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It's all in the Gut. Why we get ME/CFS

Discussion in 'The Gut: De Meirleir & Maes; H2S; Leaky Gut' started by redo, Mar 26, 2011.

  1. ggingues

    ggingues $10 gift code at iHerb GAS343 of $40

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    Not sure if i mentioned it in this thread before, but I think Low Dose Naltrexone (LDN) has helped my gut/digestion. Fewer loose stools, better digestion, therefore better health? I am feeling better than I ever have. Although I had a major flare 2 years ago, and changed a lot of things in my life!

    GG
     
  2. redo

    redo Senior Member

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    richvank. With all your knowledge of the methylation process, I'd appreciate it if you could share your thoughts of what's causing ME patients to have problems with methylation to begin with. If you're leaning towards viral mechanisms (like I am at the moment, as in the simplified sketch), microbes, autoimmunity or other things. I think genes play a role no matter what, but aren't alone enough to cause ME.
     
  3. richvank

    richvank Senior Member

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    Hi, redo.

    Here's the most recent relatively concise statement of my hypothesis:


    Statement of The Glutathione DepletionMethylation Cycle Block (GD-MCB) Model for ME/CFS

    1. There is a genetic predisposition toward developing ME/CFS, only part of which has been characterized.

    2. Some combination of a variety of stressors (physical, chemical, biological and/or psychological/emotional), the combination differing from one case to another, together with the genetic predisposition, lead to depletion of glutathione.

    3. The depletion of glutathione causes a functional deficiency of vitamin B12, so that both methylcobalamin and adenosylcobalamin become depleted.

    4. The depletion of methylcobalamin inhibits the activity of the enzyme methionine synthase in the methylation cycle.

    5. The partial block of the methylation cycle that results causes methylfolate to drain from the cells via the so-called methyl trap mechanism, eventually depleting the intracellular folates in general.

    6. The partial block of the methylation cycle also deranges the sulfur metabolism in general and stabilizes the depletion of glutathione by a vicious circle mechanism, making ME/CFS a chronic condition.

    7. The many abnormalities and symptoms of ME/CFS stem directly from this vicious circle mechanism.


    As you can see, step 2 includes quite a variety of things. It's based on the published risk studies and the questionnaire responses I have received from PWMEs over the past 15 years. I ask what preceded the onset, and specifically ask about a variety of possibilities. What I get is a wide range of responses, but they fall into the general category of "stressors," and I have been able to connect all of them to glutathione depletion, which ultimately leads to a partial methylation cycle block. The viruses, microbes and autoimmunity fit under my category of biological stressors.

    Best regards,

    Rich
     
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  4. redo

    redo Senior Member

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    Thank you for your perspective richvank. Appreciated.

    About methylation and syndromes, do you see FMS and CFS as two separate entities or overlapping syndromes which most likely are variations of the same things? Questions is really; do you think the same mechanisms are relevant for CFS related syndromes (FMS being one of many). I am not trying to be inquisitive, just wondering what your thoughts are.

    And, do you think once those stressors trigger methylation problems, that the patients will have those problems the remaining of their life?

    I have to add, I appreciate differences of opinion. I think conformity is a road block for moving forward...
     
  5. richvank

    richvank Senior Member

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    Hi, redo.

    I don't understand "pure" FM. I wish I did. It doesn't seem to have the same mechanism. For example, there doesn't seem to be oxidative stress, and the mitochondria don't seem to be dysfunctional, as evidenced by the exercise tolerance and even benefit in FM as opposed to ME/CFS.

    In our clinical study, most of the women satisfied the diagnostic criteria for both ME/CFS and FM, and two-thirds of them reported significant benefit from methylation treatment. So when the two are combined, it may be that the FM results from some aspect of the ME/CFS. But when it is "pure" FM, I don't know what the pathogenesis mechanism is. I hope to learn more about this, because it may affect more people than ME/CFS does, and as you know, there is no cure for it at present, either.

    Because there is a genetic predisposition to ME/CFS, I believe that a person will have the predisposition for their whole life. I believe that they can recover from a case of ME/CFS, and we have seen a small number of examples of people who appear to be fully recovered (able to work full-time, able to exercise, able to cope with significant stress, etc.), but I think that if their nutritional status for the important nutrients drops low enough and their stressors level gets high enough, they could develop another case of ME/CFS. I won't call it a relapse, because I truly believe that they recovered from it the first time.

    I appreciate differences of opinion, too. I have learned a great deal from them, and hope to learn a lot more. I've appreciated your focus on the gut. I think that some cases of ME/CFS do indeed start there, for example with poor diet or antibiotic treatment that kills off the beneficial bacteria and starts a chain of events that leads eventually to glutathione depletion and so on. And I also believe that once the gut is heavily involved, which occurs in most people with ME/CFS, however this disorder starts in them, it is necessary to treat the gut problems along with restoring the methylation cycle. Either one will drag the other down, so both need to be supported. The interactions between these two are manifold.

    Best regards,

    Rich
     
  6. markmc20001

    markmc20001 Guest

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    If one has a bacterial infection, what is the bet approach? What about antibiotic IV's to kill the infection, but protect gut health?
     
  7. richvank

    richvank Senior Member

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    Hi, markmc.

    What kind of bacterial infection? Do you mean bacterial dysbiosis in the gut, or intracellular bacterial infections such as chlamydia, mycoplasma or rickettsias, or something like Lyme disease and its coinfections, or a coagulase negative multiple antibiotic resistant staph infection in the sinuses, or what? All of these are found in various cases of ME/CFS.

    Rich
     
  8. markmc20001

    markmc20001 Guest

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    Hi Rich.

    I have chlamydia pneumonia and probably lyme disease. However, my gut has been messed up lately due to something. Maybe Hpylori, along with some high liver enzymes.

    It's really the gut issue I need to straighten out. I have high liver enzymes now too.

    Somehow the other day(when I asked that question) it seemed like maybe an IV would treat the Chlamydia and Lyme while leaving the Gut in better shape?

    Now I have this gut dysfunction, I've been having a tougher time cognitively. probably more than one thing going on right now with me.
     
  9. JPV

    JPV Senior Member

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    Gaia health - Gut Biota Never Recover from Antibiotic Use: Loss Extends to Future Generations by Heidi Stevenson

     
  10. drewmaster

    drewmaster

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    Hi Redo--

    I've been thinking about this, and was wondering, do you think the a fecal transplant procedure would be helpful, based upon this?

    Thanks,
    Drew
     
  11. mellster

    mellster Marco

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    Drew - I believe it def would help reducing bacteria overgrowth and gut permeability which is huge. I also do believe that most PWC's initially have the high cortisol response to this situation and the cortisol only depletes over time (adrenal fatigue).
     
  12. drewmaster

    drewmaster

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    Thanks Mellster, this is encouraging. Now I just wish I could find a clinic that would do the procedure. I've called several and they will not.

    Anyone know of anywhere in the United States that will do a fecal transplant?

    Drew
     
  13. redo

    redo Senior Member

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    Like I wrote earlier, the scheme is made just as much to sort my thoughts as it is to use for others. But nevertheless I post it, as I appreceite comments (both pro and con).

    Having got more data, I have made some changes. Especially how the fatigue almost vanished in this study http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2711959/ has got me thinking that the methylation problems are most likely a result of autoimmunity (rather than something which comes direct from a pathogen). I am not sure where to place mitochondrial problems, whether it fits best as a result of methylation problems (if someone knows if that's possible, please weigh in) or as a consequence of the immune system acting out.

    I also appreciated Richvank's video lecture on methylation, and I really think it's absolutely central to especially the fatigue symptom.

    So here's the 2.0 version of the hypothesis as to why we've got the symptoms we've got.

    [​IMG]

    Edting of the post, 14. October (adding the text below)

    How does this fit with how patients respond to treatments and stressors
    Rituximab. The treatment stops the immune system from having the detrimental effects on the patient. It's also possible that the reason the patients feel better is that it has a clearing effect on a virus, although I find that less likely at the time being.

    Antibiotics. They might also work against pathogens which are active because the immune system is having a hard time due to the retrovirus. Antibiotics may have strong immunemodulating effects and can make symptoms better that way. They can also actually have beneficial effects on the gut (if there's a pathogenic overgrowth of harmful bacteria -- of course they may have the opposite effect as well).

    Antiretrovirals. Some patients get worse. Some on this forum as well. For others it's rollercoaster ride (worse/better). As for why they get worse, it could be something similar which happens in the studies where they give ARVs to mice with MLVs (the virus gets "whipped up" and the autoimmunity exacerbates). We don't know which retrovirus we're dealing with, so it wouldn't surprise me if such mechanisms where present. Others may improve.

    Antivirals. Montoya had a study where concluded that it might be immune modulating effects which made the patients better of Valcyte. Otherwise the immune problems which causes persistence of other infections (illustrated in the immune box above) could be a reason why various antivirals work. Such as Valtrex, Valcyte and more.

    Imunovir. It might work because it has a slight effect on the virus behind the whole shebang. It might work because it has an effect on (other) viruses which are activated because of the compromised state the immune system is in, it might work because of immune modulating effects making the patient better (just because the autoimmunity gets less exacerbated).

    Mentally demanding tasks. Psychological stress or mentally demanding tasks. Stress in the psychological sense is known to make the ME symptoms more severe, at least for a short period of time. The reason for this seems to me that the stress makes the immune system function a lot worse for a period of time. It also sends more sensory signals to the brain, and with problems handling it as it is, it makes it a lot worse when this happens. I think this also has a strong connection to the gut sketch above. If there are a pathogenic mix/load of bacteria there, it can change the person. Breakdown of dopamine and noradrenalin can take a whole lot longer time. The result? Dopamine and noradrenalin builds up to way to high levels in the body (much the same as what happens when we CFS patients concentrate on a demanding subject for a period of time). It can take days or more for the ME patient to clear out the large amounts of dopamine and noradrenaline which healthy people clears out in a glimpse.

    Exercise. The vast majority of ME patients experience a symptom worsening after exercise. Not only do they get more problems with the fatigue symptom. Most symptoms get worse. This fits very well with the immune modulating effects exercise does have on ME patients, which it does not have on healthy controls. http://www.ncbi.nlm.nih.gov/pubmed/20230500 It may be the cytokines mentioned there, but it may very well be other (not yet discovered) immune abnormalities which gets exaggerated when PWME exercise.

    Other treatments?? Other stressors. Please come with suggestions as to why something fits or doesn't fit into the sketch above. If something doesn't fit, it's valuable to know! :)
     
  14. madietodd

    madietodd Senior Member

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    So Redo, where can I buy the poster? My doctor needs this (he just doesn't know it yet).

    Madie
     
  15. mellster

    mellster Marco

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    Agree I need to order this - this is IMO the best explanation for the pathway to mitochondrial dysfunction and methylation issues as well as Th1/Th2 shift. We need that as a poster ;)
     
  16. Enid

    Enid Senior Member

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    Thanks redo - very exciting work here.
     
  17. redo

    redo Senior Member

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    I am glad you liked that I posted it. As I wrote earlier, the reason I am making them is sorting my thoughts (and not presenting fact :). So I am more than willing to adjust accordingly if I change my mind, and I am not embarrassed to do so. Actually I appreciate input telling me I this or that is wrong or correct because of this and that. Here's my sketch as for the triggering.

    It's enough that the trigger is there for a short period of time. After the trigger has triggered the pathogen, it can go away, and the patient is still sick...

    I could add hormonal changes to triggers. Some gets sick in adolescence without any specific even prior to it. In these cases I suspect the patients gets a gradual onset instead of a abrupt onset. Sometimes the patient could also get a gradual onset if the virus doesn't activate as quickly as it does with others.


    [​IMG]


    It's only working model I've got as to why such totally different things such as a vaccine, an EBV infection or a giardia infection can trigger the same bucket of symptoms (ME/CFS)... I am thinking that the only common nominator between those vastly different things is that they challenge and stress the immune system for a short period of time, and in that time frame, a previously (specific) latent infection (which CFS patients share) becomes active. Now I am leaning towards that previously latent infection being a retrovirus. But I am open to other views, it might be a bacteriological infection which lies latent instead, although I find that less likely at the time being.
     
  18. redo

    redo Senior Member

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    The way the disease often begins can have some resemblance to how HIV infections begin:

    Different phases. At first patients often have a period with swollen lymph nodes, and general malaise, flu like feeling. And often the predominant symptoms later are the extreme brain fog, exhaustion, coordinating problems, plus flu like feeling et cetera. It's not a parallel to HIV, but there are some similarities. Some weeks, up to a half year or so, the first phase of the disease is there, and later on other symptoms become the main problems.

    [​IMG]
     
  19. redo

    redo Senior Member

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    As for the symptom of intolerance of chemicals. I'll try and fit that in later. I'll see where I think it goes best, and change accordingly if it doesn't fit. I am updating the post above instead of making a new one. As for the gender discrepancies. I'll fit that in later. I wrote some about that in another thread.
     
  20. heapsreal

    heapsreal iherb 10% discount code OPA989,

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