Effect of L‑arginine supplementation on homocysteine and asymmetric dimethylarginine in atherosclerotic lower limb ischemia.

Chronic lower limb ischemia is a manifestation of systemic atherosclerosis frequently accompanied by lipid metabolism disorders, endothelial dysfunction, and disturbances in the L-arginine-nitric oxide (NO) pathway. Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, and homocysteine (Hcy) are recognized markers of vascular risk. This study aimed to evaluate the effect of 2 months of oral L-arginine supplementation (6g/day) on serum ADMA and Hcy concentrations in patients with atherosclerotic lower limb ischemia, depending on lipid metabolism disorder type. In a randomized, double-masked, placebo-controlled trial, 87 patients (50 men, 37 women) were assigned to L-arginine or placebo. Subgroups were defined according to lipid abnormalities: hypertriglyceridemia, hypercholesterolemia, and mixed hyperlipidemia. ADMA was measured by HPLC, and Hcy by fluorescence polarization immunoassay at baseline, 30, and 60 days. L-arginine supplementation significantly reduced ADMA levels in patients with hypercholesterolemia after 30 and 60 days (P<0.05) and in those with mixed hyperlipidemia after 60 days (P<0.05), but not in those with isolated hypertriglyceridemia. Changes in Hcy were not statistically significant. A significant positive correlation between ADMA and Hcy was present in all subgroups, most consistently in hypercholesterolemia. Two-month L-arginine supplementation decreases ADMA concentrations in patients with atherosclerotic lower limb ischemia, with efficacy dependent on the underlying lipid disorder phenotype, suggesting a metabolism-specific modulation of the ADMA-NO axis.