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Maximum Methylation and Healing Occurs at 1000mcg Folate

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by adreno, Mar 5, 2012.

  1. adreno

    adreno 3% neanderthal

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    According to research by the NIH, maximal DNA methylation, and axonal regeneration occurred at 80mcg/kg in rats:

    http://www.nih.gov/news/health/jun2010/nichd-24.htm


    This dose translates to about 1000mcg, for a 80kg human.


    The full research article is here:

    http://www.jci.org/articles/view/40000


    From the article:

     
  2. madietodd

    madietodd Senior Member

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    Nice find, Adreno! I imagine that the rats' diet included no other sources of folates, unlike mine.
     
  3. adreno

    adreno 3% neanderthal

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    I should add that the folate was administered through injection. As we are using oral route, it would be interesting to know how much folate is absorbed orally.
     
  4. Dreambirdie

    Dreambirdie work in progress

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    Interesting, but I would take it with a big grain of salt.

    As we have witnessed here so often, finding the ideal dose of each of the methylation supplements, and the necessary co-factors, that work best for each person is an art, not a science. There are so many other factors involved, especially when you are dealing with a community of seriously ill PWME.

    Also, rats are a LOT tougher and more resilient than most of us. And I bet they have FAR FEWER food sensitivities. :)
     
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  5. adreno

    adreno 3% neanderthal

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    True, and nobody said anything about tolerance. Just because methylation peaks at a certain dose, it is by no means implied that everyone can tolerate that dose.
     
  6. drex13

    drex13 Senior Member

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    Hi Adreno,

    Wouldn't that translate into about 6400 micrograms for a person what weighs 80 kgs, and not 1000 mcgs ? (80 mcgs * 80 kgs = 6400). Or for me, I weigh about 205 lbs. which comes out to just under 93 kilograms would translate to a dose of 7440 mcgs, or 7.4 milligrams, or the dose of a deplin tablet.
     
  7. adreno

    adreno 3% neanderthal

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    I'm afraid you can't calculate it like that. It's explained here:

    www.fasebj.org/content/22/3/659.full.pdf
     
  8. snowathlete

    snowathlete

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    I think the oral route must make quite alot of difference, compared to injection.

    I have no idea how much we absorb...a quarter tops i would guess at, but i bet its alot less than that.
    Maybe someone knows?
     
  9. drex13

    drex13 Senior Member

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  10. Adster

    Adster Senior Member

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    I think this variable is often overlooked. Surely gut condition/function makes a big difference to absorption of drugs and supplements. I think the difference in actual dose between people could be significant.


     
  11. adreno

    adreno 3% neanderthal

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    It's a very good question. This study suggests 50% absorption from dietary folate, and 75% from folic acid supplements:

    http://www.ncbi.nlm.nih.gov/m/pubmed/9405587/
     
  12. adreno

    adreno 3% neanderthal

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    Also, I'm wondering about half life. For methylfolate, it's about 3 hours. So, in that case, would it then make sense to dose something like 3 x 1000mcg daily, to keep methylation running at maximum?
     
  13. Rand56

    Rand56 Senior Member

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    I take my methylfolate sublingually. Since it is my most expensive supplement being that I take Deplin size dosages <15mg>, I want more bang for my buck so to speak as far as increasing the absorption. Prior to me upping my daily dose I took the Solgar Metafolin and they actually taste good under the tongue and they disolve pretty quickly. Now I take the Thorne 5-MTHF 5mg caps 3 times per day. Even though it's not as tasty under the tongue as the Solgar Metafolin, it's not bad at all because actually there is no taste to it.
     
  14. adreno

    adreno 3% neanderthal

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    I know I will have a lot of people disagreeing with this, but there simply is no evidence that sublingual absorption is better than oral.
     
  15. snowathlete

    snowathlete

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    Are you talking about just metafolin, or in general.

    I take my B12 under the tongue, and i can feel it working in a few minutes.
    I havent tries non sublingual though, i suppose it could be as good.
     
  16. adreno

    adreno 3% neanderthal

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    Even with B12, studies show the same absorption rate. Maybe sublingual is faster. I'm aware that many people feel that sublingual works better. I use sublingual B12 also. But I'm not sure if we are simply deluding ourselves. Maybe if someone has gastrointestinal issues, sublingual works better. But in healthy people there seem to be no difference, according to the evidence I've seen.
     
  17. Lou

    Lou Senior Member

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    Hi adreno,

    "But in healthy people there seems to be no difference......." If you have ME/cfs chances are you're not THAT healthy, and gut malabsorption is a big problem for many of us, maybe a vast majority from what I've read here. Think I'm going to stick with Fred's advice on this one.

    Just another viewpoint, adreno. Thanks.
     
  18. rydra_wong

    rydra_wong Guest

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    Well the thing that bugs me is that there is no checking what genes these rats have...so what the experiment says is that that dose is potentially optimal for a normal person with no broken genes. But what about those of us with genetic defects regarding folate? I dont think it sheds light on that.

    But it sure is interesting...it implies that there IS a max limit and that going beyond it is not optimal. Which makes this all harder of course.

    Rydra

    PS. Someone on another board said they took 400units folic acid (i know, i know) and it made his high blood pressure normal,
    but then he tried 800units and his high blood pressure came back.

    I always thought he ran out of methyls after the 400 but now I wonder if he had normal folate genes and had just gone past his optimal dose.
     
  19. richvank

    richvank Senior Member

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    Hi, adreno.

    It's true that in otherwise healthy people who have an absolute B12 deficiency, it is possible to treat either orally or sublingually, so long as a high enough dosage is used. However, if a person has ME/CFS, with glutathione depletion and a functional B12 deficiency, I don't believe that oral dosing will work unless a very large dosage is used. Here's why:

    When B12 is taken orally, if a person has normal intrinsic factor production, the limit of absorption by the intrinsic factor mechanism for a single dose is about 2 micrograms. However, if larger dosages are taken orally, about 1% will be absorbed by diffusion, without intrinsic factor involvement. So, for example, if 500 micrograms are taken orally, about 5 micrograms will be absorbed apart from the intrinsic factor mechanism. This is enough to treat an otherwise healthy person who has an absolute B12 deficiency, even if it is due to pernicious anemia, which knocks out the intrinsic factor mechanism.

    However, if a person has ME/CFS, the amount of B12 that must be put into the blood is of the order of 1,000 micrograms or more per day. So if oral absorption is to be relied upon, the person would have to take about 100,000 micrograms, or 100 milligrams of B12. This is a very big dosage. However, if it is taken sublingually, the fraction absorbed will be much higher, so that something like 2,000 micrograms will do the job.

    As I posted on another thread, I think the reason why such a high dosage is needed to treat ME/CFS is that glutathione is depleted. Normally, glutathione increases the affinity for the CblC complementation group, part of the intracellular B12 metabolic pathway, by a factor of over 100. When glutathione is depleted, the affinity drops, and it is necessary to raise the concentration of B12 significantly in order to achieve a high enough rate in the B12 metabolic pathway. This is based on research done in Korea, published only a few months ago.

    Best regards,

    Rich
     
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  20. adreno

    adreno 3% neanderthal

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    I agree with you on both counts. We don't know the genetics of those rats. But aren't we bypassing this issue, by going straight to ingesting methylfolate?

    And yes, if nothing else, the study tells us that there is a bell shaped curve of methylation and neuronal healing when taking folate; that these have a peak, and do not continually increase with dose. I don't know if the same can be said with B12; studies seem to indicate the more the better.

    It is also interesting how the drug companies arrived at the dosages for metanx, deplin and cerefolin (6-15mg methylfolate daily). Were these doses just arbitrarily picked? Based on what?
     

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