Arginine therapy in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes

We would like to inform clinicians that the systematic administration of oral and intravenous L-arginine is therapeutically beneficial and clinically useful for patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), when they maintain plasma arginine concentration at least 168 μmol/l.

MELAS is associated with endothelial dysfunction by decreased plasma L-arginine, nitric oxide (NO), and cyclic guanosine monophosphate. Endothelial dysfunction is also evident using flow-mediated vasodilation measurement by high-resolution Doppler echocardiography in the forearm artery in patients with MELAS. L-arginine is known to be an important precursor of NO to normalize the endothelial function in MELAS. In our clinical trial followed by 7 years follow-up study, the systematic administration of L-arginine to patients with MELAS significantly improved the survival curve of patients compared with natural history. Maintaining plasma arginine concentration at least 168 μmol/l may prevent the ictuses through the putative pathophysiologic mechanism and optimal normalization of endothelial dysfunction.

Neither death nor bedriddenness occurred during the 2-year clinical trials, and the latter did not develop during the 7-year follow-up despite the progressively neurodegenerative and eventually life-threatening nature of MELAS. Therapeutic regimen of L-arginine on MELAS may be beneficial and clinically useful for patient care with MELAS.