The pharmacodynamics of L-arginine

TY - JOUR

T1 - The pharmacodynamics of L-arginine

AU - Böger, Rainer H

N1 - Journal Abk. laut ISI WoK Listung fehlt: ALTERN THER HEALTH M alles andere ok

PY - 2014

Y1 - 2014

N2 - L-Arginine is a precursor for nitric oxide (NO) synthesis. NO is a ubiquitous mediator that is formed by a family of enzymes called NO synthases (NOSs). In the brain, NO acts as a neurotransmitter; in the immune system, it acts as a mediator of host defense; and in the cardiovascular system, it mediates the protective effects of the intact endothelium, acting as a vasodilator and endogenous, antiatherogenic molecule. About 5 g of L-arginine are ingested each day in a normal Western diet. Plasma levels of L-arginine are not significantly reduced in most diseases, except in 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 individuals 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 for participants receiving L-arginine than for those receiving placebo. Recently, it became clear that endogenous levels of asymmetric dimethylarginine (ADMA), a competitive inhibitor of L-Arginine metabolism by NOS, may determine an individual's response to L-arginine supplementation. L-Arginine appears to exert no effect in individuals with low ADMA levels, whereas in those with high levels, L-arginine restores the L-arginine/ADMA ratio to normal 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.

AB - L-Arginine is a precursor for nitric oxide (NO) synthesis. NO is a ubiquitous mediator that is formed by a family of enzymes called NO synthases (NOSs). In the brain, NO acts as a neurotransmitter; in the immune system, it acts as a mediator of host defense; and in the cardiovascular system, it mediates the protective effects of the intact endothelium, acting as a vasodilator and endogenous, antiatherogenic molecule. About 5 g of L-arginine are ingested each day in a normal Western diet. Plasma levels of L-arginine are not significantly reduced in most diseases, except in 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 individuals 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 for participants receiving L-arginine than for those receiving placebo. Recently, it became clear that endogenous levels of asymmetric dimethylarginine (ADMA), a competitive inhibitor of L-Arginine metabolism by NOS, may determine an individual's response to L-arginine supplementation. L-Arginine appears to exert no effect in individuals with low ADMA levels, whereas in those with high levels, L-arginine restores the L-arginine/ADMA ratio to normal 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.

KW - Animals

KW - Arginine

KW - Cardiovascular Diseases

KW - Dietary Supplements

KW - Dose-Response Relationship, Drug

KW - Endothelium, Vascular

KW - Humans

KW - Nitric Oxide

KW - Nitric Oxide Synthase

M3 - SCORING: Journal article

C2 - 24755570

VL - 20

SP - 48

EP - 54

JO - ALTERN THER HEALTH M

JF - ALTERN THER HEALTH M

SN - 1078-6791

IS - 3

ER -