Nitric Oxide Wins the Day for Users 
of Its Precursor, Arginine


The Nobel Prize for Physiology for Medicine this year was awarded to three researchers, Doctors Robert F. Furchgott, Louis J. Ignarro and Ferid Murad, for their discoveries concerning nitric oxide as a signaling molecule in the cardiovascular system. Despite a growing number of medical applications, not withstanding the success of Viagra® which is based on nitric oxide, the preponderances of real advances are in the dietary supplement arena. Thus it is now exceedingly clear: The researchers, who shared a prize in excess of $900,000, are not the only winners. Arginine users are the biggest winners!

Because the amino acid arginine is solely responsible for the production of nitric oxide in the body, the research behind the Nobel Prize has enabled us to understand an entirely new level of significance regarding this important nutrient. Therefore, the myriad applications of nitric oxide are but a subset of the applications of arginine which include:

  • Growth Hormone Release
  • Increased Immune Function
  • Heart Protection
  • Blood Pressure Control
  • Memory Increase
  • Sexual Enhancement and
  • much more

The work of Furchgott et al, has established clearly that nitric oxide (NO), a gas, actually transmits important signals in our bodies. Incredible as this first seemed to other scientists when first proposed in the 1980s, after originating in a single cell, the gas, NO, penetrates through membranes and regulates the function of other cells. This discovery represents an entirely new principle for signaling in biological systems. "Ye gads!" yelped the amazed scientists about NO. "We've discovered a new neurotransmitter and it's a gas."

Discovering a New Signal Molecule
Back in 1980, Furchgott, a New York pharmacologist, was studying the effect of certain drugs on blood vessels, but his results were often contradictory. Sometimes a particular drug caused a blood vessel to contract and at other times the same drug caused it to dilate. He wondered if the intactness of the blood vessel's surface cells (the endothelium) could be involved. Furchgott devised an experiment showing that acetylcholine would dilate blood vessels only if the endothelium was intact. What he observed led him to conclude that blood vessel dilation occurs because an unknown signal molecule, produced by the endothelial cells, makes vascular smooth muscle cells relax. (Blood vessels are made up of vascular smooth muscle cells which contract or relax, meaning dilate.) Calling this signal molecule the endothelium-derived relaxing factor (EDRF), Furchgott was hot on the case.

A few years earlier, in 1977, another pharmacologist, Ferid Murad, MD, investigating the mechanism of nitroglycerin and other vasodilating compounds, found that they act by releasing NO which relaxes smooth muscle cells. The concept that a gas could regulate important cellular functions intrigued him and he speculated that endogenous factors, such as hormones, might also act through NO.

Finally in 1986, yet another pharmacologist, Louis J. Ignarro, performed a series of analyses that enabled him to conclude at the same time that the idea congealed for Robert Furchgott: EDRF and NO were one and the same. The last of the discovery blocks had slid into place. At a conference that year at which Furchgott and Ignarro presented their conclusions, the whisper of their efforts was transformed into a roar. In research laboratories around the world an enormous amount of investigatory energy was released. This was the first discovery that a gas can act as a signal molecule in a living organism.

It's a Sensation
The idea that a common air pollutant, formed when nitrogen burns, could exercise important control functions in the human body was a scientific sensation. No other known signal molecule was anything like NO, a molecule so unstable that it converts to nitrate and nitrite within 10 seconds.

How Does NO Get Produced?
There is only one essential way to produce NO in the body, and its direct precursor is the nutrient amino acid L-arginine. As arginine circulates in the blood, the enzyme, nitric oxide synthase, controls a reaction in which a terminal nitrogen atom of arginine is combined with an oxygen molecule to form NO and the amino acid L-citrulline.1 Also mediating the reaction is NADPH, which is a major niacin-containing redox-active "electron storage" compound.

An arginine supplement may be designed to increase GH releasing function, as well as for cardiovascular support. It can also enhance immune function, sexual function, memory function, and more. A drink mix containing arginine, choline, and Vitamin B5, which produce abundant amounts of NO, serves the following roles, among others:

  • In the cardiovascular system, NO operates as a signal molecule in the nervous system as a weapon against infections, as a regulator of blood pressure, and as a gate keeper of blood flow to different organs. NO also helps control the blood pressure and its distribution and helps prevent the formation of thrombi (a blood clot that can obstruct a blood vessel).
  • In the immune system, NO is produced in white blood cells (including macrophages) when the body is invaded by bacteria and parasites. Then, huge quantities of NO are produced which become toxic to the invading organisms.
  • In the brain where NO is formed in nerve cells, NO radiates out in all directions, activating all cells in the vicinity, thus modulating many functions including behavior and gastrointestinal transit flow.
  • NO is thought to be the retroactive messenger involved in long-term memory and is now thought to be important in our olfactory sensations and our capacity to identify different scents. . . .

A different arginine-containing product mainly targets enhanced sexual function. It contains arginine, ginkgo biloba (known to enhance nitric oxide sythase production and release) and niacin (a component of the biochemical mediator NADPH). Sexual dysfunction, impotence for example, can be helped by arginine-generated NO which can initiate erection of the penis by dilating the blood vessels to penile erectile tissues. From human studies under way as well as past animal experiments, NO has a similar effect on women, causing their clitoral and vaginal tissues to become more sensitive and responsive. This knowledge has already led to the development of new drugs against impotence such as Viagra®, which is now undergoing trials for women as well.

Also containing arginine is a cognitive enhancer, a vinpocetine, arginine and ascorbyl palmitate powerhouse. Vinpocetine enhances glucose delivery and oxygen distribution in the brain while arginine increases vascular elasticity through the production of NO. Ascorbyl palmitate is a fat-soluble form of Vitamin C which plays a major role, protecting the high-fat content brain tissue from oxidative damage.2

Finally, there is a skin moisturizer that provides virtually unheard of stuctural and functional improvements. Among its many ingredients is arginine. It's in a special form that makes the ingredient useful to help protect the skin from damage and to help quicken wound healing.3-5 Curiously, nitric oxide is thought to explain, in part, arginine's ability to maintain proper skin protective and healing functions.

Who Wins the Real Prize?
We, the beneficiaries of the nutrient technologies that have been fast to apply the added findings of the Nobel Laureates, may be even greater winners than the official winners. Drs. Furchgott, Ignarro and Murad may have won the Prize, but arginine users keep on winning every day and the prize is a fuller and better life. 


  1. Schmidt HH, Heinrich Hofmann, Schindler U, Shutenko ZS, Cunningham DD, Feelisch M. NO from NO synthase. Proc Natl Acad Sci. 1996;93:14492-14497.
  2. Blaauboer AJ, Novak L, Hooghwinkel GJ. Organic solvent soluble lipofuscin pigment in brain tissues of mice fed large amounts of polyunsaturated fats in presence and absence of various antioxidants. Int J Vitam Nutr Res. 1979;49:428-433.
  3. Benrath J, Zimmermann M, Gillardon F. Substance P and nitric oxide mediate wound healing of ultraviolet photodamaged rat skin: evidence for an effect of nitric oxide on keratinocyte proliferation. Neurosci Lett. 1995 Nov 10;200(1):17-20.
  4. Hansbrough JF, Herndon DN, Heimbach DM, Solem LD, Gamelli RL, Tompkins RG. Accelerated healing and reduced need for grafting in pediatric patients with burns treated with arginine-glycine-aspartic acid peptide matrix. RGD Study Group. J Burn Care Rehabil. 1995;16:377-387.
  5. Schaffer MR, Tantry U, van Wesep RA, Barbul A. Nitric oxide metabolism in wounds. J Surg Res. 1997;71:25-31. 

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