L-Arginine therapy in cardiovascular pathologies: beneficial or dangerous?

Abstract

L-Arginine is the precursor for nitric oxide synthesis. In the brain, nitric oxide acts as a neurotransmitter; in the immune system, nitric oxide acts as a mediator of host defense; in the cardiovascular system, nitric oxide mediates the protective effects of the intact endothelium, acting as an endogenous antiatherogenic molecule. About 5 g of L-arginine is taken up each day. L-Arginine plasma levels are not significantly reduced in most diseases, except end-stage renal failure during hemodialysis treatment. Nonetheless, intravenous or oral administration of L-arginine results in enhanced nitric oxide elaboration in subjects with impaired endothelial function. In clinical trials short to medium-term administration of L-arginine improved the symptoms of cardiovascular disease. In other trials, however, L-arginine was not beneficial and in one recent long-term study higher mortality of subjects receiving L-arginine than those receiving placebo was reported. These contradictory results were not understood for a long time. The endogenous inhibitor of nitric oxide synthase, asymmetric dimethylarginine, may determine a subject's response to L-arginine. L-Arginine appears to exert no effect in subjects with low asymmetric dimethylarginine levels, whereas in subjects with high asymmetric dimethylarginine levels L-arginine restores the L-arginine/asymmetric dimethylarginine ratio to normal and normalizes endothelial function. The effects of L-arginine supplementation on human physiology appear to be multicausal and dose related. Criteria need to be developed to define patients who benefit from L-arginine supplementation.