Intracellular Mechanistic Role of Nitric Oxide: A Comparative Analysis of the Effectiveness of L-Arginine and L-Citrulline Supplementation on Nitric Oxide Synthesis and Subsequent Exercise Performance in Humans

Of late, there has been a major increase in the marketing of sport nutraceuticalsclaiming to augment exercise performance and recovery due to their ability to increase nitric oxide (NO) release. NO is a labile molecule that is known to play a major role in regulating vasodilation, blood flow, platelet adhesion, immune system function, and mitochondrial respiration. Endogenous NO synthesis is carried out by pathways that are NO-synthase (NOS)-dependent and NOS-independent. L-arginine, a semi-essential conditional amino acid is known as the primary precursor to up-regulate the production of NO alongside L-citrulline within the NOS-dependent pathway. Recently, L-citrulline has also been identified as a secondary NO donor due to its potential to augment NO synthesis through the recycling of this substrate and subsequent conversion into L-arginine within the NOS-dependent pathway. Based on the significance of these two major molecules for NO synthesis, sport supplements have highlighted both L-arginine and L-citrulline as ergogenic agents capable of aiding vasodilation and incurringnitric oxide stimulation. The primary premise behind these ergogenic claims is that exogenous administration of L-arginine or L-citrulline may increase both vasodilation properties and blood flow towards the active muscles. This would increase oxygen and nutrient delivery, which is suggested to improve muscular performance and oxygen efficiency during various types of exercises as well as promote a greater clearance of metabolites such as lactate during periods of recovery. While some studies have presented significant positive effects of human performance attributed to L-arginine or L-citrulline supplementation, there have also been major conflicted findings with no significant effect noted. Therefore, the purpose of this review is to discuss the intracellular mechanisms of action of the NO-inducing nutraceuticalscontaining L-arginine and L-citrullineand whether they are capable of incurring positive effects towards human performance.