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Does Methylfolate increase your risk of Cancer?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by LozT, Jan 25, 2018.

  1. LozT

    LozT

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  2. BeautifulDay

    BeautifulDay Senior Member

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  3. alicec

    alicec Senior Member

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    The article is littered with factual errors so one can have little confidence in any conclusions it draws. Furthermore just a cursory review of what is actually known about the topic shows that the situation is complex and the simplistic claims of the article are not supported.

    To point out a few of the more egregious errors :-

    T
    Setting aside the fact that these two common SNPs on MTHFR are far from the only locations where SNPs occur on the gene, this statement shows that the author doesn't even understand what the SNP description she is quoting means and doesn't know the difference between a nucleotide and an amino acid.

    That is a very serious deficiency for someone who is pontificating about the role of the MTHFR enzyme and the need for genetic testing and purporting to give nutritional advice based on such ponfications.

    The positions given by the numbers are of course nucleotide positions and the change at the 677th position is from cytosine (C) to thymine (T). These are two of the four bases embedded in DNA that constitute the genetic code. SNPs, as the name which she spells out implies, are changes to a single letter of this code.

    Tyrosine is an amino acid. Sometimes, but by no means always, the change of a single letter in the DNA can result in a change to an amino acid in the protein made from the gene. In the case of the C677T SNP on MTHFR, an amino acid change does result, but it is from alanine to valine.

    So she hasn't just omitted a step and conflated nucleotide and protein changes. No, she is obviously parroting something she fundamentally doesn't understand. No-one who understood SNPs could make this slip.

    There certainly is a family of natural folates but it doesn't include folic acid. The latter is wholly synthetic, a product of the laboratory. There is no enzyme to produce it in our bodies nor is it produced as a product of metabolism of other folates.

    It's structural similarity to natural folate means that it can be taken up into the body via the several different classes of folate receptor (not just one as this author states, and as an aside, why is she so seemingly impressed that such a thing exists - how else does she think folates get into cells?)

    The structural similarity also means that the enzyme DHFR (dihydrofolate reductase) can process folic acid. It is converted to DHF (dihydrofolate), the natural substrate for the enzyme, which then goes on to convert DHF to THF (tetrahydrofolate) which can then enter the folate cycle.

    This second reaction is the normal role for the enzyme in the body and it does it much better than the conversion of folic acid to DHF.

    This reaction is 1,400 times slower than the normal reaction for the enzyme, and this difficulty in processing folic acid is behind the caution that many say should be exercised in using folic acid supplements even in moderate doses.

    This is because there is a natural variation of about 5 fold in the capacity of DHFR to process folic acid. So everyone does it very slowly but some people do it extremely slowly. This means that folic acid can easily accumulate.

    This is not something to brush off as the author does later in the article, because folic acid is a natural inhibitor of DHFR. So accumulating folic acid will inhibit the normal DHFR conversion of DHF to THF. This means that DHF accumulates. It in turn inhibits several other enzymes in the folate cycle, including MTHFR.

    So accumulating folic acid can interfere in the entire folate cycle.

    This failure to appreciate the complex feedback mechanisms which regulate metabolism is also behind the author's simplistic understanding of the consequences of methylfolate supplementation and more generally of methylation and its role in cancer.

    There's just too much detail to go through here but suffice to say that a process like DNA methylation which has such profound consequences for global gene expression and for critical events like progression through the cell cycle is not going to be perturbed by an overdose of some vitamin.

    There are multiple layers of controls built-in to the system and no single factor is able to override them. Furthermore the body is well able to regulate and dispose of any nutrient excess.

    Because of the critical role of folate in cell division, it is of course prudent to wonder if long term folate supplementation at high level might somehow manage to override such controls, but despite the bland assertion in the article that

    there is no real supportive evidence for the proposition.

    As this detailed review of folate and DNA methylation concludes,

    and in conclusion

    Even in cancer where folate might be expected to play a stimulatory role (cancer cells hijack the folate system and greatly upregulate some folate receptors in order to take up more folate to stimulate cell division), the situation regarding folate supplementation and DNA methylation is not at all clear.

    To quote from the same review

    So essentially there is no clear evidence that folate supplementation is problematic but nor is there enough good evidence yet that it might be harmful.
     
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  4. Gingergrrl

    Gingergrrl Senior Member

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    This is all beyond my knowledge but where would "folinic acid" fit in re: cancer risk?
     
  5. alicec

    alicec Senior Member

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    It's not clear that there is any cancer risk with folate supplementation, even for people with cancer, though in the latter case, some evidence is suggestive.

    In any case, even the people who claim there is a risk, such as the author of the article which is the subject of this thread, are concerned about high doses taken over long periods.

    Folinic is a natural folate. There is no reason to think it would have any different effect from other folates with respect to any putative cancer risk, but I have no idea if anyone has actually used folinic in any of the relevant studies.
     
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  6. LozT

    LozT

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    The thing is, if folate in high doses could cause or encourage cancer, isnt this reason alone to avoid until the research is clear, I mean, why take the risk?
     
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  7. alicec

    alicec Senior Member

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    A number of people report considerable benefit from moderate to high doses of folate (often in conjunction with B12) and consider that the benefit far outweighs a theoretically possible but undemonstrated risk.

    If we were to not do things just because there COULD be some risk associated with the action, we would be completely paralysed and life would be impossible. After all, we do things everyday where there is a known, not just theoretical risk - driving or riding in a vehicle is a good example.
     
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  8. Gingergrrl

    Gingergrrl Senior Member

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    I actually agree with you @alicec and if I tolerated high dose methylfolate and if helped me, I actually would take the risk. But since I don't, then it is not worth it to me. But I am doing some high risk treatments that are 100% worth it to me so I do get it.
     

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