No2, Nox2 users............Please Read!

(Note: This was originally posted on a different board.)

There are now quite a few supplements out there that claim to increase nitric oxide levels in the body. Examples include NO2, Nitro AKG, and NOX2. For the moment, I’m going to assume that these substances increase nitric oxide levels above the normal levels found in an otherwise healthy individual. What would this do?

The main functions of NO in various systems are listed here:

Immune system: Macrophages produce NO to kill target cells because it is cytotoxic. It disrupts the Kreb’s cycle, DNA synthesis, and mitochondrial function, making it a very effective cell killer.

Nervous system: Acts as a neurotransmitter and regulates apoptosis (cell death) in neurons. NO is also correlated with the excitation of NMDA receptors.

Circulatory system: NO stimulates the production of pro-inflammatory compounds (specifically, eiconosoids), and other pro-inflammatory compounds are known to stimulate the production of NO. NO is also a vasiodilator.

I could find no evidence or reasons to believe than NO will cause gains in strength. If anybody has any, please let me know. The “pump” effect that many report could be due to vasiodilation (assuming the supplement increases NO levels).

Of prime importance here is the function of NO in the immune and nervous systems. I’ll try to dumb this down as much as I can. O2-, or super-oxide, is the most prevalent oxidant in the body. That means: it’s bad for you. Luckily, it is not very stable. ONOO- (peroxynitrite) is another oxidant, but is much more stable. So while super-oxide can do damage, peroxynitrite can do much more. On top of that, it can pass freely through cell membranes. When super-oxide reacts with NO, it forms peroxynitrate.

In the immune system, macrophages kill target bacteria and tumor cells through a targetted release of NO, which reacts with super-oxide to form peroxynitrite. This peroxynitrite then kills the targetted bacterium or cancer cell. So basically your immune system’s defense is: poison the target cell.

This point should not be taken lightly. The more NO there is in your bloodstream, the more NO reacts with super-oxide to form peroxynitrite. But in this case, it’s not a controlled response like immune response or apoptosis in neurons.

Now here’s what makes the situation even worse. Under normal circumstances, the amount of NO in your system is closely mediated. There are three types of NOS (nitric oxide synthase, which produces NO in the body), each that responds to different things (such as the amount of calcium in cells). But like I said, let’s assume that you can increase NO levels above normal. As described above, this causes peroxynitrite levels to go up. But peroxynitrate acts through six mechanisms to increase the levels of nitric oxide even more and super-oxide - which in turn produce more peroxynitrite. This is why peroxynitrate is such a potent cell killer; it reproduces itself. Once peroxynitrite levels hit a certain point, they will be self-sustaining (1).

To summarize: when NO levels hit a certain point, there can be a permanent increase in peroxynitrite levels. This, in turn, increases your chances of a variety of ailments. Some are described below.

Fibromyalgia (FM): Causes pain in all the fibrous tissues in the body, including muscles, ligaments, and tendons. The pain can be incapacitating. It is also associated with oxidative damage. Studies show excessive levels of nitric oxide and peroxynitrite as well as excessive activity in the NMDA system (in the brain) in FM patients. Nitric oxide stimulates nociceptors, neurons that cause the sensation of pain, and peroxynitrite does as well, which could quite possibly be the primary mechanism of action in this illness (2).

Chronic Fatigue Syndrome (CFS):Incapacitating fatigue, joint pain (similar to FM pain), inability to concentrate, and flu-like symptoms. Like FM, this is associated with elevated levels of nitric oxide.

Multiple Chemical Sensitivity (MCS): A controversial condition where people have negative responses to sub-toxic levels of various chemicals. Also associated with high nitric oxide levels.

All three of these conditions are chronic, and all three of them are related. They can all develop over a long period of time. What’s even more surprising is all three of them are treated with vitamin B12 injections. Coincidentally, B12 is a potent nitric oxide scavenger (3).

I know that in my case, at least, I am no longer going to search for ways of artifically increasing nitric oxide levels. There’s no evidence that it increases muscle strength, and there’s no evidence that the “pump” is due to anything other than vasiodilation. What’s more, there’s plenty of evidence that messing with your body’s normal balance of NO will do more harm than good.

David

1. Pall ML. Elevated, sustained peroxynitrite levels as the cause of chronic fatigue syndrome. Medical Hypotheses 2000;54:115-125.
2. Pall M. L. Common etiology of posttraumatic stress disorder, fibromyalgia, chronic fatigue syndrome and multiple chemical sensitivity via elevated nitric oxide/peroxynitrite. Med Hypoth 2001;57:139-145.
3. Pall M. L. Cobalamin used in chronic fatigue syndrome therapy is a nitric oxide scavenger. J Chronic Fatigue Syndr 2001:8(2);39-44.

AlexW

The effectiveness of A-AKG in increasing NO:

I did some research on this as well. AKG is metabolized into glutamate, which is then metabolized into L-glutamine (2). But this does not mean that it is nothing more than L-glutamine, remember that glutamate is the intermediary step.

Coincidentally… while researching fibromyaglia, I found that many cases of FM can be cured by eliminating MSG from the diet. MSG metabolizes to glutamate, which is an “excitotoxin,” meaning it activates the NMDA receptors to the point of neural damage. And guess what… that leads to excessive nitric oxide levels (1). In other words, AKG does not work synergistically with arginine per se. It operates via a seperate mechanism to increase NO levels, and a potentially dangerous one. Ornithine-AKG has the same effect (2). I couldn’t find any human studies regarding the safety of AKG, but I did find in many places (none of them “legitimate” though) that no such studies exist.

In light of this, I have developed a theory. The theory is that in NO2 and related products, the AKG is the important part and the arginine is just there for show (as opposed to what many people who criticize the products think, which is that the AKG is the useless part). I have been trying to find evidence to support this by finding references that say dietary arginine does not raise NO levels. What I’ve found so far:

-Every time NO levels go up, there is an increase in arginine disposal, which would imply that the body only uses what it needs based on other controlling mechanisms (such as the NMDA part of the brain) (3).
-Two analogues of arginine, ADMA and L-NMMA, are formed when there are excess amounts of arginine in cells. Both of these analogues inhibit the synthesis of more nitric oxide. In other words, whenever the body has enough arginine, it sends a message to slow production of nitric oxide.
-The only studies I found showing that administration of arginine increased NO levels was in cases of deficiency.

If anybody has more references on this, please let me know.

David

1. Smith J. D., Terpening C. M., Schmidt S. O. F., Gums J. G. Relief of fibromyalgia symptoms following discontinuation of dietary excitotoxins. Ann Pharmacotherapy 2001;35:702-706.
2. Le Boucher J et al., Enteral administration of ornithine alpha-ketoglutarate or arginine alpha-ketoglutarate: a comparative study of their effects on glutamine pools in burn-injured rats, Crit Care Med 1997 Feb;25(2):293-8
3. Bruins MJ, Lamers WH, Meijer AJ, Soeters PB, Deutz NE. In vivo measurement of nitric oxide production in porcine gut, liver and muscle during hyperdynamic endotoxaemia. Br J Pharmacol 2002 Dec;137(8):1225-36

Hey Alex,

Give credit where credit is due. You can name the board and author and post a link to the place. It’s the right thing to do.

Interesting info, “dumbed down” to just the right level for me. :)

I stopped taking NoX2 because I didn’t feel any particular effects at all, so this gives me pause to wonder whether I’ll ever use the rest of the bottle.

Thunder,

I’m learning internet etiquette slowly but surely. I thought having the authors name in post was sufficent enough. As they say, you learn something new everyday.

AlexW

A link would be better. You “borrowed” the piece from a board not the author. :)

Borrowed sounds so much much like stealing so heres the link:

AlexW

Thanks Alex.

a very interesting post and set of links there. My understanding from reading them is that arginine by itself is ok but a-akg MAY exert some negative effects on humans.

Having not taken a-akg (my N0X2 STILL hasnt arrived!!) I can not comment on this, but arginine by itself has given me nothing but positive effects - larger veins, larger flaccid, better erections.

If it became factual that it was likely to harm us, I’d expect all of us to have the brains to stop using it, despite its ‘good’ effects - right guys?

I said something to this effect a while back, on a different board though. I was attacked. The supplement industry is pretty persuasive.

What about viagra then? It increases NO substantially and is used by thousands of men daily, without ill effects.

Thought I’d resurrect this thread from the dead. Quite a few people here who use these supplements and might like to have a read.

I’ve been using Citrulline Malate for a while now and I haven’t noticed any major difference.

:-pulse:

Beneficial effects of a long-term oral L-arginine treatment added to a hypocaloric diet and exercise training program in obese, insulin-resistant type 2 diabetic patients - PubMed

Pharmacokinetics, safety, and effects on exercise performance of L-arginine alpha-ketoglutarate in trained adult men - PubMed

There are dozens of studies on pubmed, have a search.

NO-Xplode is a great product. I have a great intuition about how clean things are and how they interact with my body. I truly enjoy NO-Xplode, and believe in it so far as a product that creates a focused, energetic feeling perfectly conducive for working out. My fiance takes it right now before she runs two miles daily, and she loves it too. I’d wear a NO-Xplode t-shirt if I had one. I really like the product. I haven’t taken it in a couple of months because it recommends taking a break after consuming a container’s worth.

I don’t think it increases NO levels per se , but rather prolongs its effects for a satisfactory erection.