L-arginine, L-citrulline, and cardiovascular health through the Nitric Oxide System

Currently, cardiovascular disease is the number one cause of morbidity and mortality in Americans. A need for research to discover nutritional approaches to promoting vascular health has emerged from this dangerous epidemic. For this reason, the past two decades have seen a sparked interest in the nutrition, biochemistry, and pharmacology of L-arginine. L-arginine is a conditionally-essential amino acid needed by the nitric oxide system. Endothelial nitric oxide synthase (eNOS) uses L-arginine to produce nitric oxide. Nitric oxide plays a critical role in maintaining the function and integrity of the endothelium by acting as a vasodilator maintaining vascular tone and structure. Dysfunction in the nitric oxide system decreases the bioavailability of nitric oxide and can induce endothelial dysfunction, which is integral in the pathogenesis of atherosclerosis. While the mechanism remains unclear, L-arginine supplementation has been shown to restore endothelial function in atherosclerotic animal models and humans. Unfortunately, there have also been negative health outcomes and low efficacy associated with high doses of oral supplementation of L-arginine. There is a safe and effective way, however, to receive the same beneficial effects of L-arginine through the consumption or supplementation of L-citrulline. L-citrulline is effectively recycled by the citrulline-nitric oxide cycle to L-arginine and plays a fundamental role in the regulation of nitric oxide levels in the body. Additionally, L-citrulline increases plasma L-arginine levels more effectively than an equal dose of L-arginine directly. In animal models, L-citrulline has been shown to upregulate eNOS, improve endothelial function, and protect against atherosclerosis. In humans, short-term doses of L-citrulline were shown to improve arterial stiffness independent of blood pressure. Interestingly, watermelon is a rich source of L-citrulline and has been shown to significantly increase plasma L-arginine concentrations, so may prove an effective alternative to oral-L-arginine or L-citrulline supplementation. In diabetic, fatty rats, watermelon pomace juice enhances arginine availability and ameliorates the metabolic syndrome. In humans, watermelon supplementation improves arterial function in adults with prehypertension. These findings are instrumental in demonstrating the importance of maintaining adequate levels of L-arginine and L-citrulline in the body in order to maintain adequate nitric oxide levels and promote cardiovascular health. Additionally, watermelon may be an effective treatment and prevention strategy for heart disease through its large contributions of L-citrulline (and less-so L-arginine) to the nitric oxide pathway.