title: The relationship between dose of vitamin E and suppression of oxidative stress in humans.
abstract: The oxidation hypothesis of atherogenesis has been the focus of much research over the past 2 decades. However, randomized placebo-controlled trials evaluating the efficacy of vitamin E in preventing cardiovascular events in aggregate have failed to show a beneficial effect. Implicit in these trials is that the dose of vitamin E tested effectively suppressed oxidative stress status but this was never determined. We defined the dose-dependent effects of vitamin E (RRR-alpha-tocopherol) to suppress plasma concentrations of F2-isoprostanes, a biomarker of free radical-mediated lipid peroxidation, in participants with polygenic hypercholesterolemia and enhanced oxidative stress, a population at risk for cardiovascular events. A time-course study was first performed in participants supplemented with 3200 IU/day of vitamin E for 20 weeks. A dose-ranging study was then performed in participants supplemented with 0, 100, 200, 400, 800, 1600, or 3200 IU/day of vitamin E for 16 weeks. In the time-course study, maximum suppression of plasma F2-isoprostane concentrations did not occur until 16 weeks of supplementation. In the dose-ranging study there was a linear trend between the dosage of vitamin E and percentage reduction in plasma F2-isoprostane concentrations which reached significance at doses of 1600 IU (35+/-2%, p<0.035) and 3200 IU (49+/-10%, p<0.005). This study provides information on the dosage of vitamin E that decreases systemic oxidant stress in vivo in humans and informs the planning and evaluation of clinical studies that assess the efficacy of vitamin E to mitigate disease.
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA. jack.roberts@vanderbilt.edu
authors.forename: L Jackson
authors.initials: LJ
authors.lastname: Roberts
authors.forename: John A
authors.initials: JA
authors.lastname: Oates
authors.forename: MacRae F
authors.initials: MF
authors.lastname: Linton
authors.forename: Sergio
authors.initials: S
authors.lastname: Fazio
authors.forename: Beth P
authors.initials: BP
authors.lastname: Meador
authors.forename: Myron D
authors.initials: MD
authors.lastname: Gross
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.forename: Jason D
authors.initials: JD
authors.lastname: Morrow
mesh_terms: D015415:Biomarkers / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D028441:F2-Isoprostanes / Q000097:blood*; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D010919:Placebos; D016032:Randomized Controlled Trials as Topic / Q000592:standards; D014810:Vitamin E / Q000008:administration & dosage*
chemical_list: D015415:Biomarkers; D028441:F2-Isoprostanes; D010919:Placebos; D014810:Vitamin E