Folic Acid level decreasing even after supplementation. Could be MTHFR?

[alicec]

MTHFD1 || c.1958G>A (p.Arg653Gln) || Autosomal Recessive || Heterozygous

MTHFD1 is a trifunctional enzyme which converts THF into intermediates which feed in to purine and pyrimidine synthesis and to MeTHF formation.

This SNP, rs2236225, affects the thermolability of the enzyme. +/+ has about a 26% reduction in metabolic activity.

This study shows that MgATP and folate can overcome the thermolability.

Other studies show that the presence of +/+ for this SNP can influence the balance of folate pathways as well as place pressure on choline supply.

Adequate supply of magnesium, folate and choline would therefore seem to be wise precautions, though +/- for this SNP would have a small effect.

MTRR || c.66A>G (p.Ile22Met) || Autosomal Recessive || Homozygous

MTRR ensures the cobalt in methylB12 remains in a properly reduced state, which in turn is necessary for the MTR enzyme to convert homocysteine to methionine.

This SNP, rs1801394, does affect the activity of the enzyme though in itself, the effect does not seem great. Some combinations of this SNP and rs1532268, can lead to a requirement of 3-4 times the ratio of MTRR to MTR to get maximal activity of MTR.

It's not clear if supply of methylB12 can overcome this but again it could be a useful precaution.

 

[trio]

MTHFD1 is a trifunctional enzyme which converts THF into intermediates which feed in to purine and pyrimidine synthesis and to MeTHF formation.

This SNP, rs2236225, affects the thermolability of the enzyme. +/+ has about a 26% reduction in metabolic activity.

This study shows that MgATP and folate can overcome the thermolability.

Other studies show that the presence of +/+ for this SNP can influence the balance of folate pathways as well as place pressure on choline supply.

Adequate supply of magnesium, folate and choline would therefore seem to be wise precautions, though +/- for this SNP would have a small effect.



MTRR ensures the cobalt in methylB12 remains in a properly reduced state, which in turn is necessary for the MTR enzyme to convert homocysteine to methionine.

This SNP, rs1801394, does affect the activity of the enzyme though in itself, the effect does not seem great. Some combinations of this SNP and rs1532268, can lead to a requirement of 3-4 times the ratio of MTRR to MTR to get maximal activity of MTR.

It's not clear if supply of methylB12 can overcome this but again it could be a useful precaution.

Hey, many thanks for your reply.
How much would these mutations affect my lifestyle? Do they really affect or affect is minimal?

My doctor told me not to take Folic acid, only Methylfolate but my multi has 400MCG of Folate but I really don't want to leave it because except Folic Acid, it has everything great and it helps me.
Would Folic Acid be harmful in these mutation?

Again, many thanks for your reply.

 

[alicec]

How much would these mutations affect my lifestyle? Do they really affect or affect is minimal?

The effect is small. Probably a healthy person eating well would cope perfectly well. When the system is placed under pressure then perhaps they might start to matter.

The classic case with folate-related SNPs is the added demand of pregnancy and a number of them show increased risk of neural tube defects. Note this is just increased risk. Ensuring adequate folate intake can overcome this.

Other diseases may place similar demands though few have been investigated.

Given the widespread metabolic derangements which appear to be associated with CFS/ME, I take the view where SNPs are known to slow enzymes, it is wise to compensate with supplementation just in case.

My doctor told me not to take Folic acid, only Methylfolate but my multi has 400MCG of Folate but I really don't want to leave it because except Folic Acid, it has everything great and it helps me.
Would Folic Acid be harmful in these mutation?

Folic acid is processed slowly in everyone and very slowly in some people. This can lead to folic acid accumulation. This in turn can feedback and inhibit a number of enzymes in folate pathways, so if these enzymes are already slowed by SNPs, possibly this might cause problems.

Your blood tests don't suggest folic acid accumulation but it is impossible to predict what effect it might be having for you. If you could find another multi without folic acid you could compare the effect of the two.

 

[trio]

@alicec Hey thanks for your reply.
Can these mutations cause premature hair graying?
Thanks

 

[alicec]

@alicec Hey thanks for your reply.
Can these mutations cause premature hair graying?
Thanks

Cause? I doubt it, I haven't even seen any studies associating the SNPs with premature greying.

I don't know anything about the subject but a quick google suggests there are multiple possible causes, nothing as simple as a couple of SNPs.

 

[Jade east]

Hair greying, loss--b12 deficiency. Given the folate issue, may be malabsorption. Can and does present without hematologic symptoms. See http://healthunlocked.com, the Pernicious anemia forum, read the attached articles first, then search hair, search folate.

 

[trio]

Hi,

I regularly take 3MG of Methylfolate daily and an Iron Tablet, still both have decreased to borderline low. I have no genetic mutations related to these. I am completely clueless.

Please help.

Thanks