Vitamin E study may shed light on previous failures

A study out of Vanderbilt University reported that randomized placebo-controlled trials evaluating the efficacy of vitamin E in preventing cardiovascular events in aggregate have failed to show a beneficial effect. The researchers suspected that the studies had been poorly designed because the trials used a single dose of vitamin E and only looked for end points such as heart attack occurrence.

The study, "The relationship between dose of vitamin E and suppression of oxidative stress in humans," reported that a dose of 3,200 International Units of vitamin E is needed to reduce oxidative stress in individuals at risk for cardiovascular disease, compared with how previous trials using lower doses failed to show any benefits for the vitamin.

Free Radical Biology and Medicine, July 2007

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-α-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.

Steve - while we should look at this purely from an observational point-of-view, we concur that the trials showing little cardiac benefit from vitamin were poorly constructed and used on sick subjects. The aforementioned study is a positive step towards dispelling vitamin E's bad-rap.