Vitamin E supplementation could elevate circulating vitamin E metabolites while modulating oxidative and inflammatory status in end-stage renal failure patients undergoing hemodialysis. Plasma concentrations of carboxyethyl-hydroxychromanols (alpha- and gamma-CEHC), ascorbic acid, alpha- and gamma-tocopherols, F2-isoprostanes, and inflammatory biomarkers [tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), ferritin, and C-reactive protein (CRP)] were measured in blood samples obtained from patients (n = 11) before and after dialysis on two occasions prior to, and at 1 and 2 mon of daily vitamin E supplementation (400 IU RRR-alpha-tocopherol). Supplementation nearly doubled plasma alpha-tocopherol concentrations (from 18 +/- 0.5 to 31 +/- 1.7 microM, P < 0.0001), whereas gamma-tocopherol concentrations decreased (from 2.8 +/- 0.3 to 1.7 +/- 0.2 microM, P = 0.001). Serum alpha-CEHC increased 10-fold from 68 +/- 3 to 771 +/- 175 nM (P < 0.0001), and gamma-CEHC increased from 837 +/- 164 to 1136 +/- 230 nM (P = 0.008). Vitamin E supplementation also increased postdialysis hematocrits from 38 +/- 1% to 41 +/- 1% (P < 0.001). Dietary antioxidant intakes (vitamins E and C) were low in most subjects; plasma ascorbic acid levels (88 +/- 27 microM) decreased significantly with dialysis (33 +/- 11 microM, P = 0.01). Plasma IL-6, CRP, TNF-alpha, and free F2-isoprostane concentrations were elevated throughout the study. There is a complex relationship between chronic inflammation and oxidative stress that is not mitigated by short-term vitamin E supplementation. Importantly, serum vitamin E metabolite concentrations that increased 10-fold within 30 d of supplementation did not increase further, suggesting routes other than urine for removal of metabolites.