Author Topic: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)  (Read 1529 times)

[Buddie]

Ok Buddies,

This is part of a thread that came from the "Protracted" area, where we were discussing ideas to actively reverse the damage benzos has caused us.  This was one of the ideas, and we will move the best of the posts on that topic here.

If you were not part of the original thread, give us a day to move the topics.  It is now 12:30 pm Eastern US time on Tuesday Nov. 6.  Please wait until Midnight Thursday Nov 8 wherever you live to make any comments on this topic.

Thank you all for your cooperation.

[...]
Your personal neuroscientist, reminding you to hang in there, and if you are going thru hell, keep going!
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[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #1 on: November 06, 2019, 09:10:00 pm »
Following
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #2 on: November 06, 2019, 09:13:53 pm »
Following. :thumbsup: :thumbsup:

Regulation of brain glutamate metabolism by nitric oxide and S-nitrosylation

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746709/#R39

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4746709/
« Last Edit: November 06, 2019, 10:54:28 pm by [Buddie] »
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #3 on: November 07, 2019, 12:43:35 am »
My initial post regarding NO/ONOO on the protracted board.
...................................................................................

An NO/ONOO(−) cycle disorder is a cascading, biochemical vicious cycle. A pathophysiological mechanism that repeats and habituates after it is triggered by certain stressors. It is theorized to be the same basic, propagating cycle that causes a myriad of multisystem, chronic illnesses - fibromyalgia, dysautonomia, PTSD, chronic fatigue, multiple chemical sensitivity, etc. etc.  Common NO/ONOO(−) cycle elements include elevated peroxynitrite and the depletion of BH4, elevated activity of the NMDA receptors and excitotoxicity (sound familiar?), an inflammatory cascade, mitochondrial dysfunction which leads to lowered energy metabolism and depletion of ATP, etc.

This biochemical process happens at a cellular level and thus, can be focused on any location or tissue in the body. Its location determines the symptoms or diseases that manifest... All of which are different, but caused by the same issues happening in different cells or tissues. LaCorte does an incredible job of elucidating the neurophysiological process that benzos initiate and how that triggers the perpetuating NO/ONOO(−) cycle. I.e. Potentiation of calcium channels and excessive NMDA activity result in calcium influx into the cell that creates nitric oxide synthesis, which leads to high peroxynitrite formation, which results in the triggering of the aforementioned cycle....... said NO/ONOO(−) cycle is caused by and results in this central couplet of low BH4 and excessive peroxynitrite, and thus the vicious cycle.

There have been studies that apparently implicate certain genes as making one more susceptible to this cycle and the accompanying diseases. Which would explain why not all of benzo users fall victim to the protracted sh*t... I actually reached out and have been speaking to the team at the University of Arizona who held the Benzo Withdrawal Symposium last month. One of the speakers, Steven Wright, really likes this theory. I do too. It seems to add up and make a lot of sense. Especially since my symptoms are basically the exact ones I mentioned; fibromyalgia, dysautonomia, PTSD, chronic fatigue, multiple chemical sensitivity, yes to all.
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #4 on: November 07, 2019, 12:55:23 am »
@[...] said the following on the protracted board...


I was very functional during tolerance, taper, and first 16 months benzo free. But something changed, I’ve gotten much worse, and vertigo has me bed bound now almost 9 months.

The NO OH NOO theory gives a sound explanation for what might of happened to me, and many of us, and why we don’t seem to get better. (A “trauma” or trigger or catalyst that starts the process. And once the process starts, it begins a cascade of events, and it’s hard to stop.)


I just wanted to echo this... My first 2 years off, I was *mostly* functional. I had some serious pain and nerve issues (w/d awoke a nerve condition called MALS that resulted in major surgery) but aside from that, I was pretty decent all things considered.
I had a setback at 2 years that has been way worse than acute and left me with new symptoms I never even had during acute (all of which align perfectly with NO/ONOO disorders).... major dysautonomia, pain in random places that mirrors fibromyalgia, other symptoms of fibro and dysautonomia like sensitivity to light and sound, chronic fatigue, chemical sensitivity, etc. All hallmarks of NO/ONOO, all arising after a stressor at 2 years post benzo.
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #5 on: November 07, 2019, 06:40:50 pm »
NO OH NOO

I was very functional during tolerance, taper, and first 16 months benzo free. But something changed, I’ve gotten much worse, and vertigo has me bed bound now almost 9 months.

The NO OH NOO theory gives a sound explanation for what might of happened to me, and many of us, and why we don’t seem to get better. (A “trauma” or trigger or catalyst that starts the process. And once the process starts, it begins a cascade of events, and it’s hard to stop.)

The very simple bio-chemical-cellular action: creation of peroxynitrite, which in turn causes a cascade of events at the cellular level, including an influx of calcium. (And your intake of calcium has no effect here).

That in turn leads to symptoms - symptoms which are unique to the individual, and even unique in certain parts of your body.

And then the symptoms that come - ones that are common for benzo, PTSD, fibromyalgia, etc., yet unique to each individual: insomnia, “anxiety”, fear, cognition, muscle tension, nerve issues, vertigo, tinnitus, etc. And what is happening in the hippocampus, amygdala, disruption to HPA axis, etc.

The cycle, the inflammation, what’s happening on the cellular level & calcium, need to be looked at.

I think the author and his theory are some of the primary references by used by S. Lacorte from BIC here https://cdn.shopify.com/s/files/1/2161/5909/files/SL.pdf

The author’s explanation of the ‘inflammation’, and the cascading events that happen next seem spot on.

Complete article here -  http://ei-resource.org/articles/chronic-fatigue-syndrome-articles/dr-palls-nitric-oxide-theory-a-treatment-options-for-chronic-fatigue-fibromyalgia-a-mcs/
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #6 on: November 07, 2019, 06:49:41 pm »
I completely agree with this, and believe that this happened to me, too. Thank you for the explanation, [...]!!
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #7 on: November 07, 2019, 07:28:06 pm »
I have a horrible feeling that diazepam was not only helping severe muscle issues I was put on it for but has also helped the Neuro symptoms of the ME/CFS I was diagnosed with in 1996 before any meds.
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[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #8 on: November 07, 2019, 09:30:28 pm »
Hi friends,


A bit about NO OH NOO theory:


It has gained popularity by research and then a book by Martin Pall Ph.D.

The theory is that a “stress” can start the process. The stress can be just about anything - an injury, exposure to a toxin, everyday life stressors, psychological stress, a virus or bacteria, mold, medicines, exposure to something traumatic, etc. etc.

The actual chemical process is NO. + OO.- ———————————> ONOO-

It is pronounced NO OH NOO

NO stands for Nitric Oxide.

A big takeaway once the process starts - it creates too much Peroxynitrite.

When there is too much Peroxynitrite in a cell, it creates all kinds of problems - elevated levels of peroxynitrite or inflammatory cytokines, oxidative stress and elevated NMDA and vanilloid receptor activity.

And when those problems happen, it creates “unexplained” illnesses and symptoms like PTSD, fibromyalgia, Chemical Sensitivities, Chronic Fatigue, insomnia, “anxiety”, fear, cognition, rage, fatigue, muscle tension, nerve issues, vertigo, tinnitus, etc. In his book he goes into greater detail, including what is happening on a molecular level, and what is happening in the hippocampus, amygdala, disruption to HPA axis, etc.


An article explaining this by Martin 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, called Explaining Unexplained Illnesses is here on Amazon - https://www.amazon.com/gp/product/078902389X/ref=ppx_yo_dt_b_asin_title_o03_s00?ie=UTF8&psc=1


He does have a supplement protocol for stopping this process.

Vitamin C
Tocopherols/Tocotrienols
Selenium
Carotenoids
Flavonoids
Reductive stress relieving agents
Mitochondrial regeneration agents
L-Carnitine/Acetyl-L-carnitine
Hydroxocobalamin/B12
Folic acid
Vitamin B6/pyridoxal phosphate
Riboflavin
Other B vitamins
Glutathione/glutathione precursors
alpha-Lipoic acid
Magnesium
SOD minerals/zinc,manganese, copper
NMDA antagonists
Riluzole
Taurine
Inosine/uric acid
Long chain omega-3 fatty acids
Agents that lower NF-kappa B activity
Curcumin
Algal supplements
Hyperbaric oxygen
Minocycline and Other Tetracyclines
Creatine
Lowered vanilloid activity
Carnosine
TRH
Magnesium
Zinc



This process seems to fit what so many of us are going thru ....




Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.

[Buddie]

Re: The NO-ONOO theory of oxidative stress as the cause of disease (ML Pall)
« Reply #9 on: November 08, 2019, 01:20:54 am »
Here is a link to a line of over-the-counter supplements that were developed by Martin Pall himself. There are 8 of them. They combine many of the things listed above by Power. In speaking to Dr. Pall, he also recommended adding magnesium, selenium, and zinc to this stack.

https://www.nutricology.com/martin-pall-products/

In a lot of his writings, he states that the supplement stacks seem to help people considerably with symptoms, but not necessarily 'cures'. To shoot for more cures, he suggests that there be extra focus on lowering the central couplet (lower peroxynitrite and raise BH4)... Some additional things that might be beneficial to add to your regimen would therefore be:
IV of vitamin C (an important one), intranasal glutathione, sauna therapy, RNA (in the form of nutritional yeast), etc. 

With this supplement regimen, I think there are two other things that are very important in downregulating the cycle...
1. Avoiding stressors that will just continue to perpetuate the cycle. 2. Avoiding EMF radiation, which seems to be a key concept in Pall's ideas - also referenced in LaCorte's.

This is not an easy regimen to follow. Lots of supplements, all quite expensive. Avoiding stress and the normal hustle and bustle and modern lifestyle...... I feel like, best case scenario, one would retreat for a few months. Exist in nature, away from stress and technology, all the while hitting this supplemental regimen hard. I think that'd give us the best chance...... But, not sure how realistic that is for most. *shrugs*
Suggestions, opinions and/or advice provided by the author of this post should not be regarded as medical advice; nor should it substitute for professional medical care. Consult your doctor before making any changes to your medication. Please read our Community Policy Documents board for further information.