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ME/CFS: A disease at war with itself
We can all agree that ME/CFS is a nasty disease, particularly in its severe form, but there are abundant nasty diseases in the world. What is unique and particularly confounding about our disease is that so much controversy surrounds it, and not only surrounds it, but invades it too.
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Does anyone have a good hypothesis of how XMRV could account for the 24hr delay?

Discussion in 'XMRV Research and Replication Studies' started by Jill, Jun 6, 2010.

  1. judderwocky

    judderwocky Senior Member

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    I think a lot of this is actually tied to specific antiviral infammatories as well.. most of the stuff our cells produce to interfere with the virus basically causes whnat you are taalking about here... these same disease states can be seen in alzheimer's patients, chemo patients (who useually have insanely high oxidative damage from the drugs)... etc....

    The breakdown in mitochondrial function is associated with inflammation produced by the cell... but this basic theory is becoming less and less theory and more and more fact... even arthritis ... most of the "autoimmune disorder" have at their heart the inflammatory issues that result in the mitochondria shutting down...

    the best analogy i can think of for people that are familiar with the biology would be to hink about a car battery... and dumping out the stuff on one half of the battery....

    the mitochondria are , and please excuse my "french" .... Damn interesting cellular organs. Truly one of natures marvels. Cofactors (coq10, carnitine... several other intermediates) basically are set up the cell uses the membrane of the mitochondria to route electrons around to places where they are used to cycle ATP production.... from a physics perspective... it doesn't get any "cooler" than this... we still can't mimic anything like that with nano technology ... [​IMG]

    as the molecules go through this process... you will notice that the co-factors that spin off are hydrogen....

    [​IMG]

    soo... you can imagine what happens when you start spreading a whole bunch of "oxidative" materials into the cell. The mitochondria is one of the most sensitive cellular organs to oxidative damage.... and is actually one of the ones that is MOST tied to aging. A lot of aging and gerentology studies are begining to focus on the life cycle of the mitochondria...

    interestingly.... they have their own DNA... and you only get it from your mother.... The sperm don't have mitochondria... so the only mitochondria you have, you got from your mother, your grandmother.... etc.

    sorry, i don't know how much of this is relevant... but i think the diagrams help illustrate the metabolics of this disorder...

    also... as someone else pointed out... ATP is a rate limiter in the production of all the cofactors and enzymes in the process to make ATP... so once you tip the scales, it gets worse....
     
  2. judderwocky

    judderwocky Senior Member

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    it cut out my other nifty picture i stole of wikipedia.... >:
    [video]http://upload.wikimedia.org/wikipedia/commons/c/c4/ETC_electron_transport_chain.svg[/video]
     
  3. judderwocky

    judderwocky Senior Member

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    i think whats also important to remember is that even though it was found in the blood of cfs patients... it was hard to find there. the animal study at least raises the implication that this disease does not have a tropism specific to the blood... the cellular markers the virus uses to enter the cell are common in most cells of most animals is what i have heard....

    i imagine you could probably detect it in SOME level of any human infected with it in the blood.... but it might be a lot less hit and miss if we looked in say, lymph tissue,
    a comparison of tropisms between the two would be very interesting though, and i agree that it is very possible their bodies handle it differently
     
  4. biophile

    biophile Places I'd rather be.

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    I agree with alex3619's approach, review what we already know about "PEM" and see how that relates to XMRV. What immediately comes to mind is additional oxidative stress, the immune response to exertion, and a disruption to metabolic processes.

    Other posters have already commented about these, and kurt's idea about a "detox delay that induces a type of dysautonomia for the exertion response" is interesting.

    Wonko says "in fact the day after exertion that causes the PEM I usually have less background symptoms than normal - until the onset". I sometimes have observed something similar. The exertion may stimulate a temporary increase in sympathetic nervous system activity which alleviates some symptoms for a while but then also contributes to the PEM crash.

    I would like to ask richvank a question relating to the GD-MCB hypothesis, at some point I started reacting adversely to therapeutic doses of some antioxidants such as vitamin C and vitamin E, why would that be?
     
  5. richvank

    richvank Senior Member

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    [QUOTE

    I would like to ask richvank a question relating to the GD-MCB hypothesis, at some point I started reacting adversely to therapeutic doses of some antioxidants such as vitamin C and vitamin E, why would that be?[/QUOTE]

    Hi, biophile.

    Normally, vitamin C is recycled (chemically reduced) by glutathione, and vitamin E is recycled by vitamin C. So if glutathione was depleted in your case (as we have found in most cases of CFS that have been tested), it may be that these antioxidants ended up having a pro-oxidant effect rather than an antioxidant effect, because they became oxidized and were not recycled. Antioxidants normally operate as a "bucket brigade" for electrons, and if part of the brigade is missing in action, problems can develop if the others are added in higher amounts.

    Best regards,

    Rich
     
  6. acer2000

    acer2000 Senior Member

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    Or it means that the virus doesn't spend any time in the blood, which might explain why doctors who are looking in the blood for it can't find it very often. Doctors need to get over the idea that all diseases are always in the blood. Maybe the issue here is that they need to test a different tissue...
     
  7. slayadragon

    slayadragon Senior Member

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    twitpic.com/photos/SlayaDragon
    Toxic Mold and PEM


    That's really interesting, Rich.

    Vitamin C has helped me so much since mold avoidance that I've been perplexed at why it doesn't help other CFSers at all.

    It sounds like by decreasing my mold exposures a great deal, I've gotten my glutathione up to a reasonable level (since, as we've discussed, satratoxin lowers the amount of available glutathione). At that point, the Vitamin C can be utilized to take a bit more of the oxidative stress off my system, thus allowing me to tolerate a bit more of the mold toxin than I would without it.

    Leverage!

    With regard to PEM: that's something that seems relevant to my own observations from "down the rabbit hole" of extreme mold avoidance, since insofar as I'm avoiding toxic mold scrupulously enough, the PEM goes away entirely.

    (If I'm hit really hard with more mold than my system can handle, it generally takes three days for me to recover fully. So that's consistent too. I'm not sure why that's the magic number though.)

    A couple of possibilities:

    1) I believe that the lowered oxygen state (Cheney's "oxygen toxicity") serves as a protective mechanism against the damage to the system that would otherwise be occurring as a response to small amounts of mold toxin (and perhaps other biotoxins). Insofar as people push themselves to go out and do things, their system will be using more oxygen. With a higher level of oxygen in the system, the protective effects of the low oxygen will not be present and the exposures to whatever amount of satratoxin will become more damaging. Thus, insofar as I'm being exposed to a low enough level of mold poison not to be an issue regardless of how much oxygen I'm using, I can expend as much energy as I like (e.g. climbing high mountains) without any PEM at all.

    2) In some cases, "going out and doing things" may involve going to places that are worse than one's home environment in terms of toxic mold. In that case, the system will suffer as a result.

    3) If a visit is away from a bad home environment for more than a day or so, the system often will start to detox. When a return is made, the system will be getting a double whammy: the toxins released from inside the body as well as the renewed high levels in the environment. A negative effect ("intensification reaction") then will occur.


    I think that the first explanation is the most common one for PEM, but the other two occur frequently as well.

    As for XMRV: as far as I can tell, at least part of the reason that my body goes nuts with inflammation anytime it encounters any stupidly small amount of mold poison is because of the pathogens in my system. Taking Valcyte/Famvir has reduced my reactivity, for instance. And a higher toxic burden seems to increase reactivity as well.

    So I'm thinking that XMRV: 1) prevents my body from detoxing as well, 2) makes other pathogens (e.g. Lyme, HHV6a, EBV) colonize or reactivate, and/or c) directly causes inflammatory response to increase.

    Maybe f I could get the XMRV under control, I wouldn't be as reactive to toxic mold. It's a nice thought anyway.

    Best, Lisa
     
  8. alex3619

    alex3619 Senior Member

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    Hi Rich

    I know you already know this, but I though it worth saying for others on this thread.

    The thing about vitamins C and E is that they are part of an interconnecting network. If one is faulty then they all are. ANY deficiency of C, E, CoQ10, lipoic acid or glutathione will train wreck the entire deal. Other antioxidants are also important (which is why I am pro-fruit and not on a high protein low carb diet). Since many of these are also cofactors in many reactions, including the mitochondria, every chemical reaction that relies on them will also be compromised. Even glutathione is critical to mitochondrial function, although you wont usually see it on any metabolic flowchart. This is because, aside from its antioxidant properties, it is necessary for the correct folding of many enzymes, without which they don't work properly.

    Minerals like zinc and molybdenum also have their parts to play in this network, as does sulphur. It is because these things interlock so much together that we have trouble separating out critical causes. It is best to treat all of them together - which is of course why Rich's simplified methylation cycle treatment was designed. Something similar has to be done with antioxidants. One single antioxidant, no matter how good, is often irrelevant.

    Bye
    Alex

    Hi, biophile.

    Normally, vitamin C is recycled (chemically reduced) by glutathione, and vitamin E is recycled by vitamin C. So if glutathione was depleted in your case (as we have found in most cases of CFS that have been tested), it may be that these antioxidants ended up having a pro-oxidant effect rather than an antioxidant effect, because they became oxidized and were not recycled. Antioxidants normally operate as a "bucket brigade" for electrons, and if part of the brigade is missing in action, problems can develop if the others are added in higher amounts.

    Best regards,

    Rich[/QUOTE]
     
  9. slayadragon

    slayadragon Senior Member

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    [/QUOTE]

    That's really interesting too.

    I recently added ALA to the supplements that I was taking, and couldn't believe how much of a detox reaction I got. That seemed peculiar and like maybe it was acting like chelation (e.g. EDTA, Modifilan) in removing stuff from my body too fast.

    But if it's an essential part of the cycle, then maybe it's more just letting my body do what it "wants" to be doing. That makes me feel much more comfortable emotionally. (Though not comfortable physically. I can't believe how painful this crap is to detox. Hard to believe I never understood that toxins were an issue for me at all, during the first dozen years of my illness.)

    So I think now that my glutathione levels are okay, or at least better, because the mold's not depleting them. I don't seem to crave glutathione the way that I crave other things anyway. Lipoceutical glutathione only occasionally tastes good, and I really don't feel like nebulizing is a good thing.

    I'm taking plenty of Vitamin C, which you say should be recycling the Vitamin E. And I'm taking ALA.

    How do I know if I have enough CoQ10? That's expensive enough that I'd prefer not to take it if I didn't have to.

    I concluded recently that I was way behind in B6 and so started a lot of P-5-P. Zinc too. (Many years ago, the people at Pfeiffer diagnosed me with pyroluria.) I occasionally take moly. I'm not sure about the sulfur....how would I know if I have enough?

    What else should I be thinking about?

    This is really helpful. Thanks.

    Best, Lisa
     
  10. judderwocky

    judderwocky Senior Member

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    have you thought about a carnitine supplement? many times its sold with ALA because they synergize so well.... also the ALA regenerates glutathione and also is show to move redox sensitive transcription factors inolved in glutathione production... its a big booster overall for that....

    but acetyl l carnitine is supposed to be better for physical energy and propionyl carnitine is supposed to be better for mental functioning.... you can also throw N acetyl cysteine (NAC) into the mix for even more glutathione and for other good effects... its given intravenously at hospitals for acetometaphen overdose, and its also used in conjunction with a lot of mental disorders because it protects nerves so well....chemo patients use to lift their fog ....

    also if you want something that you can eat .... you could try rooibos tea... another important antioxidant the body produces is super oxide dimutase and SOD... and its in pretty descent concentrations in Rooibos, (red 'bush' tea) .... most antioxidants aren't preserved that well by the time they get to you, so i like the idea of one you can cook.... you can get it at most supermarkets.... also the rooibos has a lot of good minerals... like zinc and i think ?! also selenium, which i believe is involved in one of the anti oxidant pathways....

    also... i think ALA is shown to increase sensitivity to nerve growth factor... who knows... the harsh reaction could have been nerve tissue becoming re sensitized... i noticed feeling worse at first when i took ALA... but it was a different kind of the usual weird... i always suspected it was something else... some pathway coming back "online" ... or at least i hope... sometimes i really want the worse symptoms be a sign of better things to come lol....
     
  11. slayadragon

    slayadragon Senior Member

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    Interesting suggestions.

    RE the ALA: my current symptoms are a huge amount of trigger point pain and cognitive dizziness/lack of focus.

    The trigger point pain is highly associated with detox for me. It seems part of the process. Neural therapy helps a lot. But it still hurts. It feels like there's something wrong with the detox system (maybe caused by XMRV or whatever is at the "root" of this disease?), that it would hurt so much.

    The cognitive issues feel more like I'm living in a room filled with spray paint than any of the previous cognitive issues I've had with CFS. But it happens no matter where I'm sleeping (including in a tent, and in various "good" locations), so I don't think it's the environment. And I'm not getting any of my other usual mold symptoms. It seems likely that it's a combination of detox (it's worse when I first get up and when I'm really clear of mold, both of which are big detox times) and some toxin-producing pathogen (since a large dose of Rizol, which addresses Lyme and coinfections, increased it tremendously).

    It feels like I'm getting closer to "the end" of getting the toxins and pathogens under total control. But I wish it were easier.

    I'll try some selenium too. That's a good idea.

    Thanks, Lisa
     
  12. richvank

    richvank Senior Member

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    Hi, Lisa.

    On the ALA, if there is a lot of mercury present, taking ALA can move it around. As you may know, Andy Cutler has emphasized the importance of taking ALA at frequent intervals to keep its concentration up, so that it doesn't just mobilize mercury and then release it to redistribute. I think Andy may be right about this. Perhaps this is producing symptoms in your case.

    NAC has been shown to be able to move mercury into the brain in rat experiments, so limiting its dosage to 300 mg per day if significant mercury is present has been recommended by Dr. David Quig of Doctor's Data Lab.

    Best regards,

    Rich
     
  13. natasa778

    natasa778 Senior Member

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    Also according to Cutler no ALA if you have amalgam fillings...
     
  14. judderwocky

    judderwocky Senior Member

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    A good point to watch out for if you are worried about mercury poisoning... the dosages in that study were fairly large... something like 3g of mercury for someone our size....and i've heard that its more an issue with l-cysteine supplementation

    The important thing to realize is that ALA and NAC both move the mercury around in the body and some of it does pass through the blood brain barrier ... so its sort of double edged sword... any chelator you use to move stuff out of the body has to be able to cross the barrier so that it can then take the stuff out.... which means in short run it can increase the levels in the brain (i've really only found this effect in older studies that used MASSIVE dosages of both, some of the pathways might have been overloaded, so i'm not sure how worried i am personally about this... and ive only found positive studies correlating the overall oxidative stress on the neurons and mercury....so my personal belief is that while the mercury might show up there, it doesn't have much of an effect, or it is still reduced from what the effect would be without the NAC cupplementation) .... if anybody knows of some more recent studies on this i would love to see them.... if you are worried your symptoms might be because of this, you might start with a chelator that does not cross the blood brain barrier.... i dont remember which ones do.... and then switch to one that does after some time on the others... i've heard of people doing this to remove all the mercury in their body outside their brain... then when its clear they switch to the one that can pass through the blood brain barrier to move it out .... *(if you see any errors plz let me know thx)

    mercury is such an awful chemical :(


    somebody else will have better info/studies on that than me though.... the problem with these studies is that they are almost always using animals other than humans and they are usually using dosages (and sometimes even forms) of mercury not usually seen in humans.... I would really like to hear from someone that has had a known mercury level and has used chelators to reduce them.... personal experience isn't always the most scientific way of looking at treatments... but i think they are a better gauge in some cases... i would love to know when and how their symptoms changed....i've probably been exposed to mercury at a couple places in my life come to think of it... and i would like to be able to have a benchmark

    on a weird side note... i had a chemistry prof in college that used to play with the stuff in class..... he would grab it out of cylinder and play with it on the table in front of all us. i know your thinking... he must have been nuts. and he was. he had a stroke and he started forgetting safety protocols....

    one day he was doing a demonstration with a mixture that started evolving a purple gas into the air... he told is it was oxygen... ? really? and its purple???? turns out it was iodic acid..... once he lit stick of phsophorus on fire.... it burned straight through the desk... and the floor.... he threw a trash can over the hole and went on with his lecture while the smoke leaked out of the bucket.... ahhh good times.
     

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