The antiatherosclerotic enzyme paraoxonase (PON1) is affected by disease and lifestyle. We investigated the impact of diet in diabetic foot patients from 2 European countries. Dietary intake and serum PON1 activity, using as substrate paraoxon (paraoxonase) or phenylacetate (arylesterase), were assessed in patients from Bucharest (n = 40) and Antwerp (n = 30) and in 34 healthy controls. The diabetic patients had lower paraoxonase and arylesterase activities than the controls. Arylesterase was lowest in the Bucharest patients, 116 +/- 42 U/ml, versus 141 +/- 43 and 184 +/- 49 U/ml in the Antwerp patients and controls, respectively (p < 0.0005). The Bucharest patients had worse glycemic control, higher blood pressure, lower HDL cholesterol and a diet richer in cholesterol and poorer in monounsaturated fats and fish. In contrast, their median intake of vitamins E and C, folic acid and flavonoids was higher, 82 mg (range: 4-259 mg), versus 28 mg (range: 5-169 mg) aglycone units in Antwerp (p = 0.005). Flavonoid intake predicted arylesterase independently of HDL cholesterol, region and sex (beta = 0.27; p = 0.03), and patients with high intake achieved normal levels of arylesterase (30.1 +/- 10.0 U/micromol in the highest versus 21.0 +/- 8.2 U/micromol total cholesterol in the lowest tertile; p = 0.02). A flavonoid-rich diet is positively associated with PON1 arylesterase activity in diabetic foot patients.