Diabetic patients have reduced antioxidant defenses and suffer from an increased risk of free radical-mediated diseases such as coronary heart disease. Epidemiological evidence has suggested that antioxidant dietary flavonoids may protect against heart disease, but a biological effect has yet to be demonstrated directly in humans. In this study, 10 stable type 2 diabetic patients were treated for 2 weeks on a low-flavonol diet and for 2 weeks on the same diet supplemented with 76-110 mg of flavonols (mostly quercetin) provided by 400 g of onions (and tomato sauce) and six cups of tea daily. Freshly collected lymphocytes were subjected to standard oxidative challenge with hydrogen peroxide, and DNA damage was measured by single-cell gel electrophoresis. Fasting plasma flavonol concentrations (measured by high-performance liquid chromatography) were 5.6 +/- 2.9 ng/ml on the low-flavonol diet and increased 12-fold to 72.1 +/- 15.8 ng/ml on the high-flavonol diet (P < 0.001). Oxidative damage to lymphocyte DNA was 220 +/- 12 on an arbitrary scale of 0-400 U on the low-flavonol diet and 192 +/- 14 on the high-flavonol diet (P = 0.037). This decrease was not accounted for by any change in the measurements of diabetic control (fasting plasma glucose or fructosamine) or by any change in the plasma levels of known antioxidants, including vitamin C, carotenoids, alpha-tocopherol, urate, albumin, and bilirubin. In conclusion, we have shown a biological effect of potential medical importance that appears to be associated with the absorption of dietary flavonols.