I might stick with a lower dose for another week or two and then step out if I don't see any shift.

    @PointsNorth, thanks for the input about LDI. I have actually given up on all doctors, traditional or otherwise as all they ever did was make me sicker. And yes, I have seen them all. Each and every kind, lol. I have made the most progress completely on my own and will probably stay away from outside help barring any unforeseen circumstances.

    As an aside, I have ordered the B12 oils from Greg and maybe I will see a different reaction with a different absorption method and no fillers. Trying both the Methyl by itself and AdenoMethyl combination.
     
  10. zelda

    zelda

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    Just found this post from @Vegas on another thread back from 2015. It makes a lot of sense in my personal situation and I believe something to definitely consider.

    "Supplementation with high-dose vitamins at high concentrations and co-enzymated forms not found in nature is seemingly a "high-risk/high-reward" proposition. In this instance I would venture a guess that you precipitated an epidsode of organic acidemia. L-methylmalonyl-CoA is a cobalamin-dependent enzymes, but it requires adenosylcobalamin. Circumvention of mitochondrial synthesis of adenosylcobalamin could cause accumulation of organic acids. The weakness you describe is a classic symptom of mitochondrial failure as described in many mitochondrial diseases/organic acid disorders.

    Providing adenosylcobalamin directly and bypassing conversion from hydroxocobalamin is problematic. For one, you are accelerating the isomerization of methylmalonyl-CoA to succinyl-CoA; that is what L-methylmalonyl Co-A mutase does. You can't handle the addition of this TCA intermediate and you are acidifying your cells/muscles. Succinyl-CoA also becomes available to metabolism via a-ketoglutarate, which is made available by deamination of glutamate.

    I am a bit curious if you have ever had an organic acids profile, or perhaps supplemented with other TCA co-factors...lipoic acid, riboflavin, etc. You might also have interesting reactions to Pantethine, Acetyl-carnitine, CoQ10. I'm not advocating use of any of these, particularly the last two but am simply trying to discuss what has happened. I certainly would be careful with BCAA's, though.

    As I see it, there are homologous bacterial genes that perfectly complement our own metabolisms. These anerobic microbes which are sensitive to oxidative stress have things like S-adenosylmethionine synthetase encoding, but this is coupled with butyryl-CoA dehydrogenase capabilities. In other words, rate-limiting reactions controlling methylation are tied to robust capacity by our microbes to suppress the oxidative consequences that these reactions create. I think, your problem is in your gut.

    I could hypothesize about what B vitamins and krebs cycle co-factors might make you feel a bit better, but I don't really want to fix one problem and create another. If you feel you benefit from B12, then perhaps hydroxocobalamin would be a better choice. Good luck."



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