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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    ABSTRACT: Increasing evidence indicates that reactive oxygen species (ROS), consisting of superoxide, hydrogen peroxide, and multiple others, do not only cause oxidative stress, but rather may function as signaling molecules that promote health by preventing or delaying a number of chronic diseases, and ultimately extend lifespan. While high levels of ROS are generally accepted to cause cellular damage and to promote aging, low levels of these may rather improve systemic defense mechanisms by inducing an adaptive response. This concept has been named mitochondrial hormesis or mitohormesis. We here evaluate and summarize more than 500 publications from current literature regarding such ROS-mediated low-dose signaling events, including calorie restriction, hypoxia, temperature stress, and physical activity, as well as signaling events downstream of insulin/IGF-1 receptors, AMP-dependent kinase (AMPK), target-of-rapamycin (TOR), and lastly sirtuins to culminate in control of proteostasis, unfolded protein response (UPR), stem cell maintenance and stress resistance. Additionally, consequences of interfering with such ROS signals by pharmacological or natural compounds are being discussed, concluding that particularly antioxidants are useless or even harmful.
    Dose-Response 05/2014; 12(2):288-341. DOI:10.2203/dose-response.13-035.Ristow · 1.22 Impact Factor
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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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    ABSTRACT: Supplementation with antioxidants and its benefit-risk relationship have been largely discussed in the elderly population. We evaluated whether antioxidants supplementation improved the biochemical profile associated with oxidative metabolism in elderly cardiovascular patients. Patients (n = 112) received daily supplementation with α -TP 400 mg, beta-carotene 40 mg, and vitamin C 1000 mg for 2 months (treatment). Plasma concentrations of alpha-tocopherol ( α -TP), β -carotene ( β C), ubiquinol-10 (QH-10), glutathione, and thiobarbituric acid reactive substances (TBARS) were determined before and after treatment. Response to treatment was dependent on pretreatment α -TP and β C levels. Increase in α -TP and β C levels was observed only in patients with basal levels <18 μ M for α -TP (P < 0.01) and <0.30 μ M for β C (P < 0.02). Ubiquinol-10, glutathione, and TBARS were unaffected by treatment: QH-10 (+57%, F 1,110 = 3.611, P < 0.06, and N.S.), glutathione (+21%, F 1,110 = 2.92, P < 0.09, and N.S.), and TBARS (-29%, F 1,110 = 2.26, P < 0.14, and N.S.). Treatment reduced oxidative metabolism: 5.3% versus 14.6% basal value (F 1,110 = 9.21, P < 0.0003). Basal TBARS/ α -TP ratio was higher in smokers compared to nonsmokers: 0.11 ± 0.02 versus 0.06 ± 0.01 (F 32,80 = 1.63, P < 0.04). Response to antioxidant supplementation was dependent on basal plasma levels of α -TP and β C. Smoking status was strongly associated with atherosclerotic cardiovascular disease and high TBARS/ α -TP ratio (lipid peroxidation).
    Oxidative Medicine and Cellular Longevity 12/2013; 2013(1):408260. DOI:10.1155/2013/408260 · 3.36 Impact Factor
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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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    ABSTRACT: The aim of this study was to investigate how serum retinol and carotenoids (β-carotene, β-cryptoxanthin, lutein/zeaxanthin, lycopene) are associated with biomarkers of insulin resistance. The BioCycle Study (2005-2007) is a prospective cohort of 259 healthy premenopausal women. Fasting serum samples were collected at up to sixteen clinic visits, from which retinol, carotenoids, insulin, glucose, and sex hormone-binding globulin (SHBG) were measured. Insulin resistance was estimated by the homeostasis model assessment (HOMA-IR). Linear mixed models were used to determine associations adjusting for age, race, body mass index (BMI), education, smoking, physical activity, triglycerides, and energy intake. Retinol was positively associated with HOMA-IR (β = 0.19 (95% CI: 0.07, 0.32)) units per ug/mL increase in retinol; the relationship was driven by insulin (β = 0.20 (95% CI: 0.08, 0.31)). Retinol was inversely associated with SHBG (β = -0.22 (95% CI: -0.28, -0.16)). Although no significant associations were found between serum carotenoids and HOMA-IR, β-carotene was positively associated with SHBG and β-cryptoxanthin inversely with fasting plasma glucose. Results indicate a possible role for serum retinol in the pathogenesis of type 2 diabetes. However, they do not support a strong association between individual or total serum carotenoids and insulin resistance.
    08/2013; 2013:619516. DOI:10.5402/2013/619516
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