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if we need glutathione, should I take it?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by alexa, May 22, 2011.

  1. alexa

    alexa

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    A couple of weeks past i started taking folapro, actifolate, phosphatatidyl serine 100 and methylcobalamin, all this to fix my methylation block ( as i have learned from all you wise people!) but as i understand, i am doing this in part to raise my glutathione levels. If this is true, why am I not adding gluthatione or NAC to my mix? some other methylation protocolls add this but as i understand neither Rick nor Fredd does? why? would it be bad to try?

    i am also wondering how bad it would be to take a break in my protokoll? it takes so many weeks for these pills to arrive to Sweden that i have miscalculated my stash....

    i went to malta and had four days om me, not ME but just glorious wonderfull me, i had my own thoughts and almost my own body back, i don't know if this is because the protocoll or the inosine that i started but it was wonderfull!

    love to all you out there helping eachother!
     
  2. Sallysblooms

    Sallysblooms P.O.T.S. now SO MUCH BETTER!

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    I take supplements for the methyl and MANY others. I have a long list of things I take to support my body, three times a day. My integrative doctors are amazing, they tell me what amount and brand to take of everything.

    I have been taking NAC, sublingual ATP and Liposomal Glutathione. They have been wonderful, huge difference. I have mentioned on a thread about how the ATP and Glutathione got me through a tramatic week of another surgery, pain from that, a day in the ER etc. That was two weeks ago. Before I started my supplements I couldn't have made it. I almost sailed through it now that I have added the ATP and Glutathione.
     
  3. richvank

    richvank Senior Member

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    Hi, Alexa.

    I'm glad to hear that you had a good time in Malta!

    With regard to using glutathione in CFS, when I first learned from Dr. Cheney's talks in 1999 that glutathione is depleted in most PWCs, I encouraged PWCs to boost glutathione directly in a variety of ways. This gave temporary improvements for some, while others could not tolerate the response they had. If the people who had experienced improvements in symptoms stopped boosting their glutathione, the improvements died away. In late 2004 I learned of new work in autism by S. Jill James and colleagues. They found that there was a problem in the methylation cycle in autism, and this is upstream in the biochemical pathways from where glutathione is synthesized. They also found that if they treated to lift the partial methylation cycle block, glutathione came up automatically. I suspected that this same thing was going on in CFS, so I encouraged PWCs to try the same type of treatment. It turned out to help, and it appears to bring glutathione up on a more permanent basis. So I stopped encouraging direct boosting of glutathione.

    However, one of the difficulties that some PWCs have when starting this type of treatment is that their excitotoxity-related symptoms (anxiety, insomnia, and a "wired" feeling) get worse. I think this is caused by an initial further decrease in glutathione when this treatment is started, because of diversion of more homocysteine to methionine, and less to synthesis of glutathione. So, recently, I have been suggesting that if excitotoxicity is a problem for a person, they consider adding liposomal glutathione to the treatment to see if that will help. I haven't had much feedback on this yet, so can't say whether it will really be helpful or not.

    Freddd will probably respond to your post also. His views about glutathione are different from mine, based on his personal experience and that of some others with whom he has been in contact. Freddd has found that glutathione and its precursors were very deleterious for him, and he strongly recommends that they be avoided. I suspect that Freddd himself, based on his reports, has a variant of the so-called CblC (MMACHC protein) genetic inborn error of metabolism involving the intracellular metabolism of vitamin B12. His cells are apparently not able to utilize forms of B12 other than directly supplied methyl B12 and adenosyl B12. If he introduces glutathione, his cells are not able to utilize these forms, either.

    I suspect that the reason is that it is known that glutathione will react with all the forms of B12 to form glutathionylcobalamin. Normally, the MMACHC protein in the cells is able to utilize glutathionylcobalamin and carry it on to re-form the two active coenzyme forms, methyl B12 and adenosyl B12. However, this protein appears to be mutated in Freddd's case, so that it cannot use glutathionylcobalamin. Therefore, if Freddd takes glutathione, his cells are effectively robbed of the active forms of B12, and this promotes both a block of the methylmalonate CoA mutase enzyme and the methionine synthase enzyme. The latter provokes loss of methylfolate from the cells via the "methyl trap" mechanism. The result of all this is that Freddd's cells develop a partial block in the methylation cycle as well as a drop in fuel supply to the Krebs cycle, and the overall effect is very bad for him. I don't think we know what fraction of the CFS population has this same issue. My impression from the literature is that it is fairly rare, but Freddd thinks it is more common than is generally realized.

    The type of problem Freddd has could be the cause of the intolerance to glutathione that we found earlier when people were being encouraged to try the direct boosting of glutathione. However, there are other possible causes. Recently, I have begun to suspect that deficiency of riboflavin (vitamin B2) and/or niacin (vitamin B3) and more particularly, NADPH, which is one of the active forms of niacin in the body, could be responsible. These are needed by the glutathione reductase enzyme, which normally recycles glutathione when it has become oxidized from fighting oxidative stress, one of its main roles in body. If it can't be recycled fast enough, the ratio of reduced to oxidized glutathione in the cells will drop and this impacts many biochemical reactions negatively.

    Other possible reasons why some PWCs do not tolerate glutathione directly are that it may raise the cysteine level too high, which can produce toxic auto-oxidation at high enough levels, or it may overload the sulfite oxidase enzyme as it is broken down, and that can produce symptoms if sulfite goes too high. Other possibilities are that the glutathione boosts the immune system and the detox system, and their better operation may mobilize toxins, producing symptoms.

    So there are still quite a few uncertainties in trying to understand these responses. It is somewhat puzzling that some people do have bad reactions to raising glutathione, because it normally plays so many beneficial roles in the body, and it is clearly low in most PWCs, based on lab testing. But that is the current status of the issue, from my point of view. I hope this is helpful, and if you decide to add glutathione to your treatment, I would be interested to hear how your body responds. Note that taking ordinary oral glutathione results in most of the gltutathione being broken down in the gut. However, some of the amino acids that result should be carried to the liver to provide raw materials for remaking glutathione. I favor the liposomal type, because I think there is a better chance of getting some to the brain to control excitotoxicity with this form.

    With regard to taking a break during the treatment, my view is that not much ground is lost by taking a short break, and in fact it has been encouraging to some PWCs to do so, because when they have stopped the treatment temporarily, they have found that they feel much better than they did before they started the treatment. My view is that the symptoms during treatment are a result of die-off of pathogens and mobilization of toxins, caused by improved operation of the immune system and the detoxication system of the body. I think that once toxins have been excreted, a gain has been made, and it won't be lost by a short break.

    Freddd has a different view about this. In his experience, stopping the treatment causes a lot of lost ground, which has to be won back when the treatment is resumed. It may be that his particular genetic make-up is responsible for this. When he stops supplementing the active forms of B12, I don't think his body is able to use the normal salvage pathway to keep supplying active B12 to his cells. A person with normal B12 metabolism can go for a year or more without B12 in their diet, and not develop B12 deficiency, because the liver is able to return B12 to the gut for possible reabsorption. This appears to be a built-in lifesaver for the human race, to make sure enough B12 is available to the cells when it isn't coming in with the diet for an extended time. For example, if hunter-gatherers cannot get animal-based food for some months, they can still survive.

    Best regards,

    Rich
     
  4. dannybex

    dannybex Senior Member

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  5. Freddd

    Freddd Senior Member

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    Hi Rich,

    You dramatically overstate the effect of my genes on this. Of 10 people, all sucessful on the active b12/folate protocol, all tried glutathione in any of several forms and/or precursor combos, 100% of them had detrimental effects caused by what appears to be the methyl trap. The massive amount of glutathione, many hundreds of mgs, compared to a few mgs of b12, apparently completely overwhelms the ability of everybody's body who tried it, to convert the glutathionylcobalamin back to either active form and proceeds to rapidly dump cobalamin from the body which then causes the methylfolate to be dumped from the cells causing all sorts of symptoms.

    It is somewhat puzzling that some people do have bad reactions to raising glutathione


    Well, it's no surprise at all. It's a pity that nobody was able to recognize the nature of their bad reaction accurately and tell them how to correct it. However, the symptoms are those of severe folate deficiency and if continued long enough, b12 deficiency symptoms. They can be turned around starting within hours with a sizable Metafolin dose with at least a few mgs absorbed mb12/adb12 dose. Many of the people who don't report bad reactions are just continuing their already existent folate and b12 deficiencies. When I was very ill glutathione wouldn't have worsened my symptoms and wouldn't have caused any to come back because they had never gone away in the first place. If a person is having paradoxical folate deficiency, caused by folic acid, folinic acid (Actifolate) they won't notice a glutathione induced folate deficiency. It's just more of the same. The sure way of seeing the effect is to have removed the folate and b12 deficiency symptoms in the first place, then there is something that can occur that would be recognizable. Further people who start the active b12/folate protocol with lots of obvious symptoms and no response at all are usuallty taking glutathione in some form and/or NAC with no obvious ill effects, and they start making progress almost immediately after stopping the glutathione and/or NAC. Further, Cerefolin with NAC in their side effects lists all the symptoms that are popularly called "NAC-detox" symptoms which are the same folate deficiency symptoms we are talking about here. Deplin, which doesn't have the NAC says "Metafolin is generally well tolerated and has no side effects different from placebo". The evidence is that a detrimental response to NAC and/or glutathione is quite common if the people don't already have folate and b12 deficiencies. In the Cerefolin with NAC the NAC is causing a folate deficiency despite 5mg of Metafolin. This doesn't appear to affect serum folate as the methyl trap involves cellular folate. Acute folate deficiency is not something looked for when a person has high serum folate and is on 5mg of Metafolin daily.

    A person with normal B12 metabolism can go for a year or more without B12 in their diet, and not develop B12 deficiency, because the liver is able to return B12 to the gut for possible reabsorption. This appears to be a built-in lifesaver for the human race, to make sure enough B12 is available to the cells when it isn't coming in with the diet for an extended time. For example, if hunter-gatherers cannot get animal-based food for some months, they can still survive.

    That is more or less reasonably accurate. Unfortunately virtually nobody who has become very symptomatic with b12 deficiencies appears to ever re-establish a "normal" b12 metabolism. Their symptoms begin to reassert themselves about 3 days after the last dose of mb12. Of course if their b12 metabolism were normal in the first place they wouldn't be in the fix they are in, except for vegetarian. The well known "seven year vegetarian crash" is the body starting to get significantly low on b12. The b12 metabolism crashes at this point. This includes vegetarians with clearly no genetic involvement. There is a lot of nonsense promulgated about b12, even in research, as unproven assumptions are repeated endlessly and became protected by frequent repetition.

    With regard to taking a break during the treatment, my view is that not much ground is lost by taking a short break, and in fact it has been encouraging to some PWCs to do so, because when they have stopped the treatment temporarily, they have found that they feel much better than they did before they started the treatment.

    The experience of many persons is that when they stop, and restart, and stop and restart etc that the oscillations increase in magnitude and the situation gets worse. This is assuming that they have dealt with lack of potassium and have eliminated paradoxical folate deficiency.
     
  6. alex3619

    alex3619 Senior Member

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    Hi, glutathione has many functions not discussed so far here. One of them is supporting/promoting pro-inflammatory hormone synthesis. These pro-inflammatory hormones are part of why glutathione boosts the immune system, and are felt as flu-like symptoms. However, these pathways do not appear to be properly regulated in ME/CFS. Glutathione can therefore induce too much inflammation. If flu-like symptoms are the problem, then maybe decreasing glutathione dosage or taking it only for short periods is the way to go. I ran into this problem many years ago, but never found a great solution.

    In short, I think there is a place for glutathione for most ME/CFS patients, but it is not as simple as take it or don't take it. How many of those experiencing problems have flu-like symptoms exacerbated? I don't know the answer to that, but even if the answer is most we can't sure it is due to inflammatory hormones and not some other issue. For those who do have flu-like symptoms, there might be a way to test: how are you now coping with salicylate containing foods including spices? If tolerance is improved, then the mechanism I have outlined might be in play. I am now addicted to spicy food - which is self medication in a way, as it puts a break on some of these hormones.

    Another issue is that increased glutathione levels, particularly in sudden doses, could alter protein synthesis rates. Some proteins that were scarce might become over-abundant, with secondary consequences. I have not examined this in detail, it is a very complex subject.

    Issues directly linked to methylation I leave to Rich and Freddd. They know a lot more about it than I do.

    My own opinion on the methylation problems is coming around to the view that defects in these pathways are disease accelerators, and not intrinsically causal. I think (opinion, not fact) that these problems increase the severity of illness, and that correcting them can reduce symptoms, which in itself might allow some to recover. I would be interested to see someone do a study looking at prevalence of these problems correlating with severity of ME/CFS.

    I hold this opinion with most of the metabolic issues in ME/CFS, including the oxidative stress theories. They are contributing mechanisms, and need addressing, but we need a lot more research before we can conclude they are causal.

    Bye
    Alex

    PS In those who are XMRV positive, if XMRV is shown to be a major playing (ask me next year) then glutathione could paradoxically increase viral replication at some doses - it depends on the antioxidant/pro-inflammation balance, and is complicated.
     
  7. Freddd

    Freddd Senior Member

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    HI Alex,

    The inflammation caused by glutathione occurs when it causes an acute folate deficiency. It is reversible if a person stops glutathione and takes and continues to take sufficient Metafolin, mb12 and adb12. However, the damage increases the longer such acute deficiency is maintained and not all damage is easily reversible. So it is far beter to restart the methylation cycle that also increases the glutathione naturally without causing the "glutathione detox" which is actually an acute folate deficiency and if continued, increasing mb12 and adb12 deficiencies.
     
  8. Marg

    Marg Senior Member

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    Rich and Fredd,

    I am not sure where I read this or if either of you said it. I read it is best to take the precursers of gluthathione rather than supplementing with glutathione alone because the body will stop making it if it is taken. Did I dream this?
     
  9. Sallysblooms

    Sallysblooms P.O.T.S. now SO MUCH BETTER!

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    Just like CoQ10, Vit D, hormones etc, I don't worry much about that. So important for me to get it all to support my body and what it needs. My doctor has had me on the precursers but the real thing has been better at least for me. You can take it and then take less later. I plan to take the Liposomal every other day instead of every day after a while. I take the Lipo C too. The Glutathione is so expensive so it is great to be able to take less as time goes by.
     
  10. xrunner

    xrunner Senior Member

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    That's what I read about glutathione as well but my own experience negates this.
    Three years ago I had about six months of IV phospholipid exchange i.e. IV Phos Chol (don't remember quantity) followed by 2 grams of glutathione. This was repeated after a couple of hours and followed by 10 grams of Methylcobalamin, then followed by 10 grams of Folic acid then followed by 10 grams of Hydroxycobalamin. That was twice a week. In addition I used to take a number of oral supplements as part of a mitochondrial support protocol i.e. Dr Myhill's protocol (CoQ10, Carnitine, various vitamins, etc.) Anyhow, my red cell glutathione did not change over the year. Had always been low and thus remained. Also the active detox enzymes Glutathione transferase and peroxidase, as well Superoxide dismutase were very low and remained around those levels. The treatment did not cause any bad reactions and helped reduce levels of certain toxins (pesticides, tin and nickel) that were stuck on my mitochondria.
    However, at the end of the six month treatment period those toxins were "replaced" by other toxins made up of products of lipid peroxidation (malondialdehyde) which was counterintuitive at the time given the high level of glutathione other stuff that I had received, including certain oral supplements. The treatment overall did not make me better nor worse (except financially).
    It was only at the beginning of this year that my labs showed normalised levels of glutathione and the detox enzymes mentioned earlier which correlates with much improved health conditions. I attribute that to the antimicrobial therapy I had had in the previous couple of years as well as to a "hand made" cocktail of plant antioxidants which are supposed to increase endogenous production of glutathione and other detox enzymes. I simply copied from the ingredients of Protandim a herbal based supplement. As I live in the UK and the product here is not available and neither could I order it from the US, I made my own with a few variations. There is another product that it's supposed to enhance endogenous production of antioxidant enzymes made by Biotec Foods, I tried it but but could not tolerate it.

    I mentioned all of this because in my personal experience it's been more effective trying and raise endogenous glutathione than trying to supplement with it.
    For anybody interested, there are small scale studies related to both Protandim and Biotec and I think it's worthwhile taking a look at those.
    http://www.protandim.com/clinical-proof/
    http://biotecfoods.com/isosproutplex.htm

    All the best.

    PS: For anybody interested, my home-made antioxidant blend included: Ashwagandha 1 cap, Milk Thistle 1 cap, Cordyceps 1cap, Schisandra 1cap and 1 cap of a Turmeric complex. In addition I took 2 caps of Japanese Knotweed which is a major source of Resveratrol.
     
  11. Vegas

    Vegas Senior Member

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    I use the Extra Energy Enzymes product from Biotec, and have found it to be helpful. It supposedly has a substance that mimics GPx, and as you alluded to, substances that boost endogenous production of SOD and catalase. This is an affordable supplement and one worth considering. I see you are also taking Schisandra, which along with tea polyphenols (an ingredient in protandim) has recently been found to have some protective effects against mercury toxicity. If you still have a heavy metal burden, then these substances are probably providing further protection against free radical damage.
     
  12. alexa

    alexa

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    thank you all for such comprehensive answers!
    last couple of days i have added 3 sublinguals of 50 mh glutathione, i have been feeling spacey but i am not sure if this is tied to the medication.
    I am not sure that i am doing a proper methylation, i take one tablett of folapro, one tablett of actifolate, one 1 mg sublingual of b12 and 1 tablett of phop.serine complex.
    I have taken this for about 2-3 months, i just got my test results back and my b12 was fine ( even a little too high) does this mean that i am doing it right?
    my Vitamin D was low, which is strange since i have been taking a high dose of vitamin D for a year and a half and i just came back from a vacation in Malta, does this have anything to do with methylation?
     
  13. richvank

    richvank Senior Member

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    Hi, Alexa.

    If your B12 measurement was a conventional serum B12, having a high value really won't tell you whether you have a functional B12 deficiency or not. A urine MMA test as part of a urine organic acids panel such as the Genova Diagnostics MAP panel is better, especially if run together with an amino acids test. If you haven't noticed much from the standpoint of symptoms. you may need a higher B12 dosage.

    Have you been taking an oil-based vitamin D supplement, or a "dry" one? I think the oil-based supplements are better absorbed. How high a dosage of vitamin D are you taking?
    I don't know about Malta and methylation. I imagine that people methylate about as well in Malta as they do in Moldavia or Mozambique. But that may not be what you meant :D

    Best regards,

    Rich
     
  14. heapsreal

    heapsreal iherb 10% discount code OPA989,

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