Patent filing for the use of nitric oxide with or without B-cell depletion in CFS

[alex3619]

Stimulate NO in ME/CFS patiënts is very paradoxal according to

(.. according to Marty Pall)
Marty is concerned with peroxynitrite, and that NO increases will just drive more peroxynitrite. However this depends very much on mechanisms, and its largely hypothetical. Some of us have had spontaneous remission on NO donors.

One of the primary potential drivers is a failure to synthesize NO properly, which drives the body to keep trying. What is it suspected it makes instead if the process fails? ONOO or peroxynitrite. For a subset of us, who are likely to have high blood pressure, this is an obvious thing to test. A test trumps theory.

This is discussed on a thread here somewhere. The Gorilla in the Room thread maybe?

So if you supply NO directly, for this subset, you remove the driving force that makes ONOO.

So why is there an issue with OI if these people have high blood pressure? Its because the ability to regulate or adjust blood vessel dilation is broken. Its a fundamental vascular failure.

Let me emphasize this thread is about a hypothesis, not a certainty. It might also apply only to a subset.

 

[alex3619]

Nitric oxide (NO) is a neurotransmitter with impact on cognitive function

I first encountered it in neuroscience lectures. You don't form memory properly if you are deficient.

 

[alex3619]

In particular, the present inventors recognized that an immediate relief after administration of an NO donor can be observed.

Which means its been tried on a few patients.

 

[alex3619]

Let me point out that NO donors are quite available, have been around a long time (my Dad needed one in the 70s), and are not expensive. These are typically old generic drugs, well understood, that Doctors are not afraid of.

 

[alex3619]

Do we have any good and compelling evidence for Pall's hyoptheses?

Yes, but not that it is complete. I reviewed his book in 2006 and debated with him online for many years, along with Rich. He has a good theory, but its a theory. I don't think any part of it is wrong, but it could easily be incomplete.

As I already explained, a problem in NO synthesis is thought (again, not proven that I know of) to induce lots of peroxynitrite. Its a direct driver. Yet so long as the body needs NO it will keep trying to make it.

In other words, not only could NO improve blood flow, it could remove the driving force that makes peroxynitrite in a subset of patients.

 

[alex3619]

Here is something that is a simplified take on Empirical Scepticism: reality trumps theory.

 

[alex3619]

Lastly, what does nitro "donor" mean? I didn't get that part!

I think it means it breaks down in the body, the drug is destroyed, and releases NO directly.

 

[snowathlete]

I see that Minoxidil is listed. The same is the combo of L-arginine and L-Citrulline. This is exciting.

Is Minoxidil available in a pill form? It is used to prevent hair loss in men.. Not sure if you should drink that though

Before I was ill, when the only negative in my life was my thining hair I used minoxidil. It does work on hair, surprisingly well. Once I bagged myself a wife I stopped using it.
I think I read that there was an oral form, as that was how it was discovered as a hair treatment, a side effect of a trial.

 

[alex3619]

The same is the combo of L-arginine and L-Citrulline.

This is a combination I would avoid until the science is done. Too many risks.

 

[ahmo]

I've been using Martin Pall's treatment plan for the past 3 months. Instead of arginine and citrulline, I've switched to malic acid in footbaths for *removing* (not sure the mechanism) peroxynitrite. (As per the thread Inexpensive fix for ammonia) Also extensive use of antioxidants. I've added, per his suggestions, reseveratrol, astaxanthin, and a really high intake of carrots for their antioxidant effects. I've now switched from carrots to oliveleaf tea, with the same benefits. I'd been suffering a lot from high peroxynitrite, it was quite clear that I was on the edge of crashing. Implementing these supps has really saved me.

Martin Pall http://www.thetenthparadigm.org/therapy.htm

Martin Pall March 2014 https://www.youtube.com/watch?feature=player_detailpage&v=6A7r1gemjto

 

[Sidereal]

Interesting hypothesis. Several weeks ago I had a surprising reaction along these lines with an NO-boosting supplement (beet root extract). I wrote about it on the resistant starch thread. What's astonishing is that it actually raised my BP (in my case this is a good thing since my BP is low but people normally use this supplement to lower their BP). Unfortunately, a week ago I seem to have picked up a new infection on a rare outing so now I'm crashed again.

Personally, I would steer clear of experimenting with 10 g of arginine daily in an ME/CFS population. A fraction of that would cause me nightmarish herpes reactivations.

 

[alex3619]

I'd been suffering a lot from high peroxynitrite

Yes, dealing with peroxynitrite seems to help. Marty has had some good successes. This does not prove that some subset will not benefit from more NO. It just means, as usual, it pays to be cautious and to demand good science.

 

[ahmo]

@alex3619 My very primitive understanding, is that lowering peroxy increases NO. Is this true? And I guess that doesn't mean that everyone who needs > NO has peroxy issues...

 

[snowathlete]

I first encountered it in neuroscience lectures. You don't form memory properly if you are deficient.

that is really interesting. thanks.

 

[alex3619]

@alex3619 My very primitive understanding, is that lowering peroxy increases NO. Is this true? And I guess that doesn't mean that everyone who needs > NO has peroxy issues...

I don't know if its true or not. Lowering the synthesis of peroxynitrite should increase NO, by any of several mechanisms. However getting rid of peroxynitrite through antioxidants relies on indirect effects. It might work, but I am not sure its ever been clearly demonstrated.

On the other hand, more NO can potentially drive peroxynitrite, and it can potentially lower peroxynitrite, so which is happening is an empirical question. It can be tested. Not all patients might test the same.

 

[alex3619]

that is really interesting. thanks.

Just to confuse things, you also will not form memory properly if you have too much NO running around. Its a Goldilocks thing: you want it just right.

 

[snowathlete]

And Nitric Oxide is highly involved in alcohol metabolism, right? I, along with many others are alcohol intollerant now.

 

[alex3619]

And Nitric Oxide is highly involved in alcohol metabolism, right? I, along with many others are alcohol intollerant now.

http://link.springer.com/article/10.1007/BF01991860?no-access=true

Chronic alcohol exposure, yes. Because, and I have not read the full paper, it seems that tissue damage might result in more NO. This argument might extend to any damage or poison though.

 

[alex3619]

I want to read this one: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2562584/

Its a full paper.

However here is my take on alcohol. It drives production of free radicals from the mitochondria. So if NO and radicals are both raised, so is peroxynitrite. Its not the way to go for most of us, though it does raise questions as to whether there might be a subset who benefit.

 

[deleder2k]

This is a combination I would avoid until the science is done. Too many risks.

Could it be that dangerous? What can happen? Low BP? I've tried 2x3g of L-arginine before without any side effects.

Look at this:
Oral supplementation with a combination of l-citrulline and l-arginine rapidly increases plasma l-arginine concentration and enhances NO bioavailability

Here is another one:
Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism