Nitric oxide was identified in 1998 as the mysterious “relaxing factor” that is produced by the internal lining of the arteries, known as the endothelium. Once produced inside the artery, nitric oxide signals the smooth muscle of the artery to relax and thereby dilate the artery. This results in lowered blood pressure throughout the system as well as enhanced delivery of blood to the outermost tissues such as the skin and extremities. This discovery led to three Nobel Prizes being awarded due to the fact that this discovery constituted a giant leap in cardiovascular research, and the understanding of the pathological changes in the arterial system that result in heart attack, stroke, erectile dysfunction, neuropathy, peripheral artery disease, and more.
As is often the case, the bodybuilding community was the first to seize upon this scientific breakthrough and apply it as an aid to further fitness through enhanced training intensity. In the early days of nitric oxide research, the only supplement available that could enhance the body’s ability to produce this crucial molecule was l-arginine. And since L-arginine is metabolized through eight different pathways it is not a very efficient mechanism for the enhancement of nitric oxide production by the endothelium. To compensate for this inefficiency, many bodybuilders simply supplemented huge doses of L-arginine as well as alpha-ketoglutarate, which facilitates the intestinal absorption of L-arginine. Huge doses of L-arginine may unfortunately lead to some unwanted nitric oxide side effects.
Here’s what you need to know….
There are three enzymes that are used within the body to produce nitric
oxide from various precursors that come from diet and/or supplements:
1. eNOS: used to produce nitric oxide at the level of the arterial
2. nNOS: used to produce nitric oxide at the level of the neuron (brain
3. iNOS: used by immune cells to produce nitric oxide in order to destroy pathogens (bacteria, viruses, fungi, and potential cancer cells)
The main takeaway point is the first two enzymes are anti-inflammatory in nature and prevent plaque formation in the arteries as well as degenerative changes in the brain and peripheral nervous system. The third enzyme, iNOS, is pro-inflammatory and is involved in the destruction of cells (pathogens) and if concentrated in an area for a sustained period, will be destructive to bodily tissue as well.
If an individual is plagued with a chronic inflammatory condition such as an infection or autoimmune disorder (think rheumatoid arthritis, Lupus, Sjogren’s, psoriasis, Hashimoto’s Thyroiditis, etc) then iNOS may be the most abundant enzyme available for the production of nitric oxide. In this case, any supplement that supplies the body with precursors to the production of nitric oxide will facilitate the pro-inflammatory state and accelerate the progression of the disease. Worse yet, if an individual is supplementing with an inefficient precursor such as l-arginine and therefore taking massive doses of it as a way to make up for the inefficiency, the majority of the L-arginine may be used to ramp up nitric oxide production by the immune system. This could, therefore, create a systemic inflammatory response. If the body is under attack by pathogens or is in need of a stronger response to mutant cells that pose a risk of later developing into a tumor, then this is awesome. But if the immune system is accidentally and mistakingly attacking the body (as is the case with autoimmunity) then this attack against one’s own self will also be ramped up and could, in the worst case, lead to the demise of the individual.
So how do you know if supporting nitric oxide through supplements is going to be safe for you or not? Should you roll the dice and cross your fingers?
Probably not. First, you can have a simple blood test done that will look at inflammatory markers such as cardiac c-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) and if suspected autoimmunity is in play, you can have your antibodies measured to rule it out. That said, you should begin slowly with low doses and work your way up over a longer period of time. That way, if you begin to experience any undesirable effects (such as headache, nausea, muscle or joint pain, weakness, cramping, etc), you can discontinue the dose right away and symptoms should dissipate quite rapidly. If this does occur, you should contact a doctor who is trained in Functional Medicine and seek advice. You can find a doctor by going the website for The Institute for Functional Medicine and using the doctor locator tool.
The best nitric oxide boosters do not contain massive doses of L-arginine since L-citrulline is far more efficient and, therefore, will reduce the likelihood that iNOS produced nitric oxide will rise. Look for a supplement that also supports the nervous system because it will need extra support to be able to handle the extra intensity of your workouts and will facilitate quicker recovery times. The best formulas should include ingredients such as Vinpocetine, Huperzine A, and alpha GPC for the brain and peripheral nerves. For the endothelium the formula should contain substances such as beetroot extract, hawthorn extract, and cocoa since they all have profound effects on the endothelium of the artery and facilitate the production of nitric oxide while ensuring an anti-inflammatory environment.
These supplements always do what they are designed to do, which is to increase nitric oxide production in the body. The question is: which of the three enzymes (isomers) will be involved in the production of the sought after molecule? If the answer is iNOS, it will be a very negative thing if the supplementation continues for extended periods of time. Yet if the user knows to begin with minimal dosage and titrate up slowly over time, the first sign of discomfort will act as the proverbial canary in the coal mine and will alert the individual to a previously unknown illness or pro-inflammatory state. In this way, trying a nitric oxide supplement could truly save lives as it may act as an early diagnostic tool.
For most fitness enthusiasts, however, it will simply enhance strength and endurance and provide an edge in the never-ending endeavor known as bodybuilding.