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

[[Buddie]]

Thank you very much for this, [...]!

[[Buddie]]

The more I read in Martin Pall’s book (Explaining Unexplained Illness), the more I’m convinced it’s what’s happening in our bodies in a wave, or in protracted.

It’s a type of “neuro inflammation”, and how it can localize in our bodies, creating symptoms that are common for us, yet unique to each of us. (Like how one person might get muscle tension in the shoulder, yet someone else gets muscle tension in the stomach. Or how one person might have nerve pain in the arms and hands, yet another person has it more prominently in the legs and feet.)


We took a drug that caused a brain injury. But now many of us have stopped. Why are we still so symptomatic, or have waves and windows? Pall’s explanation, although not specifically written about benzos, explains very well what is happening in the body, brain, and cells.


An article by Paul is here - http://ei-resource.org/articles/chronic-fatigue-syndrome-articles/dr-palls-nitric-oxide-theory-a-treatment-options-for-chronic-fatigue-fibromyalgia-a-mcs/


His book on Amazon - https://www.amazon.com/gp/product/078902389X/ref=ppx_yo_dt_b_asin_title_o03_s00?


(I know some of you have already seen this info.)

[[Buddie]]

This came up in response to questions [...] asked in the Lithium thread, but look at the bottom.  If anyone here can help us with that, please do:

Nov,

All good questions.

I know that lithium ions and serotonergic meds and supps work by different mechanisms, but yes they accomplish the same goal: reduction in count, firing voltage, and current flow thru glutamate receptors, particularly NMDA.  Do I know if one will work "better" than another?  I have absolutely no idea, and I SUSPECT, have no proof, that some will respond better to one than the other.  Will they be synergistic?  I SUSPECT, I really have no way to know because no one has studied this yet, that they would be additive, as in you could get some benefit from the serotonin mechanism and additional benefit from the mechanism of lithium, but not synergistic in the truest definition of the word, as in "the whole is greater than the sum of its parts, 2+2=5."

My theories on time frame and dosages are "educated guesses."

I saw a good gastro doc.  She called herself a neurological gastroenterologist, but her neurology knowledge was not that deep.  A lot of IBS comes along with something called "visceral hypersensitivity," which is a fancy way of saying you feel your colon like a normal person feels his fingertips.  I have this.  As I said, she does not know much about neurology, but she knows, "Patient has visceral hypersensitivity.  I prescribe Zoloft.  Build from 12.5 to 50 mg and in 6 months 75% of my patients are cured."

I dig, and find surprise surprise, visceral hypersensitivity is conclusively correlated with NMDA hyperfunction.

Thus the educated guess of dose and time frame.  And keep going.  Average people who benefit from SAMe benefit from between 400 and 800 mg tops.  Another educated guess.  The lithium dose was just from googling around.  Lots of psyche journals talk about the benefits of "low dose lithium" for anxiety and depression.
Here's one article:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5854802/

When they talk about low dose 150 mg, they mean 150 mg carbonate = 28 mg lithium ion, which equals 5 1/2 - 120 mg orotate supps.  My other educated guess is that anyone with health insurance will literally pay pennies a day for 150 mg lithium carbonate med, so that recommendation was purely financial.  There is no functional difference between one 150 mg carbonate med and 5 1/2 120mg orotate supps, so if it is easier/cheaper for you to use orotate the whole time, I cannot see a difference.

And the best for last:

Yes, I do think that glutamate receptor dysfunction could really be the cause of all of our misery.  BUT, that does NOT mean that the NO-ONOO mechanism does not come into play!  There are a dozen maybe dozens of different chemical reactions that control the count and function (voltage and current) of glutamate receptors, and I have absolutely if or how much the idea if NO-ONOO is important to that control.  I have only started skimming the NO-ONOO articles, and I have a few hundred pages of stuff I need to go thru first before I get to them.  But I remember seeing peroxynitrite (ONOO) NMDA and nanotubules on the same page somewhere in some article.  Nanotubules are essential for NMDA regulation and if we can tie NO-ONOO and peroxynitrite to the formulation of nanotubules, we have a strong argument that it is VERY important to NMDA.

But right now, I, [...], do not know that.  Yet.

If you [...] or anyone who has read a lot on NO-ONOO want to post or PM me a link to the paper that says "HERE! LOOK HERE! PEROXYNITRITE NMDA NANOTUBULES IS IN THIS PAPER!" that would help me a lot.

Now I am back to work.  Today is a decent day, and I intend to use it.

Be well, and thanks for the great questions I hope will foster more discussion on all three threads.

[...]

[[Buddie]]

Hi [...] - I don’t have any links, but I recommend Pall’s book. It’s very detailed. Right now I’m reading about NMDA

[[Buddie]]

Yes, I do think that glutamate receptor dysfunction could really be the cause of all of our misery.  BUT, that does NOT mean that the NO-ONOO mechanism does not come into play!  There are a dozen maybe dozens of different chemical reactions that control the count and function (voltage and current) of glutamate receptors, and I have absolutely if or how much the idea if NO-ONOO is important to that control.  I have only started skimming the NO-ONOO articles, and I have a few hundred pages of stuff I need to go thru first before I get to them.  But I remember seeing peroxynitrite (ONOO) NMDA and nanotubules on the same page somewhere in some article.  Nanotubules are essential for NMDA regulation and if we can tie NO-ONOO and peroxynitrite to the formulation of nanotubules, we have a strong argument that it is VERY important to NMDA.

If you [...] or anyone who has read a lot on NO-ONOO want to post or PM me a link to the paper that says "HERE! LOOK HERE! PEROXYNITRITE NMDA NANOTUBULES IS IN THIS PAPER!" that would help me a lot.

As Power said, Pall's book is a great suggestion.
I would like to add, make sure you read LaCorte's article as well. As that is the root of this whole connection to benzos.

https://cdn.shopify.com/s/files/1/2161/5909/files/SL.pdf

Elevated activity of the NMDA receptors is a hallmark element of the NO/ONOO cycle that is mentioned by both Pall and LaCorte. LaCorte acknowledges the role of these receptors in later stages of 'withdrawal', but in either his or Pall's work, I don't believe there are specific mentions of the formation of nanotubules... None that I have seen.

Regardless, while excessive NMDA activity is a central part of the LaCorte/Pall's NO/ONOO cycle theory, as it is with your theory, the underlying mechanism that causes both differs greatly between the two. So the proposed solutions for rectifying each issue are totally different and I can't imagine a way to tie them together in any poetic fashion.

[...], have you reached out to the University of Arizona team that held the Benzo Withdrawal Symposium? I have spoken to a couple different members of their team. They are super cool guys; receptive to discussion and also interested in finding solutions. Maybe you could run your idea of upregulated ionotropic glutamate receptors by them. See if they have any thoughts. They might be able to provide more guidance or criticism than our non-neurochemist-minds can.

[[Buddie]]

maybe these  [...].

https://www.sciencedirect.com/science/article/pii/S000629520600596X

https://www.ncbi.nlm.nih.gov/pubmed/17118345

https://ehp.niehs.nih.gov/doi/abs/10.1289/ehp.5935

and these made interesting reading also re understanding some of all this

https://www.clinicaleducation.org/resources/reviews/are-you-nitric-oxide-deficient-part-1-of-2/

https://www.clinicaleducation.org/resources/reviews/are-you-nitric-oxide-deficient-part-2-of-2/

And a you tube vid by Dr Nathan Bryan

https://youtu.be/ue4vKj9sM54

[[Buddie]]

The more I read in Martin Pall’s book (Explaining Unexplained Illness), the more I’m convinced it’s what’s happening in our bodies in a wave, or in protracted.

It’s a type of “neuro inflammation”, and how it can localize in our bodies, creating symptoms that are common for us, yet unique to each of us. (Like how one person might get muscle tension in the shoulder, yet someone else gets muscle tension in the stomach. Or how one person might have nerve pain in the arms and hands, yet another person has it more prominently in the legs and feet.)


We took a drug that caused a brain injury. But now many of us have stopped. Why are we still so symptomatic, or have waves and windows? Pall’s explanation, although not specifically written about benzos, explains very well what is happening in the body, brain, and cells.


An article by Paul is here - http://ei-resource.org/articles/chronic-fatigue-syndrome-articles/dr-palls-nitric-oxide-theory-a-treatment-options-for-chronic-fatigue-fibromyalgia-a-mcs/


His book on Amazon - https://www.amazon.com/gp/product/078902389X/ref=ppx_yo_dt_b_asin_title_o03_s00?


(I know some of you have already seen this info.)

and as it says in that article by Paul you included Nov 3

 however  that book is rather  a heavy read for many  me included.   

excessive NMDA activity is involved leading to increased nNOS activity. It follows that no single form of nitric oxide synthase is involved, but rather the common factor is nitric oxide. I have argued that the most important consequences of this are mediated not through nitric oxide itself but rather through the action of the oxidant product of nitric oxide, peroxynitrite.

 

[[Buddie]]

Just wanted to chime in real quick here. I've stopped the supplement protocol that I was trying out from some links that were orignally posted on this topic. It was said that there may be efficacy in supplementing to shift this NO cycle.... I didn't notice any positives over a two week period except for a small amount of energy in the beginning. Most of what I experienced the following days / weeks were similar but there was an added "edginess" on top of my regular symptoms. And a few days filled with feeling with feeling a little worse if that's possible. This could have been some detoxing happening... I'm not sure.

I may pick this up again in a week or so but for the time being, I am only taking EMP (vitamin / mineral combo), SAM-E, Lithium Orotate, Vitamin C, Vitamin D, and possibly some vit K2 (for the Vitamin D), ginger w/ black charcoal combo.

I was taking the following:

ALCAR
Alpha-Lipoic Acid
Ubiquinol (Q10)
Advnced Multi B
Beta Carotene
Vitamin E
Green Tea (Phytosome)
Glutathione
Selenium


Part of the protocol that I wasn't really taking:

Betaine
Zinc
Magnesium
...also missing some outlying supplements which I didn't have.

I'm not sure why but when I take magnesium and / or zinc, I feel worse. So I didn't take them really at all (I think I had one or two days of both). Betaine gives me a little bit of acid reflux so I don't like it but I was taking it every few days.

[[Buddie]]

Buddies,

I have thousands of pages I need to read in a hurry, I want to know more about Pall's NO-ONOO theory, especially how it pertains to NMDA and microtubules (I misspoke previously about "nanotubules, or maybe that is someone else's term for them)

To those of you who have read the book:
1. How many pages is it?
2. Is there information in the book beyond the available articles on PubMed, as they pertain to NMDA and microtubules?
3. If you know of an article that discussed NO-ONOO, NMDA, and Microtubules, can you post it here?

Thank you, in advance, for your help.

[...]

[[Buddie]]

Hi [...],

The book is 446 pages. In looking at the Index, I don’t see the word “microtubules”