Protein, amino acid metabolism and therapy: Edited by Erich Roth and Paul B. PencharzRegulation of nitric oxide production in health and diseaseLuiking, Yvette C; Engelen, Mariëlle PKJ; Deutz, Nicolaas EP Author Information Center for Translational Research in Aging and Longevity, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA Correspondence to Nicolaas E.P. Deutz, MD, PhD, Center for Translational Research in Aging and Longevity, Room #3.121, Donald W. Reynolds Institute on Aging, University of Arkansas for Medical Sciences, 4301 W Markham St. Slot 807, Little Rock, AR 72205, USA Tel: +1 501 352 6626; e-mail: [email protected] Current Opinion in Clinical Nutrition and Metabolic Care: January 2010 - Volume 13 - Issue 1 - p 97-104 doi: 10.1097/MCO.0b013e328332f99d Buy Metrics Abstract Purpose of review The purpose of this review is to highlight recent publications examining nitric oxide production in health and disease and its association with clinical nutrition and alterations in metabolism. Recent findings The role of the cofactor tetrahydrobiopterin in nitric oxide production and its relation with arginine availability is indicated as an important explanation for the arginine paradox. This offers potential for nitric oxide regulation by dietary factors such as arginine or its precursors and vitamin C. Because diets with a high saturated fat content induce high plasma fatty acid levels, endothelial nitric oxide production is often impaired due to a reduction in nitric oxide synthase 3 phosphorylation. Increasing the arginine availability by arginine therapy or arginase inhibition was, therefore, proposed as a potential therapy to treat hypertension. Recent studies in septic patients and transgenic mice models found that inadequate de-novo arginine production from citrulline reduces nitric oxide production. Citrulline supplementation may, therefore, be a novel therapeutic approach in conditions of arginine deficiency. Summary Both lack and excess of nitric oxide production in diseases can have various important implications in which dietary factors can play a modulating role. Future research is needed to expand our understanding of the regulation and adequate measurement of nitric oxide production at the organ level and by the different nitric oxide synthase isoforms, also in relation to clinical nutrition. © 2010 Lippincott Williams & Wilkins, Inc.