BACKGROUND: Limited data are available that evaluated the effects of high-dose vitamin E supplementation on biomarkers of kidney injury, inflammation, and oxidative stress in patients with diabetic nephropathy (DN). OBJECTIVE: This study was conducted to evaluate the effects of high-dose vitamin E supplementation on biomarkers of kidney injury, inflammation, and oxidative stress in patients with DN. METHODS: This randomized double-blind placebo-controlled clinical trial was carried out among 60 patients with DN. Patients were randomly allocated into two groups to take either 1200 IU/d of vitamin E supplements (n = 30) or placebo (n = 30) for 12 weeks. Fasting blood samples were obtained at the onset of the study and after 12-week intervention to assess biomarkers of kidney injury, inflammation, and oxidative stress. RESULTS: After 12 weeks of intervention, compared with the placebo, vitamin E supplementation resulted in a significant increase in serum vitamin E levels (+42.3 +/- 13.4 vs -0.8 +/- 0.8 nmol/mL, P < .001) and a significant decrease in urine protein (-6.8 +/- 4.3 vs -1.0 +/- 8.0 mg/dL, P = .001) and protein-to-creatinine ratio (-0.2 +/- 0.1 vs 0.0 +/- 0.1, P < .001). In addition, a significant reduction in serum tumor necrosis factor-alpha (-35.4 +/- 34.9 vs +5.6 +/- 6.2 ng/L, P < .001), matrix metalloproteinase-2 (-556.7 +/- 485.9 vs +60.4 +/- 53.7 ng/mL, P < .001), matrix metalloproteinase-9 (-1461.5 +/- 1456.0 vs +225.7 +/- 488.2 ng/L, P < .001), malondialdehyde (-0.9 +/- 0.5 vs +0.3 +/- 0.4 mu mol/L, P < .001), advanced glycation end products (-1832.2 +/- 1941.6 vs +177.3 +/- 324.1 arbitrary unit, P < .001), and insulin concentrations (-0.5 +/- 2.7 vs +0.7 +/- 1.0 mu IU/mL, P = .03) was seen after the administration of vitamin E supplements compared with the placebo. Supplementation with vitamin E had no significant effects on other biomarkers of kidney injury, fasting plasma glucose, and insulin resistance compared with the placebo. CONCLUSION: Overall, our study demonstrated that oral high-dose vitamin E supplementation for 12 weeks among DN patients had favorable effects on biomarkers of kidney injury, inflammation, and oxidative stress. (C) 2016 National Lipid Association. All rights reserved.