Choline on the Brain? A Guide to Choline in Chronic Fatigue Syndrome
http://phoenixrising.me/research-2/the-brain-in-chronic-fatigue-syndrome-mecfs/choline-on-the-brain-a-guide-to-choline-in-chronic-fatigue-syndrome-by-cort-johnson-aug-2005
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Chris Armstrong's presentation for Solve ME/CFS October 20 2016 (metabolomics)

Discussion in 'General ME/CFS News' started by Kati, Oct 20, 2016.

  1. Kati

    Kati Patient in training

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    Thank you so much will share on twitter. Canadian government needs to get educated.
     
  2. Ben H

    Ben H OMF Correspondent

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    Thankyou so mich @Kati for putting these up.

    Huge thanks to @ChrisArmstrong for this research and availability to be on here answering questions! I am stoked for this research and can't quite believe the direct input we have had from researchers the last few months. So valuable.

    I am glad the research is pointing to the probability we are all on the same page.

    The starvation link is particularly interesting to myself due to repeated phases of low calorie ketosis (for bodybuilding) the year before I became ill. I even remember the day a couple of months before I got ill that my body metabolism felt like it de-regulated (not in the sense of how ketosis feels-this was different). And it snowballed from there with gut and a viral episode.

    The anecdotal mutterings are probably worthless, but I have always wondered.


    B
     
    Last edited: Oct 21, 2016
  3. Sidereal

    Sidereal Senior Member

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    This is great stuff, thank you so much.

    Some have argued that these recent metabolomics studies showing hypometabolism in ME/CFS are meaningless and simply reflect inactivity. How plausible is this 'explanation' given that Naviaux notes in his paper that inactive people with the metabolic syndrome (abdominal obesity, hypertension, dyslipidemia etc) are in a hypermetabolic state with elevated purines, sphingolipids etc.; in other words the exact opposite of ME/CFS?
     
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  4. Richard7

    Richard7 Senior Member

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    @ChrisArmstrong

    Sarah Myhill has argued that a problem with pwcfs/me is that they are taking ATP to ADP and then onto AMP which can then be lost in urine, and she has suggested using ribose supplementation to increase ATP production.

    From what you were saying about hypoxanthine and the creation of ROS would both the conversion of ADP to AMP and the conversion of ribose to AMP increase the concentration of AMP and therefore the amount of traffic down hypoxanthine that pathway and the total concentration of ROS in the cell.

    Is Ribose likely to give some energy in the short term but make things worse overall?

    Also, early on you mentioned that your research was on women not men because the chemistry is so different, is it so different that these patterns may only apply to women?
     
  5. CCC

    CCC Senior Member

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    For those who want Chris's comments in another thread in one place:


    and

     
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  6. CCC

    CCC Senior Member

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  7. CCC

    CCC Senior Member

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    This was quite useful because I've read a lot on this forum about high lactate, when very low lactate in urine is my son's experience. Looking at his OATS test, his pyruvate was also low, and this goes some way towards explaining why.
     
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  8. ChrisArmstrong

    ChrisArmstrong

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    Well I think there are many variations ME/CFS patients. At this point this is the model we observe across cohorts. I'm currently doing some longitudinal studies on individuals to look how their metabolism changes over time so perhaps we will be able to look into this further. Weight tends to to with adiposity and macromolecules.

    There would be variations in the metabolite profile. One thing that needs to be clear and I tried to present this at the start of my talk but I have a lot to discuss. The metabolite profile constantly changes in an individual. Sleep, light, food, exercise, just about everything impacts your metabolite profile. It's constantly in flux. It's only when you test a large enough cohort that you can find the underlying mechanism that exist within group that separates it from a healthy control group. We try to keep the thought process as simple as possible, i'm sure there are variations from person to person but it's not practical to delineate all the changes of metabolism (at this stage anyway).

    Yes most diagnostic markers are metabolite markers. To be a successful marker though you usually have to find a group of metabolites that are distinct from any other disorder. Right now we've looked at metabolite differences compared to healthy, but you have to be able to find metabolite differences between ME/CFS and many other similar disorders. But yes, metabolite diagnostic markers may be found.

    Well at this stage it's a model that might describe the metabolism, the actual fix may be somewhat more complicated. The longitudinal studies we are doing are looking at seeing what treatments may improve the metabolite profile and whether this improves symptoms for the individual.
     
  9. ChrisArmstrong

    ChrisArmstrong

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    That bolded part is a typo. Sorry. :) Typed "body of" twice.
     
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  10. ChrisArmstrong

    ChrisArmstrong

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    I guess we have to prove the hypothesis before we start recommending anything at this stage. Rituximab destroys B cells, if this hyptohesis is correct then it should remove the drain on energy metabolism and should help ME/CFS in that regard as well as limiting the ROS. As Naviaux stated it may not be as simple as supplementing the cofactors that are lost, studies need to focus on studying how to bring people out of hypometabolism.
    If we use starvation or sepsis as a model, hospitals have what they call a "bundle" which is a set protocol in stages that they use to refeed people correctly and resupport their metabolism. This is done with constant monitoring and feeding by drip. I imagine something similar will be required for ME/CFS patients, maybe not as intensive but also over a longer period. The monitoring aspect appears important to counter variability between patients.
     
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  11. Sasha

    Sasha Fine, thank you

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    Thank you for being here and answering questions, @ChrisArmstrong - it's very kind of you!

    What I've always found interesting about the "stuckness" of ME/CFS and considerations about what it might take to get patients out of it is that people do have substantial spontaneous remissions (I went from being bedbound for years to - over the course of a couple of years - being able to work full-time for years, and now have been relapsed and housebound for years, for example - and I don't know what, if anything, I did to make my remission happen).

    Do you think that there's some underlying button to push that can just make everything come right, without the need for careful refeeding programmes, etc.? Any idea what that button would look like (tons of extra rest, maybe?)?
     
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  12. trishrhymes

    trishrhymes Senior Member

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    This is absolutely fascinating. I'm so grateful to you @ChrisArmstrong for your willingness to come here and answer questions.
     
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  13. aimossy

    aimossy Senior Member

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    Hi @ChrisArmstrong thanks so much for a great webinar and for being so helpful with questions.

    I will just highlight something @Mark noted about a talk Jo Cambridge gave at the RME Sweden conference just a day or so ago on the other thread. Jo's talk was really good and included some new information regarding B cell behaviour. I don't know if you may have time to check out her talk.

    Geraldine (Jo) Cambridge's lecture Rituximab for ME/CFS: Revealing immunological cues to underlying disease mechanisms starts at 02.53 https://play.vll.se/category/5/video/214/rme-konferens-19-october-2016-2

    Mark said:

    "Swedish conference thread, Jo Cambridge reports they are now finding elevated glycolysis in naive B cells of ME patients, working this up now:
    http://forums.phoenixrising.me/inde...ilable-for-streaming.47449/page-3#post-776570
    Could this hook up with the finding of non-mitochondrial excess ATP?"

    She also noted other things about B cells that were interesting I can't pull out of my memory. Ill try and find them in her talk but someone may recall them better than me right now.

    @ChrisArmstrong EDIT I just took another look at Jo's talk she said (in summary):

    Changes in B cells in both naïve and memory B cell subsets compared to healthy controls.

    Mitochondrial function.
    • energy production/supply of key metabolites
    • ? mitochondria not able to 'recover' from stress in ME/CFS?
    Found differences in the way naïve B cells use energy compared to memory B cells and differences in resting B cells. They are writing all this up right now.

    Somehow I missed the bit that Mark noted which is also really interesting. I wonder if you have thoughts about how all this might fit together.
     
    Last edited: Oct 21, 2016
  14. ChrisArmstrong

    ChrisArmstrong

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    Well the same mitochondrial pathways that occur in ME/CFS as indicated by these metabolite studies also occurs in starvation. So I don't see why the mitochondrial pathways would prevent refeeding syndrome. But I find it quite interesting that you didn't get refeeding syndrome, these are the variations that might be important in defining ME/CFS. What were you fed through the PEG?
     
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  15. ChrisArmstrong

    ChrisArmstrong

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    Well this is a hypothesis at this point. Generally the body is trying to maintain normal metabolism. Energy metabolism doesn't just require macromolecules (carbohydrates, fats, protein), it also requires cofactors, vitamins and minerals. It's common that people might be depleted of iron and vitamin b12 and this produces fatigue, this is an example of how a mineral or cofactor can cause fatigue. There should be ways to support the body and we will be looking into the best way to do this. In the cases i suggested above, people feel fatigue even if it's just iron or b12 they lack. What we invisage is more likely in ME/CFS is that it's many if not all cofactors, minerals and vitamins that are reduced
     
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  16. Richard7

    Richard7 Senior Member

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  17. hixxy

    hixxy Senior Member

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    Hydrolysed whey protein formula. You can see the fact sheet here. I also haven't really gained any weight since being on it and it's not entirely tolerated (not much in the way of alternatives available either).

    Curiously I trialled on Vivonex (totally elemental amino acid formula) orally before this while waiting to be seen in the public system and it caused pretty major biochemical shifts. I rapidly lost weight on it and my white cells and testosterone went through the floor. It was quite scary. Phosphate didn't seem to drop though.
     
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  18. ChrisArmstrong

    ChrisArmstrong

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    No problem Ben. I think it's good to discuss thoughts on here and I think the questions that are asked and anecdotal experiences are really helpful, especially for hypotheses.

    Yeah the metabolite studies in the blood seem to be pointing to the same issues.

    Your experiences are interesting. Do you still do weight lifting? I only ask because I think it's interesting that some people I have heard from say they can take anaerobic exercise (like small sets of heavy weights) but nothing aerobic without feeling awful after.
     
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  19. J.G

    J.G

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    Chris, before all else, let me thank for your presence on these forums and responding to our questions. It means the world!

    You're quite right - I ran fast of established facts in my previous post. Basically I'm asking myself whether metabolite availability of some kind is arbitrating the difference between responders and non-responders to Ritux.

    The underlying assumption is I guess twofold. First that Rituximab removes the presumed 'something in the blood' - autoantibodies, maybe - that somehow induce altered metabolic patterns in ME/CFS. And second - a big one! - that once the lid is off, the body is capable of coming out of this 'altered state' by itself in at least a proportion of patients treated with Rituximab, which coincides with improved symptoms.

    Following on from these assumptions, I wonder whether we could effectively increase the Ritux response rate by simultaneously correcting the metabolic deficiencies associated with a hypometabolic state through targeted supplementation. This might aid the snap out of hypometabolism - presuming that's what's happening in Ritux responders, of course. I would love to see a metabolomic study based on the Norwegian cohort...
     
    Last edited: Oct 21, 2016
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  20. ChrisArmstrong

    ChrisArmstrong

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    Hmmm interesting question. I haven't seen any studies that link inactivity to hypometabolism. I can imagine muscle mass would deplete with inactivity but I can't imagine how inactivity would cause hypometabolism. The plausibility of the explanation will be weighted based on the evidence, I can't comment because I'm not aware of the evidence for inactivity and hypometabolism.
     
    Last edited: Oct 21, 2016
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