Effects of vitamin e on lipid peroxidation in healthy persons

Context Oxidative stress may play a role in the development or exacerbation of many common diseases. However, results of prospective controlled trials of the effects of antioxidants such as vitamin E are contradictory. Objective To assess the effects of supplemental vitamin E on lipid peroxida tion in vivo in healthy adults. Design Randomized, double-blind, placebo-controlled trial conducted March 1 999 to June 2000. Setting A general clinical research center in a tertiary referral academic medical center. Participants Thirty healthy men and women aged 18 to 60 years. Interventions Participants were randomly assigned to receive placebo or alp ha -tocopherol dosages of 200, 400, 800, 1200, or 2000 IU/d for 8 weeks (n= 5 in each group), followed by an 8-week washout period. Main Outcome Measures Three indices of lipid peroxidation, urinary 4-hydrox ynonenal (4-HNE) and 2 isoprostanes, iPF(2 alpha)-III and IPF2 alpha-VI, me asured by gas chromatography/ mass spectrometry and compared among the 6 gr oups at baseline, 2, 4, 6, and 8 weeks, and 1, 3, and 8 weeks after discont inuation. Results Circulating vitamin E levels increased in a dose-dependent manner d uring the study. No significant effect of vitamin E on levels of urinary 4- HNE or either isoprostane was observed. Mean (SEM) baseline vs week 8 level s of iPF(2 alpha)-III were 154 (20.1) vs 168 (22.3) pg/mg of creatinine for subjects taking placebo; 165 (19.6) vs 234 (30.1) pg/mg for those taking 2 00 IU/d of vitamin E; and 195 (26.7) vs 213 (40.6) pg/mg for subjects takin g 2000 IU/d. Corresponding iPF(2 alpha)-VI levels were 1.43 (0.6) vs 1.62 ( 0.4) ng/mg of creatinine for subjects taking placebo; 1.64 (0.3) vs 1.24 (0 .8) ng/mg for those taking 200 IU/d of vitamin E; and 1.83 (0.3) vs 1.94 (0 .9) ng/mg for those taking 2000 IU/d. Baseline vs week 8 levels of 4-HNE we re 0.5 (0.04) vs 0.4 (0.05) ng/mg of creatinine for subjects taking placebo ; 0.4 (0.06) vs 0.5 (0.02) ng/mg with 200 IU/d of vitamin E; and 0.2 (0.02) vs 0.2 (0.1) ng/mg with 2000 IU/d. Conclusions Our results question the rationale for vitamin E supplementatio n in healthy individuals. Specific quantitative indices of oxidative stress in vivo should be considered as entry criteria and for dose selection in c linical trials of antioxidant drugs and vitamins in human disease.