Arginine Research Summary
Arginine, or L-arginine is an amino acid that is present in the diet as well as made in the body. It is non-essential in most healthy individuals due to our body’s ability to produce it in endothelial cells. It is a precursor for nitric oxide (NO) formation, which has numerous effects throughout the body. In the brain, NO acts as a neurotransmitter, in the immune system NO acts as a mediator of host defense, and in the cardiovascular system, NO mediates the protective effects of healthy endothelium through vasodilation and antithrombotic effects.[i] Specific to these cardiovascular effects, NO diffuses into vascular smooth muscle and results in relaxation and vasodilation. Additionally, NO decreases platelet aggregation and adhesiveness, inhibits smooth muscle proliferation, and inhibits LDL oxidation.[ii] Impaired NO synthesis is a component of a number of cardiovascular conditions, including hypertension, hyperlipidemia, peripheral vascular disease, hyperhomocysteinemia, congestive heart failure, erectile dysfunction, and cerebrovascular events.[iii][iv]
Clinical studies of L-arginine have demonstrated a wide variety of benefits in cardiovascular health, including vascular function, increased exercise capacity, and blood pressure reduction[v][vi][vii][viii]. Not all studies have demonstrated a benefit however, as arginine has been given in a wide range of doses and routes of administration. Recent data has been published demonstrating the effects of a sustained-release form of L-arginine on blood pressure (bp) at a moderate dose of 1050mg twice daily.[ix] The improved bioavailability of a sustained-release delivery of L-arginine led to clinically significant systolic bp reduction in 62% of patients. Overall systolic reduction was a non-significant 4mmHg, however in the individuals with systolic bp > 130 mmHg, the mean reduction was 11mmHg. Normotensives had a mean systolic decrease of only .2mmHg. These changes were in accordance with improvements in large artery compliance as seen by pulse wave analysis.
Recent data has emerged providing insight into the variability of patient response. The NO conversion pathway is known to be inhibited by hypercholesterolemia, oxidative stress, and asymmetrical dimethylarginine (ADMA).[x] These individuals typically have normal plasma levels of L-arginine, but the conversion pathway is inhibited. ADMA, an endogenous inhibitor of NO synthase, displaces L-arginine from its substrate binding site, and accumulates in certain pathophysiological conditions. L-arginine supplementation appears to be the most reliable method of improving the L-arginine/ADMA ratio.
[i] Boger RH. The Pharmacodynamics of L-Arginine. The Journal of Nutrition. 2007;1650S-1655S.
[ii] Naseem KM. The Role of Nitric Oxide in Cardiovascular Diseases. Mol Aspects Med. 2005;26:33-65.
[iii] Preli RB, et al. Vascular effects of dietary L-arginine supplementation. Atherosclerosis 2002;162:1-15.
[iv] Lekakis JP, et al. Oral L-arginine improves endothelial dysfunction in patients with essential hypertension. Int J Cardiol 2002;86:317-323.
[v] Maxwell AJ, et al. Nutritional therapy for peripheral arterial disease: a double-blind,placebo-controlled, randomized trial of heartBarVasc Med 2000;5:11-19.
[vi] Palloshi A, et al. Effect of oral L-arginine supplementation on blood pressure and symptoms and endothelial function in patients with systemic hypertension, positive exercise tests, and normal coronary arteries. Am J Cardiol 2004;93:933-935.
[vii] Regensteiner JG, et al. Oral L-arginine and vitamins E and C improve endothelial function in women with type 2 diabetes. Vasc med 2003;8:169-175.
[viii] Yousufuddin M, et al. A short course of L-arginine improves exercise capacity and endothelial function in chronic heart failure: a prospective, randomized, double blind trial. J Am Coll Cardiol 2001;211A.
[ix] Miller AL. The Effects of Sustained-Release L-Arginine formulation on blood pressure and vascular compliance in 29 healthy individuals. Alternative Medicine Review. March 2006.
[x] Boger RH. Asymmetric dimethylarginine (ADMA): a novel risk marker in cardiovascular medicine and beyond. Ann Med. 2006;38:126-36.