Epidemiologic studies have shown a correlation between antioxidant intake and 
coronary artery disease (CAD); however, the results of clinical trials have been 
inconsistent. We evaluated the effect of combined antioxidant supplementation on 
endothelial function and its correlation with change in low-density lipoprotein 
cholesterol (LDLC) oxidation in patients with established CAD. In a 
double-blind, placebo-controlled 12-week trial, 18 nonsmoking, nondiabetic 
patients (mean age 62.4 +/- 8.1 years) were randomized to receive placebo or 
antioxidant supplementation consisting of (a) 400 IU of vitamin E, 500 mg of 
vitamin C, and 12 mg of beta-carotene; or (b) 800 IU of vitamin E, 1000 mg of 
vitamin C, and 24 mg of beta-carotene daily. Endothelial function was evaluated 
on the basis of percent and absolute changes in brachial artery diameter in 
response to reactive hyperemia induced by occlusion-release. Baseline and 
12-week values of LDL oxidation (measured on the basis of lag phase), 
endothelial function, dietary composition, serum antioxidants, and lipids were 
measured. We noted a significant between-group difference at 12 weeks for change 
in plasma concentrations of alpha-tocopherol, vitamin C, and beta-carotene 
between the placebo and antioxidant groups (p <.05). Both placebo and treatment 
groups demonstrated a significant improvement in lag phase; however, the 
treatment group achieved a greater, although nonsignificant, magnitude of change 
compared with the placebo group (181.3 +/- 177.8 minutes vs 80.6 +/- 63.0 
minutes, P =.06). Within-group change in brachial reactivity from baseline to 
follow-up in the treatment group did not reach statistical significance (1.7% 
+/- 3.2% and 0.07 mm +/- 0.13 mm, P =.08 and P =.09, respectively), whereas an 
improved change in brachial reactivity was observed in the placebo group (2.2% 
+/- 1.9%, 0.09 mm +/- 0.06 mm, P <.05). No significant correlation was found 
between change in lag phase and change in endothelial function. On adjustment 
for confounders, antioxidant supplementation was found not to be a significant 
predictor of brachial reactivity. We conclude that antioxidant supplementation 
did not significantly alter brachial reactivity, despite significantly increased 
plasma levels of antioxidants and improved lag phase. These data should be 
confirmed in larger-scale trials and examined in studies evaluating individual 
dietary antioxidant supplementation.