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


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You are right about alpha lipoic acid's (ALA) ability to bond to mercury and create toxic organics, but I would think you would have to literally swirl a solution of ALA or the like around in your mouth to have it react with the mercury in your fillings and carry a significant dose into your body, but I do not know that for sure, nor can I find a reliable source.

 

BUT.  I used to be 100% certain that exposure to non-ionizing radiation like living beneath the power lines had no effect on people's health.  Now it looks like the magnetic fields that emanate from the power lines effect the flow of ions through our nerves.  So it does have some effect.  How significant?  No idea.  So could we someday discover that the mercury in our fillings is dangerous?  Sure.  I would bet against it, but I cannot be certain.  I think that it is smart not to get any new ones, but I also think the idea of extracting old ones is a money making scheme.

 

Intellectually, I love neurology.  I don't really care much about dentistry.  I trust my dentist.  He is a really good guy.  I asked him if I should worry about my 2 mercury fillings, and he said no, so I don't.  He uses composites now because they are better both structurally and cosmetically.

 

I think we have more important things about which to worry.

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At me last appointment my psych doc told me to try N-acetyl-cysteine as she said she has had some success with it for patients coming off of benzos.  It’s known to reduce oxidative stress and regulate glutamergic activity.  I’ve been taking it for a little more than a week and I will say that it’s been more helpful than anything I’ve tried for anxiety and nerves, including magnesium and antidepressants.  On the flip side, I’ve noticed in the past few days that I’ve felt kind of confused throughout the day and lacking motivation.  But, given the topic I thought I would mention this.
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The focus should really be aimed at glutamatergic EPSCs (Excitatory Post-Synaptic Currents) to better understand the cascade and

develop an approach to dealing with NO-ONOO and cGMP cycles.

 

Although, NO-ONOO and cGMP cycles are heavy players in neuronal death, NMDAr over-activation is still most likely the source.1

 

It is true, however, if you consider the role of nitric oxide (part of NO-ONOO) within the immune system - providing defense against cellular pathogens - basic understanding of hyper-/auto-immune models would suggest mass potential for inflammatory tissue damage.2

 

However, this isn't really anything we didn't already know about classic oxidative stress. Targeting NO-ONOO pathways would really only help to treat the symptoms and mitigate toxicity, but not address the source.

 

 

Also, please consider NO-ONOO and glutamatergic-induced altered genetic expression as both causative and sustained (in neurological perpetuity) factors within neurodegenerative and iatrogenic illness.

 

 

 

1. https://www.ncbi.nlm.nih.gov/pubmed/8931482?dopt=Abstract

 

2. https://www.ncbi.nlm.nih.gov/pubmed/26915097

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Am I ever going to be able to exercise again? My lasting symptoms are the exercise intolerance and insomnia as well as some food sensitivities. I believe this is because I didn’t slowly taper despite taking this wretched poison for only 10 measly days.

 

I did what used to be my intense weightlifting routine the first week of acute thinking it would help me heal faster and it sent me into a full blown panic attack while driving home where I nearly crashed my car.

 

I held off for a few months and worked slowly back. I would have some moments of anxiety after the workout but nothing major. Then one time in September of 2018 I did a harder workout and it sent me straight to hell for months. Two days of brain aches that manifested into worse insomnia, depression, just horrendous.

 

I abstained again until January 2019 and did a much lighter workout set and was thrown into hell yet again. This time with my entire body on fire, especially my hands. I was crying in agony. It let up after a month or so but I am deathly afraid if I’ll ever be able to exercise again.

 

I was someone who lifted 235 and weighed 170. I would run 3-4 miles 2-3x a week and even a quarter mile jog sends me into hell.

 

I simply don’t understand and scared as I’m only 38 and was in the best shape of my life before this happened. How is any of this remotely possible?

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Benzo WD causes something like ME/CFS in some ppl. I had ME prior to ever taking Benzos and they have probably been helping that as well as muscle stuff so I am fucked.

 

Post exertional malaise/symptom exacerbation is the Hall mark symptom of ME/CFS and it is known that the NOOHNOO cycle plays a roll in ME as does excess glutamate and astrocyte activation.

 

Luckily for you it seems that the ME like illness ppl get from WD typically resolves after a few years.

 

Can I suggest for now that instead of suddenly trying to do exercise you only ever do 20-20% of what you think you can. Stay within your ‘energy envelope’ and try not to raise your heart rate too much as this seems to be what makes ME symptoms worse.

 

 

 

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Benzo WD causes something like ME/CFS in some ppl. I had ME prior to ever taking Benzos and they have probably been helping that as well as muscle stuff so I am fucked.

 

Post exertional malaise/symptom exacerbation is the Hall mark symptom of ME/CFS and it is known that the NOOHNOO cycle plays a roll in ME as does excess glutamate and astrocyte activation.

 

Luckily for you it seems that the ME like illness ppl get from WD typically resolves after a few years.

 

Can I suggest for now that instead of suddenly trying to do exercise you only ever do 20-20% of what you think you can. Stay within your ‘energy envelope’ and try not to raise your heart rate too much as this seems to be what makes ME symptoms worse.

 

I haven’t done anything but gentle walking. Have not lifted since January 2019 and haven’t ran since July 2018. I am too afraid of being sent into hell again. Even just moving heavy objects caused a weird ache in my head which manifests into tingling and burning in my hands and feet. I don’t know how this is my reality from what I thought was a sleep aid for a temporary issue.

 

Is there any proof that this actually resolves? Seems like I’m fucked for life.

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Am I ever going to be able to exercise again? My lasting symptoms are the exercise intolerance and insomnia as well as some food sensitivities. I believe this is because I didn’t slowly taper despite taking this wretched poison for only 10 measly days.

 

I did what used to be my intense weightlifting routine the first week of acute thinking it would help me heal faster and it sent me into a full blown panic attack while driving home where I nearly crashed my car.

 

I held off for a few months and worked slowly back. I would have some moments of anxiety after the workout but nothing major. Then one time in September of 2018 I did a harder workout and it sent me straight to hell for months. Two days of brain aches that manifested into worse insomnia, depression, just horrendous.

 

I abstained again until January 2019 and did a much lighter workout set and was thrown into hell yet again. This time with my entire body on fire, especially my hands. I was crying in agony. It let up after a month or so but I am deathly afraid if I’ll ever be able to exercise again.

 

I was someone who lifted 235 and weighed 170. I would run 3-4 miles 2-3x a week and even a quarter mile jog sends me into hell.

 

I simply don’t understand and scared as I’m only 38 and was in the best shape of my life before this happened. How is any of this remotely possible?

 

You'll have to start out low doing something like swimming or more upper body aerobic exercise.

 

I used to run and going through all this I learned that running is the most intense exercise-induced stress the body will face.

 

Tremendous cortisol levels are required to repair muscles, taking days or even weeks. Cortisol also creates more of the glutamate neurotransmitter.

 

Over time, you'll lower the amount of glutamate created by cortisol as your heart rate (and to an extent, blood pressure) gets lower

 

To build my tolerance, I started swimming for 20-30 minutes 2-3 times per week, making sure I dosed magnesium and proper protein levels before and after.

 

You may be able to check cortisol and glutamate levels more appropriately with serotonin, but I don't advise you going on another drug just to achieve this end.

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"Nitric oxide is increasingly seen as an important factor in nerve degeneration (Doherty, 2011). Nitric oxide activates processes (Obukuro, et al., 2013) that can lead to cell death. Inhibiting the production of nitric oxide protects against various kinds of dementia (Sharma & Sharma, 2013; Sharma & Singh, 2013). Brain trauma causes a large increase in nitric oxide formation, and blocking its synthesis improves recovery (Hüttemann, et al., 2008; Gahm, et al., 2006). Organophosphates increase nitric oxide formation, and the protective anticholinergic drugs such as atropine reduce it (Chang, et al., 2001; Kim, et al., 1997). Stress, including fear (Campos, et al., 2013) and isolation (Zlatković & Filipović, 2013) can activate the formation of nitric oxide, and various mediators of inflammation also activate it. The nitric oxide in a person's exhaled breath can be used to diagnose some diseases, and it probably also reflects the level of their emotional well-being.

The increase of cholinesterase by enriched living serves to protect tissues against an accumulation of acetylcholine. The activation of nitric oxide synthesis by acetylcholine tends to block energy production, and to activate autolytic or catabolic processes, which are probably involved in the development of a thinner cerebral cortex in isolated or stressed animals. Breaking down acetylcholine rapidly, the tissue renewal processes are able to predominate in the enriched animals.

Environmental conditions that are favorable for respiratory energy production are protective against learned helplessness and neurodegeneration, and other biological problems that involve the same mechanisms. Adaptation to high altitude, which stimulates the formation of new mitochondria and increased thyroid (T3) activity, has been used for many years to treat neurological problems, and the effect has been demonstrated in animal experiments (Manukhina, et al., 2010). Bright light can reverse the cholinergic effects of inescapable stress (Flemmer, et al., 1990)."

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This is just an excerpt from one of the articles on Ray Peat's website.  I have heard him interviewed on the radio...and I think his take on things interesting and possibly applicable to our situation.

 

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"Niacinamide, like progesterone, inhibits the production of nitric oxide, and also like progesterone, it improves recovery from brain injury (Hoane, et al., 2008). In genetically altered mice with an Alzheimer's trait, niacinamide corrects the defect (Green, et al., 2008). Drugs such as atropine and antihistamines can be used in crisis situations. Bright light, without excess ultraviolet, should be available every day."

 

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Link to site here: http://raypeat.com/articles/articles/dark-side-of-stress-learned-helplessness.shtml

 

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Nitric oxide and serotonin are both neurotoxic (Joseph, et al., 1991; Skaper, et al., 1996; Parkinson, et al., 1997; Santiago, et al., 1998; Barger, et al., 2000), as a result of suppressing mitochondrial respiration. NO plays a major role in lipid peroxidation and demyelination. It's interesting to see serotonin and NO openly associated with estrogen, whose mitochondrial toxicity has been carefully hidden from public view.

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[20...]
Does this mean I should stop doing red and infrared light therapy? It's supposed to release nitric oxide. I use it for neuropathy type pain caused by withdrawal
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Do you have tightness at base of skull?

 

No I don't... my headaches mostly radiate from temples and then I just get a strange uncomfortable sensation (the best way I can describe it) which I believe to be pressure.

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  • 1 year later...

Hi

I just came across this thread the other day and been wondering if anyone has an idea if this NO-ONOO cycle could explain why some benzo users have an upbeat in WDSX after taking a vaccine?.

 

Also is there then a theory around how Benzo users, passed and present, may respond differently to getting covid or may be more susceptible to long covid (my counsellor thinks I might be if I catch it).  I haven't seen any evidence on the threads of these last 2 ideas.

 

Sorry if this post looks like a quote.  I really haven't got the hang of posting again.

 

 

 

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  • 3 weeks later...

Really - did this conversation just die out?

Has there been any new insights?  Seems like a real possibility of what is going on, but taking 15 supplements seems impossible for most of us.  Just wondering if ANYONE saw ANY sign that this is the right direction...

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I tried following the recommendations Pall has made assuming that the NO/ONOO cycle he describes is the root cause for protracted benzo withdrawal issues.

 

Sort of his silver bullet for reducing NO levels is injected hydroxocobalamin (a form of B12).  I started at injecting 2mg/day and eventually went up to 10mg/day. No joy.

 

There was a period where it seemed like it was working, but if it was it wasn't sustainable.

 

 

 

 

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Thanks Nathan for responding...Sorry to hear that but certainly not surprised.  I figured if this had a real shot at unraveling the  mystery we would see more ppl with positive result about it. 

 

Seems like no matter what we do that might help the body compensates to throw us back into the protracted withdrawal state.  Like neuroplasty gone very very wrong  :-\

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Seems like no matter what we do that might help the body compensates to throw us back into the protracted withdrawal state.  Like neuroplasty gone very very wrong  :-\

 

 

What you said there is the most consistent thing I've seen in this whole ordeal.

 

There have been a handful of things that I have tried out of a list of dozens of different trials that really seemed to work ..... for awhile.  Some of them have worked so well and for long enough that I really don't think it's placebo.  But, ultimately the body seems to compensate and return itself to this pathological state.

 

Of the things that I have tried, here's my short list of things that really seemed to have worked but were not sustainable:

 

Agmatine  - Worked very well for about 6 weeks, then ultimately become ineffective and I suffered significant rebound effects once I discontinued. When I say this one worked well, I mean that I was near normal while it was effective, at least for my mental symptoms.

 

Bacopa - Very similar to agmatine. Maybe worked not quite as long, closer to 1 month. Became ineffective then suffered significant rebound effects upon discontinuation.

 

Hydroxocobalamin (Injected) - Seemed to help but not quite as much as the first two. Did not suffer much rebound effect upon discontinuation.

 

These were the standouts from trying literally dozens of different supplements. By far, most supplements simply did nothing. No positive or negative effects. I don't think it was placebo for these three. After all, why should these three work when so many others did nothing and frankly my expectation was they would as well?  Also, the results were so consistent for so long. 4-6 weeks is a long time for me. I can sometimes kind of psych myself up for something and get a little placebo effect that might last days to maybe a week, but not to this extent and not for so long. It really felt like I was taking an effective agent that eventually my body simply compensated for which caused them to become useless in the long term.

 

I really wish I knew what was going on here, maybe it would be a clue to what our underlying issue is.

 

 

 

 

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