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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. Xara

    Xara Senior Member

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    Gimme another one, it's fun to amaze myself ;-) :)

    O never mind, back on topic.
  2. Freddd

    Freddd Senior Member

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    Hi Lotus,

    No, you are confusing things. Pointing at a gebetic cuase that would likely be implicated in my inability to utilize folinic acid and what he things about my utilization of CyanoCbl have nothing at all to do with each other. He can be quite right about a cause of a problem and wrong with a conclusion about some only partly connected item. I haven't changed my mind. The folate genetic markers have nothing to do with the very rare CblC geneticly caused disease.
  3. Lotus97

    Lotus97 Senior Member

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    You're the one who said "I have to assume he meant MTHFS." Since I know very little about SNPs, I took your word that he wasn't talking about MTHFR. And yes, I'm trying to learn as much as possible. I've also searched the SNP forums about which SNPs have problems with folic acid and folinic acid so I can figure out how many people here (including myself) need to avoid or limit either folic acid and/or folinic acid (just as Rich was doing last year). I've learned a lot from Rich and I know he's not always right, but he knows more than just about everyone here. I'm sorry hydroxocobalamin didn't work out for some of you here, but that doesn't invalidate everything he said. That's why he revised his protocol last year to give people an option to switch to methylcobalamin (and possibly also raise methylfolate) if hydroxocobalamin didn't work. It's a sad state of affairs that I have to defend Rich especially since he knew more than just about everyone else here and not just about methylation and glutathione depletion. Unless you have time to answer all of my questions, Rich is the first person I'm going to for information. I was unable to find much information in the SNP forums about the subject which is part of the reason why I'm going over Rich's posts. In another of Rich's posts he mentions MTHFR C677T specifically in regards to folinic acid. As I said, I know very little about SNPs (but I just sent in my 23andme test kit). Which MTHFR SNPs have problems with folinic acid? Is it certain MTHFR C677T? Or more. And Rich said they're "slow" at converting folinic acid to methylfolate so does that mean low doses won't cause problems (but not be helpful either)? And are they still able to use folinic acid for other functions?
    Again, that's what I'm trying to find out, but until someone proves otherwise what do you expect me to do? I agree that we need more information, but I should remind you how this thread started out. It was referencing a study that showed folinic acid to be beneficial to significant majority of people with CFS. We're never going to find a perfect protocol that suits everyone's needs (and I'm not referring to just methylation). Maybe we will find out that folinic acid is bad, but until then I'm asking the questions that very few are willing to ask. Are we going to discard everything because just a few people have problems? What about alpha lipoic acid and carnitine for people with thyroid problems? Even if it turns out they have a minimal effect on thyroid function you get my point. What about certain supplements for people with a CBS mutation? Or BHMT?
  4. Lotus97

    Lotus97 Senior Member

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  5. dbkita

    dbkita Senior Member

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    Lotus I really don't know where you going with any of this. If you read my post I in no way attacked Rich. I respect the man tremendously. If you don't believe me ... re-read my post.

    Your quote: "It's a sad state of affairs that I have to defend Rich especially since he knew more than just about everyone else here and not just about methylation and glutathione depletion." How does that remotely apply to what I posted? Did you read something I posted and think I implied something otherwise? This offended you? Why do you have to defend Rich? His work speaks for itself with most of us. Did someone appoint you? What am I missing?

    Let's get more specific.

    Again the thread you linked in the thread by Rich Vank and with Nandixon and others mentioned MTHFS not MTHFR. You added MTHFR into the discussion based on other posts of Rich's in other threads, right? If you say in these other posts that Rich is suggesting that MTHFR C667T people convert folinic acid worse , then I am sorry I simply disagree with his suggestion. Most people who end up on Rich's SMP have that SNP at least heterozygous. So then by implication most people on his protocol which has 200 mcg of folinic acid cannot convert it, right? I don't think he said that anywhere.

    MTHFR has zilch to do directly with folinic acid. Folinic acid is an intracellular buffer form of folate. MTHFS and SHMT1 directly affect its regulation. Its pretty obvious based on the 81% figure that most people can handle folinic acid at some level. I would bet my mortgage that far more than 81% of those in the study have MTHFR C667T hetero or homozygous. A person with MTHFR may indirectly have issues with high doses of folinic acid because they convert all folate forms slowly into 5mthf. But look at the folinic acid doses in the 81% study. They aren't for the squeamish. Turns out one of my doctors ready that study and some other articles and suggested 5 x 800 mcg of folinic acid. Ummm ... I told him I will think about it.

    "Unless you have time to answer all of my questions, Rich is the first person I'm going to for information."

    Ok. I am fine with the reality I am not able to answer all of your question to your satisfaction. And forgive me for saying this, but nor will I try to. You go looking at old posts of Rich's. Bump them up. Ask a question and often add your own interpretation to it. Personally I would not feel comfortable adding an interpretation unless I KNOW I am correct. I would let Rich's posts speak for themselves and open up new threads as needed. But maybe that is just me.

    When I look at the first page of the forum every day there is a lot of turnover, as other posts if not immediately replied to end up off the first page since you keep recycling stuff up. I am sorry no one got to answer your other question with 75 views. Heck I asked a question on SHMT that no one ever answered. Asked another one on sarcosine with one response but many views. And they all slide off into oblivion. What do you want me to say? I did not even see that thread due to all the churn on the first page

    Rich was a great person who helped a lot of people and we should all be thankful for that. But I don't get all my information from his posts. There are many other sources than these forums. Personally I have realized that these forums cannot or will not answer most of my burning questions. So I have to look elsewhere. End of story. I only choose to still hang out to help people when I can. My own benefit from these forums is waning rapidly. C'est la vie.

    I have worked 20 years in bioinformatics and biopharmaceutical industry. I was at the ground floor of the genomics boom in the mid 90s. I don't know each and every SNP and how they might relate to methylation. No one on this planet does. But I do know that many on here over-react to high frequency heterozygotes that distract them from their REAL health problems. I also know that no one else on here seems to know about or want to talk about haplotypes which is where the genetic "meat" is. And so a lot of Dr Yasko et al pronouncements (which Rich borrowed from in part) on single SNPs are borderline hogwash. We simply do not have enough SNPs and haplotypes detected nor their phenotype impact established. So yeah I can say with certainty that I know what we DON'T know and that makes a lot of SNP based theories highly questionable. So all we can do is what we can do as a community.

    You ask a lot of questions. Which is good. But you don't seem to almost ever like the answers. What are you looking for?

    Take for example, folic acid. Virtually everyone has now come on board to say avoid it strictly. So? You have some driving need to take folic acid? Community advice is avoid it. Done.

    Another example folinic acid. Some people have problems with it. Some people respond great. Rich tried to find theories for why. Freddd has made lots of careful empirical observations. Ok. So knowing this you could try folinic acid yourself and see what happens. Not sure the community can predict your result. But another possibility is it does little to nothing for you. Maybe boosting the folate cycle is NOT your main problem. How do you respond of late to 5mthf? If you can't tolerate it well, what do you think the best result of folinic acid can be? That it converts favorably to 5mthf. But if you can't tolerate 5mtf ... you get the idea, right? Again have you considered that the folate cycle may not be your real problem? No SNPs unless they are multiple clear as day homozygotes are going to answer this question. If you really want more information order a methylation panel for metabolites. Maybe organic and amino acids as well.

    SNPs are just guides. Based on clinical factors I bet months ago I had a CBS mutation. I hoped and hoped I was wrong while I waited for my 23andme report. Guess what I have a homozygote CBS and now I know ammonia is a factor in some of my ongoing issues. I also know a cluster swarm of heterozygotes (five of them) on MTRR mean that hb12 is a bad idea for me and probably need more mb12. Even Rich btw said something similar about MTRR.
    My BHMT gene has 3/3 genes tested all homozygote. That path is shot to *bleep*. Ok so I need to reconsider stimulating that path. But on the other hand, I know calling my baT wild type haplotyple for VDR defective is completely wrong. I also know a heterozygote MTHFRA1298c is not some sort of BH4 sentence of doom as gets bandied about.

    Clinical trumps SNPs. Clinical symptoms are where to focus imo. SNPs are just adjuncts. I got by fine for three decades with my SNPs. I never took any unusual supplements and I did just fine. Then a rare autoimmune disease and several hideous viral infections stole 12 years of my life. I don't look at all of that and blame my genes (well except for my terribly long fee that my paternal side of the family bequeathed to me). Staring at SNPs all day would never have helped me to diagnose my SPS.

    And by the way you seem to be operating under the assumption that I think folinic acid is bad. I don't and I never said that. Based on several factors (awaiting a HDRI methylation panel test kit). I suspect I need folinic acid at some level. But I am proceeding cautiously. I have done so much better over the last 3 months the last things I want to do is throw myself off. Besides I have bigger fish to fry than methylation at the moment. I show clear signs of diabetes insipidus and my high glucocorticoids for the autoimmune disease are causing problems as expected.

    I hope you find the answers you seek Lotus. Be patient. Experiment carefully. I personally write down every day what I take. I test on the weekends. I try to aim for 1-2 weeks for confirmation of good or bad (unless terrible side effect). Before I introduce a change I try my darnedest to understand why I need or want to make that change. To learn ahead of time what are the likely symptoms if there is a problem.

    But ... and this is a big one, don't assume everything is here on there forums. Methylation is important but it is not the end all be all. There can be many other sources.

    Good luck and God Bless!
    brenda, dannybex, Lotus97 and 3 others like this.
  6. Lotus97

    Lotus97 Senior Member

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    dbkita
    You seemed object to me reposting some of Rich's quotes, but maybe I read too much into your statement. As always, I appreciate your answers to my questions.:thumbsup: So if MTHFR doesn't have a problem with folinic and MTHFS possibly also needs a defect in SHMT (which Rich and Nandixon discussed in that thread), do we have any idea how common the issue is? Since Rich has 200 mcg of folinic acid in the most recent revision of his protocol and he was participating in that thread by Nandixon prior to that he seemed to think 200 folinic would be fine for most people.

    I don't take any 5mthf (methylfolate) now. I found out that the Jarrow B Right B complex that caused me problems only had 50 mcg of Quatrefolic methylfolate. I took it twice a day, but that's still only 100 mcg of methylfolate. Even too much hydroxocobalamin and folinic acid seem to cause me problems right now. I have a children's chewable multi with a small amount of coenzymated b vitamins and folinic acid which I'm taking sublingually. That's the only folinic I'm getting now except dietary folate.
  7. Freddd

    Freddd Senior Member

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    Hi Lotus,

    I would suggest that you are confusing yourself with the folates and all by the way you are doing it. As a mix of folinic and l-methylfolate will often give confusing and mixed results. Then you are trying to find meaning in the confusion based on confused ideas of what might be going on. You seem to be trying everything possible except those single or paired items in such a way as that might give unambiguous results. Good luck.
  8. dbkita

    dbkita Senior Member

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    I have to think the 81% study suggests the folinic acid pileup problem is not that common. Again I think most do not react horribly to the 200 mcg in Rich's protocol. But I think Rich and Freddd have both been trying to understand why some people do. Personally I have the SHMT defect but that alone seems to imply some (at least small) need for folinic acid. I do have several MTHFS SNPs but folinic acid does not bury me when I take it. I have talked to Freddd about my reactions to folinic acid. It is just what I would expect, my reaction is a sort of like to a slightly inferior form of L-5mthf and that was taking 800 mcg of folinic acid a day. I still contend if L5mthf is causing you issues, you have a problem going the folinic acid route since the best you can hope for is the folinic acid steadily converts to l5mthf and then you are right back where you started as you cannot tolerate 100 mcg of the latter. I would eschew folic acid and test one at a time carefully. If neither work then you have to reconsider another factor is pre-eminent whatever that factor is. Sorry I can't be more enlightening.
  9. Lotus97

    Lotus97 Senior Member

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    I have been gradually reducing folic acid although 1500 mcg of folic acid didn't block 100 mcg of methylfolate so I don't quite know if I have a problem with folic acid. Rich seemed to think the fact that folic acid uses up NADPH was a good enough reason not to take it so at least cutting back or eliminating folic acid would help me in that regard. But is it possible for folic acid to build up if I'm not converting enough and yet not block methylfolate? That's the big sticking point and I haven't been able to find an answer.

    Actually, with that children's multiple I've been taking recently I seem to feel really good after taking it. I have no idea why. The dosages are so small. There's only 25 mcg folinic acid in one tablet. I'm taking it sublingually and it takes a few hours to dissolve, but still. This is it if anyone's interested.
    http://www.integratedhealth.com/vitamin-formulas/kids-mighty-multi-chewable.html
    I have no idea what ingredient it is that seems to help. There's only 6.5 mcg methylcobalamin in one tablet. I know Caledonia claims to get benefit from 1-2 mcg of methylcobalamin, but I'm a bit skeptical (no offense). I admit I don't know much about SNPs so maybe there's an explanation. Just the combination of that multi with hydroxocobalamin sometimes seems to make me wired. I think I'm going to cut back on B6 and P5P until I get my SNP results in case I have that CBS thing. I seem to be getting a lot of folate from my food though. Depending on my meals I think I get upwards of 400 mcg of dietary folate on some days. Over 150 mcg just from my greens. As we discussed earlier, much is probably lost in cooking and/or storage. The main thing right now seems to be my adrenals. It's just that methylation seems to make things worse if I do too much.
  10. Victronix

    Victronix Senior Member

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    So far I've done okay with totally dropping any folic or folinic acid and carefully titrating up the Methylfolate (about 25 mcg every other day). Of course it's only been about a week and a half or something. I've also tried to add foods with the highest levels of folate to my diet to offset the potential deficiency.It took about 3 dosages of the 25 mcg (1 every other day) before it became tolerable enough to move up in dosage (I'm COMT++). So now I'll see what happens.

    The 2 most difficult start-up effects that I have are that 1) the muscles in my lower legs and feet get very tight, as though twisting, and my feet get freezing cold and numb (although the cold/numb aspect went away over the course of the 3 dosages). There is also a small amount of this for my hands and forearms, which will feel stiff; and 2) there is exhaustion on the day that I take it and the next morning. Other more easily tolerated start-up effects are temperature fluctuation (feeling like I have a fever when I don't) for about half the days on the first couple of dosages, and sore breasts (I presume from increased estrogen?).

    Potassium (800 mg as coconut water), made virtually no difference in the muscle / cold feet effect, so I tried increasing the B-multi (w/o folic or folinic), but its not clear that did anything either. It's possible I need to increase methyl-B12 / adeno but I'd rather not do that unless I absolutely have to, and since the effects wear off in a few days (in my very limited experience so far), I'm going to see if I can just manage it without changing the B-12. I'm already at 7000 mcg/day and basically do fine. However, I'm also in the process of increasing my thyroid dosage and at times I find I'm overstimulated, so I will have to see how things fall out.

    I guess the thing I'm working toward is getting up to a reasonable dosage of methylfolate in an amount of time that will not allow a significant deficiency to happen. I went gluten free in Nov of last year and so suddenly the massive folic acid load was cut in half. By Dec I'd gotten a terrible canker sore in my mouth that took a full 2 weeks to heal and I'm convinced that was a folate deficiency issue. I've never had anything like that. I think cutting out most folic/folinic + not having any methylfolate except the weird combo in B-Right (350 folic, 50 methylfolate), plus having malabsorption, as I seem to, sort of pulled the rug out from under me. I'm doing okay lately and haven't been sick at all in weeks now.

    Possibly I should post this on a different thread, I was just here, and started writing, sorry.
  11. Freddd

    Freddd Senior Member

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    Hi Victronix,

    A week ago I read an article that said that most of the coconut water tested didn't have the labeled amount of potassium. You might try some other sources of potassium as a A-B trial.
  12. dannybex

    dannybex Senior Member

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    Hi Lotus,

    I think the thing with folic acid -- is that it's a synthetic compound -- so that while some perhaps can break it down, that in general, it probably requires extra steps in order to do so?

    From wiki: "Folic acid is itself not biologically active, but its biological importance is due to tetrahydrofolate and other derivatives after its conversion to dihydrofolic acid in the liver."

    You might try doing a search for some of 'Asklipia's' posts -- she believed the problem with 'folic acid' was the glutamate attached to it. And wikipedia again, confirms that it's also known as "pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid".

    I did the methylation test that Rich recommended, and indeed, at least in my case, it showed that while my folic acid levels were high, I was pretty much unable to convert them into folinic or methylfolate -- they were both very low on the test. And Rich did suggest that this was the pattern he was seeing on practically everyone's results, in fact, he thought parts of mine were better than others he had seen. I'm not sure if that means that folic acid was blocking methylfolate, but it was certainly 'building up', and not converting well at all.

    That's a cool multi you found -- nice tiny amounts of various vits/minerals for those of us who can be very sensitive to supplements.
    Lotus97 likes this.
  13. Victronix

    Victronix Senior Member

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    Yes, the one I was taking had previously been labeled as 600 but later was labeled as 400. I'd emailed the company about it and they never responded. Probably I should assume between the dosage mislabeling and my absorption issues that the levels are about 1/2 of what is claimed.

    When I got home from work I still had enough side effects that I decided to increase the potassium and had at least 3 coconut waters plus a V8 (supposedly 700 mg) and then together those *did* have an impact, really helped. So that was it apparently, not taking enough.
  14. Victronix

    Victronix Senior Member

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    I wonder if it was just other things in the previous multi making you feel worse, so now that they are gone, you feel better. Does this one make you feel better than no multi?

    It's great that you are able to do this research to get these multi's out here. Phoenix Rising comes up high in google searches, so getting obscure potentially helpful supplements on here probably helps more people than we realize.
  15. aquariusgirl

    aquariusgirl Senior Member

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    apologies if this is off topic... but a post earlier in the thread got me thinking about this... if a person is very deficient in lithium and therefore has a problem with b12 transport, and then they go supplementing folate (which they are also deficient in) would that aggravate the b12 problem?
    thanks.
  16. Freddd

    Freddd Senior Member

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    Hi Dan,


    In about 1960 my mother decided that Special K, with "B12" (CyCbl) was the rage. Metrical, a liquid diet drink she decided I would use 3 days each 3 weeks when I couldn't chew having my braces tightened. It was very shortly after starting regular consumption of folic acid that I got a lot sicker for longer. Originally I had tied that to CyCbl but quickly learned it was the folic acid. Folic acid every day doubled at least the amount of illness I had, and I was done with all the usual childhood diseases too; chicken pox, measles, mumps etc. This problem with folic acid has been talked about perhaps as early as the 60s. Now that we have l-methylfolate anybody can do a direct comparison.

    And Rich did suggest that this was the pattern he was seeing on practically everyone's results, in fact, he thought parts of mine were better than others he had seen. I'm not sure if that means that folic acid was blocking methylfolate, but it was certainly 'building up', and not converting well at all.

    There is one of the videos he talks about this in too. We discussed that this inability to use folic acid was probably a concentration factor for those of us here. Now it is very clear the problems folic acid causes. I have proposed that for many of us this limited ability to utilize folic acid is what eventually lands us here. This folic acid problem is what most all of us have more or less in common. This is why I call this whole set of derivative diseases "man made deficiency disease". I've been calling it 21st century mystery disease. Now others are noticing that while the boomers have added a few months of longevity that were are a lot sicker than our parents generation. So like it or not it will probably end up the Boomer Mystery Disease. When a whole generation gets sicker in hundreds of ways it is pointing at something very fundamental. Right now we are the write-offs, the ones that suffer and die for the next 100 years while they figure out where they went wrong, the ones they have no idea of how to cure or even prevent. 60 years of research has gotten so wrong that the medical industrial complex has no idea and even have it 100% wrong and haven't a clue. So we canaries are revolting (like MAD) and finding the solutions independently.
    dannybex likes this.
  17. Freddd

    Freddd Senior Member

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    Hi Aquariusgirl,

    Interesting thought. A lot of us here certainly have cobalamin transport problems, most noticeably into the CNS. And that transport problem can be gotten around by diffusion distribution of MeCbl and AdoCbl. Methylfolate also has something to do with retaining b12 longer in the body. Folate with b12 to the brain, and I have mentioned the possibility that HyCbl can't provide enough MeCbl to the brain for safety when taking an effective form of folate.

    In breaking out of methyltrap (low b12 with folate deficiency symptoms) a little MeCbl however gotten doesn't do the trick. It's quite possible to cause problems and these have been warned against for at least 60 years. Before Metafolin I wondered how folate could be that active. That is likely why so few warned of the problem and couldn't demonstrate it.
  18. pela

    pela

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    dbkita, Thanks for the long heart-felt post. I agree with you about churning the first page of the forum. I do not enjoy seeing the first page cluttered with reruns of old, old threads that are already available to anyone who wants to read them. And please stick around. I appreciate your insight.
  19. Asklipia

    Asklipia Senior Member

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    Green tea seems to help some people. It did help me in case of Fake Folate poisoning. Most probably because it contains EGCG (epigallocatechins) that inactivate DHFR.
    So most probably the culprit folate, for me at least, is being affected by the DHFR. Folic acid, but maybe others?
    Unless it is a case of lowering the total of folates at one point.
  20. Freddd

    Freddd Senior Member

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    Hi Dbkita,

    I like the term "folinic acid pileup" because that may be all that is happening except for the 19%. Perhaps the conversion rate is just too slow when the demand for the specific methylfolate form is high. I had substantial high rate healing on several levels while maintaining folate insufficiency in the epithelial layer for years taking only folic acid. Sufficiency of methylfolate affected regrowth of the muscles and IBS, angular cheilitis and then the whole asthma, inflammation, MCS, allergies when it was more severe but that could have been lack of b12 causing methyltrap so that set of symptoms isn't as clear.

    With l-methylfolate the lower the dose the greater the insufficiency symptoms so 100mcg can be entirely intolerable while 4000mcg in a single dose could stop cold all the insufficiency symptoms. That is part of what makes it paradoxical.

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