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Folate, Vitamin B12, and MTHFR

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I participate in the 23andMe Parkinson's study and have learned there about the folate and Vitamin B12 issue related to the MTHFR mutations. So I posted this question to Ask the Nutritionist and she gave excellent information, but suggested I ask you also.


I recently had testing with these results: Vitamin B12 was 908 pg/mL and Folate RBC was 658 ng/mL. (Please note: test results may have been skewed because I had already been taking some methyfolate and B12 in the month before testing for just a couple of weeks, stopping several days before the testing.) My G.P. doctor says these numbers are fine, but 23andMe forum participants say I may still need supplementation because high folate is not good for me (not processed well), due to my MTHFR "compound heterozygous" status. But I'm unclear about type, source, dosage. Should I also request homocysteine testing? Here are excerpts from the 23andMe forum comments re: methylfolates, etc.:


Forum participant: "If you are A/G at rs1801133, and G/T at rs1801131, then your status is compound heterozygous C677T/A1298C. According to SNPedia, you would expect to have ~65% of the normal MTHFR enzyme activity."


Me: "That is exactly my situation, AG & GT. I have Parkinson's, tremor dominant type and also higher risk for VTE. I've been reading all the above and trying to understand. What exactly should I do? Take methylfolate and B12? What type and amount? Ask my MDS for a prescription?"


Participant: "Folate - high is not good for you, unless you are on high doses of l-methylfolate and low dietary intake of commercial folates. If you are compound heterozygous, you can't process it well, so most of it is unprocessed which competitively inhibits the little l-methylfolate you can make. In diabetes, the sugar is high too, but that is not good, because the high is due to excess intake and poor metabolism. The folate tests can't distinguish between the inactive dietary/supplemental folates and the active l-methylfolate. So here less is more."

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I have asked several world experts and am awaiting an answer. I am actually not sure how to answer this question, so in the meantime I will post for discussion. This is one area where critics would say 23andme has a weakness....no genetic counseling before you get the genetic test so you are prepared to interpret and act or not act on the results.

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Thank you for trying to find more info for me on this. I have been hoping some of those experts might get back to you by now and am eagerly awaiting what they have to say. Please let me know what you find out.


To be fair, I feel I should defend 23andMe a bit. I tried to make clear that this MTHFR issue is something I learned about from a user forum on 23 (and other sites & scientific journal articles), not as an official 23andMe "Established Research Report" on a condition recognized by 23. I think they do a good job of informing users about those, including locking some results, advising genetic counseling, providing useful info, etc. There does seem to be something to this MTHFR issue (some valid scientific evidence), but I don't think it is officially recognized or supported by 23 yet.

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