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Status of methylation cycle model and treatment

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by richvank, Sep 19, 2009.

  1. richvank

    richvank Senior Member

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    Hi, all.

    This is a repost of a post I just made in response to a guy named Mark on the ProHealth board. It may be of interest to people here, also.

    Hi, Mark.

    It's been about two and a half years since I proposed the Glutathione Depletion--Methylation Cycle Block hypothesis for the pathogenesis of CFS, and a simplified treatment approach based on it. About six months ago, I presented a poster paper proposing that Lyme disease is a route of entry into CFS for people who are genomically predisposed to developing a partial methylation cycle block, based on the observed depletion of glutathione by Borrelia burgdorferi.

    During the past two and a half years, I estimate that at least several hundred, and probably now over a thousand PWCs have tried this treatment. There are several physicians who have added methylation cycle treatment to their protocols. Dr. Neil Nathan and I also carried out and reported on an open-label clinical study of the simplified treatment approach on patients in his practice in Missouri.

    There have also been a large number (I don't know how many, but I have probably personally seen a couple of hundred) methylation pathways panels run by Vitamin Diagnostics in New Jersey and the European Laboratory of Nutrients in the Netherlands. For people who have CFS, nearly all have shown a partial methylation cycle block and/or glutathione depletion, most showing both.

    The treatment used by itself seems to help about two-thirds of those who try it. When it is combined with other treatments, it has brought what appears to be complete recovery to at least a few people, who have been able to return to full-time work. Some of the other treatments have been treatments for Lyme disease, mold illness, or toxic metals overload.

    Based on all of this experience, I continue to believe that this model does describe the pathogenesis of CFS for many and perhaps most PWCs.

    With regard to viruses or other pathogens, I believe that they are responsible for the onset of CFS in some cases, especially in the cluster or epidemic cases, such as the one at Incline Village. These cases fit within the GD-MCB model, except that the genomic predisposition aspect does not seem to be as important, or is not involved at all. But the rest is likely the same, i.e. that the viral infection depletes glutathione and brings on a partial block in the methylation cycle. I think the explanation for this is that the virus in the cluster cases has been particularly virulent, at least until it mutated and became less so, ending the local epidemic.

    So as far as the pathogenesis model is concerned, I think it is correct and that it is able to explain essentially all the features of CFS. The model allows for a variety of routes into this pathogenesis, i.e. a variety of etiological factors. These include the whole variety of stressors--physical, chemical, biological and psychological/emotional. The stressors involved in the onset of each case can be differerent from those involved in other cases, but they all channel into causing oxidative stress and a partial methylation cycle block.

    In most cases the oxidative stress is accompanied by a depletion of glutathione, but in a minority of cases, there is a genetic polymorphism in the glutathione peroxidase enzyme. In those cases, glutathione does not drop, but the effect is the same, because it cannot be used effectively to counter the oxidative stress without a functional glutathione peroxidase.

    There's still an issue in the model that is unsolved, and that is how the partial methylation cycle block interacts with glutathione synthesis to deplete glutathione. We know that it does, in both autism and CFS, because when the methylation cycle block is lifted, glutathione comes back up automatically. But the details of this interaction are still undefined from a theoretical biochemical standpoint.

    Note that the issue of whehter the methylation cycle block is at the root of the pathogenesis is a separate issue from what is the best way to treat it. There may be, and likely are, better ways to treat it than the simplified treatment approach. I proposed that as a simple and relatively inexpensive, and thus accessible treatment for PWCs, and at the same time a way to test the model for pathogenesis. I would say that it has been successful in testing the model, and the model has survived the test. I think we still have more to learn about treatment, though the simplified treatment approach has made a significant contribution, and for some PWCS, has been the last thing they needed to get well.

    I don't know if you have been following the "demonstration project" for treating M.E. patients that is going on in Ohio at present, which is updated on the forum called "A New Day," part of Cort Johnson's forums. The approach to treatment being used there involves IV nutrition, homeopathic neural therapy, acupuncture, proliferative therapy, and laser therapy. This is quite an innovative approach to treatment, and I can't say that I understand how it works from a fundamental scientific viewpoint. It does, however, so far appear to be a promising approach, and I am following the updates.

    I don't know the details of what is included in the IVs, and perhaps there is some B12 and folate involved, which would seem to be important for lifting the methylation cycle block. On the other hand, perhaps the other techniques used are able to cause the body to make more effective use of the resources of B12 and folate that it already has. In any case, I do think there is good evidence that many or most PWCs have a methylation cycle block, and to lift this block, the methionine synthase activity has to be increased, which entails greater functional use of B12 and folate. So I'm trying to understand how this treatment intersects with that need.

    You asked about treatment timescale. This seems to vary, depending on a variety of factors. If the simplified treatment approach is used by itself, the experience is that improvements usually occur within a couple of months, but full recovery hasn't happened for many people over a year later, though it has for a few. Lately I've been studying some of the cases with slow improvement, and I think that the lack of enough of the cofactors or enough of the amino acids to feed the methylation cycle and associated pathways may be the reasons for the slow progress in at least some of the cases. B-complex vitamins, minerals including zinc, copper, magnesium and selenium, and amino acids including methionine, serine, and the precursors for glutathione (glycine and glutamine or glutamate) are frequently found to be low.

    Dysfunction of the gut seems to be at the basis of the low amino acids. I think that's why the IV amino acids are an important part of the treatment in Ohio, but for many PWCs, it may be possible to take free-form amino acids in order to increase their absorption, even with gut dysbiosis going on.

    Beyond this, there are other treatments that may need to be added, depending on the particular case. These include attention to food sensitivities, efforts to improve the condition and function of the gut, support for the adrenal and thyroid axes, treatment of infections, treatment for mold illness if present, and treatment of heavy metal toxicity. There are various ways of approaching these issues in treatment, and physicians differ in their methods, but I think these are the things that can be required.

    So in summary, I think the theoretical model and the lab test are holding up well, and though there is more to be learned in treatment, lifting the methylation cycle block and thereby bringing up glutathione seem to be essential parts of the treatment.

    Best regards,

    Rich
  2. susan

    susan Senior Member

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    Why pill and supps make me ill

    Hi Rick,
    Can you please tell me what is happening when I cant take drugs and supplements for longer than 4 days. Some limited things I increased slowly over a period of time...ok like Max Gluthathione but then I got sicker and eventually it made me bedridden after 6 mths. Stopped and I was Ok. Fredd said he cant take it either.
    Thank you Susan
  3. Wayne

    Wayne Senior Member

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    Remarkable Synopsis

    Hi Rich,

    I meant to reply when I first saw this post; but ended up spacing it out. Anyway, I wanted to say that I thought your post here was really quite a remarkable synopsis of a number of things that are relevant to so many of us.

    Things like: 1) what the doctors you are collaborating with are discovering, and where things will likely progress; 2) the role Lyme disease can play as a pathway to ME/CFS; 3) what is happening with Mike Dessin and his doctor in Ohio; 4) the role of gut pathogenesis; 5) the role of viruses, mold, toxic metal overload; and so much more.

    It really connects a lot of dots that are on the minds of so many of us. But it is so difficult for many of us to connect those dots because of the brain dysfunction. BTW, I saw where you mentioned that the myelin sheath is dependent on the methylation cycle to sustain and repair itself; which could explain why we have so much difficulty with cognition.

    Anyway, I wanted to thank you for this remarkable synopsis. And also give it a bump for those who may have missed it the first time around.

    Regards, Wayne
  4. klutzo

    klutzo Senior Member

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    Mold

    Hi Rich,
    I always hear that mold illness should be treated if present, but how? I don't think I've ever seen a treatment protocol for mold in all my years of reading bout my CFS/FMS/LYME, other than Dr. Ritchie Shoemaker, but I passed his vision test easily both times I tried it. Several alternative practitioners have told me I have mold issues, but they were never addressed, since they all felt adrenals were my biggest problem.

    Thanks for any advice,
    klutzo
  5. richvank

    richvank Senior Member

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    Hi, Klutzo.

    If you can pass the FACT test, I think it's unlikely that you have mold illness.
    You could, however, still have a mold allergy. Mold illness involves the immune system not being able to recognize mold toxins and dispose of them. Mold allergy is an immediate, IgE type of allergy, like hay fever. Mold illness is much more serious than mold allergy. Dr. Shoemaker treats mold illness with avoidance and cholestyramine. Mold allergy is treated with avoidance. Perhaps NAET would work on mold allergy (Nambudripad Allergy Elimination Technique).

    Do you know what those alternative practitioners meant by mold "issues"? Why did they think you have mold "issues"?

    Rich
  6. klutzo

    klutzo Senior Member

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    Mold

    Hi Rich,
    Thanks for your response. Yes, I passed Dr. Shoemaker's vision test twice.

    I do have allergies to molds like hormodendrum (sp.?) and alternaria. They are so bad that I had to move to Florida, which I despise, and leave Wisconsin, the place I loved, because the only effective tx was a cortisone shot every month, five months per year, and that is malpractice. My IgG, IgM, IgE and IgA were all quite elevated when tested conventionally, even after 7 years in Florida, where my allergies were almost non-existent until the insect problem started.

    I also have other pollen allergies, severe insect sting allergies, and have had several NAET treatments for all of that, plus some MCS problems. Ironically, the insect allergies did not make themselves known until I had moved to Florida, the buggiest place in the USA, and as a result, I have had 11 allergic reactions in the past 7 years, 4 of them requiring emergency tx. I got married here, and my husband's job is not portable, so we cannot move, and I pray not to be stung every time I step outside the door.

    The NAET helped with pollens for about a year, but did not help with the insects at all. I also had acupuncture for the insects, but it did not help. I had amazing results with NAET for formaldehyde in a new bed, but the sensitivity to it remains so strong that we can't replace our ruined floors at home, and we buy all furniture except beds in consignment stores. However, just one NAET tx got me back in the bedroom after 77 days of sleeping on the screen porch!

    The alt. practitioners I've seen mostly used AK to diagnose me, and all said I had metals, yeasts, mold and weak adrenals. One dx'd my hypothyroid problem, for which I will forever be grateful. The last one dx'd Coxsackie B3 in the brain, CMV, HHV6, and tick virus ( I have Lyme). He said he'd cured my Lyme, but a Bowen QRiBb showed it was still there, so I don't know how much creedence to give to his diagnoses. All of them were surprised when my hair and 3 day metal challenge tests were normal. The one thing they all agreed on is that my adrenals are my weakest organ system. Conventional medicine disagrees, saying that 95% of my pancreas has been destroyed.

    Anyway, I guess I do not have the kind of mold problem you are talking about, which is good. As you can see, I have more than enough on my plate. Thanks so much for the explanation.

    klutzo
  7. slayadragon

    slayadragon Senior Member

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    twitpic.com/photos/SlayaDragon
    Rich van K

    Rich wrote:

    >In most cases the oxidative stress is accompanied by a depletion of glutathione, but in a minority of cases, there is a genetic polymorphism in the glutathione peroxidase enzyme. In those cases, glutathione does not drop, but the effect is the same, because it cannot be used effectively to counter the oxidative stress without a functional glutathione peroxidase.


    Hi, Rich.

    Can you tell me what test it is that measures this?

    Thanks,

    Lisa
  8. slayadragon

    slayadragon Senior Member

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    Klutzo/Rich Van K

    Rich van K wrote:

    >If you can pass the FACT test, I think it's unlikely that you have mold illness.


    I've not found that to be the case.

    Just before I moved out of my moldy house, my vcs score was very low. It felt like I was going blind.

    Within four months of moving out of the house, my vcs test went to fully normal. I was still pretty sick though.

    A number of months later, I started avoiding mold more scrupulously. My health improved immediately to close to normal.

    Periodically since then, my vcs has declined. This seems to have relatively little to do with my level of mold exposures.

    The vcs test measures the amount of toxins (neurotoxins) in the brain. And I do think that if the body is getting a lot of current exposures, the brain is going to be affected. Satratoxins (toxins made by stachybotrys) sail right through the blood-brain barrier.

    Solely based on my own experience though, it seems like the amount of toxins in the brain is variable.

    It may be that the system views the brain as a "priority" organ and makes every effort to move them from the brain to elsewhere? But that sometimes they unfortunately move into the brain on their way out? Or that they don't affect vision when they're stored deep in the brain but do as they get closer to the surface on their way out?

    Just idle speculation on my part. Someday someone will put some work into figuring this out.

    I would tend to say that a CFS sufferer who passes the vcs likely isn't living in a place with a terrible mold problem. That doesn't mean that mold (and in particular hyperreactivity to mold) isn't an issue though.

    Of course, most people likely won't address mold illness if they're not living in a really moldy place. Extreme avoidance of the sort that Erik Johnson and I pursue is way too hard.

    That's quite different than suggesting that mold's not a problem though.

    In any case, Dr. Shoemaker does not say that people who pass the vcs cannot have mold illness. It's a screening device that apparently works pretty well, but it's by no means perfect.

    Best, Lisa
  9. August59

    August59 Daughters High School Graduation

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    I think I read this somewhere. Haven't the names of some of the recommended supplements either changed their name or makeup? On the Holistic Health website some of the items listed on this forum are different than what is on the website.
  10. Sushi

    Sushi Moderator and Senior Member Albuquerque

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    Yes, the formula for Metagenics Intrinsi/B12/Folate changed and the new formula is no longer suitable. Rich Van K recommends we use Metagenics Actifolate instead.

    Sushi
  11. Dreambirdie

    Dreambirdie work in progress

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    FACT test? MOLD test?

    Two questions for anyone who knows:

    What exactly is the FACT test?

    What tests are there for moldy houses? I think mine is pretty safe, but I'd like to test it anyway.
  12. Sushi

    Sushi Moderator and Senior Member Albuquerque

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  13. August59

    August59 Daughters High School Graduation

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    Thanks Sushi - I'm having a bad time right now and I just couldn't figure out what I was picking up on, other than it just didn't sound right.
  14. richvank

    richvank Senior Member

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    To dreambirdie re: mold test for houses

    Hi, dreambirdie.

    The Environmental Protection Agency has developed a mold test for houses. It's called the ERMI test. It's available from commercial sources. Dr. Shoemaker recommends Mycometrics.com in New Jersey. They send you a filter that you can attach to a vacuum cleaner and vacuum a certain area in your bedroom and living room, and send it in for DNA analysis. They analyze for a range of molds, and give you score that you can compare to their database on a large number of houses, so you can see if yours is high in toxic molds or not, compared to the data base.

    Best regards,

    Rich
  15. Dreambirdie

    Dreambirdie work in progress

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    Rich and Sushi--

    Thanks much for your responses. I really appreciate it! ~DB
  16. August59

    August59 Daughters High School Graduation

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    Rick and Sushi

    Ditto on dreambirdie reply - Thanks

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