Cardiovascular Disorder
Extensive studies have demonstrated arginine's antiatherogenic, antiischaemic and antithrombic properties. The eventual consequence is formation of plaque in the arteries, which leads to compromised endothelial function which in turn leads to reduced vasodilation. Arginine has been shown to not only prevent further progression but also even regression of plaque formation! An interesting study by Boger and colleagues compared the effects of standard cholesterol drug lovastatin (Mevacor) with arginine in cholesterol fed rabbits. Lovastatin reduced cholesterol by 32%, but had only a weak effect on formation of plaque. Interestingly, arginine had no effect on cholesterol yet completely blocked the formation of plaque.

The initiating event in atherosclerotic plaque formation is monocyte adhesion to the endothelium followed by entry of these monocytces into the subintimal layer of the blood vessels, transformation into macrophage cells followed by uptake of lipids and eventually fatty streak/foam cell formation. Arginine is reported to reduce the adhesion of monocytes to the endothelial cells in coronary patients and in smokers. Another mechanism through which arginine may be acting is that NO has potent free radical quenching properties and hence acts as an antioxidant.

Numerous experimental and clinical studies have demonstrated the therapeutic potential of high dose arginine for the prevention and treatment of a broad spectrum of cardiovascular diseases, in preventing endothelial damage and restoration of endothelial function including: arterial hypertension, peripheral vascular disease, angina and the so called "Syndrome X". Arginine has been successfully employed for the treatment of mild-to-moderate but not severe congestive heart failure, a dose of 12.6g per day demonstrated a beneficial effect.

Diabetes
Diabetes mellitus is a metabolic disorder which strongly predisposes an individual to cardiovascular disease. Hyperglycemia is thought to cause diabetic complication via the follwing mechanism: formation of reactive oxygen species (ROS), which cause direct endothelial damage; and increased formation of advanced glycating end products (AGE's) which are toxic species that changes structure and function of physiological proteins. The net result is an increase in retinopathy, nephropathy and neuropathy. High blood glucose levels also reduce NO availability. Arginine however, can reverse the vascular effects of high glucose concentration. A small randomized, double blind, placebo-controlled study, demonstrated that 6 grams of arginine improved exercise capacity in angina patients.

Arginine reduces platelet aggregation, blood viscosity and improves blood flow and helps repair vascular injury. Arginine is considered a promising therapeutic agent for the prevention of restenosis and improving the outcome following heart transplantation and coronary bypass.

Other Benefits

a. Interstitial cystitis
A dose of 1.5g daily for 6 months in a clinical trial resulted in a significant decrease in urinary voiding discomfort and diminished abdominal and vaginal/urethral pain. Urinary frequency was significantly decreased.

b. Spermatogenesis
Arginine has been used for treating male infertility by improving spermatogenesis. Since arginine is a precursor of NO, and NO is a potent vasodilator it is conceivable that arginine would be of benefit in Penile erectile dysfunction much like the mechanism of action of Viagra.

c. Liver and brain injury
Animal studies have reported benefits in acute liver and brain injury. 

Arginine and immunity.
J Nutr. 2007 Jun;137(6 Suppl 2):1681S-1686S.
Popovic PJ, Zeh HJ, Ochoa JB.

For many years, dietary arginine supplementation, often combined with other substances, has been used as a mechanism to boost the immune system. Considerable controversy, however, exists as to the benefits and indications of dietary arginine due in part to a poor understanding of the role played by this amino acid in maintaining immune function. Emerging knowledge promises to clear this controversy and allow for arginine's safe use. In myeloid cells, arginine is mainly metabolized either by inducible nitric oxide (NO) synthases (iNOS) or by arginase 1, enzymes that are stimulated by T helper 1 or 2 cytokines, respectively. Thus, activation of iNOS or arginase (or both) reflects the type of inflammatory response in a specific disease process. Myeloid suppressor cells (MSC) expressing arginase have been described in trauma (in both mice and humans), intra-abdominal sepsis, certain infections, and prominently, cancer. Myeloid cells expressing arginase have been shown to accumulate in patients with cancer. Arginase 1 expression is also detected in mononuclear cells after trauma or surgery. MSC efficiently deplete arginine and generate ornithine. Through arginine depletion, MSC may control NO production and regulate other arginine-dependent biological processes. Low circulating arginine has been documented in trauma and cancer, suggesting that MSC may exert a systemic effect and cause a state of arginine deficiency. Simultaneously, T lymphocytes depend on arginine for proliferation, zeta-chain peptide and T-cell receptor complex expression, and the development of memory. T-cells cocultured with MSC exhibit the molecular and functional effects associated with arginine deficiency. Not surprisingly, T-cell abnormalities, including decreased proliferation and loss of the zeta-chain, are observed in cancer and after trauma.


L-Arginine, the substrate for NO synthesis: an alternative treatment for premature atherosclerosis?
Int J Cardiol. 2007 Apr 4;116(3):300-8. Epub 2006 Jul 24.
Siasos G, Tousoulis D, Antoniades C, Stefanadi E, Stefanadis C.

L-Arginine is the substrate of endothelial nitric oxide synthase (eNOS) and the main precursor of nitric oxide (NO) in the vascular endothelium. L-Arginine improves endothelial function in patients with hypercholesterolemia, hypertension and smokers, while its role in diabetes remains unclear. Oral supplementation of L-arginine leads to a significant improvement of endothelium-dependent forearm vasodilation in hypercholesterolemic patients, while intravenous infusion of L-arginine improves endothelial function in healthy smokers. L-Arginine has anti-hypertensive properties, although its effects on endothelial function in hypertensive patients needs further evaluation. In conclusion, L-arginine administration may be useful in patients with premature atherosclerosis.


Platelet nitric oxide synthesis in uremia and malnutrition: A role for l-arginine supplementation in vascular protection?
Cardiovasc Res. 2007 Jan 15;73(2):359-67. Epub 2006 Sep 30.
Brunini TM, Mendes-Ribeiro AC, Ellory JC, Mann GE.

l-arginine is the physiological precursor for nitric oxide (NO) synthesis, and availability and transport of l-arginine modulate the rates of NO biosynthesis in circulating blood cells and the vasculature. NO is involved in many vascular functions such as vasodilation and inhibition of platelet aggregation and adhesion. We have established that reduced plasma l-arginine and NO production and increased tumour necrosis factor-alpha (TNF-alpha), fibrinogen, and C-reactive protein levels in malnourished uremic patients are associated with increased aggregability of platelets. Our findings may explain the increased cardiovascular mortality in patients with deficient nutritional status, leading to inflammation, oxidative stress, impaired l-arginine-NO signalling, and platelet activation. The aim of this review is to evaluate whether disturbances in the l-arginine-NO signalling pathway in chronic renal failure and atherosclerosis are affected by malnutrition and inflammation. We have included a brief overview of membrane transporters mediating influx of l-arginine and other cationic amino acids, as these transporters are involved in the potential benefits of l-arginine supplementation and platelet function in malnourished uremic patients.