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peroxynitrite more involved than realized ?

Discussion in 'Detox: Methylation; B12; Glutathione; Chelation' started by vortex, Mar 20, 2014.

  1. vortex

    vortex

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    I would like to put for the theory that peroxynitrite is a significant obstacle to
    healing via methylation protocol in ways we havent realized by interfering
    and or destroying much of our effort by the methylation protocol and some
    degree of success in the methylation protocol comes from an inadvertent
    co-treating and overcoming peroxynitrite.

    In other words, peroxynitrite is contributing to keeping the mitochondria
    shut down in more ways than is attributed in the current theory.

    richvank theory mentions peroxynitrite inhibits methylfolate in #3 but leaves
    out some important details of its real impact in other areas downstream.

    http://forums.phoenixrising.me/inde...tion-cycle-block-hypothesis-for-me-cfs.15701/

    Yes, peroxynitrite inhibits methylfolate but it also has its hand in shutting down other cycles
    in the methylation cycle and glutathione cycle.

    Peroxynitrite directly induces destruction of the tetrahydrobiopterin
    http://www.ncbi.nlm.nih.gov/pubmed/20184376

    Peroxynitrite Inactivation of Glutathione Peroxidase
    http://www.sciencedirect.com/science/article/pii/S0003986197904070

    But in #4 Rich attributes "Glutathione depletion lowers the affinity of the CblC"
    as the start of the block/cause, theorizing this is shutting down "methionine synthase reaction" causing the block and focusing on this can fix things.

    Although he then goes back to and mentions peroxynitrite in #7
    "The elevated peroxynitrite catabolizes methylfolate, preventing its rise in the plasma"
    he mentions it inhibits methylfolate which could contribute to some of this block but
    then stops there and goes back to b-12. It almost seems like the peroxynitrite is incorporated
    into this theory by mentioning it and saying its impact is that it inhibits methylfolate but then
    stops short there.

    He then goes back to b12 in #13 by saying the treatment should revolve
    around the b-12

    "dosage of B12 is necessary to compensate for the greatly lowered affinity for cobalamin of the CblC complementation group, so as to overcome the functional B12 deficiency,"


    So if peroxynitrite can inhibit glutathione recycling and destruction of BH4 in addition to destruction of methylfolate which inhibits methionine synthase, who knows, this might be the real reason glutathione doesnt come back up and causes CFS instead of b-12. I think peroxynitrite is interfering with more steps than we realize and that by treating this with methylation boosters like methylfolate and methylcobalamin we arent just restoring methionine synthase reactions, but we may be treating peroxynitrite directly with the supplements we are using or indirectly by overdriving methionine synthase to compensate for peroxynitrite effects of destroying bh4 and glutathione peroxidase.

    hydroxocobalamin is a peroxnitrite scavenger, which may explain why people are having a good response to this cobal over methylcobalamin which should be the only one that significantly boosts methionine synthase.

    Also methylfolate is a peroxnitrite scavenger, so it makes you wonder how much methylfolate is going towards quenching peroxynitrite and how much is going towards methionine synthase ?

    So it seems like peroxynitrite is destroying alot of our efforts and is like stepping harder on the gas while having the brakes on or turning the faucet on faster to try to fill the sink because the drain is partially open.

    So I think that if this is true, then we should focus more on directly addressing peroxynitrite/nitrotyrosine scavenging directly so we dont have to put all the load on the methionine synthase reaction to overcome all of the destruction that peroxynitrite is causing.


    So perhaps adding more peroxynitrite scavengers to the methylation protocol can help non-responders and or alter or reduce some of the doses of the methylation boosters so we dont have to compensate so much for all the destruction that peroxynitrite is doing to our efforts.

    gamma tocopherol is a known peroxynitrite scavenger, can someone add to this list ?

    This document by pall discusses some strategies to lower peroxynitrite
    http://www.csom.ca/wp-content/uploa...g-was-Right-but-for-the-Wrong-Reason-25.3.pdf
     
    Last edited: Mar 20, 2014
    kyzcreig, place, DREBS and 2 others like this.
  2. SOC

    SOC Senior Member

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    @vortex, you might want to look into the work of Dr Martin Pall for more discussion on peroxynitrite in ME/CFS. Dr Pall is a biochemist who had/has ME/CFS and improved his own condition using his knowledge of biochemistry to select appropriate (to his thinking, anyway) supplements. His thinking has many similarities to Rich's and quite a few of the supplements they recommend are the same. Rich and Marty disagreed on the interpretation of how/why the supplements work for PWME, but not a lot on which supplements help.

    This page might be a place to start. Here are several small snippets:
    This page about his Allergy Research Group supplement collection lists various components of the supplements and how Dr Pall believes they benefit ME/CFS. If you search the page for "peroxynitrite", it will be easy to find which supplements he believes are peroxynitrite scavengers.
     
    Sushi likes this.
  3. vortex

    vortex

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    thanks for the info and link.

    the last link I posted was a document from Dr. Pall you mentioned.

    Since some of the supplements marty and rich recommend are the same, has anyone been helped by supplements that just help peroxynitrite and not methylation like gamma tocopherol ? Perhaps that could separate what is helping, methylation or peroxynitrite quenching.

    I think it might be both, meaning supplements that boost methylation directly and quenching peroxynitrite at the same time that is helping people.

    has anyone brought their nitrotyrosine levels down to normal range with the methylation protcol ?
     
  4. SOC

    SOC Senior Member

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    So it was. :bang-head: Even though my cognitive function is greatly improved, it obviously still isn't great. :oops:
     
    vortex likes this.
  5. Mimi

    Mimi Senior Member

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    Ashland, OR
    I just want to add that I've been having great results with BH4 supplementation. I recently started taking L-tyrosine with it to make more dopamine after noticing the similarities between adult ADD/ADHD and ME/CFS. Turns out, low dopamine was one of the original theories of what causes ME/CFS, back when the first outbreaks happened and they were wondering if it was the same thing as Post-Polio Syndrome.
     
  6. vortex

    vortex

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    interesting, thanks for sharing that it is working, I have seen many
    experts say they dont recommend using it, as it is too low a dose
    and is not worth it, better to just take more methylfolate and make
    more, but I have always wondered if that is true.

    Can you share how you are taking the bh4 ?
    what brand and how much ?

    thanks
     
  7. Mimi

    Mimi Senior Member

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    Ashland, OR
    That's silly. How could they say if they haven't tried? BH4 is a cofactor, so you don't need much. I take 2.5 mg. Ecological Formulas along with 500 mg. tyrosine 2X. As for BH4 regeneration, I only take a little methylfolate and B6 as part of my Thorne Stress B-Complex, and I'm not currently taking NADH, although I will again soon.
     
  8. DREBS

    DREBS

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    I agree with vortex. Except (and not everyone's the same) my nitric oxide is low confirmed medical test (with symptoms of chronic cold hands and feet) was always hot before CFS/ with superoxide and peroxide high which contradicts Dr. Pauls theory. This is a theory under some of the same pretenses but looking at low NO resulting in high peroxide as a cause of CFS through ATP damage. I have read palls work and find this to be much more conducive. Super interesting and compelling read. http://www.chronicfatiguetreatments...fatigue-syndrome-nitric-oxide/comment-page-1/
     
  9. DREBS

    DREBS

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    This is also a interesting conversation of that topic http://forums.phoenixrising.me/inde...ent-of-mitochondrial-replication-in-cfs.9536/
     
  10. DREBS

    DREBS

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    Scavengers include green tea tannin, flavonoids, and Uric acid a product of purines. Rich had a pretty interesting theory about low Uric acid in people with CFS but I can't find it specially, don't know if he ever made the connection but this could also be why PWC have problems low Uric acid = high peroxynitrite. Fix purine production > increase Uric acid> reduce peronxynitrite

    How do CFS patients compare to metabolic syndrome patients? Given the heterogeneous findings for many of these tests in CFS its hard to definitively say. Some CFS patients in some studies have exhibited increased waist/hip ratios, increased sympathetic nervous system activity, low growth hormone levels, high lactic acid levels, higher c-reactive protein levels, altered electrolyte levels, increased fibrinogen, IL-6 and TNF-a. Other studies have shown differently with regard to SNS activity, growth hormone, lactic acid, fibrinogen, Il-6 and TNF-a. Dr. Cheney has stated that his patients have low, not high, uric acid levels. Virtually all studies that I am aware of have indicated increased oxidative stress in CFS. At this point there do appear to be some broad similarities between the two syndromes."- Rich
     
  11. Hip

    Hip Senior Member

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    In my peroxynitrite folder on my computer, I found the following list of peroxynitrite scavengers and inhibitors which I compiled a few years ago:

    Inhibitors of Peroxynitrite Production

    N-acetyl-cysteine
    Curcumin

    Peroxynitrite Scavengers

    Alpha lipoic acid — potent
    Ebselen (flavonoid) — potent
    Melatonin — potent
    Anthocyanins (anthocyanins are in blueberry, cranberry, bilberry, black raspberry, red raspberry, blackberry, blackcurrant, cherry)
    Caffeic acid — found in coffee, especially decaf
    Citrus juices — grapefruit juice is particularly effective
    Folinic acid
    Gamma tocopherol (a form of vitamin E)
    Ginger
    Green tea
    Resveratrol
    Rosmarinic acid (found in rosemary essential oil, and lemon balm essential oil )
    Uric acid (note that the supplement inosine increases uric acid levels in the body)
    Glutathione
    Cysteine
    Tryptophan
    Lycopene
    Luteolin
    Curcumin
    Echinacea purpurea
    Selenium — behaves as an antioxidant and peroxynitrite scavenger when incorporated into selenoproteins
    Jasmine tea
    Sage
    Slippery elm

    Protection from Peroxynitrite Damage

    Q10


    This study found that the potency of peroxynitrite scavenging was in following order:
    witch hazel bark > rosemary > jasmine tea > sage > slippery elm > black walnut leaf > Queen Anne's lace > Linden flower.

    Another list of peroxynitrite scavengers is found here.

    Note however this study, which found that the evaluation of the peroxynitrite scavenging abilities of certain supplements (such as caffeic acid) may be overstated, due to not accounting for the presence of bicarbonate, which reduces the scavenging ability.

    Note that peroxynitrite is not without benefits: this study found peroxynitrite inhibits coxsackievirus.
     
    Last edited: Mar 27, 2014
    place, kyzcreig, helen1 and 2 others like this.
  12. lansbergen

    lansbergen Senior Member

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    My immunemodulator is a superoxide scavenger
     
  13. DREBS

    DREBS

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    @iansbergen What is your immune modulator?
     
  14. lansbergen

    lansbergen Senior Member

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    levamisole
     
  15. kyzcreig

    kyzcreig

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    I've had some success following the advice of Rich and especially Marty Pall.

    What confuses me however is my response to glutathione. I feel amazing when I get an IV of glutathione or vitamin C. In fact, if I dab a lot of topical glutathione on myself before sleeping I'm basically symptom free in the morning. But it doesn't last. Could something be inhibiting glutathione recycling? Maybe there is an underlying issue depleting glutathione? Is there any connection to peroxynitrite and iNOS?
     

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