Arginine Helps Counter Atherosclerosis
The Champion Among Amino Acids Holds the Key: Nitric Oxide

Got arginine? Of course you do - we all have a substantial amount of this "champion" amino acid in our bodies, performing life-sustaining functions of such stunning variety that, in that regard, it could lay claim to the title of "spice of life." Which brings sex to mind, and it is no coincidence that, without arginine, sex would be, well, kind of limp.

Arginine (technically, L-arginine) plays important roles in physiological functions of the cardiovascular, immune, central nervous, and neuroendocrine systems. Its benefits arise primarily through its ability to stimulate the production - through entirely different mechanisms - of two of the body's most important compounds: growth hormone and nitric oxide. These are two very different compounds. Growth hormone is a large, complex polypeptide molecule about 700 times heavier than tiny, simple nitric oxide, which consists of just two atoms - its formula is NO. (For a summary of arginine's many different roles in our bodies, see Arginine Keeps Kidneys in the Pink – May 2000.)

Not surprisingly, growth hormone and nitric oxide play very different roles in human physiology, but at least one thing they have in common is a tendency to counteract atherosclerosis, the buildup of fatty plaque in our arteries (with ultimately dire consequences). Here nitric oxide takes center stage, and it is arginine's role as the direct chemical precursor of NO that makes it of such great interest to medical scientists.

The discoveries of some of NO's vital roles in human physiology, in fact, were rewarded with the Nobel Prize in medicine - to the astonishment of scientists everywhere, who could scarcely believe that this poisonous industrial gas (and notorious air pollutant) could play any role in the human body except to injure it. Science is full of surprises.

Far from injuring us, NO - when it is made inside the body from arginine - helps regulate our blood pressure, among other functions. It is synthesized, with the help of an enzyme called nitric oxide synthase, in the vascular endothelium - that is, in the layer of smooth cells (called epithelial cells) that line the inside walls of blood vessels. There it exerts its vasodilating effect, i.e., it triggers the cellular responses that dilate the vessels when needed, so as to lower blood pressure (and, when appropriate, to facilitate erections).

In the central nervous system, NO is essential for motion-related learning processes that take place in the cerebellum. There is also evidence that it enhances cognitive functions throughout the brain and that it may be necessary for long-term potentiation, the mechanism involved in long-term memory. It plays a vital role in kidney function, and it is believed to have immune-system-enhancing properties. When its production is increased due to supplementation with arginine, it is responsible for an improvement in insulin sensitivity in diabetics.

There's more, but let us return to the blood vessels and the atherosclerosis that so commonly afflicts them. In both animal and human studies, it has been found that two characteristics of this disease are: (1) an impairment of the endothelium-dependent dilatation of the artery by NO, and (2) an enhanced tendency of monocytes (a type of white blood cell) to adhere to the epithelial cells. Both of these factors are believed to be due in part to a reduction in the availability of NO.

Such a reduction could be due to any number of causes, one of which is an arginine deficiency. If the latter is true - and even if it’s not - an obvious potential countermeasure would be to supplement with arginine to try to make up for the deficit in NO.

To test this hypothesis, a group of researchers at the Royal Prince Alfred Hospital and the Heart Research Institute in Sydney, Australia undertook a prospective, double-blind, crossover trial. They had previously demonstrated that oral arginine inhibits blood-platelet aggregation (which causes blood clotting) in healthy men and that it improves NO-mediated arterial dilatation in adults with excessive cholesterol levels but no overt symptoms of disease. In the present study, the bar was raised: the objective was to evaluate the effects of arginine on endothelial physiology in a group of young men with advanced symptomatic coronary atherosclerosis.1

Ten men aged 41 ± 2 years were chosen for the study. After establishing their baseline values for arterial dilatation (in the brachial artery of the forearm, using an ultrasound technique to measure the diameter), they were given 7 grams of arginine 3 times daily for 3 days, in the form of a flavored fruit drink. The placebo drink looked and tasted the same. There was a "washout" period of 10-14 days between the alternate regimens in this crossover study (the treatment group was switched to placebo, and vice versa, to eliminate the placebo effect). The arginine was well tolerated, with no side effects.

The result of this experiment was a 2.6-fold greater increase in arterial dilatation caused by arginine (4.7% increase in diameter) than by placebo (1.8%). That increase in diameter may not sound like much, but it is equivalent to a substantial 9.6% increase in the cross-sectional area of the artery, meaning improved blood flow.

In the same study, using methods too complicated to describe here, the researchers measured the effect of the arginine on the adhesion of monocytes to the patients' epithelial cells. There was a 16% reduction compared with placebo - another favorable result.

In another study, conducted at the Collegium Medicum in Cracow, Poland, researchers evaluated 14 male patients aged 39-66 years (average 54) who had suffered from peripheral arterial obliterative disease and showed atherosclerotic lesions.2 The patients were hospitalized and received 3-hour intravenous infusions daily for 14 consecutive days: first a saline placebo for 7 days, then 12.6 grams of arginine for 7 days. The results were clinically significant improvements in terms of a treadmill test for leg pain and maximum walking distance, as well as for a variety of tests for blood circulation and composition.

In a review article on the subject of arginine in coronary atherosclerosis by a team of cardiologists from Athens and London, many similar studies demonstrating the beneficial effects of supplemental arginine in heart disease are discussed, and the authors reach the following conclusion:3

"Clinical and experimental studies show that L-arginine administration may have an impact in vascular atherosclerosis. There is evidence to suggest that at the site of stenosis [a constriction], the mechanism of nitric oxide production is intact, and therefore stimulation of this pathway might provide therapeutic benefit in angina patients. Stimulation of endogenous [made by the body] nitric oxide production could inhibit atherogenesis or induce regression of pre-existing lesions. Patients with risk factors for atherosclerosis could benefit from L-arginine administration."


  1. Adams MR, McCredie R, Jessup W, Robinson J, Sullivan D, Celermajer DS. Oral L-arginine improves endothelium-dependent dilatation and reduces monocyte adhesion to endothelial cells in young men with coronary artery disease. Atherosclerosis 1997 Mar 21;129(2):261-9.
  2. Slawinski M, Grodzinska L, Kostka-Trabka E, Bieron K, Goszcz A, Gryglewski RJ. L-Arginine - substrate for NO synthesis - its beneficial effects in therapy of patients with peripheral arterial disease: comparison with placebo - preliminary results. Acta Physiol Hung 1996; 84(4):457-8.
  3. Tentolouris C, Tousoulis D, Goumas G, Stefanadis C, Davies G, Toutouzas P. L-Arginine in coronary atherosclerosis. Int J Cardiol 2000;75:123-8.

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