The 12th Invest in ME Research Conference June, 2017, Part 2
MEMum presents the second article in a series of three about the recent 12th Invest In ME International Conference (IIMEC12) in London.
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Methylfolate vs Folic Acid: Myths vs. Facts

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by mgk, Jan 2, 2016.

  1. mgk

    mgk Senior Member

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    I came across this video recently and wanted to post it because this side of the argument is often underrepresented here. It basically argues that most of the claims on the internet about methylfolate are false and that folic acid is just as effective as methylfolate, even for people with MTHFR polymorphisms.



    Disclaimer: I'm not trying to make a value judgement or "pick sides." I just wanted to post it up for discussion.
     
    Last edited: Jan 3, 2016
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  2. mgk

    mgk Senior Member

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    One thing I found especially interesting is that in some people, folic acid levels can increase after taking methylfolate. He mentions it around 19:20 when he starts analyzing that study with the two graphs. Here's the relevant part from the study:
    Why only 2 of 24? Something to do with too much folate as he mentioned? There's definitely something interesting going on there.

    Here's a link to the full study by the way: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807663/
     
  3. sickntired771

    sickntired771

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    Whats weird is my genetics report shows I have a double mutation for MTHFR yet for some reason I take methylfolate and don't feel different but feel better when I have a lot of folic acid? What's up with that?
     
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  4. Sea

    Sea Senior Member

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    Thanks mgk. I have looked for information like this before and not been able to find any.

    It has never made sense to me to say that those with MTHFR cannot convert Folic Acid to Methylfolate, and that it is dangerous for them, when the studies show that Neural tube defects have been reduced since the introduction of Folic Acid food fortification - often especially in those with the MTHFR deficiency. If it were true that MTHFR deficiency patients cannot convert Folic Acid then surely the Neural tube defect rate would go up, especially in those with the defective enzyme.

    I have asked questions on several of the MTHFR information sites and I have been ignored, ridiculed or had my questions deleted. When I asked why the Neural tube defects were shown to have been reduced I was told it was only for those who didn't have MTHFR deficiency, and that in those who did the rates were increased. When I asked for evidence I was ignored and the question deleted.

    I have no doubt Methylfolate is better for some, but the reasoning put forward that it is related to MTHFR doesn't hold up.
     
  5. dannybex

    dannybex Senior Member

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    So less than ten percent of those who took methylfolate had increased levels of folic acid. Someone on another thread also hypothesized something about too much methylfolate could become oxidized and turn into folic -- but that doesn't seem to make sense either.

    It may have something to do with other genetic polymorphisms?

    But at least it's only happening (in that study sample anyway) in a small percentage of patients.

    Aahh -- found the other thread:

    http://forums.phoenixrising.me/inde...rs-why-you-need-high-dose-methylfolate.32295/

    Perhaps @Leopardtail would like to comment on the study?
     
  6. nandixon

    nandixon Senior Member

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    The authors in the study give the following possible explanation:

    [Bold added] That makes the most sense to me, and I certainly disagree with the explanation given by Stephen Chaney in the video, who believes it supports his belief that folic acid is naturally made in the human body. There are no enzymes in the human body known to make folic acid. The one enzyme, DHFR, that might be capable of that transformation - by running in reverse, never does so because attempting to go from dihydrofolic acid to folic acid is thermodynamically too far uphill.

    Chaney makes other errors and, almost worse, unless he's remarkably ignorant he does some very purposeful twisting of things to make it appear as though methylfolate is itself an artificial substance, rather than folic acid. He's clearly very biased in his beliefs. I only could stomach watching about the first third of the video (plus the part at 19:20), because I felt like I was listening to a spokesperson for the folic acid lobby.
     
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  7. Sea

    Sea Senior Member

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    It does make sense, and yet I've also seen claims that Methylfolate is displaced by Folic Acid, hence the recommendation not only to supplement with Methylfolate, but to conscientiously avoid Folic Acid. Interesting that of the 2 who had FA in their blood after supplementing Methylfolate, one had the MTHFR deficiency and the other did not.

    His point is that the Methylfolate supplements are made from Folic Acid in a chemical process. He denies that Methylfolate supplements are natural as some manufacturers and advocates claim. I would like to see evidence for or against that information. He doesn't say that Folic Acid supplements are natural either, but he does believe that Folic Acid can be produced naturally in the body, as is Methylfolate
     
    Last edited: Jan 3, 2016
  8. mgk

    mgk Senior Member

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    I don't know but I'm curious: were you taking an equal amount of methylfolate and folic acid? And how much did it take to make you feel better?

    Also do you need to keep taking large amounts of folic acid in order to feel better, or does it seem to taper off and replenish?
     
  9. mgk

    mgk Senior Member

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    Ah, thanks for pointing that out. Serves me right for skimming. That is an interesting argument, but the question that immediately comes to mind is: why did it happen only in 2 people? There were 11 others who received folic acid on the first day... Also one of the spikes happened on a person that received methylfolate on the first day (so no folic acid before). There's clearly something more complicated going on that we don't understand yet.

    @Sea beat me to it, but his argument was that folic acid is non-enzymatically formed as a part of normal folate metabolism because of the oxidative environment in the cell (explained around 15:50).

    I'm not a biochemist so I don't know if that's really possible. He presents it as fact, but I can't find any other source to support what he says. Does anyone know?

    I agree that his first point about "natural" was quite weak. When most people say methylfolate is natural, they don't mean it's derived from food, they mean it's the form that's active in the body. In any case, I'm sure I'm not the only one who would like to know what other errors he made.
     
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  10. nandixon

    nandixon Senior Member

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    Yes, the displacement may work both ways. But the point the authors are making is that they believe the reason why two of the 24 trial participants taking methylfolate also showed the presence of folic acid was because of previously ingested folic acid that was in a storage form and then released/displaced by the methylfolate - versus a biochemical transformation of methylfolate to folic acid, which is what Chaney proposes in the video.

    The individual homozygous TT for MTHFR C677T was the person they noted had been given folic acid (FA) on day 1, and methylfolate on day 2.

    Methylfolate and folinic acid (not to be confused with folic acid) are the predominant folates occurring in plant/vegetable material. The methylfolate produced by chemical synthesis from folic acid is exactly identical to the methylfolate present in plants. The only difference is that in ingested vegetables the folate is initially in a polyglutamated form.
     
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  11. ahmo

    ahmo Senior Member

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  12. nandixon

    nandixon Senior Member

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    The intracellular compartments that contain folates are environments that are highly reducing. There is not going to be any significant formation of folic acid by oxidation of dihydrofolic acid which is itself only a very weak antioxidant.

    Just in the parts I watched, and I'm forgetting some things, but besides attempting to present methylfolate as an artificial substance, he also suggests that a normal role for the enzyme DHFR is to reduce folic acid - a substance that is not naturally present in the human body.

    He also claims that taking folic acid and methylfolate will have the same identical effect in the human body. But, as one example, folic acid is an inhibitor of DHFR while methylfolate is not. Thus folic acid will, for example, interfere with the recycling of BH2 to BH4 by DHFR.

    He also claims that folic acid works as well as methylfolate, yet the conversion of folic acid to methylfolate requires several steps, one or more of which may not be very efficient in some people. It's true that even people with significant MTHFR defects can normally use folic acid (or better folinic acid) in place of methylfolate and be able to make sufficient methylfolate. The problem, though, is what sort of excess amount of folic acid will be required to do this and, more importantly, what will the effects be of that excess amount in terms of inhibition or stimulation of certain enzymes or genes.
     
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  13. Sea

    Sea Senior Member

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    No I haven't dismissed Ben Lynch, although his was one of the sites where my questions went unanswered.

    The video doesn't dismiss that there are some people for whom methylfolate works better. Although he does go on about the placebo effect I don't think he entirely disagrees that methylfolate may be a better choice for some people. He just says it isn't because of the MTHFR mutation. It is probably an as yet unidentified genetic deficiency.
     
  14. Sea

    Sea Senior Member

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    So the individual who was CC showed FA in their blood on study day 1 then? Interesting this was after 4 weeks of no FA supplementation or fortified foods and a negative test for FA before the supplementation of methylfolate. It is a shame we only have hypotheses at this point rather than hard evidence as to how this happens.

    Also just to note for those who don't read the entire study: Study Day 1 and Study Day 2 are separated by 6 days of no supplementation. I was a bit confused at first thinking they crossed over a day apart, but they didn't.
     
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  15. armyswat

    armyswat

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    This video is a myth and easily can be said that he doesn't know what he's talking about or he's FDA and big pharma supporter or could be a paid government person (Yes they exist)
    Folic Acid doesn't work, but 1% of the world can actually convert it to the active folate form.. so it's kind of useless.

    The funny thing is that FDA has approved it, if FDA approves something, it's a red flag, it means it causes more harm than good most of the time (They usually never approve the healthy stuff and stuff that works). and also they do not approve methyl folate or methyl cobalamin which are natural but do approve synthetic stuff like Folic Acid or cyano cobalamin which do really more harm than good.
     
    Last edited: Jan 3, 2016
  16. bertiedog

    bertiedog Senior Member

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    Do you have evidence for the above statement?

    Thanks

    Pam
     
  17. Sea

    Sea Senior Member

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    I would rather a conversation centred on facts. The video may be wrong in some of his conclusions, but I'd like to see what the different studies can tell us.

    Folic Acid doesn't work for 99%? How is it then that Neural tube defects have decreased in direct proportion to fortification of the food supply with FA and the recommendation for prenatal FA supplementation?

    We probably need to define what we mean by the word "natural". Nan says methylfolate supplements are natural because it is exactly the same form as found in our body. This video says methylfolate supplements are not natural because they are made via a chemical process from synthetic folic acid, hence the argument that folic acid is synthetic and methylfolate is not does not make sense.
     
  18. Valentijn

    Valentijn Senior Member

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    It probably depends on the actual mutations. Some only reduce methylfolate production a bit, and are extremely common. So the MTHFR enzyme is still present in the body, just in lower amounts and/or with slower conversion. But in some cases where there is only a partial deficiency, simply increasing the substrate (folic acid in this case) can mean that the existing enzyme is more likely to encounter that substrate and will transform it more efficiently.

    But there are also very serious MTHFR mutations where enzyme activity is near 0%. In that case, there's no enzyme present at all, so increasing the substrate isn't going to help. Perhaps that is when folic acid is of less use, and methylfolate is more important.

    Though if you have both folic acid and methylfolate as supplement options, and there's no indication that methylfolate can cause problems, there's no reason not to take the active form instead of the inactive.
     
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  19. armyswat

    armyswat

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    Yes sure, enter their own website and search for approved things. they do not approve healthy stuff, they wouldn't even approve 5-HTP which is 100% plant derived which works better than any synthetic anti depressant with all of their side effects and non working and other stuff..
    http://www.accessdata.fda.gov/scripts/cder/drugsatfda/

    feel free to search write everything to see if it's approved or not. you'll notice they do not approve healthy stuff. they are harm for the civilians.

    http://www.fda.gov/Food/IngredientsPackagingLabeling/FoodAdditivesIngredients/ucm091048.htm

    They approved aspartame, fructose corn syrup, chlorine in water, fluoride.. what not?
    all the dangerous stuff.. GMO's which are banned in 36 countries...... and many of their substances are banned worldwide in europe...... 1,000 banned by Europe and 9 banned by FDA http://personalcaretruth.com/2011/0...ver-1000-chemicals-the-fda-has-only-banned-9/

    Never trust the FDA, never.

    Take in note that 70% of U.S are over weight and disease is epidemic...... who is responsible? the people or the FDA, Monsanto, big pharma?
    They make you believe that it's the people's fault, but does the same thing happens in europe or any other place? it could only happen if the government is corrupt.

    Informative video


    They're trying to promote something that first the FDA approved. Secondly promote something that doesn't work and does not exist in the nature. Trust nature more the way we are designed, trust less the FDA which are all about non natural synthetic man made things.
     
    Last edited: Jan 3, 2016
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  20. mgk

    mgk Senior Member

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    In that case, the entire bodily requirement of methylfolate would have to be provided exogenously, right? Because methylfolate would give its methyl group to homocysteine and then become "stuck" again.

    All else being equal, it doesn't seem like there's an in-between requirement for methylfolate: either you need tons of it, or you don't need to take it at all, and providing more substrate with any kind of folate would fix the deficiency.

    It's not clear to me that methylfolate can't cause problems. The potential downside of active forms is that they bypass the body's feedback mechanisms. In this case, I think it's telling that the MTHFR enzyme is inhibited by SAMe and not methylfolate.

    The body has multiple pathways of making and re-generating SAMe, so it doesn't seem like an uncommon situation when there would be plenty of SAMe (after a meal), yet not enough THF and the other downstream forms of folate.

    What happens when someone has plenty of SAMe and takes methylfolate? Homocysteine probably goes lower than it otherwise might, and takes substrate away from other important compounds like glutathione. It would also produce more methionine which is probably not a good thing either.
     
    Last edited: Jan 3, 2016

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