Oxidative stress, caused by an imbalance between antioxidant capacity and reactive oxygen species, may be an early event in a metabolic cascade elicited by a high glycemic index (GI) diet, ultimately increasing the risk for cardiovascular disease and diabetes. We conducted a feeding study to evaluate the acute effects of low-GI compared with high-GI diets on oxidative stress and cardiovascular disease risk factors. The crossover study comprised two 10-day in-patient admissions to a clinical research center. For the admissions, 12 overweight or obese (BMI: 27-45 kg/m(2)) male subjects aged 18-35 years consumed low-GI or high-GI diets controlled for potentially confounding nutrients. On day 7, after an overnight fast and then during a 5-h postprandial period, we assessed total antioxidant capacity (total and perchloric acid (PCA) protein-precipitated plasma oxygen radical absorbance capacity (ORAC) assay) and oxidative stress status (urinary F(2alpha)-isoprostanes (F(2)IP)). On day 10, we measured cardiovascular disease risk factors. Under fasting conditions, total antioxidant capacity was significantly higher during the low-GI vs. high-GI diet based on total ORAC (11,736 +/- 668 vs. 10,381 +/- 612 micromol Trolox equivalents/l, P = 0.002) and PCA-ORAC (1,276 +/- 96 vs. 1,210 +/- 96 micromol Trolox equivalents/l, P = 0.02). Area under the postprandial response curve also differed significantly between the two diets for total ORAC and PCA-ORAC. No diet effects were observed for the other variables. Enhancement in plasma total antioxidant capacity occurs within 1 week on a low-GI diet, before changes in other risk factors, raising the possibility that this phenomenon may mediate, at least in part, the previously reported effects of GI on health.