Vitamin E and Risk of Type 2 Diabetes in the Women's Health Study Randomized Controlled Trial

Simin Liu; I-Min Lee; Yiqing Song; Martin Van Denburgh; Nancy R. Cook; JoAnn E. Manson; Julie E. Buring


Diabetes. 2006;55(10):2856-2862. 

In This Article

Abstract and Introduction


We directly assessed the efficacy of vitamin E supplements for primary prevention of type 2 diabetes among apparently healthy women in the Women's Health Study randomized trial. Between 1992 and 2004, 38,716 apparently healthy U.S. women aged ≥45 years and free of diabetes, cancer, and cardiovascular disease were in two randomly assigned intervention groups and received 600 IU of vitamin E (α-tocopherol, n = 19,347) or placebo (n = 19,369) on alternate days. During a median 10-year follow-up, there were 827 cases of incident type 2 diabetes in the vitamin E group and 869 in the placebo group, a nonsignificant 5% risk reduction (relative risk [RR] 0.95 [95% CI 0.87-1.05], P = 0.31). There was no evidence that diabetes risk factors including age, BMI, postmenopausal hormone use, multivitamin use, physical activity, alcohol intake, and smoking status modified the effect of vitamin E on the risk of type 2 diabetes. In a sensitivity analysis taking compliance into account, women in the vitamin E group had an RR of 0.93 (95% CI 0.83-1.04) (P = 0.21) compared with those randomized to placebo. In this large trial with 10-year follow-up, alternate-day doses of 600 IU vitamin E provided no significant benefit for type 2 diabetes in initially healthy women.


Oxidative stress due to increased production of reactive oxygen species and decreased antioxidant status have been implicated in the pathogenesis of type 2 diabetes and its complications.[1,2,3,4] Experimental studies suggested that oxidative stress impaired pancreatic ß-cell insulin secretion,[2,5] interfered with glucose disposal in peripheral tissues,[2,3] and elicited systemic inflammation,[3] thereby accelerating the development and progression of type 2 diabetes. Vitamin E is a major lipid-soluble chain-breaking antioxidant with anti-inflammatory properties.[6,7] In vitro studies indicated that vitamin E may improve insulin action and insulin secretion by protecting peripheral tissues and ß-cells from free radical-mediated damage, leading to the hypothesis that this vitamin may help delay the development of type 2 diabetes.[6,7,8]

In animal models, diabetes can be induced by reactive free radicals,[9] and vitamin E can act as scavengers of these oxygen radicals in preventing the development of diabetes.[10,11,12] In observational epidemiologic studies, an inverse association between serum or plasma levels of α-tocopherol and type 2 diabetes risk was observed in some,[13,14,15,16] but not all, case-control and cohort studies.[17,18] In a large cohort of Finnsh men and women, those who self-selected for higher intake of dietary vitamin E experienced a significantly decreased incidence of type 2 diabetes.[19] However, observational studies cannot fully address biases due to selection of the study population, measurement error of dietary vitamin E intake, and residual confounding from other unmeasured or imperfectly measured risk factors such as highly correlated dietary or lifestyle factors.[20] Well-designed and -conducted randomized trials, the most reliable design strategy, can avoid most of the biases inherent in observational studies and help evaluate a possible causal relationship between vitamin E and risk of type 2 diabetes;[20] however, there are no previous trials examining the efficacy of vitamin E supplementation in the primary prevention of type 2 diabetes thus far.

To provide direct evidence, we examined whether vitamin E supplementation decreased the incidence of type 2 diabetes in the Women's Health Study (WHS), a randomized, double-blind, placebo-controlled trial conducted over an average duration of 10.1 years.


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