The effect of citrulline and arginine supplementation on lactic acidemia in MELAS syndrome

•MELAS syndrome is a common mitochondrial disease.•Nitric oxide (NO) deficiency in MELAS may aggravate lactic acidosis.•Arginine and citrulline are NO precursors and can restore NO production in MELAS.•We assessed the effect of arginine and citrulline on lactate in adults with MELAS.•Lactate decreased with citrulline or arginine with more reduction after citrulline.

Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome is a mitochondrial disorder in which nitric oxide (NO) deficiency may play a role in the pathogenesis of several complications including stroke-like episodes and lactic acidosis. Supplementing the NO precursors arginine and citrulline restores NO production in MELAS syndrome. In this study we evaluated the effect of arginine or citrulline on lactic acidemia in adults with MELAS syndrome. Plasma lactate decreased significantly after citrulline supplementation, whereas the effect of arginine supplementation did not reach statistical significance. These results support the potential therapeutic utility of arginine and citrulline in MELAS syndrome and suggest that citrulline supplementation may be more efficacious. However, therapeutic efficacy of these compounds should be further evaluated in clinical trials.