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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Nitric oxide and its possible implication in ME/CFS (Part 1 of 2)

Discussion in 'Phoenix Rising Articles' started by Legendrew, Aug 25, 2014.

  1. alex3619

    alex3619 Senior Member

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    Dealing with multiple measures etc. can be good, but also misleading. It depends on the accuracy of the model being used. Further if interventions or changes are being looked at over time then it can get sucked into problems such as the hill climbing problem (reference to an artificial intelligence issue) where you can find local optima and minima and think it defines the space.

    I do agree though that we need to map all the interacting factors and then measure them all. I have long thought that we really need to see if the percentages of patients who have particular issues or fall into particular subgroups can actually do that for many subgroups simultaneously.

    While the deficits of the current CDC investigation are obvious, it at least allows for many variables to be studied simultaneously. I do not know enough about specific measures though to tell if its adequate.

    Another problem that can arise is due to the nature of that being measured. Most measures from blood are whole body averages. There are also temporal issues. This tells us far less than I like about what is happening in specific locations, or at specific times.

    Yet investigation has to start somewhere.

    Yet static timepoint measures tell us not that much about dynamic issues.

    One thing that might would be to take a small number of patients, say 10, then track every kind of testing there is over time, say 100 days. That is probably too long for patients to cope, so maybe 10 days would suffice, or every tenth day over a long time frame, or something similar. In other words we need detailed longitudinal measures.

    Sadly our scientific process is still not advanced enough to deal with real complexity in large complex dynamic processes. Yet we have to start somewhere.
     
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  2. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    http://townsendletter.com/FebMarch2010/cureNO0210.html

    Table 1: Agents with Favorable Response in Clinical Trials Predicted to Lower Aspects of the NO/ONOO− Cycle.

    Agent(s) Probable Mechanism Comments


    flavonoids, ecklonia cava extract, algal supplements

    chain breaking and other antioxidant activity

    Some may act as peroxynitrite scavengers.

    NMDA antagonists, other agents that indirectly lower NMDA activity; magnesium

    All act to lower excessive NMDA activity


    acetyl carnitine/carnitine, coenzyme Q10, low hyperbaric or normobaric oxygen

    Improved mitochondrial function

    Oxygen must be used with caution, particularly in severe cases of CFS/ME

    hydroxocobalamin form of vitamin B12

    Reduced in vivo to a form that is a potent nitric oxide scavenger.

    Higher dosage (i.e., 5 to 10 mg) needed than is needed to treat a B12 deficiency; Typically used via IM injection, as an inhalant, or via nasal spray to obtain high blood levels; oral or sublingual should be useful but are clearly suboptimal because of limited absorption.

    high-dose folates

    Serves as precursor of 5-methyltetrahydrofolate (5-MTHF), a potent peroxynitrite scavenger.

    Unclear whether folic acid, folinic acid, 5-MTHF and/or other forms of folate should be used; folic and folinic acid tested in published trials.

    D-ribose, RNA, inosine

    All act to increase uric acid levels (peroxynitrite scavenger); all may act to help restore ATP pools.

    Published trial on D-ribose; trial currently in progress suggesting inosine can be helpful.

    IV high dose, buffered ascorbate

    Lowers both ends of central couplet (see below); may be particularly helpful agent.

    Discussed in detail below.

    sauna therapy

    Acts to increase BH4 availabiity; mechanism via increased synthesis of GTP cyclohydrolase I.13

    Trials published on MCS, FM and CFS/ME; discussed further below.

    fish oil

    Established as anti-inflammatory agent.

    May also improve brain function.

    Most studies involved CFS/ME and/or FM; however studies with sauna therapy and IV ascorbate have been published with MCS patients.
     
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  3. lansbergen

    lansbergen Senior Member

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    Test between flares or during flare?
     
  4. ahmo

    ahmo Senior Member

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    These last weeks my quest has been to understand NO and ammonia. I searched for a website for Martin Pall several times, but found nothing. Now @Gondwanaland linked me to an article about NO/ONOO- on the Inspire website. (This site puts a dark shield over the content unless you've joined. But I was able to copy the content and paste into a document, got the whole page fine....Having joined and then unjoined, I'm no longer able to access the page.:meh:) From that site I followed a link to a Yahoo NO/ONOO- forum, to which Pall, at least historically, responds. And from there I found his website.
    I found the Yahoo group to be pretty inactive, with most of the posts of the past year concerning MCS and EMFs. However, it exists as a forum for asking questions. And in the File section there are a number of files and links. The forum and website are named The Tenth Paradigm.

    I've also gotten much closer to understanding Pall's work from his 2 hour video from March 2014. The last 20" lists his suggested supplements, which are also covered on his site. I've gotten good symptom relief following his suggestions to add ALCAR, AdB12, reseveratrol, watermelon, switch my E succinate to Gamma E.

    https://www.youtube.com/watch?feature=player_detailpage&v=6A7r1gemjto


     
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  5. hvac14400

    hvac14400 fatty & acid : )

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    this.
    i've never been veiny to any extent, but nowadays this got much worse - no any pump whatsoever in the gym.

    some food for though from my personal experience - eatin table salt as crazy (like 1/2 teaspoon 30min before each meal, sublingual) does indeed makes me feel much better and stronger.

    on the other hand any NO busters like arginine, citrulline, beet juice always makes me feel weaker, in the gym at least.

    is there any way to determine the case - low blood volume or not? any definitive signs of NO overproduction only?
     
  6. Leopardtail

    Leopardtail Senior Member

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    Definitive certainty in medicine is not quite as elusive as the holy grail, but almost. The best you can hope for is usually strong hunch worth investigating.

    NO affects so much, I suspect it would be difficult to be sure though @alex3619 might have a better idea. But the issue might not only be NO overproduction, but production of ONOO instead of NO.

    The two things that told me that blood volume as the issue were: I felt much better if I could drink a full two pints of water swiftly. I felt great when given 1.5litres of saline solution.

    The two most common causes of low blood volume if you have not had serious injury are the two anti-urination hormones, one cauess sodium loss, the other potassium loss.
    1. If you are craving salty food and still have low normal or low Sodium that indicates Aldosterone deficiency might be the issue.
    2. If you are craving Potassium Sources such as Potatoes or Bananas and still have low Potassium that could indicate AVP deficiency.
    The two hormones themselves can be tested for but GPs are not fond of doing the tests, they prefer the cheaper serum electrolytes which we often mess up the results of by compensating with diet.
     
    Last edited: Apr 1, 2016
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  7. Leopardtail

    Leopardtail Senior Member

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    Hi Heaps,

    A very comprehensive list there!

    It's also worth mentioning that good BH4 availability is required to produce NO rather than NOO or ONOO. It's effect in NO production is very similar to that of Cobamide if deficient when the producing enzyme is formed.
     
  8. alex3619

    alex3619 Senior Member

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    Let me point out some cross links in research. There was a paper last year I think that discussed possible acetylcholine receptor autoantibodies. Just a few days ago, there was a paper discussing ion channelopathy and acetylcholine receptor snps, single nucleotide polymorphisms. Different aspects of a bigger picture may be emerging, though the details are as yet elusive and any of this research may not stand up to long term scrutiny.

    If all this is right there might be different types of ME and CFS, each targeting slightly different parts of the same interlocking pathways. So some might respond to NO very well, and others might not,

    All of this is still very speculative, but its also encouraging.
     
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  9. hvac14400

    hvac14400 fatty & acid : )

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    i think trough the last years my electrolytes are going down constantly, all of them, so i have low normal sodium and potassium at the same time. and this is how my gym shirt looks like after just 3-4 sessions (front and back):


    P930010t4.JPG P93001s05.JPG


    so there's definitely something is going on with a mineral loss.
    my aldosterone was 335 pg/ml (ref 40-310 and 10-160), so def no deficiency here.
    direct renin was 35.7 mcME/ml (ref 4-46 and 4-40)
    ACTH 45 pg/ml (ref <46)

    don't know about AVP, but since it stimulates ACTH secretion it's probably ok too?
     
  10. Leopardtail

    Leopardtail Senior Member

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    When I had low blood volume, I did not sweat at all, my body preserved the fluid, so my gut hunch unless somebody else knows better would be you do not have that issue.

    I wonder whether this might be more in the realm of expertise a Sports Nutritionist would have rather than an ME forum - I am just thinking electrolytes and sport are commonly discussed?
     
    Last edited: Apr 2, 2016
  11. Leopardtail

    Leopardtail Senior Member

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    I think we have both been of the view for some time Alex that ME represents multiple subgroups each with different aetiologies. My personal suspicion is that there may well not be single aetiology per individual patient, rather a combination of two or three interlocking factors. Personally, pre-ME I have always sweated profuseley despite previously good fitness, hence my issue with blood volume may always have had an underyling water metabolism issue without the same impact as now.
     
  12. hvac14400

    hvac14400 fatty & acid : )

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    interesting.
    maybe you're not hydrated that well - i drink like 3-4 L of clear water a day.
    but anyway - the more pronounced effects of low blood volume/pressure i experience - the more i sweat in the gym, not less, that's for sure.

    i was doing sports before i got CFS, but never experienced such a massive salts loss ever in my life.

    me too, except that am still sweatin like a mofo to this day.
     
  13. *GG*

    *GG* senior member

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    What are these pics of?

    GG
     
  14. Leopardtail

    Leopardtail Senior Member

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    In my case I was drinking 14 litres of liquid a day to keep volume levels barely acceptable! My body just was not able to retain fluid due to Aldosterone deficiency. Medication side effects were also an issue.

    ACTH can be stimulated by CRH with no AVP present, so not that does not necessarily follow!
    A better indication would be how often you urinate and whether you feel dry with the levels of water you drink.
    Having a good electrolyte balance makes hormone imblance seem unlikely, but it does depend on your electrolyte intake, I confounded tests by drinking salty water.

    I don't really know enough about the regulatory mechanism for sweating to advise you on that. That was my reason for wondering whether a sports nutritionist might be a better source of advice re electrolyte consumation and sweating out what may be electrolytes.
     
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  15. hvac14400

    hvac14400 fatty & acid : )

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    :nervous:
     

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