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      Effects of Antioxidant Vitamins C and E on Atherosclerosis in Lipid-Fed Rabbits


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          Background: Antioxidant vitamins are hypothesized to help prevent atherosclerosis by blocking lipoprotein oxidation. We investigated the effects of dietary vitamins C and E on atherosclerosis in rabbits. Methods and Results: Forty New Zealand male rabbits were divided into 4 groups: 0.3% cholesterol diet with (LV) and without vitamin (LC), and 0.5% cholesterol diet with (HV) and without vitamins (HC). The treated groups consumed 137 ± 8 mg/day vitamin C and 80 ± 4 mg/day vitamin E for 10 weeks. Vitamin treatment did not significantly affect serum lipids. α-Tocopherol values were significantly higher in both serum (mg/dl) and omental fat (µg/g) among the treated rabbits (3.9 ± 0.5 and 31.6 ± 2.1 for LV, 1.7 ± 0.2 and 12.1 ± 1.9 for LC, 5.6 ± 0.8 and 51.3 ± 9.3 for HV and 1.9 ± 0.3 and 8.2 ± 0.4 for HC; p < 0.001). Vitamin treatment did not affect the percent of surface lesions in the aorta and pulmonary artery (23.8 ± 5.2 and 20.1 ± 3.3% for LV, 19.8 ± 5.6 and 23.2 ± 3.5% for LC, 28.1 ± 6.5 and 51.1 ± 4.2% for HV and 32.4 ± 5.5 and 43.7 ± 3.9% for HC, respectively; p = 0.981 and p = 0.562. Conclusions: Although significantly higher values of α-tocopherol were found in both serum and omental fat, antioxidant vitamins C and E did not demonstrate a significant protective effect on atherosclerosis in lipid-fed rabbits during the 10-week study period.

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          Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease.

          Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders. We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial -- the Beta Carotene and Retinol Efficacy Trial -- involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo. A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P=0.02), as compared with the placebo group. There were no statistically significant differences in the risks of other types of cancer. In the active-treatment group, the relative risk of death from any cause was 1.17 (95 percent confidence interval, 1.03 to 1.33); of death from lung cancer, 1.46 (95 percent confidence interval, 1.07 to 2.00); and of death from cardiovascular disease, 1.26 (95 percent confidence interval, 0.99 to 1.61). On the basis of these findings, the randomized trial was stopped 21 months earlier than planned; follow-up will continue for another 5 years. After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.
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            Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease.

            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. 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. Among 11,036 physicians randomly assigned to receive beta carotene and 11,035 assigned to receive placebo, there were virtually no early or late differences in the overall incidence of malignant neoplasms or cardiovascular disease, or in overall mortality. In the beta carotene group, 1273 men had any malignant neoplasm (except nonmelanoma skin cancer), as compared with 1293 in the placebo group (relative risk, 0.98; 95 percent confidence interval, 0.91 to 1.06). There were also no significant differences in the number of cases of lung cancer (82 in the beta carotene group vs. 88 in the placebo group); the number of deaths from cancer (386 vs. 380), deaths from any cause (979 vs. 968), or deaths from cardiovascular disease (338 vs. 313); the number of men with myocardial infarction (468 vs. 489); the number with stroke (367 vs. 382); or the number with any one of the previous three end points (967 vs. 972). Among current and former smokers, there were also no significant early or late differences in any of these end points. In this trial among healthy men, 12 years of supplementation with beta carotene produced neither benefit nor harm in terms of the incidence of malignant neoplasms, cardiovascular disease, or death from all causes.
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              Vitamin E consumption and the risk of coronary heart disease in men.

              The oxidative modification of low-density lipoproteins increases their incorporation into the arterial intima, an essential step in atherogenesis. Although dietary antioxidants, such as vitamin C, carotene, and vitamin E, have been hypothesized to prevent coronary heart disease, prospective epidemiologic data are sparse. In 1986, 39,910 U.S. male health professionals 40 to 75 years of age who were free of diagnosed coronary heart disease, diabetes, and hypercholesterolemia completed detailed dietary questionnaires that assessed their usual intake of vitamin C, carotene, and vitamin E in addition to other nutrients. During four years of follow-up, we documented 667 cases of coronary disease. After controlling for age and several coronary risk factors, we observed a lower risk of coronary disease among men with higher intakes of vitamin E (P for trend = 0.003). For men consuming more than 60 IU per day of vitamin E, the multivariate relative risk was 0.64 (95 percent confidence interval, 0.49 to 0.83) as compared with those consuming less than 7.5 IU per day. As compared with men who did not take vitamin E supplements, men who took at least 100 IU per day for at least two years had a multivariate relative risk of coronary disease of 0.63 (95 percent confidence interval, 0.47 to 0.84). Carotene intake was not associated with a lower risk of coronary disease among those who had never smoked, but it was inversely associated with the risk among current smokers (relative risk, 0.30; 95 percent confidence interval, 0.11 to 0.82) and former smokers (relative risk, 0.60; 95 percent confidence interval, 0.38 to 0.94). In contrast, a high intake of vitamin C was not associated with a lower risk of coronary disease. These data do not prove a causal relation, but they provide evidence of an association between a high intake of vitamin E and a lower risk of coronary heart disease in men. Public policy recommendations with regard to the use of vitamin E supplements should await the results of additional studies.

                Author and article information

                S. Karger AG
                March 1998
                16 March 1998
                : 89
                : 3
                : 189-194
                Cardiovascular Division, Department of Medicine and Cardiovascular Research Institute, University of California, San Francisco, Calif., USA
                6786 Cardiology 1998;89:189–194
                © 1998 S. Karger AG, Basel

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                Page count
                Figures: 1, Tables: 2, References: 44, Pages: 6
                General Cardiology, Basic Science


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