Supplementation with antioxidants and its benefit-risk relationship have been largely discussed in the elderly population. We evaluated whether antioxidants supplementation improved the biochemical profile associated with oxidative metabolism in elderly cardiovascular patients. Patients (n = 112) received daily supplementation with α-TP 400 mg, beta-carotene 40 mg, and vitamin C 1000 mg for 2 months (treatment). Plasma concentrations of alpha-tocopherol (α-TP), β-carotene (βC), ubiquinol-10 (QH-10), glutathione, and thiobarbituric acid reactive substances (TBARS) were determined before and after treatment. Response to treatment was dependent on pretreatment α-TP and βC levels. Increase in α-TP and βC levels was observed only in patients with basal levels <18 μM for α-TP (P < 0.01) and <0.30 μM for βC (P < 0.02). Ubiquinol-10, glutathione, and TBARS were unaffected by treatment: QH-10 (+57%, F(1,110) = 3.611, P < 0.06, and N.S.), glutathione (+21%, F(1,110) = 2.92, P < 0.09, and N.S.), and TBARS (-29%, F(1,110) = 2.26, P < 0.14, and N.S.). Treatment reduced oxidative metabolism: 5.3% versus 14.6% basal value (F(1,110) = 9.21, P < 0.0003). Basal TBARS/α-TP ratio was higher in smokers compared to nonsmokers: 0.11 ± 0.02 versus 0.06 ± 0.01 (F(32,80) = 1.63, P < 0.04). Response to antioxidant supplementation was dependent on basal plasma levels of α-TP and βC. Smoking status was strongly associated with atherosclerotic cardiovascular disease and high TBARS/α-TP ratio (lipid peroxidation).