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Too many free methyl groups

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by retireddpm, Aug 26, 2010.

  1. markmc20001

    markmc20001 Guest

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    Aquariusgirl, I took doxy, amox, and occasional flagyl for about 1 year (for CPN). I'm not convinced that I did any better than I am doing with vitamins alone. But certainly learned alot.
  2. markmc20001

    markmc20001 Guest

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    Hi joopiter, The paraestheisa feeling your getting.....is it like a burning in the legs and feet at night by any chance? The bottoms of my feet are burning at night right before bed usually. I have also experienced the same kind of burning from ABX, NAC, Glutathione, and probably something else I can't remember. A guess is it may be CPN(chlmyadia pneumonia) die off for me.... However, that is only based on what I have read on CPNHELP.org, hard to know. Can you suggest any good, yet easy reading on the methyaltion cycle? I have seen that chart a number of times but don;t have a great grip on chemistry to interpret that.
  3. Joopiter76

    Joopiter76 Senior Member

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    Mark:
    no they are not burning its like a light vibration an they are "falling asleep" even when I sit half an hour or so. Burning mainly of the skin can also mean B5 deficiency. According to my doc, this is very often seen, even more often than B6 for example. I improved a bit by adding 3x1g B5 (Pantothenic acid) per day, I have a cortisol problem so this is needed therfore anyway.

    @ AQ:
    the zinc connection is that you need zinc to phosphorylate and so activate B6 to p5p. So no zinc no p5p and so high cystathionine. If you are a member of the CFS-Yasko yahoo group you can download the explanation in the folder test interpretations. the descriptions are very good. I dont know if you can take much p5p or B6 if you have overactive CBS but there are other markers that indicate B6 deficiency. Have a look at the descriptions.
  4. markmc20001

    markmc20001 Guest

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    ahhhh.....yep, I think I may have been doing better taking b5 and pantethine before. I guess pantethine is the active form of b5, but I can't tell the difference and just took them both.

    I have messed up "adrenals". I read about someone else's improvement with PABA with pantethine for adrenals and tried it. Maybe that is something you have tried or aware of already.

    That zinc is something I can definitely feel when I am deficient. Sounds like you have had some great docs.

    Thanks
    Mark
  5. aquariusgirl

    aquariusgirl Senior Member

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    I was thinking the same thing. You got lucky with your doc Joopiter, whoever he/she is.

    Thanks for the info.
  6. aquariusgirl

    aquariusgirl Senior Member

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    MB12 in DAN! protocol
    Just wanted to amend what I said earlier on this thread. I said DAN! docs were prescribing large doses of MB12, but from what I can glean on autism lists, it's actually quite small, 0.6 or 0.3 mg/ml.

    I took 15 mg of methyl b12 .. sublinguals .. the other day. I was sick for 2 days afterwards.
  7. Joopiter76

    Joopiter76 Senior Member

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    @AQ: do you take TMG (Betaine) ?? This would leed to improved converting of homocysteine to methionine so homocysteine may be less converted to cystathionine. But ask Rich to confirm this.
  8. aquariusgirl

    aquariusgirl Senior Member

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    No, the general advice is to steer clear of betaine because it supports the BHMT shortcut at the expense of the long way around the cycle.

    I think the only reason my cystathionine is elevated is because I'm doing these amino acid IVs. I would have thought more B6 to help convert the cystathionine to AKG or cysteine would be the way to go...but there are probably some ohter missing pieces that you need to ensure the flow goes toward glutathione rather than taurine.

    This is above my pay grade....and I think I'm yanking this thread off topic.. so I may post another thread.

    I could use some help figuring this out!
  9. Joopiter76

    Joopiter76 Senior Member

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    So if I take TMG I will lower m-B12 synthesis?? And so on I will lower purine synthesis?? But I wonder why is TMG suggested to take? How much is really needed to fix methylation cycle block?
  10. aquariusgirl

    aquariusgirl Senior Member

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    check this out.. from dr amy yasko's site. www.ch3nutrigenomics.com

    http://ch3buddies.com/Pathway_Diagrams/diagram_5.pdf

    you need the long way around the cycle for purine synthesis

    where does the advice to supplement tmg come from?

    how much *what* does it take to fix the block?

    it takes time.. and you have to remove those metals that inhibit the reactions...

    I'm not sure what you're asking.
  11. Joopiter76

    Joopiter76 Senior Member

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    your graph is good, as I can see the cofactors. do you have some more useful like this one. I know the papers from Rich and from Yaskos page. But there arent the cofactors included.

    *what* = TMG
    so I mean how much TMG should I take. Or when I take Betaine for stomach acid I automatically take TMG. So how much is useful and which dose shouldnt be exceeded?

    http://www.dramyyasko.com/diagrams-listing/
    see last graph: theres the TMG
  12. Freddd

    Freddd Senior Member

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    Hi Joopiter,

    TMG supplies about 30 times as many donatable methyl groups mg per mg as methylb12. So, one might think that 0.033mg of TMG has the same methylating power as 1mg of methylb12. If a person takes 500mg of TMG then they are taking as many methyl groups as if they took 15,000 mg (15 grams, not mcg) of methylb12.

    SAM-e supplies 3 times as many methyl groups mg per mg. So a typical dose of 400mg of SAM-e supplies as many methyl groups as 1200mg (NOT mcg, 1.2 grams) of mb12. This would be equivalent to the methyl groups found in 1200 1mg injections of mb12 of of 1200 5mg sublinguals each held for about 90 minutes all at once.

    A typical egg with the 113 mgs of choline it contains, has about 5000 times the methyl groups of 1mg of mb12 into serum.

    So if the the startup effects of 1mg of mb12 are attributed to it's meager methyl content than an egg or 1mg of SAM-e (not the 200-600mg of a typical dose) or 33mcg of TMG or choline ought to put a person on the roof.

    Telling somebody to avoid methylb12 because of it's meager quantity of methyl groups in light of the quantities of methyl groups from other sources, it ought to be clear the startup effects of mb12 are about all sorts of other things but very little attributable to the methyl groups it brings into the body per se. Mb12 isn't magic. It's donatable methyl groups are not magically 1000 times more powerful than the methyl groups from other sources. Since it clearly isn't based on the quantity of methyl groups brought into the body by mb12 it has to be the qualities of the complete methylcobalamin itself, and there are several forms of mb12 with somewhat different effects and effectiveness that has nothing whatsoever to do with the methyl group itself.

    It's quite possible I am misinterpreting something here about the methyl groups quantitatively or qualitatively, though as far as I know CH3 is CH3 no matter where it starts out.

    Mb12 is important because of all it does. Perhpas it can perform it's tasks better because it doesn't compete for methyl groups.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754772/
    A simple, convenient method to synthesize cobalamins: synthesis of homocysteinylcobalamin, N -acetylcysteinylcobalamin, 2-N -acetylamino-2-carbomethoxyethanethiolatocobalamin, sulfitocobalamin and nitrocobalamin
    In the MeCbl-dependent methionine synthase reaction, a methyl group is transferred from methyltetrahydrofolate to homocysteine via MeCbl to generate methionine and tetrahydrofolate. Impairment of this reaction leads to elevated serum levels of homocysteine, which is associated with an increased risk of cardiovascular, peripheral vascular and cerebrovascular diseases

    Synthesis of thiolatocobalamins
    All syntheses were carried out under red-light-only conditions, due to the potential light sensitivity of thiolatocobalamins.43 Unless specifically stated otherwise, all syntheses were carried out under aerobic conditions.
  13. Freddd

    Freddd Senior Member

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    Hi Aquariusgirl,

    15mg of sublinguals, dependent upon the sublinguals and technique, could absorb in the range of 2-4mg, more or less. The level of reaction you had is not suprising if you are deficienct and have not titrated up to that dose. If taken as a single dose it might have been enough to diffuse into the CNS. Something to remember, people without the symptoms have no reaction at all to that amount or even 4x that amount. I have given sublingual tablets to more than 1000 people after checking for symptoms. Nobody without symptoms had significant response. Normally the more the symptoms and more severe the symptoms the more startup response a person has.

    As the startup responses are the sum of a whole lot of stalled and broken processes they are perceived as a worsening and/or shifting of symptoms requiring some days to months to diminish, change and improve.
  14. Freddd

    Freddd Senior Member

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    Hi Aquariusgirl,

    A number of us tried the glutathione precursors. One guy is a vegetarian, a couple more might be. Every one of them has or had a bunch of b12 deficiency symptoms. Several had FMS/CFS diagnoses. Some took precursors and some glutathione infusions or other form. Every one of the persons had been taking the active b12s, most with metafolin, for some months to years before trying the glutathione. Every one of them had a good deal of correction of symptoms and healing while taking the active b12s except one person who had been taking the glutathione the entire time. Every one of the persons involved had a sudden resurgence of symptoms when they took the glutathione and the longer they took the glutathione the worse the returned deficiency symptoms got. After stopping the glutathione, large doses of metafolin and active b12s caused some startup responses all over again and noticably started reversing the induced symptoms within hours. The only similarity of all the people responding as I did was that they had already significant improvment form the mb12/adb12/metafolin. If people had been taking hycbl or nothing they appear to not have the return of those affected symptoms because those sysmptoms had never gone away in the first place so there was no return of those deficiency symptoms, they had never gone away.

    was struggling to understand Fredd's rational for not using glutathione

    It's very simple. The glutathione started causing the return of selected methylb12 deficiency symptoms, the return of selected adenosylb12 deficiency symptoms and selected metafolin deficiency symptoms. If a person hasn't had those specific symptoms go away in the first place how could they possibly be felt returning? Since folic acid and hycbl doesn't affect those symptoms in the first place there is no basis of comparison. Either the person didn't have them orioginally or they alrady had the same symptoms and had never seen them go away so thereby unable to return. However, after a while some folks taking inactive cobalamin and folates did develop "glutathione detox reaction" which is quite widespread. This reaction is composed of Metafolin deficiency symptoms, methylb12 deficiency symptoms and adb12 deficiency symptoms. When some of these folks then tried the metafolin, mb12 and adb12 they were able to reverse the "glutathione detox reaction" very quickly.

    So presumably if we standarized the original situation, say 1 year on active b12s and active folate before trying the glutathione, we would see more consistant results of the return of symptoms. If I had tried glutathione before I had tried mb12, adb12 and metafolin and mostly healed, and it helped some of my 300 symptoms, I might have come to a different opinion of it initially. However, as soon as I had gotten rid of the symptoms glutathione causes I would have been aware of their return.
  15. aquariusgirl

    aquariusgirl Senior Member

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    Hi Fredd

    No argument here when it comes to being B12 deficient. I am clearly deficient.

    I actually was reading your long B12 thread when I popped the last of those 3 5mg methyl B12 pills. Right after i popped the last one, i read about how you advise to cut them in quarters & titrate up.

    Timing is everything, right?

    Still not convinced that start-up symptoms isn't the same thing as major detox (kidneys hurt like hell the day afterwards...)

    Thank you for reiterating your argument against using glut. Tough to make sense of this w/out a scientific rationale to explain it...

    I really have got some great value out of your stuff (dosage, brands, response) & I will continue to read it, and see how other folks respond as I try and reconcile it (or not) with what the DAN movement and Amy Yasko and Dick Deth and Rich Van Konyenburg have shared with us.
  16. aquariusgirl

    aquariusgirl Senior Member

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    Joopiter

    Amy yasko has more pathways diagrams on her website. You will need to register as a guest or sign up.. at www.ch3nutrigenomics.com.

    Go to the forum called Pathways Diagrams.

    For Dick Deth's take on TMG or betaine....google RIchard Deth, biochat and he talks about it in there. It's just a Q&A that an anonymous autism mom wrote up...but he talks about it in there.

    I think its' from 2005.
  17. Freddd

    Freddd Senior Member

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    Hi Aquariusgirl,

    I am preparing a very complete response to Rich which might help clarify things, or not, which I will post tomorrow if all goes well timewise.

    Still not convinced that start-up symptoms isn't the same thing as major detox (kidneys hurt like hell the day afterwards...)

    Let's consider how mb12 works in detox. For some items the cobalamin combines with a toxin such as cyanide or Nitrous Oxide thereby making the toxin non-toxic but also disabling the methylb12 in the process. This toxin attached to cobalamin is preferrentially and rapidly excreted by the kidneys. Only one of the two kinds of kidney tubules can filter out cobalamin. Other items are affected by the methyl group The kidneys are a specialized epithelial tissue. Epithelial tissues in general are often inflammed and rapidly damaged by b12 and methylfolate deficiencies. So there is the possiblity that your kidneys are damaged or inflammed and being affected by the mb12 levels as the epithelial tissues go through healing startup. As mb12 allows us to be far more aware of the damage that exists that may be what is occurring.

    Also remember that the nerves leading to the kidneys may also be damaged by deficiency and immediately affected by increasing transmission "loudness" before the damage is repaired, making the damage far more apparant. Spasms often occur, anywhere there are muscles connected to nerves. That could include the kidneys (sphincters etc). While some of the startup responses may be "detox", there are over 600 processes (according to research I have read) that lack of mb12 can stall. As most everybody with a multitude of symptoms have intense startup responses, the exact startup responses being highly varied as are the symptoms, I can certainly agree that some of the startup responses may be due to some of the many possible detox reponses, but that most of the startup responses are concerned with the deficiency caused inflammations in many different tissues and neurological damages and malfunctions and mitochondria startup. When nerves are affected it is common for them to hurt a lot. Neurological healing IS painful. Pain and hypersensitivity are steps along the neurological healing path coming back from numb or nearly so. I had a painful burning bladder and urethra for 5 or 6 years at least. When I started the mb12 it hurt worse than ever for a few days and then at 9-10 days switched to intense itching from the pain and that faded over the next week and was finally gone.

    Thank you for reiterating your argument against using glut. Tough to make sense of this w/out a scientific rationale to explain it...

    Some of that will be forthcoming. Unfortunately the question doesn't appear to have been researched directly so so the answers will be from around the edges of other research and people's real world results.
  18. Freddd

    Freddd Senior Member

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    Hi Rich,

    I am responding to your last post on this chain a piece at a time. There will be additional segments.

    Richvank Said:

    And to tell people with CFS that they should avoid glutathione because it produced problems for freddd just does not make sense, in my opinion

    and I object to applying his personal results directly to explaining what goes on in everyone who has CFS.

    Rich, that is more than a simple misstatement. I object to you so blatently ignoring or misrepresenting most everything I say except what you can use to support your theories. So, I will aid you in making sense of what I have actually said about the whole thing, latest version as I have included details from several different posts and have had further understanding as time and additional changes have occurred. My results were duplicated in kind by each and every person. What differed was the degree. I had the longest lasting and possibly the most severe response. I also had the longest last symptoms and the most damage, especially severe damage not yet healed. However, the longer each person continued the worse and more widespread were the symptoms returning. Also I am very sensitive to the effects of Metafolin and it's lack. That was the quickest and most severe induced deficiency in all persons and is the main set of symptoms for socalled "glutathione detox". Not only do you appear to ignore each time I tell you that there were multiple people who had the same types of results as I had with glutathione infusions, gluathione in some other way, NAC/L-glutamine, some other combinations of a cysteine and gluitamine precursors and undenatured whey. As is common here many people are experimenting with diets of one kind or limited by major food intolerances. I was both a vegetarian and had limited foods choice because of food intolerances and frequent nausea. Some people had CFS/FMS diagnosis, some had b12 deficiency diagnosis and some had no diagnoses or tons of others. Mosr of us started at the same time and nobody spoke up with results until I mentioned that I was unable to continue the trial at 6 weeks because of the severity and nature of the responses being clear. It became clear as various people posted or emailed me with their results that 100% of the people who had responses, 100% of the people who announced that they were going to try glutathione, had been taking mb12, adb12 and often Metafolin or Folinic Acid for some period of time and had achieved a substantial amount of healing. A couple of people who had been taking glutathione at the time we posted our results who had not been getting results with mb12/adb12/Metafolin then discontinued glutamine and slowly started getting results. Having glutathione on board appears to completely prevent mb12/adb12/Metafolin startup responses of any kind and also prevents any healing from taking place. The startup is very slow after quitting glutathione which is not surprising considering how long the results lasted for me and some others. While I had a batch of startup responses with the first dose of each MB12 and ADB12 following 4.8mg of Metafolin I had delayed startup of epidermal healing until 18-19 months following cessation of glutathione, reinstating the condition that prevailed just before starting glutathione.

    I suppose that to put a different light on this is that we have found a way to STOP Metafolin/methylb12 startup responses very quickly though nobody has tested that hypothesis yet.

    A number of us tried the glutathione precursors. One guy is a vegetarian, a couple more might be. Every one of them has or had a bunch of b12 deficiency symptoms. Several had FMS/CFS diagnoses. Some took precursors and some glutathione infusions or other form. Every one of the persons had been taking the active b12s, most with metafolin, for some months to years before trying the glutathione. Every one of them had a good deal of correction of symptoms and healing while taking the active b12s except several persons who had been taking the glutathione the entire time. Every one of the persons involved had a sudden resurgence of symptoms when they took the glutathione and the longer they took the glutathione the worse the returned deficiency symptoms got. After stopping the glutathione, large doses of metafolin and active b12s caused some startup responses all over again and noticably started reversing the induced symptoms within hours. The only similarity of all the people responding as I did was that they had already significant improvment from the mb12/adb12/metafolin. If people had been taking hycbl or nothing they appear to not have the return of those affected symptoms because those sysmptoms had never gone away in the first place so there was no return of those deficiency symptoms, they had never gone away.

    It's very simple. The glutathione started causing the return of selected methylb12 deficiency symptoms, the return of selected adenosylb12 deficiency symptoms and selected metafolin deficiency symptoms. If a person hasn't had those specific symptoms go away in the first place how could they possibly be felt returning? Since folic acid and hycbl doesn't affect those symptoms in the first place there is no basis of comparison. Either the person didn't have them orioginally or they alrady had the same symptoms and had never seen them go away so thereby unable to return. However, after a while some folks taking inactive cobalamin and folates did develop "glutathione detox reaction" which is quite widespread. This reaction is composed of Metafolin deficiency symptoms, methylb12 deficiency symptoms and adb12 deficiency symptoms. When some of these folks then tried the metafolin, mb12 and adb12 they were able to reverse the "glutathione detox reaction" very quickly.

    Speculation on the role of methylb12 involving glutathione.

    Taking everything into account it appears that excess (whatever that actually means) glutathione is treated as a toxin by methylb12. It promptly forms glutathionylcbl from mb12 and then is flushed much more rapidly from the body via the kidneys, much more like cycbl, than mb12. This difference is easily visible by anybody taking large enough doses of mb12. The level of red in the urine was characteristic of approximately doubling the dose of mb12. Again this is shared by everybody taking enough mb12 to visibly color the urine. As mb12 has been shown to have dose proportionate healing response up to 1500mcg daily dose and in other research up to approximately 50,000mcg daily, though the curve may have a essentially level zone between lower dose proportionality and higher dose proportionality, lots of people, hundreds to thousands so far, that have posted or corresponded with me about the powerful healing effects of "well in excess of transport system saturation doses" of methylb12. When that unbound mb12 disappears and the unbound adb12 disappears, then the effectiveness more or less disappears. I am far far far from alone in this. This is the majority response to mb12/adb12, not the response of one person.

    As it turns out my results are much more predictive of favorable results than any prediction of results on the simplified methylation program.

    We need to do 1-2 year symptom/sign matched pair and maybe with 50% crossover at 6-12 months study to see the very real differences which I am quite willing to predict and bet will be there.
  19. Freddd

    Freddd Senior Member

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    Hi Joopiter,

    I wonder what it indicates in my case as I took daily Oh-B12 inj. for over a year and MMA raised !! I guess I have a converting problem or the A-b12 is oxidized faster than it can be synthesized

    In my experience very few people actually fullfill the practical need for adb12 by taking cycbl, Hycbl or mb12. Taking adb12 directly after 6-12 months on any other form of b12 will cause an immediate startup effect as the mitochondria start working better. Adb12 goes into the mitochondria and stays for the life of the cell as far as I know. In practical terms, body level (muscles mostly) turn over only at cell death. B12 dosn't normally "oxidize". However, cyanide will convert it to a plus 3 oxidation state as cyanocobalmin if the cyanide can get at it. Nitrous oxide does the same, oxidzie it permanently. As adb12 is locked up in mitochiondria it does not appear to be available as vulnerable to all the problems mb12 is vulnerable to. It takes me about 3 weeks without adb12 to develop enough unmet demand that I notice a dose at all. If it was only for my body I would take a single 3mg sublingual once a week. As I also have a CNS level deficiency as demonstrated by a sudden startup respose to a 51mg sublinguial dose. However, that can be duplicated by 18mg taken as a single dose once a week 1 hour folowing an injection of mb12. One person I know requires 15mg/day or so to keep brainfog at bay.

    Two of us have tried adb12 by injection. For me 5mg injected with 5mg of mb12 (10mg total for diffusion gradiant) is in no way superior to the sublingual. In addition the adb12 injectable is muxch more fragile than mb12 injectable and breaks down in under 10 days in the same conditions in which mb12 lasts for months. Further larger daily doses caused changes in mood and personality that appear similar to mb12 deficiency or glutathione consumption.

    My suggestion is to take a 3mg adb12 under the lip for 45-120 minutes once each day until taking another makes no difference. That might happen within 2-4 days. Then try once a week and see if there is any noticable effect after each dose. If there is, take more often. If there isn't, once a week should be plenty unless you find a CNS response when you test for that. Remember that each 3mg tablet puts only about 600mcg into serum and is quite sufficient for most people


    I would suggest that 95% of all the healing your body might do is doable on 1-20mg sublingual per day. That amounts to 200-4000mcg daily. I can find no reason at all to inject unless the 50mg sublingual test shows CNS deficiency. In that case you will likely need more than 5mg each and every day for the CNS to heal. Less is ineffective. In general because of poor practices and other factors beyond their control at most pharmacies injectable mb12 is not reliable or of suitable quality. The 5 star mb12 sublinguals will be more effective and relaible for the most part.

    I guess the question is how much active b12 is immedeately distroyed. As the strength of oxidative and nitrosative stress is very different in PWCs.

    Almost none is immediately destroyed under most circumstances. It doesn't stick around the body long enough. The kidneys excrete it so fast that the serum halflife starts at 30 minutes or so immediately after injection and increases over the first 12 hours to 4 hours. It is estimated that 99% of the active, and inactive, b12s are excreted in the first 24 hours totally unchanged according to research, and the only visible presence in urine is usually in the first 3-4 hours of collection. The only exception to that I have seen is with glutathione which appears to destry the active b12s immediately (whether oxidized or not I couldn't say) and excreted about twice as fast by the kidneys as determined by urine colorimetry.

    Active b12 responses correlate to the arrays of symptoms, not diagnoses. I had most all of the FMS and CFS symptoms for 16-30 years (depending upon symptom) and a whokle lot more, and I had hugely intense startup responses almost across the board.

    CFS/FMS is assoicated with low cerebral spinal fluid cobalamin levels according to relatively recent research. That research is currently being done across a spectrum of diseases that involve the neurology.
  20. Freddd

    Freddd Senior Member

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    Hi Markmc,


    The bottoms of my feet are burning at night right before bed usually. I have also experienced the same kind of burning from ABX, NAC, Glutathione, and probably something else I can't remember.

    Glutathione in my experience and that of others is that it genueinely worsens neuropathies which increases paresthesias such as burning and vibration. The difference between that and what mb12/Metafolin does is that with the glutathione the symptoms keep getting worse. Witrh the mb12 and metafolin, they feel more intense but as they fade feeling returns, usually hypersensitive at first before fading to normal. This comes from real experience from multiple people who have tread that path.

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