Background Observational studies suggest that people who consume more fruits and vegetables containing beta carotene have somewhat lower risks of cancer and cardiovascular disease, and earlier basic research suggested plausible mechanisms. Because large randomized trials of long duration were necessary to test this hypothesis directly, we conducted a trial of beta carotene supplementation. Methods In a randomized, double-blind, placebo-controlled trial of beta carotene (50 mg on alternate days), we enrolled 22,071 male physicians, 40 to 84 years of age, in the United States; 11 percent were current smokers and 39 percent were former smokers at the beginning of the study in 1982. By December 31, 1995, the scheduled end of the study, fewer than 1 percent had been lost to follow-up, and compliance was 78 percent in the group that received beta carotene. Results Among 11,036 physicians randomly assigned to receive beta carotene and 11,035 assigned to receive placebo, there were virtually no early or late diff...

https://www.nejm.org/doi/pdf/10.1056/NEJM199605023341801

Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease.

Objective: To study the association between dietary intake of flavonoids and subsequent coronary mortality. Design: A cohort study based on data collected at the Finnish mobile clinic health examination survey from 1967-72 and followed up until 1992. Settings: 30 communities from different parts of Finland. Subjects: 5133 Finnish men and women aged 30-69 years and free from heart disease at baseline. Main outcome measure: Dietary intake of flavonoids, total mortality, and coronary mortality. Results: In women a significant inverse gradient was observed between dietary intake of flavonoids and total and coronary mortality. The relative risks between highest and lowest quarters of flavonoid intake adjusted for age, smoking, serum cholesterol concentration, blood pressure, and body mass index were 0.69 (95% confidence interval 0.53 to 0.90) and 0.54 (0.33 to 0.87) for total and coronary mortality, respectively. The corresponding values for men were 0.76 (0.63 to 0.93) and 0.78 (0.56 to 1.08), respectively. Adjustment for intake of antioxidant vitamins and fatty acids weakened the associations for women; the relative risks for coronary heart disease were 0.73 (0.41 to 1.32) and 0.67 (0.44 to 1.00) in women and men, respectively. Intakes of onions and apples, the main dietary sources of flavonoids, presented similar associations. The relative risks for coronary mortality between highest and lowest quarters of apple intake were 0.57 (0.36 to 0.91) and 0.81 (0.61 to 1.09) for women and men, respectively. The corresponding values for onions were 0.50 (0.30 to 0.82) and 0.74 (0.53 to 1.02), respectively. Conclusion: The results suggest that people with very low intakes of flavonoids have higher risks of coronary disease. Key messages Key messages The protective effect of flavonoids was associated with a diet high in intake of apples and onions The effect may be mediated through prevention of oxidation of low density lipoproteins but other mechanisms could be involved Flavonoids offer an explanation for the suggested beneficial effect of fruits and vegetables in coronary heart disease Further studies should concentrate on the effects of various flavonoid compounds and on populations with different intakes

/pdf/flavonoid-intake-and-coronary-mortality-in-finland-a-cohort-6lc9w53pi2.pdf

Flavonoid intake and coronary mortality in Finland: a cohort study

Toward a new recommended dietary allowance for vitamin C based on antioxidant and health effects in humans

High-sensitivity C-reactive protein: clinical importance.

Design of Physicians' Health Study II—A Randomized Trial of Beta-Carotene, Vitamins E and C, and Multivitamins, in Prevention of Cancer, Cardiovascular Disease, and Eye Disease, and Review of Results of Completed Trials

AB3-2: Relationship between fish consumption and the development of atrial fibrillation in men

Background: Vitamin C, vitamin E, and b-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 longterm effects of supplementation with vitamin C, vitamin E, and b-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-a-tocopherol acetate, 600 IU every other day), b-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 b-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 b-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.

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

Effect of Combined Folic Acid, Vitamin B 6 , and Vitamin B 12 on Cancer Risk in Women

Physical Activity, Fitness, and the Prevention of Cardiovascular Disease

INCREASED FREE RADICAL ACTIVITY and high lipid oxidation impair glucose disposal in the peripheral tissues and exacerbate diabetic complications. These observations suggest a role for oxidative stress in the pathogenesis of type 2 diabetes mellitus (DM). Because of its extended system of conjugated double bonds, b-carotene can scavenge peroxyl radicals and exert strong antioxidant activity, suggesting a protective effect against the development of type 2 DM. Indirect evidence supporting such a protective role for b-carotene comes from several observational studies relating increased intake of vegetables that are rich in carotenoids with a lower risk of type 2 DM. In addition, a recent dietary trial indicates that among people with impaired glucose tolerance, those assigned to a diet with more vegetables have a lower incidence of type 2 DM. It is possible, however, that the observed reduction in risk associated with vegetables rich in carotenoids may be due not to their b-carotene content but rather to other nutrients in these foods or to other dietary or lifestyle factors. Moreover, biases due to selection of subjects, misclassification of exposure, and residual confounding cannot be fully addressed in observational studies, and no previous randomized trial has directly assessed the efficacy of b-carotene to prevent type 2 DM. To address this question, we examined the effect of long-term supplementation with b-carotene on the incidence of type 2 DM in the Physicians’ Health Study, a randomized 12-year trial of 22 071 US male physicians.

Long-term b-Carotene Supplementation and Risk of Type 2 Diabetes Mellitus

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