Countering Nitric Oxide

percyval577

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If Nitric Oxide is high in the brain its effects could be countered (effects, message #18).
The following integredients in 0.75 l water are not a miracle but can be quite a good help sometimes
(in my experiences).

in gram:
250-500 ... TYR --- tyrosine
50 .............Se --- selenium
100 ...........VitC --- vitamine C
250 .. ........TRP --- tryptophan
10 .............Zn --- zinc
150 ...........K --- potassium
166 ...................Taurin

166 - 250 .Met --- metionine
50 ............HIS --- histidine ............. in addition these last two integredients help me for some reason
.................Hops in alcoholfree beer is a potent inhibitor of NO production by iNOS, in my experience.


Acetylcholine, GABA and NMDAR´s are not already countered. ->

HERE COULD BE UNKNOWN SIDEEFFECTS - on the long run
As an Anticholinergic I use (seperatly) tomatoegreen: 10cm in 2cl hot water for one minute.
This lasts for a couple of days. I take only half a teaspoon or something like that
and put it into drinks. Good an effect.
Tomatoeplants contain to a small extent alkaloids which are strong anticholinergics (a poison).
All Nightshades/Solanaceae contain alkaloids, eg tabaco.
HERE COULD BE UNKNOWN SIDEEFFECTS - there are no experiences with tomatoegreen

GABA can be countered (elevated) by eating oranges or drinking orangejuice (in my experience).
NO production via (high amount of) NMDR´s stays uncountered here.
It´s not a good idea to add inhibitors like Agmatine or Dextrometorphan without capsula, the PNS gets a bit deaf. Dextrometorphane can be bought as cough syrup, but it might be as well a bad idea to add it to the water.
 
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Wishful

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Peroxynitrite (made from NO and superoxide) scavengers make my symptoms much worse, so if anything I have too little NO. ...or maybe too little superoxide. I haven't considered it important enough a question to experiment with little blue pills. :rolleyes:
 

Judee

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I thought nitric oxide was a very very good thing to have on board.
I get the impression from the many posts I have seen talking for and/or against it that some pwME/CFS benefit from the increase in NO but that others feel worse. (I think I'm in the latter category.)

I've wondered about the mechanism of that. It seems to work that same way with choline. If I take choline, I get horrible brain fog but others recommend it. ???

If someone like @Hip could comment on both of these, I would appreciate the clarification. Also suggestions on how to undo the damage when we have taken one or the other and need an antidote would be very helpful.

@percyval577, I'm glad you posted this and plan to try some of these things. :)

Edit: Oh, and Gaba--horrible, horrible brain fog from that.
 
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percyval577

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I've wondered about the mechanism of that. It seems to work that same way with choline. If I take choline, I get horrible brain fog but others recommend it. ???

Edit: Oh, and Gaba--horrible, horrible brain fog from that.
Hallo Judee, I tried to examine the possibilies of choline in respect of acetylcholine here. It is very short, I put it in small letters. Don´t know if this helps. I need to diminsh acetylcholine and better avoid choline, in eggs eg.

Gaba might appear to react on nitric oxide differently in different brain regions, this could also be an issue. There are not many papers on gaba and nitric oxide, but it could be guessed under the preassumption that manganese elevates nitric oxide. There are more papers on the relation manganese - gaba, Some of the literature can be found here in post #18.

@Runner5 and @Wishful I would be curious what you would experience. I know that I have to much nitric oxide from bad effects that arise from arginine, the precursor of nitric oxide.
 
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Wishful

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I haven't experimented with choline or gaba levels. L-arginine and citrulline had no noticeable effects on me, so I don't think I'm producing too little NO. Reducing peroxynitrite level (taking peroxynitrite scavengers) does dramatically increase my symptoms, so I guess that the problem is that peroxynitrite does something important (such as destroying superoxide dismutase), and reducing that function has significant effects.
 

Learner1

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Reducing peroxynitrite level (taking peroxynitrite scavengers) does dramatically increase my symptoms, so I guess that the problem is that peroxynitrite does something important (such as destroying superoxide dismutase), and reducing that function has significant effects.
This doesn't make much sense. Peroxynitrites inhibit mitochondria complex I and damage mitochondrial membranes. Removing peroxynitrites should help.

Peroxynitrites are formed instantaneously with high NO when superoxide are formed when making ATP in mitochondria, and there's not enough superoxide dismutase to neutralize the superoxide radicals.

I'd be curious of how you know you are monitoring your peroxynitrite status to know if your scavenger intake is indeed effective.

Could it be possible that there are other reasons you develop symptoms from taking the scavengers? Which ones are you taking? (Mobilizing toxins without being able to fully excrete them so they get reabsorbed could be a possibility.)
 

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Wishful

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Biology isn't as simple as 'peroxynitrite is bad'. It has all sorts of effects, some of which are beneficial and some of which are critical for proper function. Maybe they reduce mitochondrial function by 5%, but affect something critical reaction by 50%. My hypothesis is that many of my symptoms arise from kynurenines, which are produced through IDO (indole oxidase) using superoxide. As far as I understand, IDO hangs around until deactivated by peroxynitrite. Therefore, reducing peroxynitrite would result in a longer lifespan for IDO, increasing TRP->kynurenine catabolism. That's just an amateur's hypothesis, since I don't know the reaction rates and all other factors involved. It just fits what I've observed.

I can't measure cerebral peroxynitrite levels. The stuff has a very short half-life and only travels very short distances, so it probably stays mostly in the cell, or maybe the mitochondria, where it's produced. What I have done is tried several known peroxynitrite scavengers--cinnamon, turmeric, resveratol, and a couple others I can't remember at the moment. All of them cause a very strong worsening of my symptoms. I'd have to dig through my journal to find the time delay for that. Most of these have antioxidant properties too, so it's not easy to determine which is responsible, but I've tried antioxidants that aren't listed among strong peroxynitrite scavengers, and they don't have a strong effect.

In the early days, when I thought this was some weird chronic inflammation, I believed that I wasn't producing enough superoxide. Vitamin C and other antioxidants seemed to make me feel worse. Maybe that was due to peroxynitrite scavenging too; I'm not sure.

I think some researcher should do some tests on me to verify this effect, since it's an interesting repeatable effect. They should also study the cumin effect and the T2 effect. Alas, my emailbox is empty of requests for blood or CSF samples... :(
 

Hip

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If someone like @Hip could comment on both of these, I would appreciate the clarification.
I don't think there is any consensus as to whether high levels of NO are good or bad. NO is a reactive nitrogen species, which like reactive oxygen species, can damage cells. But at the same time, if the high NO is there for a reason, countering a viral infection for example (the immune system makes NO to inhibit pathogens), lowering NO could be counterproductive.

Whitlock had the idea that ME/CFS and autism may be due to low NO, whereas Pall thinks ME/CFS might be due to high NO (and high peroxynitrite). A thread discussing Whitlock's low NO ideas is found here.
 

percyval577

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Arginine can also activate latent herpes viruses, which could be responsible for some of those bad effects. Just a thought.
Good point. I have just read here somewhere that arginine would serve EBV. Interestingly just my onset.

"know" yes it is only one influence that possibly points to nitric oxide. Along with others then it gives the idea. Sorry for the inaccuracy, rather important.

A further point is that it seems that my EBV sometimes reactivates, but it does not worsen my neurological symptoms (whereas small amounts of bacteria do, in ham eg).
 

Runner5

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I eat a lot of beets, I thought that was supposed to increase NO. I think though this thread is above my pay-grade of understanding. :D
 

Wayne

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I think though this thread is above my pay-grade of understanding. :D
It seems most thread are for me... ;) Just to mention, my understanding--and it could be incorrect--is that it's actually beet roots that increase NO, and beets only do so quite minimally. My local coop actually sells beet root, which I bought. Now if I could just get started on doing some experimenting with it. All these monumental tasks on my "to do" list. :angel:
 

Wishful

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@Wishful you could have nitrotyrosine levels measured which could give you an idea of of you have high or low peroxynitrite levels.
Yes, that would provide a number, though it would be hard to get a CSF sample tested, and serum levels of that might be misleading. However, then what? Where do I find an expert who can interpret the number properly and use it to prescribe possible treatments? If a ME/CFS researcher asked for a CSF or blood sample to see if this gave some insight into the disorder, I'd certainly be willing, but without that sort of research effort to follow, it seems a waste of effort. This peroxynitrite scavenger effect seems to be one of those individual ME/CFS issues, since other people have reported reduced symptoms from cinnamon, turmeric, and other effective scavengers.

I've become a bit disillusioned with making a big effort to isolate some factor of my disorder in the hope of getting some progress, and then finding that no one in the medical system cares. :(
 

percyval577

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Whitlock had the idea that ME/CFS and autism may be due to low NO, whereas Pall thinks ME/CFS might be due to high NO (and high peroxynitrite).
Nitric oxide has been guessed to cause central senzitation. Especially interesting in view of GET, because GET then could not yield any long term progress, logically. And this is especially what we report, if not the opposite, as we even can get worse.


Ferraro, Sardo 2004: "Nitric Oxide and brain hyperexitability."
concluding marks​
"...in this review we have reported and discussed evidence supporting either the pro-convulsant/neurotoxic or the anti-convulsant/neuroprotetive effects, or both. Although no definitive conclusions are possible yet, one can observe that the NO system, characterized by a surpsising functional adaptability, is able to induce totally different effects on neuronal hyperexitability,

in relation to the modifactions induced on neighbouring neurotransmitters
by different epileptic models."



Nijs, van de Velde, Meirleir 2005: "Pain in patients with chronic fatique syndrom: does nitric oxide trigger central sensitation."
abstract​
"Previous studies have provided evidence supportative of the clinical importance of widespread pain in patients with chronic fatique syndrom (CFS): pain severity may account for 26-34% of the variability in the CFS patients,´s activity limitations and participation restrictions.

The etiology of wide spreaad pain in CFS remains to be elucidated, but sensitation of the central nervous system has been suggsted to take part of CFS pathophysiology. It is hypothesised that nitric oxide (NO)-dependent reduction in inhibitory activity of the central nervous system and consequent central sensitation accounts for chronic widespread pain in CFS patients."

"In addition, the evidence adressing behaviroul changes in CFS patients fits the central sensitation-hypothesis: catastrophizing, avoidance behaviour, and somatization may result in, or are initiated by sensitation of the central nervous system."


(As above indicated, NO will change almost all sorts of nerves.)
 

Crux

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Hi @percyval577 ;

I'm trialing bile acids and tudca for many reasons, but , I saw that tudca is an effective iNOS inhibitor.

I'm on day 3, but feeling better, still could be placebo, don't know. Feet aren't numb today, one of my NO (?) symptoms.
I'm going to report to @mariovitali , when I'm more sure.

Here's a paper about it - involves animal testing :
https://www.nature.com/articles/s41598-018-21621-5

I see you've had some issues with manganese. I noticed - when searching - that Parkinson's patients have been found to have elevated manganese in their brains. Have you ever had any Parkinson's type symptoms ?
 
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Hallo @Crux, finally I manage to answere. The three days of PR maintainance have thrown me out of line and thinking is still a real task for me!
I'm trialing bile acids and tudca for many reasons, but , I saw that tudca is an effective iNOS inhibitor.
I have tried some iNOS inhibitors, but mostly they got out of work pretty soon. The strongest effects I noticed from only 50mg doxycycline (I had some for rosacea), which worked for three times marvelously (I took it on day 1, 4, 7), but then stopped and never came back, sadly. Milk thistle was two times good, but than stopped and there was no effect anymore after these two nice times, sadly. Maybe I can take quite a higher amount and it may have some effect?
One influence though stayed until now, it´s hops in beer without and with alcohol. It´s not very strong but can be quite pleasant. For one year, and in addition in the last two autumns and winters I noticed a strong synergy effect with alcohol (which alone isn´t of any good effect). In summer, beer isn´t good too, and can be pretty unpleasant. This might be a dependence on the ratio of melatonine and vitD both of which are iNOS inhibitors, so my body might preferre melatonine over vitD, under my conditions.
I also tried hops tea, but it turned out that the tea gives quite a bit from its - low, I think it was only 50µg in 100g hops - manganese into the water, whereas in beer almost no manganese at all is found.
And yes, manganese contributes to iNOS activity, in my case it obviously has been the first impact, and strongly enough, and then the arginine release for "serving" EBV had made also its contribution, and thats my catastrophy, obviously enough.
Feet aren't numb today, one of my NO (?) symptoms.
I wonder this too. All my lower limbs have been awfully squezzed. It´s such nice that I got and get relief from this pain. I meet the canadian criteria, but why do I haven´t any muscle pain, instead this glove and stocking pain, heavily? My skin has been kind of numb/deaf all over, it was filled with chewing gum. Also this is vanishing.
It could also be that EBV makes it somehow likely that some special regions in the brain get more affected, and that this would be the explanation. And other PwME might also suffer from NO disturbance neverhteless.

The last week now I made a third discovery: I already noticed that lysine and metionin and strangly (in a combo) even histidine can/could have good effects, but why? So, I just came across the Fluge 2016 paper where he puts on page three this nice figure one showing the TCA cycle in mitochondria. Now there are some amino acids shown which might (I still don´t know how strong the evidence is, apparently strong enough though) fuel the TCA cycle, eg these ones I already tried! So I take it for a fact that some of my mitochondria (in basal ganglia and thalamus as it looks) do not work well and can threfore holpen by these amino acids! Of course, I blame NO for having changed them. So this rn looks like an promising influence (maybe only on top of my influence by low manganese on iNOS).

I see you've had some issues with manganese. I noticed - when searching - that Parkinson's patients have been found to have elevated manganese in their brains. Have you ever had any Parkinson's type symptoms ?
Rather no I would say, but my face might sometimes look a bit frozen like PwPD. Since I was 15 I suffer from morbus scheuermann to small degree, it might be compared to the posture difficulties of PwPD. After my EBV then I have shrunken for 4cm! Interestingly I regained only this year 1cm (obviously through posture) by the combo of gaba and taurine (both of which are told to cross the BBB not well though), and tyrosine and very carefully tryptophan. I think in both cases the basal ganglia are affected, but I would think it´s only by accident that in both cases - in PD and my case - manganese is invovlved.
I looked a couple of times at PD but there doesn´t seem to be anything strong similar. As far as I remember the manganese accumulates in the substantia nigra which degenerates, but the manganese might not be the cause (though via NO and exitatory toxiticy it would be thinkinkable), according to a good article which I have not present rn.
There also has been the parkinson like Manganism from fume. Here no degeneration of neurons could be detected though the disturbance progrediates even when the inhalation of the fume has stopped. I remember that there has been found a treatment, I don´t recall how strong the good influence is/was though. I should look again because the mechanism of action in the case of Manganism should invovle NO. One article proposed that differrent amounts of manganese would cause different symptoms, incuding PD (in the case of PD I now think the article is not right).
 
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