l-Arginine enhances the triglyceride-lowering effect of simvastatin in patients with elevated plasma triglycerides

We recently noticed a possible triglyceride-lowering effect during dietary supplementation with l-arginine. The major limitation of prior studies on l-arginine, however, was that triglyceride levels were not the primary end point, and patients were not necessarily hypertriglyceridemic. Therefore, we conducted a 2-arm, randomized, double-blind study in 33 hypertriglyceridemic patients to investigate the hypothesis that oral l-arginine may lower serum triglyceride levels in hypertriglyceridemic patients on and off statins. The study consisted of a 6-week run-in phase, 6 weeks of treatment with l-arginine (n = 22, 1.5 g bid) or placebo (n = 11), and a 6-week extension period where simvastatin (20 mg qd) was added. All patients received dietary advice during each study visit. Routine and lipid laboratory parameters were determined in the local routine clinical laboratory. Treatment with l-arginine alone had no effects on serum lipids compared to placebo. The combination of l-arginine with simvastatin led to a significantly stronger reduction in triglycerides compared to placebo plus simvastatin (−140.5 ± 149.2 mg/dL vs −56.1 ± 85.0 mg/dL; P = .048). In addition, we found simvastatin-induced increases in aspartate transaminase and fibrinogen to be attenuated by l-arginine as compared to placebo. We conclude from our data that l-arginine enhances the effects of simvastatin on lipid metabolism, but it has no triglyceride-lowering effects when given alone.