L-Arginine  is  involved  in  numerous  areas  of  human  physiology – protein  production,  wound  healing,  erectile  function  and  fertility.  Arginine also effects cardiovascular function because of arginine-induced  production of nitric oxide (NO) which is a key messenger molecule involved in endocrine  function, vascular regulation and immune activity.

However, in the body about 50-percent  of  ingested L-arginine  is  rapidly  metabolized by the enzyme arginase to L-ornithine which is a central part of the urea cycle.1 Hence, only half of  L-arginine can be processed by four other enzymes, including endothelial  nitric  oxide  synthase  (eNOS) which converts it into nitric  oxide.2

However, this process can be further complicated by  asymmetrical  dimethylarginine  (ADMA) – a naturally occurring component of human blood plasma – which also competes  with  L-arginine  for  binding  with  endothelial  nitric  oxide  synthase  (eNOS),  subsequently  down-regulating  activity  of  this  vital  enzyme. Hence, ADMA interferes with L-arginine in the production of nitric oxide, a key chemical involved in normal endothelial function and, by extension, cardiovascular health.

Increased plasma ADMA has been shown to be an  independent  risk  factor  for  cardiovascular  disease because of its inhibitory activity on eNOS.3 As it was observed, oral L-arginine  supplementation  overrides  the  inhibitory  effect of ADMA  on  eNOS  and  improves  vascular  function in those with high ADMA levels.4-6 Direct alteration of ADMA levels with supplements of L-arginine have been suggested.7-8

Bearing in mind all processes L-arginine is involved in, there is no other way to maintain sufficient NO production in the body but taking daily l-arginine supplementation.

1 Castillo L, Sanchez M, Vogt J, et al. Plasma arginine, citrulline, and ornithine kinetics in adults, with observations on nitric oxide synthesis. Am J Physiol 1995;268:E360-E367.

2. Meijer AJ, Lamers WH, Chamuleau RA. Nitrogen metabolism and ornithine cycle function. Physiol Rev 1990;70:701-748.
3.Determination of asymmetric dimethylarginine (ADMA) using a novel ELISA assay by Walter de Gruyter,Clin Chem Lab Med 2004;42(12):1377–1383  2004
4.Boger RH, Vallance P, Cooke JP. Asymmetric dimethylarginine (ADMA): a key regulator of nitric oxide synthase. Atherosclerosis  Suppl 2003;4:1-3.
5.Boger RH. Asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, explains the “Larginine paradox” and acts as a novel cardiovascular risk factor. J Nutr 2004;134:2842S-2847S.
6.Boger RH, Ron ES. L-Arginine improves vascular function by overcoming deleterious effects of ADMA, a novel cardiovascular risk factor. Altern Med Rev 2005;10:14-23.

7. Bode-Boger SM, Muke J, Surdacki A, Brabant G, Boger RH, Frolich JC (2003). “Oral L-arginine improves endothelial function in healthy individuals older than 70 years”. Vasc Med 8 (2): 77–81. doi:10.1191/1358863x03vm474oa. PMID 14518608.

8.John P. Cooke (2002). The Cardiovascular Cure. Random House. ISBN 0-7679-0881-3.