NO2 Exposed - Part 2
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
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).
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), and each 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 and super-oxide even more - which in turn produces 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.
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.