Very low homocysteine & MTR/MTRR

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Can anyone please help me work out what I need?

I have been treated by Dr and ND with methylb12 lozenges and hydroxy injections.

At present I'm taking a small amount of Methylfolate and methylb12 but feel dreadful some days and fine others. More makes me feel overmethylated and angry. I'm homozygous for MTR & MTRR & MAO I think high b12 intake without folate is dangerous as it will feed MTR which wants folate as well. My feeling is though that feeding this cycle in general is just pushing it all out the CBS pathway & generally leaving me undermethylated as I have no homocysteine to regenerate into methionine and create neurotransmitters etc. I do struggle with high sulphur & ammonia.
I have CBS SUOX & other snps just 1 MTHFR snp 1298c.

Also, after being treated by health professionals for methylation issues I have had chronic yeast infections (18mths now) which led to taking metronidazole during my last pregnancy close to delivery which I still very much regret due to the effects on my son's gut and our breastfeeding relationship.

Please help offer suggestions, should I be on hydroxyb12 only and food based folate or folinic acid only?
 

nandixon

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@Lilmaz, I figured you were, because people who are homozygous for MTR A2756G often have low homocysteine (Hcy). That SNP causes a relatively strong upregulation of MTR and thus faster processing of Hcy into methionine.

People homozygous for MTR A2756G are likely already overmethylating, e.g., inhibiting gene expression by methylation of gene promoter regions.

For these people, it seems to me that taking extra B12 and/or folate is just adding fuel to what is already a fire, so to speak, and not a good idea because gene expression may be dampened down too much (i.e., an unfavorable epigenetic regulation).

Note that MTR A2756G has rather the opposite effect of MTHFR C677T, where homozygosity can cause undermethylation.

The definitive study showing the increased methylation MTR A2756G causes is the 2014 reference I've attached.
 

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Thank you so much. My practitioner thought I was overmethylated as I had high copper and normal histamine but I got worse on folic acid (William Walsh protocol) so she changed her mind to undermethylated. I seem to have symptoms of high histamine at times though. Whether that is from my gut or my methylation speeds & slows I'm not sure.
 
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My blood levels of b12 are very high even without supplementation.
Is this a conversion problem?
Initially on mb12 I felt wonderful. Same with SAMe. Then awful.
I have COMT snps as well so I think getting overmethylated & high estrogen easily upsets things. No one seems to know how to balance things.
I've also been taking inositol for PCOS, is this a bad idea if overmethylating?
 

nandixon

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@nandixon if MTRR is homozygous (downreg?) won't this mean b12 is in short supply as MTR is using it up?
I think your low homocysteine is suggesting that there's not an undermethylation issue to be worried about. Although, to possibly gain some better insight you might have your methionine level checked with an amino acid panel of some kind. I'd guess that methionine should be either normal or high in your case.

(I'm not sure how significant MTRR K350A, rs162036, actually is. In any event, I think I'd tend to view any down-regulation of MTRR as a potentially beneficial offset to help put the brakes on your MTR A2756G.)
 
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Can anyone please help me work out what I need?

I have been treated by Dr and ND with methylb12 lozenges and hydroxy injections.

At present I'm taking a small amount of Methylfolate and methylb12 but feel dreadful some days and fine others. More makes me feel overmethylated and angry. I'm homozygous for MTR & MTRR & MAO I think high b12 intake without folate is dangerous as it will feed MTR which wants folate as well. My feeling is though that feeding this cycle in general is just pushing it all out the CBS pathway & generally leaving me undermethylated as I have no homocysteine to regenerate into methionine and create neurotransmitters etc. I do struggle with high sulphur & ammonia.
I have CBS SUOX & other snps just 1 MTHFR snp 1298c.

Also, after being treated by health professionals for methylation issues I have had chronic yeast infections (18mths now) which led to taking metronidazole during my last pregnancy close to delivery which I still very much regret due to the effects on my son's gut and our breastfeeding relationship.

Please help offer suggestions, should I be on hydroxyb12 only and food based folate or folinic acid only?
Hi @Lilmaz have you managed to correct your issues?