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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Blood parameters indicative of oxidative stress are associated with symptom expression in CFS

Discussion in 'Latest ME/CFS Research' started by nanonug, Mar 4, 2018.

  1. nanonug

    nanonug Senior Member

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    From https://www.ncbi.nlm.nih.gov/pubmed/10905542:

    Full blood counts, ESR, CRP, haematinics and markers for oxidative stress were measured for 33 patients diagnosed with chronic fatigue syndrome (CFS) and 27 age and sex matched controls. All participants also completed symptom questionnaires. CFS patients had increases in malondialdehyde (P <0.006), methaemoglobin (P <0.02), mean erythrocyte volume (P <0.02) and 2,3-diphosphoglycerate (P <0.04) compared with controls. Multiple regression analysis found methaemoglobin to be the principal component that differentiated between CFS patients and control subjects. Methaemoglobin was found to be the major component associated with variation in symptom expression in CFS patients (R(2) = 0.99, P <0.00001), which included fatigue, musculoskeletal symptoms, pain and sleep disturbance. Variation in levels of malondialdehyde and 2,3-diphosphoglycerate were associated with variations in cognitive symptoms and sleep disturbance (R(2) = 0.99, P <0.00001). These data suggest that oxidative stress due to excess free radical formation is a contributor to the pathology of CFS and was associated with symptom presentation.

    More info about methaemoglobin here: https://forums.phoenixrising.me/index.php?threads/methemoglobinemia.58065/
     
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  2. Zara

    Zara

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    Very interesting. My thoughts on this..

    Methaemoglobin: red bloodcells which carries oxygen due to the hemoglobine is callled oxyheamoglobin. When hemoglobine fails to carry or bind oxygen this leads to methaemoglobin.

    I asked my self what if our red bloodcells can not cary efficient amount of oxygen. And this leads to a degree of hypoxia. Where tissues and organs dont get enough oxygen e.g. brain, lungs and heart.

    I looked hypoxia up. And there are different types. But i found histotoxic hypoxia very applicable to our problem.

    Histotoxic hypoxia refers to a reduction in ATP production by the mitochondria due to a defect in the cellular usage of oxygen

    A cause of histotoxic hypoxia: inflammation, ischemia. Like in neuroinflammation diseases.

    A cause of metheahemoglobin is defect in mitochondria, pyrovate kinase deficiency.

    Sounds all very familiar.
     
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  3. Murph

    Murph :)

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    methaemoglobin
    ˌmɛθiːməˈɡləʊbɪn,mɛtˌhiːməˈɡləʊbɪn/
    noun
    Biochemistry
    noun: methaemoglobin; noun: methemoglobin; noun: met-haemoglobin; noun: met-hemoglobin
    1. a stable oxidized form of haemoglobin which is unable to release oxygen to the tissues, produced in some inherited abnormalities and by oxidizing drugs.
    looks like something it would be good to measure in patients!

    That paper is from 2000 but a couple of the researchers are still around.

    McGregor NR is this guy
    , and Butt HL is still collaborating with @ChrisArmstrong .

    I'm increasingly convinced this is vascular, and that some of the symptoms have to do with insufficient oxygen getting around the body. (Im convinced that another part of the symptoms have to do with an acute immune response. )
     
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  4. pattismith

    pattismith Senior Member

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    I didn't checked my methemoglobinemia, but I tryed Methylene Blue and saw no improvement.

    Methemoglobinemia could explain the dark color of blood.
     
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  5. nanonug

    nanonug Senior Member

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    There are several possible reasons for methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency is one of them. In the case of glucose-6-phosphate dehydrogenase deficiency (or maybe even hypofunction), methylene blue would have no effect.
     
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  6. pattismith

    pattismith Senior Member

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    I don't know why I didn't check it before, I will do that :thumbsup:
     
  7. Nine lives

    Nine lives

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    Methylene blue is contraindicated with G6PD.

    I react as if I have G6PD ( but levels look good in blood) BTW,I found this out when doing a parasite cleanse last year with a practitioner who used a lot of western products with Chinese herbs. We traced reaction (RBC destruction) to various Chinese herbs that were on G6PD (do not take list).
     
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  8. pattismith

    pattismith Senior Member

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    checked and I am ok for that one

    upload_2018-3-9_13-48-5.png
     
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  9. nanonug

    nanonug Senior Member

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    That's good news.

    Wondering what the change in value might be following vigorous exercise, though. Methemoglobin appears to increase following vigorous exercise for pretty much everyone but I'm wondering if for people with our condition the change is more dramatic. With proper controls, this would make a nice research subject.
     
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  10. sb4

    sb4 Senior Member

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    So trying to piece this together here.

    There is oxidative stress (from a virus / bacteria / whatever). To try and stop this red blood cells phosphorylate pyruvate kinase to stop glucose being converted to pyruvate and instead redirect it to NADPH pathways (???) which make reducing molecules. The oxidative stress however is too much and overpowers this pathway leading to the oxidation of Fe(2+) to Fe(3+) [Methemoglobinemia]. This colors the blood darker and means less O2 can be carried and delivered to cells. The cells, now receiving less O2, down regulate mitochondrial respiration, and produce small amounts of energy anaerobically. This leads to low energy and lots of lactic acid build up.

    This explains why Defoe found that putting CFS cells in normal blood cures them. This also explains why he thinks it's in the blood. Explains the dark colored blood, the instant lactic acid build up upon exertion, the heart pounding, etc.

    This leaves the question, why do CFS cells look normal when pyruvate is added? We know that CFS cells are capable of producing a decent amount of pyruvate to convert to lactic acid and applying more shouldn't make it any more likely to oxidize through mitochondria as insufficient O2 would still be a problem.

    So why does B1, B3, Q10, help? The only way I could see this situation resolving is through helping the blood cells reduce or removing the stressor.
     
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  11. nanonug

    nanonug Senior Member

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    I don't have readily available answers to your questions but I wonder if it has, somehow, something to do with the following:

    Mechanistic studies of the oxidation of oxyhemoglobin by peroxynitrite

    Abstract
    The strong oxidizing and nitrating agent peroxynitrite has been shown to diffuse into erythrocytes and oxidize oxyhemoglobin (oxyHb) to metHb. Because the value of the second-order rate constant for this reaction is on the order of 10(4) M(-)(1) s(-)(1) and the oxyHb concentration is about 20 mM (expressed per heme), this process is rather fast and oxyHb is considered a sink for peroxynitrite. In this work, we showed that the reaction of oxyHb with peroxynitrite, both in the presence and absence of CO(2), proceeds via the formation of oxoiron(iv)hemoglobin (ferrylHb), which in a second step is reduced to metHb and nitrate by its reaction with NO(2)(*). In the presence of physiological relevant amounts of CO(2), ferrylHb is generated by the reaction of NO(2)(*) with the coordinated superoxide of oxyHb (HbFe(III)O(2)(*)(-)). This reaction proceeds via formation of a peroxynitrato-metHb complex (HbFe(III)OONO(2)), which decomposes to generate the one-electron oxidized form of ferrylHb, the oxoiron(iv) form of hemoglobin with a radical localized on the globin. CO(3)(*)(-), the second radical formed from the reaction of peroxynitrite with CO(2), is also scavenged efficiently by oxyHb, in a reaction that finally leads to metHb production. Taken together, our results indicate that oxyHb not only scavenges peroxynitrite but also the radicals produced by its decomposition.

    If peroxynitrite is involved, and considering that peroxynitrite depends on superoxide production for its existence, I also wonder whether properly supplementing with superoxide dismutase would be a way to at least alleviate the problem.
     
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  12. sb4

    sb4 Senior Member

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    Very interesting. It's also interesting to note that the proposed mechanism of how nnEMF damages cells is through VGCC and subsequent peroxynitrate generation. This falls in line with the increase of illness such as ours with the increase of EMFs.

    I may have thought of an answer to my question. Perhaps things that divert glucose towards oxidation instead of glycolysis to lactate help because once you are running on lactate metabolism, you are in a sort of viscous circle. Lactic acid is apparently associated with NO production. NO displaces O2 from CytC C oxidase preventing respiration. Furthermore, Lactic acid reduces CO2 production, not only through shutting down respiration but I think it does through other ways like increasing stress hormones and estrogen. Now the decreased CO2 production leads to less CO2 in the blood. CO2 is needed in the blood to allow haemaglobin to hold on to oxygen (Bohr effect), which will further increase the methaemaglobin problem and lead to more lactate. The lower CO2, the more encoraged you are to take quick deep breathes which blow out even more CO2 and increase stress hormones which further reduces glucose oxidation. This also explains why people have success with the Buteyko Method.

    So this would explain why taking things that encourage glucose oxidation help, by braking the cycle. Thiamine is a Carbonic anhydrase Inhibitor. Carbonic anhydrase turns CO2 into Bicarbonate and protons. By inhibiting this you will get more blood CO2 and therefore more blood O2. Now there is more O2 in the cells, but since they are stuck in a lactic acid vicious circle, they won't use it without help. Thiamine inhibits pyruvate dehydrogenase kinase and stimulates pyruvate dehydrogenase just like your dichloroaceatate. Niacin lowers free fatty acids which tips the randle cycle more in favor of glucose oxidation as opposed to fat and oppose to lactate production. I guess CoQ10 also encouraes respiration.

    Now you have flipped the switch somewhat by both increasing O2 and shifting the balance more towards respiration instead of glycolysis. This produces a ton more ATP, less stress hormones, and you can now do more, think clearer, before getting worn out.
     
  13. sb4

    sb4 Senior Member

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    In regards to peroxynitrite, this study is interesting on it's effects on platelets. https://www.ncbi.nlm.nih.gov/pubmed/23200902

    Now healthy high energy platelets I think are important for blood flow. Basically, Pollacks work on water has shown you can get water (blood) to flow through tubes just with hydrophilic substances and light. If the platelets mitochondria are poorly functioning due to peroxynitrite, then they will presumably be less charged / lower redox and clump together. Healthy ones should have high charge, repel each other and therefore help blood flow.

    This makes sense on why my heart is always pounding really hard, my blood flow is compromised due to oxidised sickly platelets, meaning it needs more force with every pump; and my blood is carrying less oxygen due to peroxynitrite induced methaemoglobin, meaning less oxygen is delivered to tissues per pump and my platelets are producing even more lactate and less CO2. This also makes sense why light therapy (red light increases platelet mitochondrial respiration by displacing NO) has helped me.
     
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  14. Nine lives

    Nine lives

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    For peroxynitrite, I use hydroxyl B12 (as per Martin Pall's NO/ONOO theory). I had MCS from childhood and the hydroxyl B12 I believe helps with my EHS that started a few years ago). I use AOR sublinguals and now a nasal spray.
     
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  15. gregh286

    gregh286 Senior Member

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    best post read in ages sb4.
    even the findings on whitney with very low bh4,......strengthening Martin Palls work on no onoo cycle.
    Surely they would have discovered peroxynitrate in CFS subjects,,,,
    Mine too......high HR in crash,,,,,bigger the crash the higher the HR. Heart pumping sticky serum.....low NO from endothelium......peroxynitrate induced poor mito function.

    Certainly palls cocktails Vit E, flavanoids, Folates, B12, Inosine help me greatly. Quite a bit of overlap with Richs methylation protocol also.
     
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  16. neweimear

    neweimear Senior Member

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  17. gregh286

    gregh286 Senior Member

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    hi @sb4
    you're in UK, you ever try breakspear. Seems they have picked up the NO ONOO cycle, must be recently because it was never part of their literature before
    https://breakspearmedical.com/wp-co...kspear_Medical_ME_CFS_Treatment_Programme.pdf
     
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  18. sb4

    sb4 Senior Member

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    Thanks. Are these through IV? How much improvement did you get?

    Didn't know of it until now. Looks very interesting although also probably too expensive for me. It does say it accepts NHS referrals although I have almost no chance of that happening, still won't hurt to try though.
     
  19. PinkPanda

    PinkPanda Senior Member

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    https://en.wikipedia.org/wiki/Methemoglobin

    https://en.wikipedia.org/wiki/Cytochrome_b5_reductase

    Vitamin B2 is pretty helpful for me, I've been having some mixed reactions to B3 lately. NADH/H+ of course depends on B3/NAD+, but also on energy processes, citric acid cycle,.. in general.
     
    Last edited: Mar 15, 2018
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  20. gregh286

    gregh286 Senior Member

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    Last edited: Mar 15, 2018
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