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List of ME/CFS abnormalities explainable by the GD-MCB hypothesis

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by richvank, Aug 17, 2011.

  1. richvank

    richvank Senior Member

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    Here is my current list of the abnormalities found in ME/CFS that I believe can be explained by the Glutathione Depletion--Methylation Cycle Block hypothesis:

    1. Glutathione depletion
    2. Oxidative stress
    3. Alcohol intolerance
    4. Buildup of toxins
    5. Multiple chemical sensitivities
    6. Shift to Th2 immune response
    7. Failure of T lymphocytes to proliferate when stimulated by mitogens
    8. Persistence of RNase-L activation and cleavage to form LMW RNase-L
    9. Reactivation of viral and intracellular bacterial infections
    10. Accumulation of infections over time
    11. Lymphadenopathy
    12. Low or dysregulated secretion of some peptide hormones.
    13. Misfolding of proteins
    14. Disruption of the sleep-wake cycle
    15. Deficiency of perforin secretion
    16. Depletion of intracellular magnesium
    17. Muscle twitching
    18. Mitral valve prolapse
    19. Blunting of the HPA axis
    20. Sensitivity to stress
    21. Panic attacks
    22. Hypoglycemia
    23. Low blood pressure
    24. Low secretory IgA
    25. Mitochondrial dysfunction
    26. Low VO2 max
    27. Hypocapnia
    28. Low peripheral body temperature
    29. Fatigue and post-exertional exhaustion
    30. Weight gain and weight loss
    31. Low serum amino acids levels
    32. Shortness of breath
    33. Weakness
    34. Elevated methylmalonate
    35. Elevated homocysteine
    36. Parasthesia, neuropathy
    37. Elevated formiminoglutamate
    38. Low WBC
    39. Low RBC
    40. Elevated MCV and MCH
    41. Deficits in synthesis of creatine, choline, carnitine, coenzyme Q10 and melatonin
    42. Rise in histamine
    43. Neurotransmitter abnormalities
    44. Emotional lability
    45. Excitotoxicity (anxiety, nervousness, insomnia, sensory sensitization)
    46. Myelin disrepair
    47. Slow mental processing speed
    48. Electromagnetic hypersensitivity
    49. Diastolic dysfunction and low cardiac output
    50. Diabetes insipidus (polyuria, constant thirst)
    51. Low total blood volume
    52. Orthostatic hypotension and POTS
    53. Loss of temperature regulation
    54. Low stomach acid production
    55. Slow gastric emptying and GERD
    56. Bacterial dysbiosis, yeast infections
    57. Irritable bowel syndrome (bloating, abdominal pain, diarrhea, constipation)
    58. Leaky gut syndrome
    59. Food sensitivities
    60. Hashimotos thyroiditis


    Best regards,

    Rich
     
  2. Enid

    Enid Senior Member

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    Thanks Rich for this and all your work in understanding and aiding us here.
     
  3. fla

    fla Senior Member

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    That's quite a list. Are there any symptoms which are not yet explained by the GD-MCB hypothesis?
     
  4. Sasha

    Sasha Fine, thank you

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    That's some list, rich! More than one for every week of the year. What a menu of horrible symptoms our bodies are choosing from. Very interesting that your hypothesis covers them.
     
  5. richvank

    richvank Senior Member

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    Hi, fla.

    Pain is one I haven't figured out a good mechanism for, but the people in the clinical study of the methylation treatment reported a significant decrease in pain, so it must be connected as well. Perhaps the threshold of pain is lowered when the mitochondria of the pain sensing cells or others in their neuronal pathways become dysfunctional due to glutathione depletion.

    One can always come up with hypotheses, but I try to make sure there is a basis in biochemistry when I cook up a hypothesis to explain one of the abnormalities in ME/CFS, so that I can have some confidence that it is likely to be valid. Of course, until proven, it is still a hypothesis.

    As you probably know, there is a huge number of symptoms in ME/CFS if you add up all the symptoms that various people report. I haven't studied all of them, but in view of the fact that so many appear to stem from the vicious circle mechanism described by the GC-MCB hypothesis, I would guess that very few of them are not produced by this mechanism.

    I should note that there can be comorbidities. For example, some people have Lyme disease that has caused the onset of ME/CFS, so they have both. Some of their symptoms will be caused specifically by the Borrelia bacteria in that case.

    Best regards,

    Rich
     
  6. fla

    fla Senior Member

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    Are PENE muscle pain and headaches two different mechanisms? Are both forms of pain unexplained by the GC-MCB hypothesis so far? Sorry for all the questions but your knowledge is invaluable and finding the missing pieces will someday give us the full picture.
     
  7. hixxy

    hixxy Woof woof

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    Pain could be caused be multiple of the abnormalities already in your list.
     
  8. richvank

    richvank Senior Member

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    Hi, fla.

    I don't know. Pain is a topic I would like to understand better. I've signed up for the fibromyalgia workshops at the upcoming Ottawa conference, hoping to learn a little more about this.
    As I mentioned earlier, the women who were treated to lift the partial methylation cycle block reported a lessening of their pain, so it does seem that pain is linked to the vicious cycle mechanism described by the GD-MCB hypothesis. I just don't understand the detailed mechanism so far, and I think I have identified biochemical mechanisms for the other abnormalities that I've listed. From my point of view, I would say that the mechanisms I have identified for a large number of the abnormalities in ME/CFS do suggest that this vicious circle is the core mechanism in the pathophysiology of this disorder, and the observation that the major symptoms improve across the board for most of those who treat to lift the partial methylation cycle block is consistent with this. I think that all of this provides a good basis for saying that this type of treatment is likely to be beneficial for most people with ME/CFS, and that it should be more widely used.

    Best regards,

    Rich
     
  9. richvank

    richvank Senior Member

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    Hi, hixxy.

    I think you're right about this. For example, the depletion of glutathione could be producing mito dysfunction in neurons in the pain-sensing pathways, lowering their pain thresholds, and causing them to produce the sensation of pain when there is no tissue damage going on, and no reason for the pain signal to be sent. Maybe I should just offer that as a hypothesis for the pain in ME/CFS, but I would like to do a little more study before I am ready to add pain to my list.

    Thanks for your comment.

    Rich
     
  10. Sallysblooms

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

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    Thank you very much for all of your help.
     
  11. drex13

    drex13 Senior Member

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    Hi Rich,

    Thanks for the comprehensive list. I would would like to throw in my two cents in regards to the pain issue. Prior to starting Hydroxo b12 and Methymate B, I was one who experienced muscle, joint pain, and /or what I would term non specific or generalised pain. One of the things I have noticed since adding those two supplements (along with some lauricidin), and basically having no cofactors in place other than magnesium and potassium (which I did find to be important), is a significant reduction in pain. I have recently added the folinic acid, will be ordering phosphatydil serine tomorrow, but am still up in the air about the Yasko multi (since it has folic acid). I like the idea of a multi, rather than having to figure out and take a bunch of individual pills.

    In my limited experience with the SMP, I have found what I consider to be a significant improvement in pain. My pain was not constant, but would flare up once or twice a week, and my entire body would hurt. I have not experienced this in several weeks.
     
  12. Sallysblooms

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

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    Douglas Labs Ultra Preventive X is really good, my doctor likes it for a multi. I don't take all of the pills it calls for each day though since it has b6 and I cannot take much, sensitive to it. I don't think you can put all you need into a multi. Lipo GSH and C, powders etc cannot be added. I have many supplements to address all of my needs.
     
  13. drex13

    drex13 Senior Member

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    .
    Thanks, I'll check it out
     
  14. fla

    fla Senior Member

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    I asked my GP to follow me through this protocol and he (says he) read it and did not want to do it because he's not sure about it. I'm seeing an immunologist next month who knows a little about M.E. (which is rare around these parts) and I'll bounce it off of him.

    Why aren't more people trying this protocol? Trouble getting a Dr to follow you through it or other reasons?
     
  15. harrycat

    harrycat

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    Fla - I gave up with my GP in England a long time ago. If I'd listened to their advice I'd still be on painkillers, antidepressants and learning to live with it. I hope there are some other folk who have more positive experiences but my view on the NHS treating people with FMS / CFS is that they do a terrible job.

    I wish there were more options for people like us in the UK.... It's a sad state of affairs IMHO.

    Fla- nutritional support has turned my life around and I urge you to try it if at all possible.
     
  16. madietodd

    madietodd Senior Member

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    Rich, this looks like an excellent multi. If you get a chance to look at it, I'd love to know what you think.

    Madie
     
  17. Valentijn

    Valentijn Activity Level: 3

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    Odd that he's nervous about it ... it's just supplements, which most GPs don't think have any affect anyhow :) It's all available without a doctor being involved, for the truly desperate, but it's very nice to work with a doctor that understands the general theories as well, and can help test and guide things.
     
  18. Sasha

    Sasha Fine, thank you

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    Hi fla - I think that's a really important question. I'm also in the UK and trying Freddd's protocol but now at rich's doses, and without the help of a doctor.

    I didn't consider trying the protocol for a long time because, with no background at all in biology, I didn't understand it and it looked incredibly complicated, with (to my anxious perception!) people having horrible reactions and asking complicated questions with complicated answers about what they should do about it.

    However, so many people seemed to be benefitting that I started on Freddd's protocol. Being brain foggy, even with the summary that he provides, I found it difficult to understand (I still don't think I understand it - I need something very "1. Do A. 2. Do B. If C happens, do D. If E happens, do F." and so on).

    So, I started it without understanding the biochemistry. I had problems, but I posted about them and got informative replies both from Freddd and rich, plus others. I still don't understand the biochemistry and I'd have been forced to have given up weeks ago if it hadn't been for Freddd and rich's support.

    I wonder if a lot of other PWME have the same problem with trying the protocols: brainfog and lack of specialist knowledge in the face of a complex intervention plus a protocol that requires a great deal of knowledge to fix things if it presents problems.

    I would so love to have a doctor to help me with this - to give me the genetic and blood tests that would rule out the blind alleys and keep my electrolyte levels safe. I don't think this protocol is easy. But I hope that if enough of us do it with good enough results, it will lead to pressure for research and eventually doctor-assisted application of the protocol.
     
  19. richvank

    richvank Senior Member

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    Hi. Madie.

    Yes, the Douglas Labs Ultra Preventive X does look like a very good formula. I note that its folate is in the form of Metafolin, and its B12 is in the form of methylcobalamin.
    There is always the possibility that an individual person might have a sensitivity to one or more of the ingredients, as is true in other comprehensive multis, including the Yasko multi, but generally speaking, I would say that this one looks very good.

    For people who need a more "bare bones" multi because of sensitivities, another one to try might be the Thorne Basic Nutrients IV, which doesn't have as many ingredients, but is designed to be hypoallergenic.

    Best regards,

    Rich

    Rich
     
  20. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Hi Rich,

    one more for your list is nk dysfunction which i thought was a biggy.
    Also failure of T-lymphocytes to be stimulated, does this mean low T cells? As my t cells and some others i know have had hi numbers, from other stuff i have read is that cfsers have abnormal t-cells ie high or low t-cells numbers. I recently read where it may not be a numbers thing just like nk cells but a matter of function. Maybe for myself im producing more t-cells to compensate for their poor function or even producing more to compensate for poor nk function.
    Also from this dysfunctional immune system comes herpes virus reactivation for many like ebv, cmv hhv6 etc. and bacterial infections, or just co-infections in general.

    cheers!!!
     

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