Effects of vitamins C and E and beta-carotene on the risk of type 2 diabetes in women at high risk of cardiovascular disease: a randomized controlled trial

Abstract

Background: Vitamin C, vitamin E, and beta-carotene are major antioxidants and as such may protect against the development of type 2 diabetes via reduction of oxidative stress.

Objective: The purpose of this study was to investigate the long-term effects of supplementation with vitamin C, vitamin E, and beta-carotene for primary prevention of type 2 diabetes.

Design: In the Women's Antioxidant Cardiovascular Study, a randomized trial that occurred between 1995 and 2005, 8171 female health professionals aged > or =40 y with either a history of cardiovascular disease (CVD) or > or =3 CVD risk factors were randomly assigned to receive vitamin C (ascorbic acid, 500 mg every day), vitamin E (RRR-alpha-tocopherol acetate, 600 IU every other day), beta-carotene (50 mg every other day), or their respective placebos.

Results: During a median follow-up of 9.2 y, a total of 895 incident cases occurred among 6574 women who were free of diabetes at baseline. There was a trend toward a modest reduction in diabetes risk in women assigned to receive vitamin C compared with those assigned to receive placebo [relative risk (RR): 0.89; 95% CI: 0.78, 1.02; P = 0.09], whereas a trend for a slight elevation in diabetes risk was observed for vitamin E treatment (RR: 1.13; 95% CI: 0.99, 1.29; P = 0.07). However, neither of these effects reached statistical significance. No significant effect was observed for beta-carotene treatment (RR: 0.97; 95% CI: 0.85, 1.11; P = 0.68).

Conclusion: Our randomized trial data showed no significant overall effects of vitamin C, vitamin E, and beta-carotene on risk of developing type 2 diabetes in women at high risk of CVD. This trial was registered at clinicaltrials.gov as NCT00000541.

FIGURE 1

Flow diagram illustrating diabetes outcomes in the randomly assigned treatment components of the Women's Antioxidant Cardiovascular Study (WACS). A total of 1597 participants who had a diagnosis of type 2 diabetes at baseline were excluded in the analysis.

FIGURE 2

Cumulative incidence of type 2 diabetes by randomized antioxidant intervention. (A) Active vitamin C compared with placebo; (B) active vitamin E compared with placebo; and (C) active β-carotene compared with placebo in the Women's Antioxidant Cardiovascular Study. Kaplan-Meier survival curves were used to estimate the overall cumulative incidence over time for each active vitamin group and its corresponding placebo group. The log-rank test was performed to compute the P values for the differences.

FIGURE 3

Relative risks (95% CIs) of type 2 diabetes by 8 combinations of all 3 active antioxidant assignments relative to the all placebo group in the Women's Antioxidant Cardiovascular Study. We used Cox proportional hazards models to calculate the estimates of relative risks and 95% CIs for each antioxidant treatment alone, after adjustment for age and other randomized treatments. We also tested interactions of the 3 antioxidant agents by using all of the 2-way and 3-way interaction terms in the Cox model and found no significant results. VC, vitamin C; VE, vitamin E; BC, β-carotene.