High intakes of whole grain foods are inversely related to the incidence of coronary heart diseases and type 2 diabetes, but the mechanisms remain unclear. Our study aimed to evaluate the effects of a diet rich in whole grains compared with a diet containing the same amount of refined grains on insulin sensitivity and markers of lipid peroxidation and inflammation. In a randomized crossover study, 22 women and 8 men (BMI 28 +/- 2) were given either whole-grain or refined-grain products (3 bread slices, 2 crisp bread slices, 1 portion muesli, and 1 portion pasta) to include in their habitual daily diet for two 6-wk periods. Peripheral insulin sensitivity was determined by euglycemic hyperinsulinemic clamp tests. 8-Iso-prostaglandin F(2alpha) (8-iso PGF(2alpha)), an F(2)-isoprostane, was measured in the urine as a marker of lipid peroxidation, and highly sensitive C-reactive protein and IL-6 were analyzed in plasma as markers of inflammation. Peripheral insulin sensitivity [mg glucose . kg body wt(-1) . min(-1) per unit plasma insulin (mU/L) x 100] did not improve when subjects consumed whole-grain products (6.8 +/- 3.0 at baseline and 6.5 +/- 2.7 after 6 wk) or refined products (6.4 +/- 2.9 and 6.9 +/- 3.2, respectively) and there were no differences between the 2 periods. Whole-grain consumption also did not affect 8-iso-PGF(2alpha) in urine, IL-6 and C-reactive protein in plasma, blood pressure, or serum lipid concentrations. In conclusion, substitution of whole grains (mainly based on milled wheat) for refined-grain products in the habitual daily diet of healthy moderately overweight adults for 6-wk did not affect insulin sensitivity or markers of lipid peroxidation and inflammation.