Relationship between time course and dose of vitamin E and oxidative stress in haemodialysis patients: a randomised controlled trial

Background: Oxidative stress and inflammation are associated with increased cardiovascular morbidity and mortality particularly in patients with end stage kidney disease. Observational data support the contention that increased antioxidant intake with nutrients such as vitamin E is correlated with reduced cardiovascular morbidity and mortality in the general population. Unfortunately, most clinical intervention trials using vitamin E have failed to support this relationship. The SPACE study conducted in hemodialysis patients had a positive outcome however this has not been translated into clinical practice perhaps because of the negativity generated from studies in the general population. The failure of studies using vitamin E other than the SPACE study may simply be as a consequence of choosing the wrong form of Vitamin E, prescribed at the wrong dose, for the wrong duration to the wrong patients. Future research in this area should focus on treating patients with established measured abnormalities of oxidative stress, with a safe vitamin E formulation that is proven to be effective, at least in part, in reversing the observed oxidative stress abnormalities. Methods: Therefore, the aim of this study is to investigate the effect of different doses of vitamin E supplementation on oxidative stress markers in hemodialysis patients with proven abnormalities of oxidative stress. The study will consist of a time-course study and a dose-ranging study. In the time course study eight patients will be required to take 1600 IU/day natural (RRR) alpha tocopherol for 20 weeks. Blood will be collected every two weeks and analysed for a marker of oxidative stress (plasma isoprostanes) and alpha tocopherol. The optimum time period to decrease oxidative stress (by 50%) will be determined from this study. It is hypothesised that this will occur within 16 weeks. In the dose-ranging study 48 patients will be randomised to either placebo, 100IU/day, 200IU/day, 400IU/day, 800IU/day or 1600IU/day of natural (RRR) alpha tocopherol for a time period determined from the time course study. Blood will be collected at baseline and at the end of the study and analysed for a plasma isoprostanes and alpha tocopherol. It is hypothesised that doses =800 IU of vitamin E will be required to decrease oxidative stress by 50%.