I have been blessed with two homozygous double mutations on the MTR gene (5-methyltetrahydrofolate-homocysteine-methyltransferase or methionine synthase).
One is rs 1805087 (aka A2756G, for which I am GG) and it seems to be an uregulation that can be quite beneficial, assuming that it gets the raw materials it needs. There is some quite conflicting info about this SNP out there.
The other one is rs 2275565 for which I am also double homozygous. I have little information about it, but it seems to be an upregulation also.
Now, MTR is of course the thing that revs up your entire methylation cycle. By using methylfolate and methylcobalamin to create methionine from homocysteine. And I have none of the associated nasty MTRR or MTHFR mutations that could complicate things further. So my genetic cocktail is a little weird.
Anyhow, given that this mutations are really rare (A2756G GG is like 2% chance only for Europeans), there is little information on the net. The likelihood of having these two homozyguous mutations is less than 0.5%.
Here's what I have been trying to do over the recent years:
1) supplement 1000mcg - 3000mcg adenosylcobalamin to ensure that the metabolical needs for B12 are taken care of for the ATP cycle despite the MTR using a ton of methylcobalamin. I think they are interconvertable in the body to some degree. But not always, and I want to ensure that the ATP cycle has the B12 it needs despite MTR being on overdrive
2) supplement a little with methylcobalamin, but I am not getting good reactions from higher amounts. Likely because the MTR is on overdrive
3) supplement with methylfolate to provide the other reagent for MTR. This things is damn expensive though. Cannot afford like 5-15mg doses, though I have tried and thought they were beneficial
4) supplement both creatine and lecithin (for phosphatidylcholine) thus lowering the body's need to methyl groups by up to 50%. These are the two processes that use up to 50% of the methyl groups in the form of SAMe in the body.
5) supplement TMG and B6 to try to shunt some homocysteine down the the alternative paths
People also say that pro-glutathione compounds like NAC and ALA should be avoided. But I have been using them for 25 years with great results. And some people say the exact oppsite. Has something to do with glutathionyl-cobalamin. Haven't looked into that yet.
Anyhow, the more I have been thinking about it, the more it seems to me that the really limiting factor for MTR, assuming no MTRR mutations or issues with B12 absorption (intrinsic factor) is actually that damn pricey methylfolate. MTR uses it. And if it is revved up, then it uses more. So I suspect that people like me would generally benefit from methylfolate, adenosylcobalamin, maybe from methylcobalamin and somehow tuning down the MTR a little bit, if possible.
Anyone similarly situated or with insights out there? Would appreciate anything. Most of the talk on the other forums is meaningless noise. Most people do not even understand that A2756G is an UPregulation. The MTR works especially well and fast. So sort of a born hypermethylator.
Edited by Ukko, 01 April 2017 - 02:10 PM.