Amongst the numerous co-adjuvant therapies which could influence the incidence and progression of diabetic complications, antioxidants and flavanoids are currently being tested in several clinical trials. In this study we investigated the effects of Daflono(R) 500, which is made up of the flavonoids diosmin (90%) and heperidin (10%), in a group of 28 Type 1 diabetic patients in a double blind placebo-controlled study Parameters of glycation and oxidative stress were measured before and after the intervention. Treatment with this flavonoid had no side effects and was followed by a decrease in HbA(1c), from 8.85+/-1.57 to 8.47+/-1.40% (p=0.017). This decrease was more pronounced in the patients,With higher initial HbA(1c) but was unrelated to glycaemic control as monitored by the mean and fluctuations of daily glycaemia, Decrease in HbA(1c) was accompanied by an increase in glutathione peroxidase activity, from 119+/-68 to 145+/-42 U/l haemolysate (p=0.015), a tendency for increase in plasma protein thiols and an increase in the lag time of the copper-induced in vitro oxidability of non-HDL lipoproteins, from 96+/-24 to 111+/-28 min (p=0.005). These parameters did not change significantly after receiving placebo. Other parameters of antioxidant capacity such as blood GSH, catalase and superoxide dismutase activities, as well as in vitro formation of thiobarbituric acid reactive substances (TBARS), were unaffected by either flavonoid or placebo. Our results suggest that the flavonoid-induced decrease in glycation is associated with an increase in the antioxidant component dependent on the levels and activities of thiol-containing proteins such as glutathione peroxidase. One mechanism which could explain these effects is the protection of vitamin C and E from consumption by oxidative processes.