Impaired nitric oxide production has been implicated in the pathogenesis of mitochondrial encephalomyopathy, lactic acidosis and stroke like episiodes (MELAS). Arginine supplementation is often employed as a precursor for nitric oxide and can have therapeutic effects in stroke-like episodes associated with MELAS.
El-Hattab et al (Mol Gen Metab 105 (2012) 607-614) reported that citrulline has an increased potential for de novo nitric oxide synthesis compared with arginine. This may be due to inherent characteristics of arginine metabolism including: higher arginine clearance and elevated asymmetric dimethylarginine, in addition to decreased de novo arginine synthesis when citrulline levels are depleted.
While much work remains to be done in this area, citrulline is an interesting alternative to arginine therapy in MELAS.
Hilary Vernon, MD PhD