Another request for help with my Detox and Methylation SNPs

[StephenWard9]

Hi all

Im a bit bewildered trying understand the functional impact of methylation and detox SNPs. There's a lot of information out there but it's difficult for me to work out what's the most important.

I've attached my Genetic Genie SNPs for detox and methylation. I would be greatful if anyone could offer up any thoughts..

Also, I've had various other tests done and my homocysteine is low, B12 high, Estradiol E2 high

Thank you!

 

[caledonia]

See my signature link for the SNPs Interpretation Guide and more.
You have lot of double mutations, but don't discount the single mutations either.

 

[alicec]

There's nothing much to worry about there. The methylation SNPs that do something are -

COMT V158M does slow the enzyme but +/- would have a small effect. Supplementation with the cofactor magnesium could help to stimulate a sluggish enzyme.

There is no foundation to the Yasko stuff that COMT = too much dopamine and hence intolerance of methyl groups and that VDR Taq offsets this somehow since it lowers vit D which in turn stimulates dopamine production.

COMT and intolerance of methyl groups is pure speculation and plenty of people have put it to the test and found it not to be the case. Some people are sensitive to methyl groups but it has little to do with COMT.

VDR Taq affects the VDR, not vit D and actually has been shown to have little effect.

MTHFR A1298C does have a slight slowing of the enzyme but even +/+ is not great. Supplementation with the cofactor B2 and some methylfolate could be helpful.

The Yasko stuff about this SNP affecting the backwards reaction of the enzyme in which a molecule of BH4 is generated, and thus that the SNP compromises BH4, is yet another of her total misreadings of research.

The enzyme does not run backwards and it does not regenerate BH4, though methylfolate does act as a peroxynitrile scavenger so it could have a BH4 sparing effect.

The SNP simply has a small slowing effect on the normal (forward) action of the enzyme. Here is a post about this SNP.

MTRR A66G and K350A do slow the enzyme but +/- would have a small effect. Some methylB12 could be helpful.

None of the other flagged SNPs have any effect to speak of.

Here is a recent thread which talks about some resources which can be helpful in understanding SNPs.

With the detox SNPs, often it is combinations that matter rather than individual SNPs. Promethease does a fair job in aligning SNP combinations with research about allele types affecting things like drug metabolism.

CYP 1B1L432V and CYP2D6 S486T for which you are +/+ should be checked carefully. I think these may well affect the metabolism of some drugs.

The first GSTP SNP could have some effect but you are +/- so not a big effect. Maybe make sure that glutathione precursors are in ample supply, plus adequate methylation can help with glutathionation. There are very mixed reports about direct glutathione supplementation. Some find it helpful, others a disaster.

The SOD2 doesn't do much.

NAT2 tends to be combinations. Promethease could help with that.

 

[Penn]

I am hoping that knowledgeable folks may help me here. I am interested in genealogy and ordered the Ancestry test. I have been looking at the bonus genetic testing and from googling I have noticed people really concerned with certain methylation markers. Somehow I came here.
I stopped my multi vitamin immediately from fear of folic acid!!. A while back I happened to be tested for B12 which was normal at 861 range 211-946 and folate was greater than 20 with a range of 3.10- 17.50. I was looking at the methylation snps and have homozygous the following, ++C6777t, BHMT,FUT2,MAOB,PEMT,SOD 2and 3,SHMT,VDR BSM, and VDR TAQ. My 1298 is normal. I am past having children but have Fibromyalgia and CFS. Do you think these markers are significant for health? Thank you

 

[alicec]

BHMT,FUT2,MAOB,PEMT,SOD 2and 3,SHMT

We would need to know what SNPs associated with these genes are being identified. I am not familiar with the Ancestry analysis, though I imagine it would include a limited range of SNPs, maybe a bit like the Genetic Genie analysis.

The BHMT variants identified by Genetic Genie do little to nothing, nor does SOD 2, not sure about SOD 3.

Some FUT2 SNPs can be significant for B12 and gut health, but only +/+.

Some PEMT SNPs could have significance for choline metabolism.

MTHFR C677T +/+ would definitely slow the enzyme and you may well benefit from supplements of B2 (the cofactor for the enzyme) and methyl folate. Proceed cautiously with the latter - some people are sensitive to it.

VDR Taq and Bsm have little to no effect.

 

[Penn]

Thank you @alicec for the help you and others give to people.
I wonder if my high -20 -folate result was from taking the 400 mcg folic acid in my multivitamin or could I still take folic acid but in a smaller amount, say, 200mcg? Or maybe it is best to switch to something like 100 mcg methyl folate to start? I am such a novice that I don't know what is causing the high folate. at the time my doctor said nothing about the high result-I just happened to look back now at my test from last year.

 

[alicec]

I wonder if my high -20 -folate result was from taking the 400 mcg folic acid in my multivitamin or could I still take folic acid but in a smaller amount, say, 200mcg? Or maybe it is best to switch to something like 100 mcg methyl folate to start?

Personally, I'd ditch the folic acid for methyl folate. Start low and increase slowly and as well consider adding active B12 (methyl and adenosyl) since folate and B12 work together.

Way back, I had only supplemented the small amount of folic acid and cyanocobalomin in a multivitamin but had very high folate and B12 blood levels. The doctors ordering the blood tests had no clue about what this meant.

It was only when I organised an OAT test and found I had functional folate and B12 deficiencies, that I realised the high blood levels meant I wasn't actually absorbing and using the vitamins. Changing to the active form of folate and B12 quickly turned around the functional deficiencies.

Blood tests for folate and B12 mean very little, apart from revealing frank deficiency if low.

It seems that for everyone, conversion of folic acid to active forms is a very slow process and it is easy to overwhelm the mechanism. In some people, it is even more of a problem and folic acid quickly builds up. It is claimed that SNPs in MTHFR are responsible for this difficulty but I don't think there is any evidence for this being the mechanism. Nevertheless it happens and the accumulated folic acid may interfere with active forms. Best to avoid it.

 

[Penn]

Thank you @alice for your advice!