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The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)


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Before WD I was much better after doing the Dr Wahl diet for three years.

She cured her MS.

 

There is a TED talk on YouTube.

 

The basic premise of that and Dr Sarah Myhills work on ME/CFS is mend the mitochondria and everything else will get better.

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Thank you Sky.  60 pages I can squeeze in.  On it.

 

Ajusta,

 

Mend the mitochondria.  Hmm. Hmm. Hmm.  The problem with MS is it often goes into remission all on its own, so it is VERY hard to tell what helped and what did not.  But you did not have MS.  You have ME/CFS followed a diet and felt better?  I will add Wahl and Myhill to the (long, sigh) list.

 

How did you end up on a benzo and in benzo wd?

 

ramcon1

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It neuter spine, had surgery - on diazepam 20 years for severe muscle spasm etc after that.

Made terrible mistake deciding g to stop it.

WD literally crush g my spine and can’t take anything g.

Was on Zopiclone too as when first got ME couldn’t sleep at all - like not enough oxygen getting to brain. When first got off diazepam, same tho g bit cou,d feel it was throat closing and choking me.

 

 

 

 

Info is n ME research h to be published.

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Ajusta,

 

Wow.  So docs thru diazepam and Zopiclone on top of your ME/CFS.  Well, I guess that is just where medicine is these days.  It is up to us to change it.

 

I am sorry you are suffering so, and hope your days get better.

 

ramcon1

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I just scanned the posts on here, and please forgive me if this has been mentioned before, but I'm very interested in how Vitamin C works with nitric oxide. Can someone please explain this to me? https://www.ncbi.nlm.nih.gov/pubmed/12522125

 

Thank you!!

 

As it relates specifically to the NO/ONOO cycle, this is what Dr. Pall says about Vitamin C.

 

'There are three effects of ascorbate that may be expected to occur in response to such high levels:

 

Ascorbate is a scavenger of peroxynitrite and its breakdown products, but has only modest scavenging activity at normal ascorbate blood levels.30-32 It will be expected to have much greater scavenging activity with levels many times the normal upper level.

When peroxynitrite oxidizes BH4, the initial product is B, the one electron oxidation product. B can be reduced back to BH4 by ascorbate, which is, of course, a reducing agent.30,32 However, B is itself unstable and will probably therefore require high levels of ascorbate to efficiently produce such reduction.9,10,30

 

The very high levels of ascorbate produced by such IV treatment produces hydrogen peroxide via ascobate oxidation and concomitant reduction of molecular oxygen.21-24,33,34 Hydrogen peroxide is known to be able to induce the enzyme GTP cyclohydrolase I, the first and rate-limiting enzyme in the de novo pathway to synthesize BH4.35-37 It follows that IV ascorbate may be expected to increase the availability of BH4 by this mechanism, as well as by the preceding one.

 

It follows that IV ascorbate may be able to favorably affect both sides of the central couplet, lowering peroxynitrite and its products and also, via two distinct mechanisms, increasing availability of BH4. This set of three mechanisms collectively produces a rationale for the use of IV ascorbate in the treatment of these multisystem illnesses. To my knowledge, there has been no previous rationale for such treatment, despite its reported effectiveness.'

 

This is specifically about HIGH levels of ascorbate. Likely only achievable via IV, though he doesn't rule out the possibility of supplementation having benefits.

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Oh, wow, I can't seem to understand that either, but thank you for adding it, Nov3.

 

I'm finding that drinking lemon water every day has a calming effect on my system, and I just started it the day before yesterday. I remember I used to drink it every day, and I was very calm. I don't know why I stopped. But I've been tremendously anxious during the benzo mess, and I'm sure that's caused lots of inflammation. I'm going to keep drinking the lemon water and hope that it'll settle me down.

 

I also got an unexpected boost today: For years I haven't felt hungry at all. I would eat when it would be time to eat, but I had NO hunger pangs or anything telling me I was hungry. After a few bites, my stomach would swell up into benzo belly, and it would hurt. But today I was lying down in the afternoon and suddenly felt ravenous!!! I went into the kitchen and had a big meal, enjoyed every morsel. THAT'S how I used to feel before benzos. I truly think the lemon water is having a good effect on my stomach because of its alkalinity and blood-purifying properties. And maybe something else that I'm not aware of.

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This is the best explanation I’ve read from Pall’s book (Explaining Unexplained Illnesses - the NO OH NOO Cycle)

 

 

Once the cycle gets started by any one of a number of stressors ... a feedback loop that maintains the cycle & consequences of the cycle - excess nitric oxide, superoxide, Peroxynitrite, intracellular calcium, and inflammatory cytokines, along with excessive activity of NMDA & vanilloid receptors, and NF-KB, and substantial oxidative damage to mitochondrial components.

 

 

Any stressor can start this cycle - it can even be too much exercise!

 

 

The symptoms vary from individual to individual .... but they are the cluster of symptoms found in Chronic Fatigue, Fibromyalgia, PTSD, Chemical Sensitivity, etc. (And maybe benzo waves & protracted???)

 

The symptoms can be local in your body (your knee, or stomach, or headache, etc.). They can also be the entire body (anxiety, insomnia, fatigue, tremor, etc.)

 

 

 

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I have really felt stress after exercise, unfortunately, and many here are exercise intolerant for that reason.

 

Does this have anything to do with the vagus nerve?

 

Thanks!

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Hi Terry38,

 

There could be many reasons for the after exercise stress. I know a year ago I could work out 100% every day. Today I can’t do any exercise.

 

What the author is saying is excessive exercise could be the trigger to start the NO OH NOO cycle.

 

I don’t think it has anything to do with the vagus nerve.

 

 

:)

 

 

 

 

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Thank you, Power!

 

Have you had your catecholamines checked, particularly norepinephrine? That could tell you something about why you have difficulty exercising. My norepinephrine was, at one point, off the charts. Too much stress on the system.

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Terry and All,

 

I will not comment on the vitamin C stuff until I have adequately studied the whole NO-ONOO theory.  Yes we need BH4 to make our neurotransmitters, but how that relates to No-ONOO?  I don't know enough about that.  Yet.

 

What I can tell you with 100% certainty is why so many of us are "exercise intolerant."  Exercise, and the body heat it generates, both cause the body to raise blood levels of glutamate and histamine which poke our glutamate receptors.

 

I can feel my "head pushing" and "cravings" increase when I exercise on a bad day.

 

I am not saying exercise is unrelated to the NO-ONOO cycle. I do nit know enough to comment on that.  I just know that we "feel" the glutamate and histamine.

 

(I suspect, but cannot yet prove, that the elevated glutamate as tolerated contributes to healing)

 

Ramcon1

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Greek,

 

I love you because you literally confirm everything I know.  Exercise boosts glutamate and histamine, but also serotonin, thus the mood.

 

For what it is worth, I think it is a good idea to do light exercise as tolerated, and there are good threads that discuss this.  They had their reasons and I have mine (a little glutamate, histamine, and serotonin as tolerated SHOULD help us heal), but it has many benefits.

 

Ramcon1

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Terry -

Basically, high doses of vitamin C help with the main two things that perpetuate the NO/ONOO cycle - high peroxynitrite and low BH4.

High dose Vitamin C (IV) scavenges peroxynitrite and increases BH4.

 

...For what it's worth, many people, myself and Power included, have full blown setbacks from exercising.

Our stories echo one another in that we were pretty well off months/years after withdrawal... and then after hard work outs/cardio, we had a major setback (or trigger) and are now pretty much effed. Months and months after that exercise-induced trigger/setback.

 

Power sent me an interesting note from Pall's book where he talks about 'Overtraining Syndrome'. Stating that it can cause a trigger for the NO/ONOO cycle, HPA axis dysfunction, inflammatory cytokines, etc... If the NO/ONOO theory as it relates to benzos is accurate, this could help explain why working out too hard can cause A LOT of problems.

 

Ramcon,

in your theory, could the high levels of blood glutamate from exercise cause a setback or a 'kindling'?

 

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In my theory, glutamate from exercise should help STOP issues in the long run as our body adapts to the extra glutamate.

 

But now you tell me you and a few other members have had major "I was fine now I am not months/years later" brought on only by rigorous exercise?

 

I am going to start a thread right now.

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  • 1 month later...
To be honest, did you consider that the drug caused permanent damage to the CNS?Does that mean we can't fully recover?Whether those with worsening symptoms are experiencing secondary brain damage, including problems with excitotoxicity and oxidative stress.
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I asked my doctor about the head pressure I’m experiencing and all the other symptoms and he told me me my symptoms are psychosomatic. Ok so they’re psychosomatic, but what does that really mean?
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They're not psychosomatic; they're physical. That comes first, I believe. Then when you feel the physical symptoms coming on, your mind tries to figure out a mental reason. But I believe the reaction is firstly a physical reaction.

 

Your doctor sounds clueless. Is he?

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I asked my doctor about the head pressure I’m experiencing and all the other symptoms and he told me me my symptoms are psychosomatic. Ok so they’re psychosomatic, but what does that really mean?

 

Mr Google says...

 

'' A psychosomatic illness originates from emotional stress and manifests in the body as physical pain and other symptoms. Depression can contribute to psychosomatic illness, especially when the body's immune system has been weakened by severe and/or chronic stress. ''

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He’s a nice guy, willing to help me taper but they don’t know what causes mental illness or benzo withdrawal. They just say that it’s an increase in anxiety. The funny thing is that they’re right, but it’s such a generalized statement. I brought up some of the concepts we’ve been discussing on this thread (up regulation of glutamate receptors etc.) and he said he knew nothing of this.
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Is anyone able to comment on whether taking fairly high doses of Vit C will chelate metals?

 

Vit C is not causing any issues for me but if take Alpha Lipoic Acid or Serrapeptase get worse head fizzing, whooshing, terror, sweating etc.

 

I have a mouth full of mercury.

 

Also holistic dentist says having two different metals in mouth could be causing problems but can’t afford to do anything g about it even was well enough.

 

 

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Hey all.  Happy New Year.  Hope you are all hanging in there. 

 

Just a few facts for the worried:

 

While in a normal person, a good dose of vitamin C can have a lot of health benefits, evidence that it can actually chelate, heavy metals is sketchy at best.  If you can tolerate it, it won't hurt you, but don't expect it to take heavy metals out of your blood.

 

The mercury in your fillings cannot make you sick.  Almost all of the mercury in a filling is chemically bound to the other metals (silver, tin, etc.) so cannot form the toxic organics that hurt our neurology.  I am not a fan of the FDA, but I do believe the NIH

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388771/

 

And while psychosomatic illnesses are REAL illnesses; think of a heart attack "caused" by stress.  That happens and it does not get any more real than that; our issues are NOT psychosomatic, they are neurological. The problem is, no one knows how to measure and treat the neurological damage, yet, which is of course why we are here.  If you doc is helping you taper, keep him.  That is the only reason I still see my psychiatrist.  When he tells you your issues are psychosomatic, nod your head and smile.  It make take a few years, but we will have the last laugh on that one, I promise you that.

 

Lastly, and of no consequence to anyone else, I cannot tolerate vitamin C.  I can take the small amount in an apple, but ANY fortification in a food or even the filler ascorbyl palmitate in some supps will rev the crap out of me.  If you look on the threads about lithium and SAMe/serotonin, I found sources of lithium orotate and SAMe that specifically did not have any potential triggers like ascorbyl palmitate.

 

I hope this made some of you worry a bit less.

 

YPN,

 

Ramcon1

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My understanding is that ALA, for instance, can change to form of mercury in teeth which means it can be drawn into brain and other tissues?
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