Song Y, Cook NR, Albert CM, Van Denburgh M, Manson JE. 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. Am J Clin Nutr 90, 429-437

Division of Preventive Medicine and Cardiology Division, Harvard School of Public Health, Boston, MA 02215, USA.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 06/2009; 90(2):429-37. DOI: 10.3945/ajcn.2009.27491
Source: PubMed


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.
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.
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.
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).
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 as NCT00000541.

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    • "In contrast to the studies in lower model organisms cited above, several prospective intervention trials did not find any health-promoting effects of antioxidant supplementation . Unexpectedly, most interventional studies found a lack of effects in humans (Greenberg et al. 1994, Liu et al. 1999, Rautalahti et al. 1999, Virtamo et al. 2000, Various 2002, Sacco et al. 2003, Zureik et al. 2004, Czernichow et al. 2005, Czernichow et al. 2006, Cook et al. 2007, Kataja- Tuomola et al. 2008, Sesso et al. 2008, Katsiki and Manes 2009, Lin et al. 2009, Song et al. 2009), whereas others even suggested detrimental effects on human health, for instance promotion of cancer growth or induction of diseases with negative impact on human lifespan (Albanes et al. 1996, Omenn et al. 1996, Vivekananthan et al. 2003, Lonn et al. 2005, Bjelakovic et al. 2007, Ward et al. 2007, Lippman et al. 2009, Schipper 2004, DeNicola et al. 2011, Abner et al. 2011). Consistently, several studies overexpressing antioxidant enzymes in mice failed to exert positive effects on lifespan or associated parameters (Jang et al. 2009, Muller et al. 2007, Perez et al. 2011). "
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    • "Vitamin C (ascorbic acid), vitamin E (í µí»¼-tocopherol), and í µí»½carotene are considered important antioxidants in humans and were tested in this study [21] "
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    • "In fact, β-carotene was not associated with HOMA-IR, insulin, or glucose. While findings from observational studies have produced equivocal results [7, 8], our results agree with the findings from large randomized controlled trials negating a protective role of β-carotene in the pathogenesis of insulin resistance [17, 19, 38]. We add to these findings the lack of association also among premenopausal women, a group not well captured in clinical trials. "
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