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Study: Folinic acid beneficial to 81% of CFS patients...plus biomarker?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by dannybex, Feb 8, 2013.

  1. dannybex

    dannybex Senior Member

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    Thanks Fred -- I appreciate it. I may try to reduce the folinic at some point and see how it goes. :)
  2. Lotus97

    Lotus97 Senior Member

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    If methylfolate performs all the functions of methylfolate then why would Rich have people take both folinic acid and methylfolate?
  3. alex3619

    alex3619 Senior Member

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    Lotus97 Folinic acid is cheaper and many people can process it OK. Its a simpler and cheaper way to get folate. The trouble is that not everyone can use it properly, so methylfolate is more reliable. I also suspect that there might be a buffering effect. By taking folinic acid there will be a delay in conversion to methyl folate, and this might act a little like having sustained release methyl folate.
    Radio and Dreambirdie like this.
  4. Lotus97

    Lotus97 Senior Member

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    It's kind of tricky because some people do have certain polymorphisms that prevent them from converting folinic to methylfolate which is why Rich recommends both, but he says folinic acid accomplishes certain things that methylfolate can't. Although for methylation, it seems that only methylfolate is necessary.
    Folinic acid is helpful for a couple of reasons. One is that it is very versatile, in that it can be converted to other forms of folate, which are needed to make DNA, RNA, and purines in general. Another factor is that folinic acid is polyglutamated when it is inside the cells, and this can help to lower the amount of free glutamate, which is an excitotoxin. Excitotoxicity is a problem in CFS, and it is often exacerbated when methylation cycle treatment is entered upon.
    alex3619 and Dreambirdie like this.
  5. Dreambirdie

    Dreambirdie work in progress

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    This is interesting. Thanks for your posts about it, Lotus.

    I'd like to know what brand and what dose of folinic people take?
  6. Lotus97

    Lotus97 Senior Member

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    alex3619
    That is interesting what you say about folinic acid being like a timed release methylfolate since methylfolate is needed to recycle B12. Taking both could potentially increase the length of time methylfolate and B12 stay in your system. Of course that's assuming one can make the conversion. Rich seemed to think most people could although Freddd seems to disagree. I know Yasko did a lot of SNP testing, but that was only on autistic children so I'm not sure how much data we actually have on this. In that study Dannybex posted it seems like most people are able to process it, but I haven't looked to closely at the study.

    Dreambirdie
    I have a Thorne b complex with 100 mcg of folinic acid and 100 mcg methylfolate. I also get at least 300 mcg of plant folate which some people have said is similar to folinic acid although Rich seemed to think there was both methylfolate and folinic acid in plant folate (?)
    Dreambirdie likes this.
  7. Freddd

    Freddd Senior Member

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    Hi Lotus,

    At a later time he looked deeper after several of our folate specific discussions and found the methylfolate path for all the same reactions and conceded that folinic was entirely unneeded. It needed more MeCbl to be available.
  8. Freddd

    Freddd Senior Member

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    Hi Lotus,

    Rich seemed to think there was both methylfolate and folinic acid in plant folate

    That is correct as far as I know. The problem is that it appears that unconverted accumulates and can block 10 to 20 times as much methylfolate however it does so, established pragmartically by systematic trials. The difference between folic acid and folinic acid in these regards may be due to serum halflife as the unconverted form. When it does so it can do it faster and harder than folic acid, maybe because it requires less to establish blockage.

    that's assuming one can make the conversion. Rich seemed to think most people could although Freddd seems to disagree.

    I don't disagree. I think most people can make the conversion up to a certain point or if they are not too run down of any one of the Deadlock quartet which can then block the conversion as it requires ATP etc to convert. In other words, you have to have some to make some. That is why it is demonstrably a 4 way deadlock.

    I think that this is the way to do the folate. First get healing started and all balanced out if it will start with AdoCbl, MeCbl and l-methylfolate. Then try whatever forms of folate one might want to try. Notice how it continues working for a month without return of some folate insufficiency symptoms or pronounced slowdown of healing or not. Then try a crossover to L-methylfolate. It could take 3-5 days before it can show a difference if there were increased symptoms and even a couple of weeks to a month to see a more substantial difference. Then there are any doubts about which folate is superior or truely equal, run more full cycles. Subtle symptoms become more obvious after one sees them 3 or 4 times.

    It's a problem that each of us can only know for ourselves. I try to remove all the complicated assumptions where so many things can go wrong so as to be more able to understand it and try to follow the clues.
  9. Freddd

    Freddd Senior Member

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    Hi Lotus,

    He started suggesting folinic years before l-methylfolate was available, as the only superior to folic acid form available. That's why I tried it and plunged into folate insufficiency worse than ever. It took 3 days to build up and it got so bad in a week I went back to folic acid.
  10. Lotus97

    Lotus97 Senior Member

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    Rich's most recent protocol is only about 5 months old and he still recommends both folinic acid and methylfolate. As I mentioned earlier he says that folinic performs specific functions that methylfolate does not. This is what Rich has said:
    Folinic acid is helpful for a couple of reasons. One is that it is very versatile, in that it can be converted to other forms of folate, which are needed to make DNA, RNA, and purines in general. Another factor is that folinic acid is polyglutamated when it is inside the cells, and this can help to lower the amount of free glutamate, which is an excitotoxin. Excitotoxicity is a problem in CFS, and it is often exacerbated when methylation cycle treatment is entered upon.
    The article dannybex referenced also mentions some other functions of folinic acid
    Folinic acid co-enzymes are responsible for several important metabolic functions. These include the formation of DNA and RNA, the formation of heme protein in hemoglobin, formation of amino acids and the formation of glutathione
    Have you considered getting your SNP tested so we can figure out how many people in this community have the same issues? The study dannybex referenced seems to suggest that folinic acid had a positive effect on the vast majority of participants who had all been diagnosed with CFS.
  11. Freddd

    Freddd Senior Member

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    Hi Lotus,

    Have you considered getting your SNP tested so we can figure out how many people in this community have the same issues? The study dannybex referenced seems to suggest that folinic acid had a positive effect on the vast majority of participants who had all been diagnosed with CFS


    I have considered it but don't have the money. Also, the things tested won't tell enough of the story and I am absolutely positive that no matter what partial interpretations are made they will not come up with what actually works.

    Yes, and iflinic acid probably did help a majority of people for any number of reasons. That is in no way inconsistant with several forms paradoxical folate deficiency. If I had tried to use 400mcg of folinic acid instead of folic acid before I ever took MeCbl, AdoCbl, l-methylfolate and LCF and I hadn't gotten healing going which puts a lot more pressure on l-methylfoate specifically, it probably would have made no difference. It's only after healing started that my folate deficiency symptoms got worse while everything else got better. I'm glad to have gained understanding because the paradoxical folate deficiency is the missing understadninbg and can happen to anybody who has a strongg healing startup. Insufficiency symptoms start at a tiny amount less than needed in the moment, and grow very severe with severe insufficiency even to death. It is a smoothly dose proportionate situation unlike MeCBL and AdoCbl.

    I know he revised it. then. He still had the same fundamentals underlying his understandings. I finally understood the source of some of his misunderstandings, that the neurons in the brain were dependent upon glucose metabolism not fatty acid Krebs cycle metabolism which requires AdoCbl and LCF. It wasn't until Parkinson's studies brought up problems of mitochondria damaging the brain generating MMA and having low cobalamin. So that and other similar significant differences in how we interpret things, the basis of understanding, change our very understandings leads to substantial differences in understanding why some things may be happening. So ATP startup in the brain, completely unsuspected by Rich, is thereby interpeted as any numbers of other things but NEVER ATP startup. That was an impossible answer in his mind prior to the discussion maybe a year ago and he never showed any expressed difference that I am aware of. That changes how things are interpreted. When the assumptions are wrong the inerpretations are wrong.
  12. dbkita

    dbkita Senior Member

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    Can you explain this section a bit more? Trying to understand why your folate deficiency symptoms got worse. Also specifically which symptoms were attributed to the folate deficiency assuming everything else was in place. I am assuming you had no methyl trap, correct? As you were on active B12s? Just trying differentiate ATP dysfunction from folate and / or b12 deficiency.

    I am confused.

    Of course the brain / neurons have active Krebs cycle going. You seemed to be implying that the Krebs cycle is a fatty acid only metabolic pathway.

    A main source of the aerobic Krebs cycle is glucose(+ oxygen). That is at the heart of carboyhydrate metabolism. Glucose is turned into pyruvate via glycolysis inside of cells. Pyruvate then enters the Krebs cycle as oxacetalate. The brain can also get energy from ketosis (by converting ketones to acetyl COA) when needed in a pinch when blood sugar is low, but that is not strictly speaking fatty acid metabolism.

    The brain dominantly uses the Krebs cycle based on carbohydrate metabolism. The brain cannot make use of fatty acids but can use ketones to help it when glucose is unavailable. However, the ketosis pathway does not need LCF to my knowledge. I suspect adb12 may be more about continued health of the mitochondria.

    Just because there are indications of low B12 in certain neurodegenerative diseases does not in any way prove that neuronal mitochondria make heavy use of the methymalonic pathway as a primary energy source.

    As an aside, for neurons, where there is some controversy is relevance of glucose (classical hypothesis) vs. the astrocyte-neuron lactate shuttle for certain types of neuron states. But that is probably not important to this discussion.
  13. Lotus97

    Lotus97 Senior Member

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    I don't know about "ATP startup" specifically, but Rich was well aware of mitochondrial dysfunction being a big part of this. His protocol did address that issue. Why he didn't focus more on Krebs and ATP might be explained in his goals listed for the protocol:
    • To keep the protocol simple, with a minimum number of supplements, while preserving its effectiveness.
    • To keep the cost low while preserving effectiveness.
  14. triffid113

    triffid113 Day of the Square Peg

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    Interesting. I also find that I can do with the B12 in my Thorne Basic B and don't need additional sublinguals, at least not during allergy season. I have so much trouble keeping my zinc, and therefore stomach acid levels, up during allergy season that I am thinking of adding a mB12 sublingual to my allergy-season-only protocol.
  15. triffid113

    triffid113 Day of the Square Peg

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    OMG! I WILL have to look this up because I take 2g C with my mfolate! But I read that C + mfolate -> raise BH4 and I have BH4 issues. The damn BH4 test is $300 so I can't test BH4 and then try while separating mfolate from C. I have not had a single BH4 test yet, but my father had no detectable BH4 in him when he died so now I have a burning need to know how my BH4 is doing. It may be that if I could measure and thus control BH4 to correct it that I would become unstable tho as I am pretty sure it is the BH4 deficiency preventing me from sensitivity to methyls in rgeards to my two COMT +/+.

    But let's rationalize this...I achieved a perfect Hcy of 6.3 even taking 800 mcg metafolin plus 2g mineral ascorbates at the same time. So...now I find it hard to see why I should change? I hit the target, so...?
  16. dbkita

    dbkita Senior Member

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    Vitamin C helps Bh4 by aiding recycling from BH4 to BH4. Mfolate aids BH4 but I have not yet heard a real reason how it does it. The fact that vitamin C destabilizes mfolate is independent of the fact that both help BH4 levels.

    Note I think buffered mineral ascorbates have a much less deleterious effect on Metafolin absorption. I think ascorbic acid is MUCH worse. I can attest to this by personal experience. Makes sense theoretically as well.

    Your COMT +/+ while a challenge in its own rights is actually very protective against a low BH4 (less needed to make catecholamines since more are lying around longer). However, the COMT +/+ will do nothing for serotonin production which is just as important as dopamine.

    As you probably know, BH4 mitigation is also based on removing factors that lower it such as aluminum, ammonia. etc. BH4 is used with adb12 in reducing peroxynitrite. BH4 is key for making NO and for functioning of the urea cycle. That is a lot of demands on one poor little molecule.

    But one of the biggest drains is of course inflammation. The production pathyway for biopterin is shunted to neopterin when there is high inflammation. Some of Yasko's latest presentations suggest this is maybe the MAJOR pathway disruption of BH4 at an epigenetic level.

    Your homocysteine look great. But it is not the only relevant diagnostic. More important is how you feel. Do you have enough neurotransmitters? What are your energy and pain levels like? How do you sleep, etc.? Lab tests are sometimes of limited utility.

    Btw which test are you referring to for BH4? Which company? Do you mean a neopterin / biopterin test or something else? Just curious.
  17. Freddd

    Freddd Senior Member

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  18. taniaaust1

    taniaaust1 Senior Member

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    I have found a combo of folinic acid (normal folate did nothing, I needed folinic) and methylB12 (hydroxy B12 only helped my memory a little), really helped me in several different of my ME/CFS symptoms (including improved my ability to do things eg increased stamina and possible improvement on the POTS and also makes me able to get up at a more normal hour) but then who knows why it helped as my specialist put me on it due to my MTHFR polymophism not the ME/CFS

    The brand my specialist told me to get and Im on is Source Naturals .. MegaFolinic (800mcg per day thou I think my specialist wants me to increase my dose).
  19. taniaaust1

    taniaaust1 Senior Member

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    what I dont understand is why they dont make ME/CFS like they do with another illnesses by taking a handful of the common test abnormality findings and saying something like one has to have 2-3 of those for a diagnoses eg i 94% of ME/CFS patients have this one.. this one be a great one to use for something like that.

    it seems to me thou that those high up just do not want to make ME/CFS a valid illnesses hence use test abnormalities.
  20. Lotus97

    Lotus97 Senior Member

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    That's the brand I bought, but I haven't started taking it yet as I'm not ready to up my folate dosage yet. I think it's the best-priced folinic out there. It's hard to split up though if you want to take less than 800 mcg. I found an exacto knife works reasonably well.

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