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Repeat Test Reveals Dramatic Drop in ME/CFS Exercise Capacity

Discussion in 'Phoenix Rising Articles' started by Mark, Jul 29, 2013.

  1. alex3619

    alex3619 Senior Member

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    The problem with PEM and current science is that it is still a syndrome. We don't understand it. I suspect its a composite symptom cluster with multiple issues, each of which has their own time scale. Some aspects of it are being unravelled though, from mitochondrial and delayed energy production issues, to more immediate muscle lactate responses.

    Given that this involves metabolism, nerve signals, hormonal signals and immunological signals, each with its own time frame, the way to think of PEM might be one to many overlapping curves, each with its own maximum intensity spike\s, and what we experience is the combination of these effects. In terms of waves, this means intensification or nullification based on how the waves superimpose on each other. Three big waves coincide and whammo, you have big symptoms.

    Which leads me to a question I have not thought about much, are there stages to PEM, with different symptoms in those stages?
     
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  2. SOC

    SOC Moderator and Senior Member

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    Good question, Alex, and well worth some research. If only we had the funding. :(

    I've wondered a lot lately about the definition of PEM. It seems that if you've experienced it, it's easy to identify. It's entirely different from fatigue, or exhaustion, or any other symptom in the same class. I've had exhaustion along with PEM/PENE, but it was clearly much more than just exhaustion. I frequently wonder if most of our doctors, and researchers even more so, don't really get it.

    I sometimes think some patients who believe they have PEM, actually have other types of fatiguing symptoms and/or exercise intolerance which, while disabling in their own right, are different from PENE -- post-exertional neuro-immune exhaustion.

    Now that I've cleared a number of viruses (for the time being, anyway), my experience of PEM is different -- much less flu-like and multisystem collapse, and more mostly exhaustion. Is it just less severe PEM, or do I only get some fatiguing symptoms but not true PEM? Is it that it would just take more now for me to get the whole system collapse thing, or that I wouldn't get there at all, although I would have extreme mental and physical fatigue? Frankly, I'm not going to experiment with testing to destruction unless it's for some valuable scientific research. ;) I kinda like not being crashed. :D

    I'd love to see more research on PEM --- What is it, exactly? Are there stages to PEM? Are there different flavors of PEM? Do different types of exertion -- physical, mental, emotional -- cause different types of PEM or is it all the same PEM?
     
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  3. alex3619

    alex3619 Senior Member

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    Quark, strangeness and charm versions of PEM?

    http://en.wikipedia.org/wiki/Quark,_Strangeness_and_Charm

    http://en.wikipedia.org/wiki/Quark
     
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  4. Valentijn

    Valentijn Activity Level: 3

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    I started taking Yohimbe, a bark extract, about two weeks ago, and I haven't had any PEM while on it despite exceeding my limitations pretty badly, by flying back home (10+ hours in the airplane, 3-4 hours in airports). My heart rate was elevated for most of the trip, 100-105 on the airplane, and 105-130 after getting off the airplane, which would usually mean a bad crash.

    So I still have my abnormal reaction to exertion shown by raised heart rate and/or dropping oxygen levels, but I don't seem to be crashing afterward. Basically there have been a couple recent papers by the Lights, showing a three-fold increase in ADRA2A expression after exertion in ME patients, but not in well-matched sedentary controls. And ADRA2A is capable of accounting for much of the symptoms of PEM, as well as suppressing norepinephrine production, which can cause orthostatic intolerance.

    So I switched from taking an NRI to taking Yohimbe, which is a very potent antagonist of ADRA2A, and my OI symptoms have remained under control, in addition to thus far avoiding PEM. Gut motility has also improved, to the extent that I've had to cut my daily magnesium dose in half. I've had none of the muscle twitches or cramps that I would usually get from cutting back magnesium.

    So in my very brief experience thus far, it seems possible that the up-regulation of that one gene after exertion can account for all of my PEM symptoms, both physical and cognitive, as well as a few other symptoms. Hence my experience says there's just one stage, with a single trigger - though there's obviously something triggering that abnormal reaction, since gene expression is normal prior to exertion.

    Of course, there's also symptoms immediately following over-exertion (pain, weakness, etc), but I think those are a separate issue from PEM.
     
  5. lansbergen

    lansbergen Senior Member

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    I tried one magnesium tablet once and it gave me bad diaree. I never did it again. As I treat the step after ADRA2A upregulation with the immuneregulator I use that makes sense to me now.

    Keep digging valentijn
     
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  6. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    A message by beaverfury here yesterday contains a link to a paper that excites me greatly as I believe that it may provide an important clue to how exertion can perpetuate ME autoimmunity, and perhaps also how the gut can be involved in the process of PEM being caused.

    Unable to get the full text of that paper, I did some searching and found this one.

    Put together with this paper that shows how excessive gut permeability could lead to, and perpetuate, autoimmune disease, some good clinical research addressing these issues in combination could perhaps scotch the psychoquacks' nonsense once and for all, and prove how GET can not only exacerbate symptoms on various timescales but also make recovery impossible.
     
  7. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Anything suggested by the great Valentijn :love: has to be worth looking into. So I did me some searching for info on Yohimbe.

    Looks like it's not for me, unfortunately.

    For example this page says

    No thanks! :eek: I can do without that complication.

    This lot is further cause for concern for me:

    OK, it only says 'associated', but I already have high blood pressure, and the others are common ME symptoms. It may be that further searches will reveal actual evidence, but it's 'No' to Yohimbe for me.
     
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  8. peggy-sue

    peggy-sue

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    My reaction to the mention of Yohombin was an immediate; "eeeeeeeek!"

    (something from the recesses of pharmacology studies and from work)

    I couldn't remember what it was, or what was scary about it, but I remembered it was scary.

    Early on in being ill, I found that mental overdoings could cause physical PEM and vice versa.

    I'm not quite so sure this still happens. Sometimes, if I've been very happy, I will get a payback of being really down.

    Mostly nowadays, PEM is an exacerbation of everything, my "baseline" level of functioning reduces.

    I get that peculiar difficulty with breathing that Alex describes - as if the air hasn't got enough oxygen in it - (I do not know what thin air at altitude feels like, I'm only imagining) and that while I am labouring to breathe, it's still not doing what it it supposed to!

    PEM should be a priority for research.
     
  9. Valentijn

    Valentijn Activity Level: 3

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    It is heavily marketed as a male erection type drug, probably due to improvements in circulation. Many sources go way overboard in trying to make it look effective, to the extent that my bottle of it says "Not for use by females" :rofl:

    Anyhow, I do about 1/4 of the recommended daily maximum on the bottle, split into two doses. So a quite small dose. My heart rate has lowered, not raised, probably due to my pulse pressure rising to a normal level. I haven't experienced any side effects yet.

    But yeah, if you don't have a problem with norepinehprine getting low, then your ADRA2A gene might not be getting overexpressed after exertion, or your body is compensating differently than the hypotensive folks. In which case, Yohimbe might not help, and might cause problems.

    I haven't had any increase in libido, and no signs of growing a penis yet :thumbsup:
     
  10. lansbergen

    lansbergen Senior Member

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    Or maybe a med prevents the drop.
     
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  11. Valentijn

    Valentijn Activity Level: 3

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    It has been banned from OTC sales in some countries, as well as in Australia. Possibly due to it raising norepinephrine and potentially epinephrine quite a bit, if taken in large doses. But pretty much the only thing it does is down-regulate three closely related genes, one of which is over-expressed in ME patients (and another of which might be involved in fibromyalgia).

    Ideally it probably should be regulated due to the impact it has on the central nervous system, and it can be prescribed by a doctor in some countries. But here in the Netherlands, it's illegal to manufacture or sell it as a supplement, and it's not available in any form as a prescription. So once again, the medical system drops the ball, and we do the best we can with what's available.

    The only other drugs which act as antagonists to ADRA2A are less powerful and far less specific. So probably much more side effects, and issues with tolerance, withdrawal, etc. And it's a nice alternative for people who can't get a doctor to give them any prescription, for whatever reasons.
     
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  12. Valentijn

    Valentijn Activity Level: 3

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    I finally remembered to check my blood pressure properly: 130/88 with a pulse of 72. That means my pulse pressure is 42, whereas prior to starting Yohimbe it mostly stayed around 35, and my pulse was usually around 85 when rested.
     
  13. lansbergen

    lansbergen Senior Member

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    As the pulse of atletes is lower than of normal people the psych could conclude you are less deconditionded now. :D:D:D
     
  14. Valentijn

    Valentijn Activity Level: 3

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    But ... but ... drugs can't help me! Only exercise! A psychologist and an extremely egotistical neurologist said so, hence it must be true :rolleyes:
     
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  15. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    Trouble is, I don't know what my adrenaline/noradrenaline(aka epinephrine/norepinephrine - how on earth does one pronounce these?!) levels are. I have doubts over whether a UK doctor would be willing to test them. Or do you test them yourself?

    Glad you've managed not to change sex yet! :thumbsup:
     
  16. Valentijn

    Valentijn Activity Level: 3

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    I got mine tested privately at a local lab which has blood platelet testing as an option, with my US ND signing off on it. They also do international testing, but you'd still have to get blood drawn somewhere. But it's a fairly common test, so I'd be surprised if there aren't private labs in the UK offering it.

    If you have low blood pressure and/or low pulse pressure (difference between systolic and diastolic values), then norepinephrine is a reasonable culprit. But if un-medicated pulse pressure and blood pressure are high or normal, then low epinephrine seems unlikely.
     
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  17. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    OK, thanks. I can take my own blood samples if no special technique is needed (e.g. if it is particularly important to avoid leakage from blood cells - I don't have the expertise for that). But it sounds as though it's unnecessary in this case.
     
  18. peggy-sue

    peggy-sue

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    Adrenaline is pronounced a-dren-a-lin
    Noradrenaline is pronounced nor-a-dren-a-lin

    the "e" at the end should not be pronounced or alter the sound of the word.

    Epinephrin(e) norepinephrin(e) are pretty much the same..

    e-pin-e-frin

    nor-e-pin-e-frin

    ;) I think.... but as we all know, that can be dodgy in PWME .:p
     
  19. MeSci

    MeSci ME/CFS since 1995; activity level 6

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    But which syllable(s) is/are stressed in the latter two?

    They seem such cumbersome (if perhaps more accurate) words. I can't imagine saying that someone is an epinephrine junkie or that they enjoy epinephrine rushes!
     
  20. SOC

    SOC Moderator and Senior Member

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    Do you have a brand suggestion? When I did a brief hunt at my favorite supplements site, all the brands I saw looked a bit dodgy. If I'm going to try something a little risky, I like to stick with brands I'm fairly confident have in the bottle what is claimed to be there.

    Do you mind saying how much is 1/4 of the max dose on your bottle?

    I need to find a doc who will test norepinephrine. Unfortunately, there's not an ND or similar anywhere near here. All "evidence-based medicine" in my neck of the woods. If only that phrase actually meant what it says....
     
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