Citrulline, Nitric Oxide, and Type 2 Diabetes

Abstract

L-citrulline (Cit), a neutral, non-essential, and non-protein amino acid, is a precursor of L-arginine (Arg) and is involved in nitric oxide (NO) synthesis. Since oral ingestion of Cit can effectively elevate total Arg flux in the entire body and promote NO production, its supplementation has recently received much attention in the realm of cardio-metabolic diseases where NO metabolism is disrupted. Although preliminary data obtained from in vitro and in vivo animal experiments indicates that Cit improves glucose and insulin homeostasis and can effectively prevent hyperglycemia-induced complications such as inflammation, oxidative stress, renal dysfunction, and endothelial dysfunction, these findings are yet to be realized in well-designed longterm clinical studies in patients with type 2 diabetes (T2D). If Cit is shown to be an effective anti-diabetic agent with a good safety profile, its supplementation will be superior to that of Arg because it effectively increases systemic Arg availability more than Arg itself, and hence NO production.