Randomized, Double-Blind, Placebo-Controlled Study of Supplemental Oral l -Arginine in Patients With Heart Failure

Abstract

Background Patients with heart failure have reduced peripheral blood flow at rest, during exercise, and in response to endothelium-dependent vasodilators. Nitric oxide formed from l -arginine metabolism in endothelial cells contributes to regulation of blood flow under these conditions. A randomized, double-blind crossover study design was used to determine whether supplemental oral l -arginine can augment peripheral blood flow and improve functional status in patients with moderate to severe heart failure. Methods and Results Fifteen subjects were given 6 weeks of oral l -arginine hydrochloride (5.6 to 12.6 g/d) and 6 weeks of matched placebo capsules in random sequence. Compared with placebo, supplemental oral l -arginine significantly increased forearm blood flow during forearm exercise, on average from 5.1±2.8 to 6.6±3.4 mL·min −1 ·dL −1 ( P <.05). Furthermore, functional status was significantly better on l -arginine compared with placebo, as indicated by increased distances during a 6-minute walk test (390±91 versus 422±86 m, P <.05) and lower scores on the Living With Heart Failure questionnaire (55±28 versus 42±26, P <.05). Oral l -arginine also improved arterial compliance from 1.99±0.38 to 2.36±0.30 mL/mm Hg ( P <.001) and reduced circulating levels of endothelin from 1.9±1.1 to 1.5±1.1 pmol/L ( P <.05). Conclusions Supplemental oral l -arginine had beneficial effects in patients with heart failure. Further studies are needed to confirm the therapeutic potential of supplemental oral l -arginine and to identify mechanisms of action in patients with heart failure.