Effects of combined supplementation with B vitamins and antioxidants on plasma levels of asymmetric dimethylarginine (ADMA) in subjects with elevated risk for cardiovascular disease

Elevated plasma asymmetric dimethylarginine (ADMA) concentrations have been suggested as a potential risk factor for cardiovascular disease (CVD). Studies indicate a linkage between hyperhomocysteinemia, oxidative stress and ADMA metabolism. We tested the hypothesis that combined supplementation of B vitamins and antioxidants reduces ADMA concentrations in subjects with at least two CVD risk factors. A total of 123 men and women (58 +/- 8.1 years) were randomly assigned to take either a preparation including B vitamins and antioxidants (verum) or placebo for 6 months in a double-blind design. Blood concentrations of ADMA, symmetric dimethylarginine (SDMA), L-arginine, B vitamins, total homocysteine (tHcy), a-tocopherol, antioxidant capacity (TEAC), and oxLDL were measured pre- and post-intervention. Treatment with verum significantly decreased tHcy (-2.14 mu mol/L; P < 0.00 1) and significantly increased TEAC values (+39.3 ; P < 0.022), but no effect on ADMA was observed. OxLDL was significantly reduced in verum (-7.3 U/L; P = 0.001) and placebo (-9.2 U/L; P < 0.001). At baseline, significant correlations were found only between ADMA and SDMA (r = 0.28 1; P = 0.002), L-arginine/ADMA and SDMA (r = -0.294; P < 0.001), L-arginine/ADMA and oxLDL (r = -0.28 1; P = 0.0 16), and L-arginine/ADMA and age (r = -0.23 1; P = 0.0 10). Our results indicate that combined supplementation of B vitamins and antioxidants is not an adequate strategy to reduce ADMA plasma levels in subjects with elevated CVD risk. (c) 2006 Elsevier Ireland Ltd. All rights.