Members with knowledge of no/onoo hypothesis

Davsey27

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In Martin Pall's theory, would tested N.O. levels be elevated or reduced?
I think Martin Pall had mentioned that in conditions like me/cfs,mcas,gulf war syndrome there is elevated no

There maybe exceptions but it seems that through whatever mechanism excess oxidative stress is likely
 
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Interesting. I've been checking my N.O. levels over the past week or so, and was surprised to find that it was 'depleted'.
My theory is that endogenous N.O. is compromised by peroxynitrite production.
I experimented by munching a whole bag of rocket (arugula) - which is packed with nitrates - and this boosted my N.O. levels over a 24hr period.
How do you go about reducing ONOO?
 
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I'm no expert but I've seen it suggested that one of the primary potential drivers of ONOO is a failure to synthesize NO properly and this failure to synthesize NO properly drives the body to keep trying to produce it (NO) so that may be a reason why it could be seen to be in excess.

One part of the equation can be a BH4 (tetrahydrobiopterin) deficiency. BH4 is an essential cofactor for making nitric oxide so Kuvan that Learner1 benefits from can be addressing both a BH4 and NO conversion deficiency.

Interestingly, a subset of people with ME/CFS have found that supplying NO directly (with some form of NO donor) gives them significant symptom improvement, so doing this could be then be removing the driving force that makes ONOO.
 
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I'm no expert but I've seen it suggested that one of the primary potential drivers of ONOO is a failure to synthesize NO properly and this failure to synthesize NO properly drives the body to keep trying to produce it (NO) so that may be a reason why it could be seen to be in excess.

One part of the equation can be a BH4 (tetrahydrobiopterin) deficiency. BH4 is an essential cofactor for making nitric oxide so Kuvan that Learner1 benefits from can be addressing both a BH4 and NO conversion deficiency.

Interestingly, a subset of people with ME/CFS have found that supplying NO directly (with some form of NO donor) gives them significant symptom improvement, so doing this could be then be removing the driving force that makes ONOO.
Thanks for this. Very interesting and may explain why my systemic levels of NO are low. My presumption is that eating foods high in nitrates bypasses this endogenous process and directly bumps up NO.
Haven't heard of Kuvan - will research that.
 
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Very interesting and may explain why my systemic levels of NO are low. My presumption is that eating foods high in nitrates bypasses this endogenous process and directly bumps up NO.
Nitric oxide researcher Dave Whitlock disagrees with Pall's hypothesis and interestingly, he suggests getting NO from your diet is the best bang for your buck.
http://web.archive.org/web/20150403...tments/chronic-fatigue-syndrome-nitric-oxide/
Haven't heard of Kuvan - will research that
Kuvan is still an expensive prescription med and other BH4 supplements may be inferior products.
https://forums.phoenixrising.me/thr...ansmitters-treating-nitrosative-stress.79994/
 
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Nitric oxide researcher Dave Whitlock disagrees with Pall's hypothesis and interestingly, he suggests getting NO from your diet is the best bang for your buck.
http://web.archive.org/web/20150403...tments/chronic-fatigue-syndrome-nitric-oxide/

Kuvan is still an expensive prescription med and other BH4 supplements may be inferior products.
https://forums.phoenixrising.me/thr...ansmitters-treating-nitrosative-stress.79994/
Re Kuvan: yes, I noted that. Support of BH4 production via methyl folate seems a more feasible tactic.
Fwiw, a half bag of babyleaf salad with arugula (rocket) raises my NO from 'depleted' to 'target' or even 'high' within an hour and a half. The level diminshes over time, but there is still some effect more than 12 hrs later.
 
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That's not a bad idea - damage control if all else fails - though prevenging peroxynitrate in the first place might be better. if increasing NO without preventy peroxynitrate, might be like subbing one bad thing with another.

remind me what ONOO stands for?

and very ineresing all those componds make your me symptoms worse.
 
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But if your boosting your NO, how are you keeping it from forming peroxynitrite ?
It's only a hypothesis that NO can be the "x factor" to cause ME/CFS symptoms due to peroxynitite (ONOO) and no one has substantiated evidence of cause and effect from it. NO itself can also terminate some free radical processes and stop radical chain propagation reactions so that is presumably what is happening in the subset where NO supplementation is significantly beneficial.
 
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This is a fascinating paper dealing with peroxynitrite, uncoupling of eNOS, scavengers of peroxynitrite which prevent uncoupling of eNOS (including urate and ascorbate)

https://pubmed.ncbi.nlm.nih.gov/15963955/
'treatment [....] with the combination of either urate with ascorbate or urate with cysteine completely prevented eNOS uncoupling caused by ONOO-. We conclude that the reducing and acidic properties of urate are important in effective scavenging of peroxynitrite and that cysteine and ascorbate markedly augment urate's antioxidant effect by reducing urate-derived radicals.'
 
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One study on the metabolic features of CFS / ME finds that:

'Plasma uric acid (urate) was decreased in males with CFS (Table 2, Males). Uric acid is the end product of purine metabolism and an important antioxidant molecule'.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5027464/#s1title

I would imagine that prevention of ENOS uncoupling would curtail the feedback loop of overproduction of NO.
I suppose it would be sensible to get my uric acid levels checked before attempting to increase them (given risks of gout / kidney stones with elevated urate).
 
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@kangaSue
But regardless of whether any theory that says peroxynitite is involved in CFS is true or not, it is undisputated that peroxynitite is BAD because it is an oxidizer. And when you increase NO, in the presense of superoxide (which alot of us have to excess), then the NO and the superoxide react to form peroxynitite .

So it is back to the original question to those who are trying to boost their NO levels, was wondering if they are doing something in addition to deal with an expected rise in peroxynite. Wishful had a good idea to then scavenge that oxidizer with assorted things she listed, but maybe those how have been increasing their NO have done other things (or those).

lookd likr muck...just posted a link to how to nuetralize the peroxynite, so that's cool.
 
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@muckledug
Thanks for posting that study. I will read the paper. I know what you mean about wanting to check levels before playing around; i try to do that to, but sometimes give up ;in the name of too much to do. In my case, i think my blood uric acid was "fine" (will look again) - I had it chekced because of joint pains- but i have high oxalic acid in urine. (and my urine is very acidic plus have high urine ammonia levels. I eat very low protein, so not sure what that's all about-

(but if i say any more, the exuberant gatekeepers will WHISK away my post and put it in some new topic of their creation. so i guess that's a side note for moderators, which also may get whisked away...: please consider not being too religious about pruning side discussins that pop up. Some of the best things i've read are from those free associated thinking that end up off-topic and theyre not findable/and or not as helpful when pulled out context. keep in mind that the rest of the crowd can - and do - police things well when they get too off topic. )
 
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ok, just read the abstract. The paper itself will have to wait til i have the energy to play 2FA. So one also needs, as you were saying, ascorbate or cysteine at the same time as the uric acid in part to prevent the new oxidizing problems caused by uric acid. it alwasy gets so complicated once one starts playing the grand Biochemist in the sky.

I wonder how much leeway one hs as with "at the same time" - having to have vit C or cysteine there at same time. Also wonders how much bodily cysteine it may use up if say one tends to have an adequate supply of cysteine levels usually.

.