This Amino Acid Powerhouse Is the Primary Source of Nitric Oxide

Look up sanguine in a dictionary and you will find that it has two different definitions: it means "of the color of blood or relating to blood," and it also means "cheerfully confident and optimistic," i.e., having a healthy attitude. The historical origins of these seemingly unrelated meanings reflect how important blood - and our circulatory system in general - is in maintaining overall health. Blood brings oxygen and nutrients to our cells via our arteries, and it removes carbon dioxide and other waste products from them via our veins. It then returns to the lungs (via the heart) for reoxygenation, and the cycle continues. Along the way, the blood passes through our kidneys, spleen, and liver, all of which perform cleansing functions to rid it of various wastes.

In this article we will see how the common amino acid arginine can help (in a surprising way) to maintain the health and optimal functioning of our circulatory system - veins as well as arteries. Arginine is well known for its beneficial roles in many physiological processes, such as increasing muscle tone, improving immune function, and enhancing sexual function.

Any problems with our arteries or veins that impair our robust, yet also delicate, circulatory system can have disastrous consequences. One of the most common disorders of the circulatory system is atherosclerosis, a form of hardening of the lining of the arteries. In this condition, a fatty material called plaque is deposited on the inner layer, or epithelial-cell layer, of the arteries. As the plaque buildup increases over time, it causes a constriction of the arterial volume - the space within the arteries - and this, in turn, restricts blood flow and increases our blood pressure.

When it is formed inside the body 
from the amino acid arginine, 
nitric oxide has a plethora of 
useful functions.

Ultimately, atherosclerosis can seriously impair the blood supply to different parts of the body - dramatically so if a piece of plaque breaks off and completely obstructs an artery. If blood supply to the heart is obstructed, a heart attack can occur. If blood supply to a portion of the brain is cut off, a stroke (think of it as a "brain attack") can occur.

Although heart attacks and strokes represent the worst-case scenarios in a circulatory system that is deteriorating, smaller reductions in proper blood flow can rob the body of important nutrients and prevent it from working at its peak form. We consider a certain amount of deterioration of our circulatory system to be a natural part of aging. But, as with most other seemingly inevitable conditions, we can take steps to counteract it.

Studies have shown that one compound in particular plays a key role in maintaining the circulatory system: nitric oxide. It is counterintuitive, to put it mildly, that this compound, which is a poisonous gas and notorious air pollutant (and, incidentally, a free radical), can actually benefit the body. But when it is formed inside the body from the amino acid arginine, nitric oxide has a plethora of useful functions. In the central nervous system, it is essential for motion-related learning processes that take place in the cerebellum. It is also believed to enhance cognitive functions throughout the brain and may therefore be necessary for long-term memory. It plays a vital role in kidney function, and it is believed to have immune-system-enhancing properties. As if that weren't enough, nitric oxide plays a major role in sexual function for men, and it may do so for women as well.

Several studies have shown that nitric oxide plays a direct role in preventing atherosclerosis. Its action is believed to be twofold. First, it acts as a vasodilator, i.e., it induces the dilation (widening) of arteries in response to certain kinds of stress and other factors. This dilation increases the arterial volume and facilitates blood flow, while lowering blood pressure - the exact opposite of the effects caused by atherosclerotic plaque buildup. Conditions that reduce nitric oxide levels are believed to impair the ability of arteries to dilate properly.

Second, nitric oxide is believed to decrease the tendency of monocytes (a type of large white blood cell that constitutes roughly 5% of all the body's white blood cells) to adhere to the epithelial cells that line the arteries. In this respect, nitric oxide can reduce the plaque formation that leads to atherosclerosis, and worse.

Nitric oxide is an important compound for proper arterial function. In recent years its role in regulating venous function as well has become clearer, and several studies have demonstrated its importance in this area. In one study, investigators examined the role of nitric oxide in regulating blood volume in the veins of 24 healthy human subjects, of whom 16 were men and 8 were women.1 Their ages ranged from 27 to 75 years, with an average age of 50. None had a history of smoking, hypertension, diabetes, or high cholesterol. Furthermore, none had a family history of heart disease.

The investigators measured venous volume - the space within the veins - by labeling the subjects' blood cells with harmless, low-level radioactive tracers and then measuring the resulting radioactivity in their forearms, where the technique is easy to apply. They found that they could decrease the venous volume by infusing a compound into the subjects' bloodstream that is known to inhibit the action of a key enzyme in the biochemical pathway for nitric oxide production, i.e., its effect is to reduce nitric oxide. The fact that venous volume decreased in this experiment thus proved that nitric oxide is necessary for maintaining normal levels of blood flow in our veins.

Next, the investigators tried infusing a compound that stimulates nitric oxide production into the patients' bloodstream, and they found that this increased their venous volume. The response was dose-dependent; that is, the increase in venous volume was proportional to the amount of compound administered. This experiment provided further proof of nitric oxide's role in maintaining proper blood flow in our veins as well as our arteries. In their paper, the researchers concluded that "Nitric oxide has an important role in the regulation of venous tone and contributes to resting venous tone in healthy human subjects."

Other experiments on the veins of living humans and sheep have shown a similar effect of nitric oxide on venous function.2-4

So we know that nitric oxide is vital for maintaining a healthy circulatory system. But how can we increase the levels of this remarkable compound in our bodies? Nitric oxide is produced primarily from a simple amino acid, arginine, through a direct chemical reaction. The discovery that this normally poisonous gas could come from such an unlikely source and could actually be beneficial to our health was so surprising that most scientists could scarcely believe it - but it won the discoverers a Nobel Prize in medicine and physiology.

Arginine is not an essential amino acid - that is, it is not an essential part of our diet (although it is found in many common foods) and can be made by the body from other substances. It plays important roles in the physiological functions not just of the cardiovascular system but of various other systems of the human body as well, including the immune, central nervous, and endocrine systems. Its benefits arise primarily through its ability to stimulate the production of growth hormone and to serve as a source of nitric oxide in the body.

"Nitric oxide has an important 
role in the regulation of 
venous tone and contributes to 
resting venous tone in healthy 
human subjects."

Growth hormone is an extremely important compound in its own right. Natural production of this hormone declines dramatically as we age. In fact, these reduced concentrations may be associated with many of the "inevitable" processes of aging. A few of the reported benefits of growth hormone in adults include its ability to accelerate wound healing, improve muscle-to-fat ratio, and increase skin elasticity.

The many benefits of both nitric oxide and growth hormone can be obtained through arginine. For this reason, arginine is clearly one of the best nutrient bargains currently available. It should be a component in every serious life extender's nutritional program.

Arginine can be found in many foods, including chocolate, wheat germ, wheat flour, buckwheat, granola, oatmeal, dairy products, beef, pork, nuts, seeds, poultry, seafood, chickpeas, and soybeans. However, it is difficult, if not impossible, to obtain high enough levels of arginine from food alone. To obtain the full range of arginine's theoretical benefits, supplementation is necessary.

Remember: supplemental arginine may be a good way to help keep ourselves healthy and sanguine - inside and outside.


  1. Blackman DJ, Morris-Thurgood JA, Atherton JJ, Ellis GR, Anderson RA, Cockcroft JR, Frenneaux MP. Endothelium-derived nitric oxide contributes to the regulation of venous tone in humans. Circulation 2000;101:165-70.
  2. Vallance P. Nitric oxide sythesized from L-arginine mediates endothelium dependent dilation in human veins in vivo. Cardiovasc Res 2000;45(1):143-7.
  3. Kemp BK, Smolich JJ, Ritchie BC, Cocks TM. Endothelium-dependent relaxations in sheep pulmonary arteries and veins: resistance to block by NG-nitro-L-arginine in pulmonary hypertension. Br J Pharmacol 1995;116(5):2457-67.
  4. Vallance P, Collier J, Moncada S. Nitric oxide synthesized from L-arginine mediates endothelium dependent dilation in human veins in vivo. Cardiovasc Res 1989;23(12):1053-7.