NO/ONOO- A New Paradigm of Human Disease: Martin Pall website

[ahmo]

So are you taking something that helps with the conversion? That's what I wonder.

Nothing specific.
Maybe like @Gondwanaland mentions re vitamins: I've reduced the P5P (B6). What's curious is that I'd taken the same dose for about 1.5 years.

Just adding this because of the diagram: over the last couple weeks I'm not needing GABA. I've been using GABA for many years, thought it was pretty essential. In the Anxiety Summit, one of the presenter said it's only due to permeable blood brain barrier, and that she prefers not to use it, as it's a rather large molecule. I've seen elsewhere that it's effectiveness is due to BBB permeability. It's curious that I'm no longer self-testing + for needing it, nor do I experience any symptoms suggesting I need it. So another pointer to a shift for me. T

he most recent thing I've done is add proteolytic enzymes, away from meals, for clearing organs. This has only been the past week, and I've not needed GABA for longer than that. The most sustained thing I can think of is shifting from a combination of ornithine, arginine, citrulline, lysine to malic acid only, 5 months ago.

@alex3619 thanks.

 

[Gondwanaland]

@ahmo I think you should read this

 

[ahmo]

@Gondwanaland So if there's been an increase in gut bacteria, creating an increase in B6, then I'd need to lower my dose...! Well, I'm pretty unimpressed with the amount of bloating I'm having, and fervently hoping my Candida/bacterial protocol eliminates it!

 

[picante]

The other 2 episodes involve B vitamins. First B2, which I added to my otherwise very low dose B complex, hoping this would let me eat green veggies.100mg for 1-2 days, then 50mg for another day. It was great to eat some lettuce, but 2 days later I felt like I was drowning in "ammonia" and it took many days to eliminate.

Most recently I was needing a lot of ammonia-reducing supps, antioxidants. It occurred to me that maybe my P5P was contributing. I quit my 33mg dose for 2 days, then reduced it to 1/2, and now, again, I've stopped having the symptoms, and am no longer in high need for all the supps.

I'm wondering again about "episodes" from B vits, since so many of us seem to experience them. My response to B2 (FMN) was low-back inflammation (arthritis).

@ahmo & @Gondwanaland: Are any of your B vits. derived from yeast?

 

[picante]

Well, I'm pretty unimpressed with the amount of bloating I'm having,

I started experiencing bloatation again on Freddd's protocol. It suddenly decreased drastically when I switched off the Ad/Me B12 oil. Perhaps it was the high ratio of Ad:Me (3:1).

"Bloatation" is my term for the helium-balloon kind of bloating. It's very firm like a balloon and feels like it might pop if I eat any more. It seems to be neurological. It happens while I'm eating, before the food gets to my intestines.

 

[ahmo]

"Bloatation" is my term for the helium-balloon kind of bloating. It's very firm like a balloon and feels like it might pop if I eat any more. It seems to be neurological. It happens while I'm eating, before the food gets to my intestines.

I blotation! Mine seems to be pretty much all the time these days. My AdB12: MB12 ratio, near as I can work it out, is 40mg AdB12, once a week : 1 squirt MB12 oil, 6 days/week. Do you know the dose of oil per squirt? my memory says 50mg, but I don't trust my memory!

No idea where my B vits come from. neither bottle says.

 

[Gondwanaland]

@ahmo & @Gondwanaland: Are any of your B vits. derived from yeast?

There should be very few brands that I think would NOT use yeast-derived B vits... Plus most enzymes are mold derived (A. niger)

 

[nandixon]

Can you see how the urea cycle feeds ONOO-? I think excess serotonin does too ( @nandixon )

I might be wrong, but in a purely biochemistry sense I don't think that extra arginine produced from ammonia in the Urea Cycle is going to tend to cause an increase in peroxynitrite due to more arginine being available for nitric oxide synthase (NOS). More likely I think it's a lack of arginine that will cause decoupling of NOS and thus the peroxynitrite production. (Lack of BH4 also causes decoupling, as well as other issues.)

However, in a pathological sense, elevated ammonia levels can definitely give rise to peroxynitrite by, for example, a deleterious effect on microglia. See, e.g.:

Oxidative and nitrosative stress in ammonia neurotoxicity

and

Microglia contribute to ammonia-induced astrocyte swelling in culture

So my best guess is that it does seem that excess ammonia can cause peroxynitrite production, but not due to an increase in arginine from the ammonia (I don't think), but rather because of the neurotoxic effects of ammonia.

(I haven't looked at serotonin here but if its production is up-regulated for some reason, then I guess that might reduce BH4 levels - which could then contribute to decoupling of NOS and peroxynitrite.)

 

[Gondwanaland]

@nandixon yes, that's what I meant

 

[picante]

I actually swing between 3 different beliefs when my brain winds up in Dorothy's poppy field: 1) it's ammonia, 2) it's sulfites not converting to sulfates, 3) it's peroxynitrite.

A unified theory of these three processes might help me, too, if I can understand it. My brain worked much better before I started methylation. And I could eat two eggs a day.

LOOK WHAT I FOUND, I'm so excited:

At any rate, TMG is required to prevent post meal surges in homocysteine, the neurotoxin. You want to be able to clear it away asap and you need TMG to do that. mB12+mfolate is the slow path.

Could that be it? The thing that plagued me for -- I dunno -- 12 or 15 years, and is now plaguing me intermittently again. This is how it happens: sit down to eat, start feeling full waaaay too soon, start bloating, get groggy-brained (I'm sure someone drugged me), go sleep it off.

Sulfites definitely trigger this when I accidentally eat any. But sometimes it's something innocuous like oatmeal with blueberries. Restaurant salad always does (it's sprayed with sulfites). Actually, it can be anything.

My homocysteine was smack in mid-range last July. But how quickly can the level change? Judging by my bloatation, it can change less than halfway through dinner.

 

[Gondwanaland]

@picante what about your BHMT status to convert TMG to DMG?
Edit- I suppose it's also needed to convert Hcy into Met?

 

[picante]

I haven't got that far, @Gondwanaland. I want to know whether homocysteine swings can cause those symptoms that fast. They're neurotoxic symptoms! This is a 22-year mystery I'm solving, . I HOPE! X 22 years = (well, you know).

 

[ahmo]

@picante I've just found this site, pretty exhaustive info re sulfites: http://www.learningtarget.com/nosulfites/index.htm

 

[RustyJ]

OK, a few quotes from Pall's website:

This reciprocal relationship between peroxynitrite and BH4 depletion is, then a potential vicious cycle within the larger NO/ONOO- cycle and may constitute the essential core of the cycle. Lowering of this central couplet will be expected to produce a clinical improvement in these diseases, but will produce an increase in nitric oxide. So while I think that the net effect of nitric oxide in these diseases is negative one, agents that increase nitric oxide by lowering this central couplet should be helpful.

I've read this 20 times. To me Pall seems to be suggesting in the last line of the above quote that agents which increase NO should be effective. Yet elsewhere posters say Pall says to decrease NO. Have I read this wrong?

 

[ahmo]

@RustyJ I can't answer that. My take-away is my need to stay on top of peroxynitrite, an antioxidant strategy. Pall's website is no longer available, unfortunately, but in my signature is another site with a summary of his theory, and an excellent vid with slides, so you can stop and read. Also, a couple of pr articles on NO.

http://phoenixrising.me/archives/18836
Nitric oxide and its possible implication in ME/CFS (Part 1 of 2)
http://phoenixrising.me/archives/25528 Part 2

http://forums.phoenixrising.me/inde...-mitochondrial-replication-in-cfs.9536/page-2
Peroxynitrite and the impairment of mitochondrial replication in CFS

HIP: Whitlock’s blog entry http://daedalus2u.blogspot.com/2008/06/mechanism-for-mitochondria-failure.html is the best place to start reading about his low NO ratchet theory of CFS and autism.