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Low Folate Symptoms/Paradoxical Folate Deficiency

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by arx, Aug 25, 2012.

  1. Critterina

    Critterina Senior Member

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    Thanks, Valentijn.
    Well, that's surprising to me based on my reaction when I added folinic acid to my regimen, but I made a lot of changes at once, so perhaps I need to isolate the change and try again. Hmmm, how would it complicate things for an MTHFR C677T mutation then, I wonder? If it's not depriving it of substrate, (which would affect more than C677T people), what could it be doing?

    Thanks. That was a good one, but that wasn't it. Maybe I confused or conflated something.
  2. Valentijn

    Valentijn Activity Level: 3

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    No idea, and I don't think the papers I saw really speculated about it - or I just wasn't interested in the "why" so skimmed over it :rolleyes:
  3. aaron_c

    aaron_c Senior Member

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    @adreno

    I know this is an old thread, but...

    Somewhere on the forums I came across this article. It indicates that B2 is a cofactor for MTHFR, and that the C677T mutation causes B2 to bind poorly. Meaning that maybe the extra B2 helped you make more 5-MTHF, allowing you to get out of the--I think this was the "donut hole?"

    And since it's been so long, how are you doing with the methylcobalamin and all that? And how much did you take of mB12 and B2?

    Thanks!
    brenda likes this.
  4. adreno

    adreno 3% neanderthal

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    Actually, at this point I take only a B complex (Thorne) and 800mcg methylfolate. That's it. I am doing okay, and I don't seem to feel better on the higher doses.
  5. aaron_c

    aaron_c Senior Member

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    @adreno
    When you ramped up the B12, what symptoms did extra B2 (and potassium and zinc, if you took them all together) alleviate?
  6. brenda

    brenda Senior Member

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    Methylb12 gives me worsening insomnia but b2 helps. All b vitamins use up b2. Sorry no time to give evidence. You could look up the l love b2 thread.
  7. adreno

    adreno 3% neanderthal

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    I basically felt like shite. I also had angular chelitis at some point.
  8. Leon

    Leon

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    For what it's worth, I'm SHMT +/- and MTHFR C677T, and my blood profile is:

    Folinic acid: 8.3 nmol/l (ref: 1.2-11.7 nmol/l)
    5-MTHF: 16.4 nmol/l (ref: 8.4-72.6 nmol/l).

    Also, THF: 0.48 nmol/l (ref: 0.6-6.8 nmol/l)

    Amy Yasko says: "Based on the research of Dr. Patrick Stover, I’ve concluded that the SHMT mutation often shifts the methylation cycle away from both the long and short routes through the methylation cycle into a side reaction that leads to the production of thymidine ..." Clearly, I'm privileging conversion of 5,10-methylene-THF to pyrimidine/DNA, as shown by my reservoir of folinic acid (my 10-formyl-THF is also high), but showing problems getting back to 5-MTHF. Throw in potential problems with MTHFRS, and you can see that taking folinic acid is unlikely to be helpful. Yet, Amy Yasko recommends supplementing with folinic acid, since this will regulate SHMT activity, and promote methylation. I can only assume this means that taking folinic acid inhibits the portion of SHMT that converts 5,10-methylene-THF to folinic acid through negative feedback, thereby promoting the conversion of 5,10-methylene-THF to 5-MTHF, whilst maintaining levels of folinic acid through supplementation for DNA synthesis. This will, in turn, bring THF up. That would be the system "in balance".

    Quite why a mutation in the SHMT gene should maintain conversion of THF to 5,10-methylene-THF but cause "shunting" of 5,10-methylene-THF to folinic acid, I don't know. One argument is that infection can cause high chain ferritin, which increases SHMT activity and pyrimidine synthesis. Taking apolactoferrin would presumably help regulate SHMT activity. I wonder how many people who can't tolerate folinic acid, as well as potentially having clues in the relevant MTHFRS gene, have infections that habour iron.
    Last edited: Sep 14, 2014
    aaron_c likes this.
  9. Valentijn

    Valentijn Activity Level: 3

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    @Leon - I generally stop reading after "Yasko says...". She's not a source of scientific research, and really has proven herself to be untrustworthy when it comes to her interpretations of research.
  10. Leon

    Leon

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    @Valentijn - I'm not one of her patients, but if you'd care to share, I'd be interested in knowing why in particular the hard line? By the by, I've read about the iron asociation elsewhere.
    Last edited: Sep 14, 2014
  11. Valentijn

    Valentijn Activity Level: 3

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    Because she can't tell the difference between half a gene being removed from a lab yeast and the effects of a very minor change in a single SNP which doesn't even result in a mutation in the encoded protein.

    She either can't understand research, or she's willing to spin it wildly to support the sale of her products.
  12. Leon

    Leon

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    I must admit that you're post about the COMT gene did get me reflecting that the notion of up- and down-regulation is potentially misleading when structural changes might not take place in the gene, aka Yasko and others.

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