Selenium in health and disease III

The human diet contains a great variety of natural mutagens and carcinogens, as well as many natural antimutagens and anticarcinogens. Many of these mutagens and carcinogens may act through the generation of oxygen radicals. Oxygen radicals may also play a major role as endogenous initiators of degenerative processes, such as DNA damage and mutation (and promotion), that may be related to cancer, heart disease, and aging. Dietary intake of natural antioxidants could be an important aspect of the body's defense mechanism against these agents. Many antioxidants are being identified as anticarcinogens. Characterizing and optimizing such defense systems may be an important part of a strategy of minimizing cancer and other age-related diseases.

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.

Interest in the antioxidant vitamin E as a possible protective nutrient against coronary disease has intensified with the recognition that oxidized low-density lipoprotein may be involved in atherogenesis. In 1980, 87,245 female nurses 34 to 59 years of age who were free of diagnosed cardiovascular disease and cancer completed dietary questionnaires that assessed their consumption of a wide range of nutrients, including vitamin E. During follow-up of up to eight years (679,485 person-years) that was 97 percent complete, we documented 552 cases of major coronary disease (437 nonfatal myocardial infarctions and 115 deaths due to coronary disease). As compared with women in the lowest fifth of the cohort with respect to vitamin E intake, those in the top fifth had a relative risk of major coronary disease of 0.66 (95 percent confidence interval, 0.50 to 0.87) after adjustment for age and smoking. Further adjustment for a variety of other coronary risk factors and nutrients, including other antioxidants, had little effect on the results. Most of the variability in intake and reduction in risk was attributable to vitamin E consumed as supplements. Women who took vitamin E supplements for short periods had little apparent benefit, but those who took them for more than two years had a relative risk of major coronary disease of 0.59 (95 percent confidence interval, 0.38 to 0.91) after adjustment for age, smoking status, risk factors for coronary disease, and use of other antioxidant nutrients (including multi-vitamins). Although these prospective data do not prove a cause-and-effect relation, they suggest that among middle-aged women the use of vitamin E supplements is associated with a reduced risk of coronary heart disease. Randomized trials of vitamin E in the primary and secondary prevention of coronary disease are being conducted; public policy recommendations about the widespread use of vitamin E should await the results of these trials.