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

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 >= 40 y with either a history of cardiovascular disease (CVD) 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. Am J Clin Nutr 2009; 90: 429-37.