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VITAMIN E SUPPLEMENT USE ASSOCIATED WITH REDUCED RISK OF HEART DISEASE

This article was originally published in The Tan Sheet

Executive Summary

VITAMIN E SUPPLEMENT USE ASSOCIATED WITH REDUCED RISK OF HEART DISEASE in two large-scale epidemiological studies published in the May 20 New England Journal of Medicine. The two studies, the Nurses' Health Study conducted by Meir Stampfer, MD, et al. and the Health Professional Follow-up Study conducted by Eric Rimm et al., looked at the possible benefits of vitamin E, vitamin C and beta carotene on coronary disease in over 120,000 volunteers and found a significantly reduced risk of cardiac events in those volunteers taking high doses of vitamin E. In an editorial appearing in the same issue of NEJM, Daniel Steinberg, MD/PhD, University of California-San Diego, noted that the studies show "that the use of large doses of vitamin E supplements is associated with a significantly decreased risk of coronary heart disease." However, he recommended that "proof" of vitamin E's potential benefit in preventing coronary heart disease "must include at least some valid clinical intervention trials demonstrating the magnitude of the benefit to be obtained in humans." "Epidemiologic correlations alone" Steinberg cautioned, "no matter how high the level of statistical significance, cannot establish causal relations, as the authors of these papers recognize." He further added, "The probability that the relation is a causal one remains a matter of judgment." He postulated that the beneficial effect seen in the study may be due to the antioxidizing effect of vitamins on oxidized low density lipoproteins. The Nurses' Health Study looked at the effects of vitamin C and vitamin E in 87,245 female nurses, aged 34 to 59 who were free of diagnosed cardiovascular disease and cancer. In 1980, the volunteers were asked to complete a dietary questionnaire that listed 61 food items with specific portion size. The researchers computed the average daily intake of nutrients by multiplying the frequency of consumption of each item by the nutrient content. On each subsequent biennial questionnaire, from the 1982 questionnaire until the final one in 1988, participants were asked to report whether they regularly used supplements, and if so, the exact brand and type. The authors of the article "Vitamin E Consumption and the Risk of Coronary Heart Disease in Women," based on the Nurses' Health Study, found that the risk of major coronary disease among women who took vitamin E supplements for two or more years was about "40% lower than the risk in women who did not take these supplements." In addition, the researchers noted, "the lower risk of coronary disease was associated primarily with the intake of vitamin E from supplements rather than from the diet." Adjusted for age and smoking, the study found the relative risk of coronary heart disease for women who took multivitamins was .78 (95% confidence interval). Women who took vitamin E supplements reduced their risk of heart disease even further to .57. The authors of the study attributed the reduced risk in the vitamin E group to the fact that the amount of vitamin E in multivitamins is typically 30 IUs or less whereas vitamin E supplements normally contain 100 IUs or more. The researchers also found that vitamin C taken alone did not provide an apparent cardioprotective benefit. In the Health Professionals Follow-up Study, researchers looked at the dietary intake of vitamins C and E and beta carotene by 39,910 male health professionals to determine whether antioxidants can prevent coronary heart disease. Compared with the men who took the least amount of vitamin E, usually from dietary sources, those who consumed the most vitamin E had an age-adjusted relative risk of coronary heart disease of .59 (95% confidence interval). "We found an inverse association between vitamin E intake and coronary disease that was weak at best when only dietary sources were taken into account," the researchers reported. "At the higher levels of intake reached with supplementation, the association became significant." The study found that men "who took at least 100 IU per day for at least two years" reduced their risk of coronary disease by 37% when compared to men who did not take vitamin E supplements. In an another similarity with the Nurses' Health Study, the study in male health professionals found no association between vitamin C intake and reduced risk of cardiac event. Vitamin C use, in fact, increased the relative risk of a cardiac event by 25%. Rimm et al. also found "a significant inverse association between beta carotene intake and coronary disease among current and former smokers." Current smokers who consumed the largest amounts of beta carotene in the study reduced their risk of heart disease by 70% versus smokers who consumed little beta carotene. Former smokers consuming large amounts of beta carotene reduced their risk of heart disease by 40% compared with former smokers with low beta carotene diets. "The reduction in risk among current smokers was significant even . . . [for those] whose intake was equivalent to half a carrot per day," the researchers stated. The Health Professionals Follow-up Study was initiated in 1986 and involves a total of 51,529 male health professionals between the ages of 40 and 75, including: 29,683 dentists, 10,098 veterinarians, 4,185 pharmacists, 3,745 optometrists, 3,745 osteopaths and 1,600 podiatrists. Participants completed a detailed questionnaire at the start of the study on their medical dietary history. Follow-up questionnaires were sent in 1988 and 1990. Those failing to fill out a significant portion of the questionnaire and participants with a prior heart condition or at risk of heart disease were excluded from the study. In both studies published in the NEJM, the authors recognized that patient self-selection could have played a role in the results -- that those volunteers with better health profiles would be more likely to take vitamins and supplements. However, the authors of both studies felt that the results from vitamin C intake argue against self-selection. In both studies, participants taking vitamin C supplements did not show a lower risk of cardiac events. In his editorial, Steinberg also voiced concern over the lack of data showing the potential long-term effects of very large doses of vitamin E supplements. "Studies in humans have rarely gone beyond six months and have never involved thousands of subjects," he noted, adding: "Are we really sure that 500 or 1,000 IU of vitamin E carries no risk over a five-year period? A 20- year period?" Steinberg also suggested that medical professionals should consider "how many patients will slack off on their adherence to better-established, but somewhat more onerous, preventive measures such as cholesterol-lowering diet, regular exercise and smoking cessation" before lending "our imprimatur to the widespread use of a still unproved treatment . . . that requires the patient only to pop a few pills." Until the medical community reaches a consensus on the value of antioxidants and their potentially beneficial role in neutralizing oxidized LDL, Steinberg suggested that "we must play by the rules and insist on large, long-term, double blind clinical trials." In addition, epidemiologic evidence of vitamin E's potential benefit in preventing cataracts appears in a study published in the May issue of Epidemiology. The Johns Hopkins study looked at nutritional risk factors of 660 subjects and found that those participants taking high levels of vitamin E reduced their risk of nuclear opacity by 48% but did not show a reduced risk for cortical opacity.
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