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The relationship between dose of vitamin E and suppression of oxidative stress in humans.

Roberts LJ, Oates JA, Linton MF, Fazio S, Meador BP, Gross MD, Shyr Y, Morrow JD
Free Radic Biol Med. 2007 43 (10): 1388-93

PMID: 17936185 · PMCID: PMC2072864 · DOI:10.1016/j.freeradbiomed.2007.06.019

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.

MeSH Terms (13)

Biomarkers Dose-Response Relationship, Drug Double-Blind Method F2-Isoprostanes Female Humans Hypercholesterolemia Lipid Peroxidation Male Oxidative Stress Placebos Randomized Controlled Trials as Topic Vitamin E

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