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!
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
