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Slides available from richvank's talk on the Yasko protocol applied to CFS

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by richvank, Sep 9, 2010.

  1. richvank

    richvank Senior Member

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  2. George

    George waitin' fer rabbits

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    Nice presentation. I'm going to have to read it about 2 more times to really get it but it's very well laid out.

    Thanks tons for link, this is really nice Rich.
  3. richvank

    richvank Senior Member

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    Thanks, George. Yeah, it's quite a mouthful, isn't it?

    They gave me an hour, and I filled it, and then some!

    Rich
  4. MDL

    MDL

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    Rich,
    What is the role of hydrogen sulfide in the transsulfuration pathway?
    Do you believe that it plays a role in CFS?
    Were you part of the group credited in your report who became very excited about my hypothesis paper?
    Why has hydrogen sulfide disappeared from your slides?

    I look forward to your reply.
    Marian Lemle
  5. aquariusgirl

    aquariusgirl Senior Member

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    Marian

    Thank you for your work on hydrogen sulfide. Are there treatments or precautions one can take if one tests positive with De Meirleir's test for hydrogen sulfide?

    Rich: sorry for hijacking your thread. As you know I have come a long way by working on my methylation cycle thanks to your work and that of amy yasko.
  6. jenbooks

    jenbooks Guest

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    The slides look very interesting.
    I also appreciate posts you put up from the XMRV conference.
    I just want to note, and this is only obliquely related, that when I get IV glutathione, I have a much better response to Wellness than to many other types. They have a patented method to stabilize it. I can feel a gladness in my whole body, an increase in energy and overall wellness, and a boost in both mood and calm.

    In the state we're in at the moment, the doctor I'm seeing was using a local glutathione and it seemed no better than water to me. I finally convinced him to let me use Wellness. It's a remarkable difference.

    I do best when I get about 1200 mg weekly. More often and I sometimes feel almost too energized. Less often and I have more fatigue.

    It really amazes me how much it helps me (temporarily). I suppose I could lift my methylation with precursors (oral) and perhaps not need it, but since it works for me and feels safe, I've continued. I do have the Liv-On labs oral liposomal glutathione here, which I mean to try.

    It isn't for everyone though. A lyme friend of mine who does well on abx and antivirals that I can't tolerate, gets sick with IV or oral liposomal glutathione.
  7. MDL

    MDL

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    Hi aquariusgirl,
    Yes, I agree that we should not hijack Rich's thread.

    The answer to your question about treatments and precautions is complicated and could probably fill a book. I'd be happy to send you a private message, but please bear in mind that I am not a doctor.
  8. richvank

    richvank Senior Member

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    Why has hydrogen sulfide disappeared from your slides?



    Hi, Marian.

    It's good to see you here!

    Yes, I still do believe that hydrogen sulfide plays a role in at least quite a few cases of CFS.

    At this point, Kenny and his group probably have quite a bit of data from their urine test, but I don't know how it has been running. A few people have posted their results here in a poll:

    http://www.forums.aboutmecfs.org/poll.php?do=showresults&pollid=4

    As you can see, most were positive for hydrogen sulfide. Because they were self-selected, we can't say what the actual percentage of positive cases is among the entire CFS population, but it does seem to be a significant fraction.

    I think Kenny is planning to publish about this, so I don't want to steal his thunder, but I think he has some good evidence for the importance of gut bacteria-generated H2S in at least a significant fraction of cases. I'd better not say more than that, but maybe you have communicated with him about his results.

    As you know, there are two potential sources of excess H2S in the body: the human metabolism and the metabolism of bacteria in the gut. Amy Yasko has suggested that, especially in people who have upregulating polymorphisms in the CBS enzyme, hydrogen sulfide can be produced by the enzyme homocysteine desulfhydrase. She has quoted Devlin's biochemistry text, which says, "When the need is for energy, and not for cysteine, homocysteine is metabolized by homocysteine desulfhydrase to alpha-ketobutyrate [though Amy has actually misquoted this as alpha-ketoglutarate], NH3, and H2S."

    This enzyme apparently is not present in humans, but as you know, both CBS and CTH (aka CGL) are capable of producing H2S under appropriate circumstances. In an earlier statement of the mechanism for what I've called the "Glutathione Depletion--Methylation Cycle Block" hypothesis, I suggested that because of the oxidative stress that is well-established to be present in CFS, cysteine will tend to oxidize to form cystine. Then, based on research in mice, I suggested that CTH will decompose cystine and introduce a pathway in which H2S is produced. You can see a slide showing this in my OHM talk in 2008 (at www.cfsresearch.org). I also included this in my poster paper at the 2009 IACFS/ME conference, where I had the pleasure of meeting you!

    Among others, after the conference I sent this paper to Ruma Banerjee, who is perhaps the foremost researcher on this part of the metabolism. She wrote back to me that this reaction does not occur in humans, based on her research. Accordingly, I took this part out of my hypothesis for the talk I gave in July, 2010 at the Yasko Protocol Conference.

    At this point, I still think there must be a reaction that diverts some sulfur to form H2S, at least in some of the CFS patients. Perhaps the reaction I suggested actually does occur in humans under conditions of oxidative stress, while it doesn't occur under normal conditions. Or perhaps CBS or CTH uses a different substrate, such as homocysteine or cysteine. Ruma and her group have published a couple of papers recently discussing the various reactions that could be involved. The problem for me is that I'm not sure if the favored reactions would be different under conditions of oxidative stress. Tapan Audhya told me that he has found elevated thiosulfate in the urine in autism and CFS patients, and that could be produced in the reaction I suggested originally, together with H2S. So I think there is more that needs to be nailed down here, but in view of what Ruma wrote to me, I thought it best to pull that part out for now. This, however, is a working hypothesis, not an established theory, and if I get more evidence supporting this reaction or another that will produce H2S, I will put it back in!

    As I think you know, Kenny believes that the H2S elevation he sees in his urine test is coming from gut bacteria. I think he bases this on the observation that when he is able to correct the dysbiosis, the H2S level in the urine drops down. As I wrote above, I think he plans to publish on this.

    I started looking into the literature on production of H2S by gut bacteria, but then got waylaid by the retroviral developments, which have been pretty exciting lately. I hope to get back to that when I can. But I did manage to find out that there are two categories of bacteria that can be in the gut and can produce H2S. The first is the sulfate-reducing bacteria, which use sulfate as their terminal electron acceptor, reducing it to H2S. The second is the bacteria that are able to metabolize sulfur-containing amino acids, such as cysteine. If I understood correctly, this second group is usually the main H2S producing group under normal conditions. However, as we know, the gut is not operating normally in CFS, so I think it's possible that the SRBs could be the main producers in CFS. I just don't know. Maybe Kenny does.

    Well anyway, I haven't finished trying to understand the role of H2S in CFS, and I would like to get a better grip on it. I do believe it is important, but I don't know the relative importance of the human and bacterial metabolisms in producing H2S, and for the bacteria, I don't know which category is the main producer in CFS. For the human metabolism, I also don't know which reaction is dominant. So as you can see, there is a whole lot that I don't know! I still do believe that H2S plays an important role in at least a significant fraction of the PWCs, and I still believe that you did a great job. Hopefully I will get time to study all of this some more, and hopefully also, Kenny will shed some light on what he has been finding.

    If you have some more insight into these issues, I would love to read it. And don't worry about hijacking my thread. If the moderators don't object to discussing these things here, I certainly don't!

    Best regards,

    Rich
  9. MDL

    MDL

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    Hi Rich,

    Thank you for your thoughtful reply. I wish I had your facility with words, although at this point I would settle for just finishing this post without losing it.
    I have only read the abstract of Ruma Banerjee's Redox Biochemistry of Hydrogen Sulfide, but apparently she too thinks that H2S might be the evolutionary matriarch of the family of gasotransmitters. These are early days...but I think this field is going to produce some important insights! Yes, H2S is complex because it is so pervasive and fundamental, yet in some ways, the lesson may turn out to be rather simple. In any case, there is something new to learn every day.
    Regarding your study, a few questions: CBS was mentioned, but did you look for it? Your improvement rate is very impressive, and you should be congratulated. I am always curious about the outliers, though, because they can hold a key to a greater understanding. Do you have any thoughts on why the protocol works in some and not in others? Also, what happens when the protocol is stopped? Does improvement continue?
    Thanks so much-
    Marian
  10. richvank

    richvank Senior Member

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    Hi, Marian.

    I think you have a great facility with words!

    If you mean did we characterize the CBS polymorphisms in the patients in our clinical study, yes, we did characterize one of them: The CBS C699T polymorphism. And we found that it does make a difference in terms of how much the metabolites are drained from the methylation cycle, as you can see in our 2009 poster paper at www.cfsresearch.org However, we did not measure H2S, so we don't have evidence as to whether the presence of this polymorphism causes more H2S to be produced. We had only so much money, so we had to limit the lab tests, which were the most expensive part.

    We were pretty happy about the improvement the patients experienced, too. Of course, I wouldn't have complained if they all had recovered completely! :)-)

    Yes, I do have some thoughts about why some did not seem to benefit from the treatment. I've posted about this somewhere on this forum before, but I'll try to remember what I wrote. Some are low in amino acids, particularly methionine, but other important ones are serine, cysteine, glutamate (or glutamine) and glycine. These are needed to feed this part of the metabolism. Some are low in vitamin and mineral cofactors for the enzymes in this part of the metabolism, including B vitamins, zinc, selenium, manganese, magnesium and copper. Some have high body burdens of toxic heavy metals, particularly mercury, and it can block several of the enzymes in this part of the metabolism. Some have ongoing conditions that continue to place heavy demands on glutathione, so that it is difficult to raise its level. These include mold illness and Lyme disease and its coinfections. Some have heavy viral loads that deplete glutathione. Perhaps the newly discovered retroviruses are involved here, too.

    I don't know what happens when the protocol is stopped. We did not continue to follow the women in the study, because Dr. Nathan moved his practice from Missouri to California after the completion of the study. I suspect that some of the women continued with the supplements on their own, hoping to get more improvement. Of the people in the internet groups, I think most have continued to take the supplements, or at least part of them. I have suggested to people that it might be a good idea to take maintenance doses of some of the supplements, such as B12, FolaPro, and N-acetylcysteine after they recover (if they do!) in order to prevent relapses. But we don't have controlled study of these things. There was only so much we could do with the financial support we had. I was mainly hoping to test the hypothesis, and I think we were able to do that, at least to some extent. The results seem to me to be consistent with the hypothesis, though I can't say that this small study without a control group proved the hypothesis.

    At this point I'm pretty sure that glutathione depletion and partial methylation cycle block are important parts of the pathogenesis of most cases of CFS, but they are not the whole story. I'm very interested to see how this will mesh with the retroviruses. There is a big "chicken and egg" question which is not yet resolved. Methylation is known to be able to silence genes, so healthy methylation may put the retroviruses into latency. On the other hand, the viruses might act to deplete glutathione. So it will be interesting to see how these things fit together. If they are both significant parts of the pathogenesis, they have to fit together somehow. And the gut bugs play an important role, too, perhaps to a large degree by generating H2S. Kenny has emphasized the importance of the D-lactate produced by the dysbiotic gut bugs, too. It's a complex problem.

    Best regards,

    Rich
  11. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    hi Rich,

    nk cell dysfunction is a common immune abnormality in cfs, do u have evidence that the methylation cycle treatment increases nk cell function in cfs patients ?

    cheers!!!!
  12. richvank

    richvank Senior Member

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    Hi, heapsreal.

    I don't have direct evidence of this. I would love to see lab test results on NK cell activity before and after several months of methylation cycle treatment in a person who started out with a lab-verified partial methylation cycle block. As you know, lab tests have to be paid for. Very few people who have ME/CFS will go back and repeat lab tests after they are feeling better. Only scientists do this, and somebody has to pay for it! :)-)

    Best regards,

    Rich
  13. MDL

    MDL

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    Rich,
    Complex indeed! What is needed here is a mutifactorial analysis to ferret out relative importance. One thing jumped out at me, though. Do you know whether viruses might act to deplete glutathione? If so, I would think that could be very important.
    All best,
    Marian
  14. richvank

    richvank Senior Member

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    Hi, Marian.

    It's known that glutathione is depleted in AIDS. Whether the retroviruses that have been reported to be associated with CFS will cause glutathione depletion, I don't know yet.

    Best regards,

    Rich
  15. kurt

    kurt Senior Member

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    There is evidence for this in a non-CFS study, an old study that showed improved NK function on B12 therapy. Another forum member, Megan, brought this to my attention, a fascinating study:

    Perhaps the effect these researcher measured is in part responsible for improvements of CFS patients, with B12 helping our NK cells...
  16. ukme

    ukme Senior Member

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    Very interesting, thanks for posting.
    However I think Rich you have since replaced Intrinsi with actifolate?
  17. richvank

    richvank Senior Member

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    Hi, Kurt.

    Thanks for this abstract. I will try to track down the complete paper. I'm guessing that the role of B12 here was to improve the function of the methylation cycle, which in turn should help the entire sulfur metabolism, including the synthesis of glutathione. If so, this would support the hypothesis I've suggested for the low NK cell activity. On the other hand, something else could be going on! :)-)

    Best regards,

    Rich
  18. richvank

    richvank Senior Member

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    Hi, ukme.

    That's correct. Metagenics changed the formulation of Intrinsi, eliminating the folinic acid, and I think it's important to have that, in order to support synthesis of DNA and RNA until the methylation cycle gets going better.

    Best regards,

    Rich
  19. kurt

    kurt Senior Member

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    oops, I did not put the full URL in my post, that has been corrected. So you can now click on the link in post #15 for the full paper.
  20. Joopiter76

    Joopiter76 Senior Member

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    I can confirm the importance of folinic acid, as folic acid in doses above 1mg makes me very tired and worse, but just little amounts of folinic acid gave me much more energy, in both cases my lymph nodes get swollen within ours which lasts about 12h especially over night. So to ad pure folinic acid the tablets of megafolinic can be easily cut in pieces.

    what I ask regarding the cytotoxic activity of the NKs or the CD8s is if NADPH may play a role as glucose 6 phosphate dehydrogenase deficiency which leeds to low NADPH and so to reduced GSH as NADPH is used to regenerate GSSG. NADPH is also needed for the oxitative burst. But as I know G6PDH deficiency is inborn and not acquired. NADPH plays an imprtant role in almost every rodox reaction including the methylation cycle. I found NADPH on the graph from Dr. Amys site: http://www.knowyourgenetics.com/The Methylation Pathway_files/diagram-1.jpg (on the right bottom site) But I dont understand in what way NADPH is lowered by a sulfite/sulfate problem?? I guess Rich knows.......

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