L-Arginine is an essential amino acid for infants and growing children, and it is a conditionally essential
amino acid for adult mammals, as it is important in situations in which requirements exceed
production,such as pregnancy. [2] .

L-Arginine is a substrate for at least five enzymes identified in mammals, including
arginase,arginine-glycine transaminase, kyotorphine synthase, nitric oxide synthase (NOS) and
arginine decarboxylase. [4] It has a significant metabolic role as the product of ammonia detoxification,
the urea cycle metabolite, the precursor of proteins, ornithine, urea and creatinine, and the amino acid
involved in the formation of active enzyme centers. [3] Its side effects are rare and mostly mild and
dose-dependent.  [1]

What is L-Arginine?
L-arginine is the substrate for the enzyme nitric oxide synthase (NOS), which is responsible for the
production of nitric oxide (NO), an endogenous messenger molecule involved in many of the processes
associated with the development of atherosclerosis.
Acute and chronic administration of L-arginine has been shown to improve endothelial function in
animal models of hypercholesterolemia and atherosclerosis.

Researchers have debated whether dietary L-arginine supplementation can provide valuable health
benefits as it augment NO production in man. In fact, some clinical studies involving healthy volunteers
or patients suffering from hypertension and diabetes indicate that L-arginine may also regulate
vascular hemostasis. Futhermore, animals and in vitro studies suggest that L-arginine may have a
complex antiaggregatory, anticoagulatory and profibrinolytic effects. [1,3]

Diseases such as heart attack, stroke or critical atherosclerotic leg ischaemia are very common and
they are the main cause of deaths in the age group over 40 years. Patients with advanced leg
ischaemia can be treated surgically. However in distal disseminated
occlusions, surgery is technically impossible.

It is believed that endothelium plays a crucial role in the maintenance of vascular tone and structure.
While, nitric oxide (N)) is one of the major endothelium-derived vasoactive mediators; an endogenous
messenger molecule formed in healthy vascular endothelium from the amino acid precursor L-arginine.
Endothelial dysfunction is caused by various cardiovascular risk factors, metabolic diseases, systemic
or local inflammation. One mechanism that explains the occurrence of endothelial dysfunction is the
presence of elevated blood levels of asymmetric dimethylarginine (ADMA)--an L-arginine analogue that
inhibits NO formation and thereby can impair vascular function. Supplementation with L-arginine has
been shown to increase of nitric oxide synthesis, restore vascular function and to improve the clinical
symptoms of various diseases associated with vascular dysfunction. [5,6] Poland researchers suggest
that the clinical effectiveness of L-arginine is comparable to conventional pharmacotherapy; L-arginine
supplementation may contribute to better results of atherosclerosis treatment.

The mechanisms by which L-arginine improves endothelial nitric oxide bioactivity include increased
intracellular uptake via the high-affinity cationic transporter; substrate competition with asymmetric
dimethylarginine, a naturally occurring inhibitor of nitric oxide synthase; direct antioxidant activity;
stimulated release of histamine from mast cells, which produces a vasodilator response; decreased
activity of norepinephrine, which promotes the effect of endogenous vasodilators including nitric oxide;
and increased insulin secretion, which causes vasodilation. [8, 9]

Researchers also believe that L-arginine metabolites may have some benefits on renal disease. It is
because administration of exogenous L-arginine protected some subjects in ischemic acute renal
failure. [7] Infusion of L-arginine in experimental animals increases renal plasma flow (RPF) and
glomerular filtration rate (GFR). Despite persistent hyperglycemia, the administration of L-arginine is
also found to prevent the development of hyperfiltration and ameliorated proteinuria in diabetic rats.

A few studies suggest the side effect of L-arginine
supplementation is mild and dose-dependent. However, High dose of L-arginine intraperitoneal
administration has been reported to cause side effects, such as pancreatitis. [11]

This article summarizes only 11 of the most recent review articles on the uses of L-arginine on certain
conditions. L-arginine may have much more benefits (side effects as well) on various conditions.

[1] Bode-Boger SM. Influence of L-arginine on development of atherosclerosis: what is the therapeutically assured?
Dtsch Med Wochenschr. 2005 Mar 18;130(11):593-8. [2] Bronte V et al, Regulation of immune responses by L-arginine
metabolism. Nat Rev Immunol. 2005 Aug;5(8):641-54. [3] Cylwik D, et al, L-arginine and cardiovascular system.
Pharmacol Rep. 2005 Jan-Feb;57(1):14-22. [4] Nakaki T, Kato R. Beneficial circulatory effect of L-arginine. Jpn J
Pharmacol. 1994 Oct;66(2):167-71. [5] Boger RH, L-Arginine improves vascular function by overcoming deleterious
effects of ADMA, a novel cardiovascular risk factor. Altern Med Rev. 2005 Mar;10(1):14-23. [6] Kielar M, et al, New
possibilities in treatment of atherosclerosis--increase of nitric oxide synthesis by L-arginine supplementationPol
Merkuriusz Lek. 2004 Dec;17(102):656-60. [7] Cherla G, Role of L-arginine in the pathogenesis and treatment of renal
disease. J Nutr. 2004 Oct;134(10 Suppl):2801S-2806S; discussion 2818S-2819S. [8] Loscalzo J. L-arginine and
atherothrombosis. J Nutr. 2004 Oct;134(10 Suppl):2798S-2800S; discussion 2818S-2819S. [9] Stuehr DJ. Enzymes of
the L-arginine to nitric oxide pathway. J Nutr. 2004 Oct;134(10 Suppl):2748S-2751S; discussion 2765S-2767S. [10]
Klahr S, et al, L-arginine as a therapeutic tool in kidney disease. Semin Nephrol. 2004 Jul;24(4):389-94. [11] Hegyi P,
L-arginine-induced experimental pancreatitis. World J Gastroenterol. 2004 Jul 15;10(14):2003-9.
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