Following consecutive 12-wk administration of tablets containing 0, 200 or 400 mg grape seed extract (calculated as proanthocyanidin) to 61 healthy subjects with LDL cholesterol (LDL-C) levels of 100 to 180 mg/dL, effects of such treatment compared to administration of placebo tablets on malondialdehyde-modified LDL (MDA-LDL), representing one oxidized type of LDL, were investigated by a single blind method. MDA-LDL level in the 200 mg (calculated as proanthocyanidin) group was significantly (p = 0.008) reduced compared to the basal level, 12 wk after the start of administration. In the 400 mg (calculated as proanthocyanidin) group, a significant decrease in MDA-LDL level compared to the basal level was found 6 and 12 wk after the start of administration (6 wk: p = 0.015, 12 wk: p = 0.009). Subjects with high levels of MDA-LDL/ApoB (MDA-LDL/ApoB > or = 100 mU/mL) in the 200 mg group showed significantly (p = 0.011) reduced MDA-LDL levels at 12 wk after the start of administration. In the 400 mg group, significant decreases in MDA-LDL level compared to the basal level were seen 6 and 12 wk after the start of administration (6 wk: p = 0.001, 12 wk: p < 0.001); and at week 6, significantly (p = 0.048) lower values were observed compared to those in patients who took placebo tablets (0 mg proanthocyanidin). In subjects demonstrating the least body weight changes during the test period (less than +/- 1.0 kg) in the 400 mg group, there was an increasing trend (p = 0.088) in adiponectin levels 12 wk after the start of treatment. These results suggested that tablets containing grape seed extract exerted reducing effects on oxidized LDL, and might be useful in preventing lifestyle-related diseases such as arteriosclerosis.