Glutathione & Precursors - Detox or Induced Methylb12 and Methylfolate Deficiencies?

Hi Ross,

The "leaky gut" symptoms appear to be caused by tissue breakdown and malfunction caused by prolonged methylb12 and/or methylfolate deficiency.

Hi, Athene.

What form of B12 did you use, and was this form recommended by Dr. de Meirleir?

Thanks.

Rich

Hi Rich,

I am using hydroxocobalamin. This is what KDM prescribed. He recommended the specific brand indirectly (by pointing me toward a specific pharmacy).

I have used another brand of injectable hydroxoB12 when I ran out, same dose, but with a MASSIVE difference in effect. One brand left me with headache by 4pm every day but the one KDM endorsed keeps me headache free. So I think maybe this backs up Freddd's conclusion with the tablets, that B12 comes in variable qualities.

KDM prescribed Methyl B12 for my son, BTW. I assume he has concluded I don't have genetic methylation problems as I was fine till the age of 16, but my son has been ill since a baby so could have problems converting it. That's only my assumption.

And this is all the more reason to proceed with treating the methylation block...thanks Freddd

Hi Athene,

Very interesting on having differences you could experience between 2 different batches of injectable hyb12.

I would expect that you would find even more difference with methylb12. And don't forget the adenosylb12. People can have four different deficiencies all at the same time; CSF/CNS adb12, CSF/CNS mb12, body adb12 and body mb12. Treating one of them can leave 3 untouched. The usual treatments leave at least 2 untouched.

Three strong drugs failed to control my precancerous bile reflux and the awful gastritis it caused. L-glutamine fixed it in 24 hours and has kept it away ever since. I was very close to having Barrett's esophagus and already have a precancer in my stomach.

I had been taking the B12 lozenges daily, and all that other stuff for 3 months already, when I started the L-glutamine. I have no symptoms from taking L-glutamine. I take 7 grams in water at 2 am daily. Without it, my needed 2 am meds make my stomach hurt immediately.

There is no way I am stopping the L-glutamine until I see that I can go without it without suffering that horrible pain and lack of sleep from bile reflux starting at or before 5 am every morning. This problem was non-existent before I had my gallbladder removed in 2007, so I do not blame it on lack of B12 since I've had this disease since 1986 and did not have this problem at all before the gallbladder was taken out.

So far, I have noticed that Methyl B12 seems to help me the most by far over the Adenosyl B12. I am alternating days, which is how I can tell. I had been taking oral methyl B12 for about 15 years before this, at doses about 33,000 times the RDA,in a multi that had TMG, high dose L-carnitine, etc. in it, so I was getting a little, even before the high dose lozenges.

klutzo

Hi Klutzo,

I have no idea what effect if any glutamine may have. I took it with NAC with which it becomes glutathione generating, very effectively so judging by the results.

So far, I have noticed that Methyl B12 seems to help me the most by far over the Adenosyl B12. I am alternating days, which is how I can tell.

Adenosylb12 has very little if any repeat startupup because the level in the mitochondria is maintained easily. I have to go 2-3 weeks without before I can feel it at all. If you are feeling the effects of methylb12 each day my suggestion is take it very day and increase the dose until it no longer makes any noticable difference as long as you keep taking it.

Glutathione Information on Facebook

Hi Guys,

Don't know if this has been posted before - I came across it at a friend's posting on FB and thought it was interesting.

http://www.facebook.com/#!/video/video.php?v=281022985752&ref=nf

Take care,

HW

Question to all... Has anyone tried the Max GLX product? I am a patient of Klimas and she actually recommended this gluatathione precursor along with a B1/B6/B12 sublingual. She said some people are having excellent results with this. Rich, any thoughts?

Hi, goldiland.

I'm familiar with this product, and I think it will help to boost glutathione in many people. However, in CFS, I think it will be a temporary boost, in that if the person stops taking the product, the glutathione level will drop back down again. I've found that it's necessary to lift the partial methylation cycle block, which lies upstream of glutathione synthesis in the methylation cycle, in order to be able to restore glutathione on a more permanent basis. You can find the protocol I've suggested at www.cfsresearch.org by clicking on CFS/M.E. and then on my name.

Thanks for letting us know that Dr. Klimas is recommending something related to glutathione. I first tried to get her interested in glutathione when I met her at the CFS State of the Science conference in October, 2000, and I tried again at several subsequent CFS conferences. I don't think she took me seriously, and I made myself obnoxious in my efforts to get the message across to her, for which I later apologized to her and her group. I'm glad to hear that she now appears to be thinking seriously about glutathione. Since January, 2007, I have tried to interest her in treating to lift the methylation cycle block, which I have found to be necessary to lift glutathione on a permanent basis in CFS. So far, I don't think she is taking that seriously, though I have sent her many reports of benefit from people who have tried it. I've heard that she has been recommending B vitamins lately, including B12 and sometimes including folic acid, but as far as I know, she hasn't been recommending the reduced forms of folate (folinic or 5-methyl tetrahydrofolate, aka Metafolin or FolaPro). I really wish she would try combining a high dosage of sublingual hydroxocobalamin B12 with these forms of folate, as in the protocol mentioned above, because I think that she would then see for herself what this combination will do. If she ever takes hold of this, I think she will be very pleased with the results, as will her patients.

Thanks again for the information, and I wish you the best.

Rich

[QUOTE

Thanks for letting us know that Dr. Klimas is recommending something related to glutathione. I first tried to get her interested in glutathione when I met her at the CFS State of the Science conference in October, 2000, and I tried again at several subsequent CFS conferences. I don't think she took me seriously, and I made myself obnoxious in my efforts to get the message across to her, for which I later apologized to her and her group. I'm glad to hear that she now appears to be thinking seriously about glutathione. Since January, 2007, I have tried to interest her in treating to lift the methylation cycle block, which I have found to be necessary to lift glutathione on a permanent basis in CFS. So far, I don't think she is taking that seriously, though I have sent her many reports of benefit from people who have tried it. I've heard that she has been recommending B vitamins lately, including B12 and sometimes including folic acid, but as far as I know, she hasn't been recommending the reduced forms of folate (folinic or 5-methyl tetrahydrofolate, aka Metafolin or FolaPro). I really wish she would try combining a high dosage of sublingual hydroxocobalamin B12 with these forms of folate, as in the protocol mentioned above, because I think that she would then see for herself what this combination will do. If she ever takes hold of this, I think she will be very pleased with the results, as will her patients.

Thanks again for the information, and I wish you the best.

Rich[/QUOTE]

Hi, goldiland.

I just wrote to Dr. Klimas again this morning to encourage her to try lifting the partial methylation cycle block in her patients. I'm really happy to hear that it seems that she is moving in that direction.

Best regards and thanks again,

Rich

Hi Goldiland,

Yes, I tried it. I often try several forms of things to see comparitive effects. MaxGLX was what I started with. It worked nearly immediately. Within several hours the symptoms had started that grew rapidely to full fledged folate and b12 deficiencies with body wide inflammation. Even after stopping the precursors it took large doses of Metafolin, mb12 and adb12 to get the induced deficiecincies under control. Now, a year later, I appear to have fully recovered rom the damage it did but I still need much higher doses of Metafolin than I did prior to trying it. Those who end up with "glutathione detox reaction" will be pleased to know that the glutathione "detox" reaction can be ended in several days with high dose Metafolin and high dose active b12s as the symptoms of glutathione "detox" reaction are identical with the deficiency symptoms of those 3 vitamins and are quickly relieved by them.

I need to chime in and say like so many others, the first paragraph went ok and then I was LOST. Info overload. I can't take glutathione. It makes me so sick. I had the $450 test by Genovations I think it was to analyze my liver. I have a genetic marker or DNA marker making it extremely hard to detox. My doctor spent an hour on the phone with the company and he said, "there really isn't much that can be done." GREAT. I just had an IV of EDTA on Thursday. Spent 4 days in bed. Went today and had a Myer's push thinking the minerals might help. I am ready for bed. I feel like so much of the problem is detoxing. But what do you do? Some are just not as lucky at being able to do so.

Thanks for info Fredd and Rich.

Rich, I have asked Klimas multiple times about methylation pathway research and there is no question that she believes that CFS patients have blocked detoxification pathways. But as you know, there are often multiple ways to skin a cat and her primary way is to improve overall cellular function and shift immune system from overdrive TH2 to more balanced response. For improved mitochondiral function, she instructed me to start taking daily 200-300 mg of CoQ10 for a month (I currently take 100 mg) and then start the Max GL. I have asked her about whether the glutathione precursor may cause detox side-effects and she didn't at all seem concerned. I am concerned about it regardless (and more so reading what Fredd has to say) so I'd be interested in what combination of supplements are needed to prevent severe detox reaction. I'll check out the post/info you referenced and if you have any other advice, would appreciate. I have made a lot of progress in recovering over past 1 1/2 years after bad relapse, have gotten to maybe 80% and am kind of stuck at this point. Haven't been stuck in bed though for a long time and would like to keep it that way!

Also, I understand the hypothesis that our NK cells are low in perforin and are basically shooting blanks at invaders. Have you found that lifting methylation block ultimately increases NK activity?


Regards,
Gregg

Hi, Gregg.

I'm glad to hear about the progress you've made. That's great!

I'm also happy to hear that you have raised the methylation issue with Dr. Klimas. She has certainly heard about it many times from me, too.

I believe that the glutathione depletion and methylation cycle block explain why the immune response is shifted to Th2 in CFS, and I explained that in my January 2007 poster paper, of which I gave a copy to Dr. Klimas. It can be found on the cfsresearch.org website. The reasons are that glutathione is particularly needed for the Th1 response, and a functioning folate system is needed to produce new DNA and RNA to support the proliferation of T cells. Both of these have problems because of the methylation cycle block. Co Q-10 is depleted because methylation is required for its synthesis. The same is true of carnitine, also found to be low in CFS. Supplementing Co Q-10 and carnitine can help the mitochondria a little, but it doesn't get at the fundamental issue. The basic cause of mito dysfunction in CFS is glutathione depletion, in my opinion. If you look at all the problems Dr. Howard at Acumen Lab finds in the mitochondria, they can all be traced back to low glutathione, initially. The methylation cycle block does lower the availability of Co-Q10 and carnitine, and those do contribute, but the main problem is low glutathione, and that won't be fixed until the partial methylation cycle block is lifted.

In my opinion, freddd's own deleterious response to building glutathione was due to his particular mutation in the intracellular B12 processing enzymes. Once glutathionylcobalamin formed, I don't think his cells were able to convert it to the coenzyme forms of B12. I don't think this problem is very common in PWCs. Many, and probably most, find that building glutathione by direct means actually helps them to feel better, though some do not tolerate it well. Nevertheless, in late 2004 I shifted my treatment recommendations from direct efforts to build glutathione to efforts to lift the partial methylation cycle block, which is what is hindering glutathione from staying at normal levels. Just boosting glutathione directly or with its precursors can help temporarily, but if one stops, the glutathione level drops back down again, because the basic problem is upstream in the sulfur metabolism at the methylation cycle.

It's true that Kevin Maher, who used to be in Dr. Klimas's group, discovered that the NK cells have low perforin levels in CFS. My hypothesis for that is that low glutathione in the NK cells lowers the production of perforin. Perforin normally has quite a few disulfide bonds in its structure, and secretory proteins that have disulfide bonds are particularly sensitive to glutathione depletion in the cells that make them. Glutathione is necessary to keep the cysteine residues in the protein chain chemically reduced until the proper partners can be joined togehter in the endoplasmic reticulum. If the molecules are not properly made, they are recycled through the proteosomes, and the output of good molecules goes down. So far, this is a hypothesis, and the measurements have not been made to see whether the perforin production goes up after the glutathione levels have been restored. I think that would be a very good thing to measure, and Dr. Klimas's group would probably be one of the best groups to do it, if they ever become interested enough and can get the necessary funding. I think they would have to bring someone in who is familiar with basic biochemistry, though, rather than immunology, to collaborate with the people who are there.

Best regards,

Rich

I hust wanted to say that I have been taking all the first list and second list of supplements recommended by Freddd to get methylation going, and getting really fantastic results. I wanted to see if I could do anything else to improve further, so I decided to bite the bullet and take glutathione. I figured you don't know unless you try it and see.
The effect was fabulous. I feel far better, clearer headed and more energetic. The effect was overnight.
So I just wanted to say, in my totally unscientific way, that I honestly think it is worth it for anyone to try. I know it makes many people feel worse but if it makes you feel better, it is fabulous.

Hi Athene,

As I mentioned somewhere back in the posts that it may be dose related or other factors that affect the response. Also, for some people the "glutathione detox reaction" developed only over time rather than right away. That too might indicate dose related as on a relatively low dose it might take months for the level to build up until it is troublesome. My best advice is if certain types of symptoms start up that you hadn't had in a while or ever, that fit the descriptions given, is that you be aware of the possiblity of a problem. Many who have your initial experience also have it change further down the road. Good luck.

I didn't know it could take a long time to build up like that. Thanks for the warning Freddd... always there to guide and help!

bad reax to nebulised glut.....maybe I overdid it?

nebulised 2 theramood glutathione capsules the other day. felt like hell for the following 3 days. I assume I took too much and my body went into viral killing mode but I just don't know....

Athene,
What brand of glutathione are you taking? I would like to give it a try.