Elsevier

The Journal of Nutrition

Volume 137, Issue 6, June 2007, Pages 1650S-1655S
The Journal of Nutrition

The Pharmacodynamics of L-Arginine123

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Abstract

L-Arginine is a precursor for nitric oxide (NO) synthesis. NO is a ubiquitous mediator that is formed by a family of enzymes named NO synthases. 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 the intact endothelium, acting as a vasodilator and endogenous antiatherogenic molecule. About 5 g of L-arginine is ingested each day in a normal Western diet. L-Arginine plasma levels are not significantly reduced in most disease conditions, except end-stage renal failure during hemodialysis treatment. Nonetheless, intravenous or dietary (oral) administration of relatively large doses of L-arginine has been shown to result in enhanced NO formation in subjects with impaired endothelial function at baseline. In several controlled clinical trials, long-term administration of L-arginine has been shown to improve the symptoms of cardiovascular disease. However, in other trials L-arginine was not beneficial, and in a recent study, the authors reported higher mortality of subjects receiving L-arginine than those receiving placebo. Recently it became clear that endogenous levels of asymmetric dimethylarginine (ADMA), a competitive inhibitor of L-arginine metabolism by NO synthase, may determine a subject’s response to L-arginine supplementation. L-Arginine appears to exert no effect in subjects with low ADMA levels, whereas in subjects with high ADMA levels, L-arginine restores the L-arginine/ADMA ratio to normal levels and thereby normalizes endothelial function. In conclusion, the effects of L-arginine supplementation on human physiology appear to be multicausal and dose-related. Doses of 3–8 g/d appear to be safe and not to cause acute pharmacologic effects in humans.

Abbreviations

ADMA
asymmetric dimethylarginine
NO
nitric oxide
NOS
nitric oxide synthase

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1

Published in a supplement to The Journal of Nutrition. Presented at the conference “The Sixth Workshop on the Assessment of Adequate and Safe Intake of Dietary Amino Acids” held November 6–7, 2006 in Budapest. The conference was sponsored by the International Council on Amino Acid Science (ICAAS). The organizing committee for the workshop was David H. Baker, Dennis M. Bier, Luc A. Cynober, Yuzo Hayashi, Motoni Kadowaki, Sidney M. Morris, Jr., and Andrew G. Renwick. The Guest Editors for the supplement were David H. Baker, Dennis M. Bier, Luc A. Cynober, Motoni Kadowaki, Sidney M. Morris, Jr., and Andrew G. Renwick. Disclosures: all Editors and members of the organizing committee received travel support from ICAAS to attend the workshop and an honorarium for organizing the meeting.

2

Author disclosures: R. H. Böger’s travel expenses to attend the meeting were paid by ICAAS.

3

Supported by the Deutsche Forschungsgemeinschaft (grants Bo 1431/3-1, Bo 1431/3-2, Bo 1431/4-1), the Else-Kröner-Fresenius Foundation, and the German Heart Foundation.