Invest in ME Conference 12: First Class in Every Way
OverTheHills wraps up our series of articles on this year's 12th Invest in ME International Conference (IIMEC12) in London with some reflections on her experience as a patient attending the conference for the first time.
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Methylfolate Alternative?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by gracee41, Nov 2, 2014.

  1. gracee41

    gracee41 Senior Member

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    I've read that many folks are sensitive to Methyl B12. I happen to be one of them. Dr. Yasko recommends Hydroxy or Adenosyl B12 for those folks. I've also read that many people are not able to take Methylfolate either. What does a person take if they cannot tolerate Methylfolate?
     
  2. sueami

    sueami Senior Member

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    Front Range Colorado
    Folinic acid is the recommended alternative to methylfolate. I am supposed to use both Mfolate and folinic acid because I have SHMT mutations that affect the transport of methylfolate into the folate cycle. But because I am compound hetero on the MTHFR snps, I also need methyl folate, so I've been taking both.
     
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  3. gracee41

    gracee41 Senior Member

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    Thanks very much Sueami. This is all very new to me as I just received my dna/genetic test results in September. I am hetero SHMT2. I am also compound hetero on the MTHFR snps. Appears I will need to take both methylfolate and folinic acid as well then. I had to stop using my methyl b cream because of the side effects. I just ordered B12 Hydroxy and will start very slowly with it since my body tends to react to almost every supplement or med I take regardless of what it is.
     
  4. sueami

    sueami Senior Member

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    I'm going to copy in an analysis of my snps that Gary, the researcher who developed b12 transdermoil, sent me. It's quite dense but I think full of research-based detail. You might find it of use, since you share some snps with me:

    I'm not sure that he's right in dismissing hetero mutations as having little effect, and in fact he's finding with at least one of his clients on this board that the customer's need for mb12 is much higher than he would have expected. Perhaps he right though, that it's the +/+ mutation somewhere upstream that is causing problems in a long cycle and we just are thinking the hetero mutation at the end of the cycle is the reason for the slowdown.

    But I do think his analysis sheds some light on various snps I did not grasp the function of before.


    Looking at how people go with the profiles, I think that the major problems/concerns are really the +/+ mutations. Generally if you have +/- it means that one copy of the protein is working properly. 50% of the population will have +/- so one has to assume that one does reasonably well on it.

    Mutations in any of the cycles are cumulative, so that if you have say 2 genes with mutations in the folate cycle, the cycle will run very slowly. It is like a series of large pipes, with one very small pipe in the series. The flow of water depends upon the smallest pipe. Thus if you have +/+ this restricts you flow dramatically. Now the other thing is that all the reactions "back up" behind the restriction.

    In the data that I have sent you back you will see a column that has the co-factors (the enzyme helpers) that are required for the enzyme to work properly. With nearly all the mutations, the mutations mean that the enzyme can lose hold of the co-factor if the concentration drops. Thus, if an enzyme needs FAD (from vitamin B2) and there is a mutation in the enzyme, it is critical that you keep the levels of the vitamins very high. You will see that basically you need SAM, FAD and pyridoxal phosphate as the main co-factors.

    Going through your mutations (+/+) you can see major problems in your folate cycle with Methylenetetrahydrofolate dehydrogenase, 5,10 methylenetetrahydrofolate synthase, and serine hydroxymethyltransferase. FYI you are the only person that I have seen with this series of mutations as +/+. Your folate cycle will run very slowly. You will also have trouble with utilizing folate (folic acid) as once you have made THF, SHMT is the enzyme for taking it into the folate cycle. I would think that for your folate supplementation you will need to incorporate folinic acid. Your MTHFR alleles means that you will need to also have 5MTHF to run your methylation cycle (obviously you know this. 5MTHF is the normal dietary folate).

    Looking at the generation of SAM, which can come via Betaine, 5MTHF/MeCbl/MTR, or methionine, your BHMT +/+ means that supplementing with betaine is probably not going to be great. Now it appears that we evolved to get methyl groups from betaine and up to 50% of SAM is normally generated from betaine.

    You have MTRR +/+, which means that your usage of methylB12 is very high, as you can't convert oxidized Co(II)B12 back to Co(III)B12, so you will be continually having to supplement in with more MeCbl. The other problem is that you wil basically not be able to supplement with CN-B12, because you use MTRR and decyanase to kick the CN group out of CN-B12. Studies also suggest that hydroxyB12 will not be very useful for you. Now, there is another associated methylation problem with your PEMT mutation. PEMT is normally involved in using SAM to convert phosphatidylethanolamine to phosphatidylcholine.

    Now this could be seen as an advantage as you can't use SAM and you would think that this would put less strain on your SAM, BUT you need to make phosphatidylcholine (PC) for you lipids in your cell membranes. An alternative pathway is to make PC from choline. In this case however, you will sacrifice your choline, which is used in making acetylcholine, which is one of your most important neurotransmitters. To overcome this, you will need to have lecithin which is basically phosphatidylcholine. It comes from eating eggs.

    The other major snp you have is in MAO. This is the most common double mutation seen in CFS and ASD. You need MAO to break down dopamine, nor-epinephrine and epinephrine. You can find out how bad this is by using Dr Google to look at the side effects of MAO inhibitors. It is pretty bad and curiously it is very similar to many of the symptoms that are listed on the B12 deficiency symptom list that you can see at http://b12oils.com/deficiencyfrm.htm If you fill out the form I can let you know which of the symptoms may be entirely due to MAO. To overcome this you need to supplement with lots of vitamin B2, BUT you need to have an active thyroid function to do this as you can't turn B2 into FAD and FMN if you thyroid is not working well.

    My suggestion, you need 5MTHF and folinic acid if you can get it. Split the doses so that you get a smaller dose 2 x per day.

    You need to sort out your thyroid function as many of the CFS like symptoms are due to low FAD. You thus need to take vitamin B2 and have normal thyroid. The fact that you reacted so strongly suggests that you are a bit out of whack. You also need it to help MTHFR, MTRR, MAO, and DAO and NOS. Oh FAD is also in the one enzyme that is common in CAC and your eletron transport chain. You won't get good energy transfer if you are low in vitamin B2.
    If you have found that the sub-lingual AdoB12 was working then you should do well on the Ado/MeCbl mix.
    Keep up the vitamin D3 and sun-baking. The higher the levels the better. Oh and I did find VDR Taq mutation, which means that you have trouble keeping vitamin D3 in your body, so the effect of low vitamin D3 will be worse for you.
     
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  5. PeterPositive

    PeterPositive Senior Member

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    @gracee41
    In my experience (which may not work for others) the problem with methyl-B12 and methyl-folate is simply to start low, even super low and be patient.

    E.g. even 50mcg of both would be good if they don't cause any harm. Then you can raise the dosage with time. It took me two years to be able to take moderately high doses of both.

    Other forms such as Hydroxy-B12 didn't do much for me. When I tried substituting methyl-B12 for Hydroxy-B12 for 10 days I felt my energies fade away and lack of motivation and mental fog returning. It seems many others have experienced similar issues. People like Freddd in a very dramatic way, not my case.

    As I said... a bit of experimentation is necessary, we're all different, but I can attest the superiority of methyl-B12 over the other forms. If you can also put some Adeno-B12 with the Methyl-B12 even better. Adeno-B12 usually is well tolerated by everyone.
     
  6. gracee41

    gracee41 Senior Member

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    Thank you for the feedback and the analysis of the SNP's. That's a lot to take in. I am going to print off the analysis for future reference. At the moment, I am going to focus on the B12 hydroxy since I was not able to tolerate the methyl cream even in very small amounts. I'm hoping and praying I can even tolerate the hydroxy. Does anyone know if B12 hydroxy or Adeno tends to cause low potassium like methyl B12 does?
     

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