BACKGROUND/OBJECTIVES: The objectives were to evaluate the effects of improvement of vitamin D status on biomarkers of oxidative stress (OS) in type 2 diabetic (T2D) subjects and whether vitamin D receptor (VDR)-FokI polymorphisms could modulate the response to vitamin D3 intake. SUBJECTS/METHODS: Subjects with T2D were allocated to one of the two groups to receive either plain doogh (PD; containing 150 mg calcium and no vitamin D/250 ml, n(1) = 50) or vitamin D3-fortified doogh (FD; containing 500 IU/250 ml, n(1) = 50) twice a day for 12 weeks. Outcomes were changes in serum 25-hydroxyvitamin D (25(OH) D), superoxide dismutase, glutathione (GSH), total antioxidant capacity (TAC) and malondialdehyde (MDA). VDR genotypes in 140 T2D subjects in FD were determined by FokI restriction enzyme. RESULTS: After 12 weeks, serum 25(OH) D increased significantly in FD (from 38.5 +/- 202.2 to 72.0 +/- 23.5, Po0.001) as compared with PD (from 38.8 +/- 22.8 to 33.4 +/- 22.8, P = 0.28). Comparisons between FD and PD revealed significant differences in changes of serum MDA (-0.54 +/- 0.82 mu mol/l vs +0.17 +/- 1 mu mol/l, Po0.001), GSH (+8.4 +/- 40.1 ng/l vs -13.1 +/- 29.4 ng/l, P = 0.002) and TAC (+0.14 +/- 0.43 mmol/l vs +0.02 +/- 0.45 mmol/l bovine serum albumin equivalent, P = 0.03). Although there was no significant association between FokI genotypes and OS biomarkers, ff variant subgroup showed the weakest response to vitamin D. CONCLUSIONS: Improvement of vitamin D status via daily intake of FD ameliorates OS biomarkers in T2D subjects and the interactive effect of FokI genotypes cannot be ruled out.