Epidemiologic studies have demonstrated an association between increased intake of antioxidant vitamins such as vitamin E and vitamin C and reduced morbidity and mortality from coronary artery disease. This association has been explained on the basis of the “oxidative-modification hypothesis” of atherosclerosis, which proposes that atherogenesis is initiated by oxidation of the lipids in low-density lipoprotein (LDL), also termed lipid peroxidation. As a corollary to this hypothesis, antioxidants that inhibit lipid peroxidation in LDL should limit atherosclerosis and its clinical manifestations, such as myocardial infarction and stroke. In this review, we will evaluate the current literature involving antioxidants and vascular . . .

Antioxidants and Atherosclerotic Heart Disease

Risk of angina pectoris and plasma concentrations of vitamins A, C, and E and carotene

Oxidation of lipoproteins is hypothesized to promote atherosclerosis and, thus, a high intake of antioxidant nutrients may protect against coronary heart disease. The relation between the intakes of dietary carotene, vitamin C, and vitamin E and the subsequent coronary mortality was studied in a cohort of 5,133 Finnish men and women aged 30-69 years and initially free from heart disease. Food consumption was estimated by the dietary history method covering the total habitual diet during the previous year. Altogether, 244 new fatal coronary heart disease cases occurred during a mean follow-up of 14 years beginning in 1966-1972. An inverse association was observed between dietary vitamin E intake and coronary mortality in both men and women with relative risks of 0.68 (p for trend = 0.01) and 0.35 (p for trend < 0.01), respectively, between the highest and lowest tertiles of the intake. Similar associations were observed for the dietary intake of vitamin C and carotenoids among women and for the intake of important food sources of these micronutrients, i.e., of vegetables and fruits, among both men and women. The associations were not attributable to confounding by major nondietary risk factors of coronary heart disease, i.e., age, smoking, serum cholesterol, hypertension, or relative weight. The results support the hypothesis that antioxidant vitamins protect against coronary heart disease, but it cannot be excluded that foods rich in these micronutrients also contain other constituents that provide the protection.

Antioxidant Vitamin Intake and Coronary Mortality in a Longitudinal Population Study

Objective: The British Nutrition Foundation was recently commissioned by the Food Standards Agency to conduct a review of the government's research programme on Antioxidants in Food . Part of this work involved an independent review of the scientific literature on the role of antioxidants in chronic disease prevention, which is presented in this paper. Background: There is consistent evidence that diets rich in fruit and vegetables and other plant foods are associated with moderately lower overall mortality rates and lower death rates from cardiovascular disease and some types of cancer. The ‘antioxidant hypothesis’ proposes that vitamin C, vitamin E, carotenoids and other antioxidant nutrients afford protection against chronic diseases by decreasing oxidative damage. Results: Although scientific rationale and observational studies have been convincing, randomised primary and secondary intervention trials have failed to show any consistent benefit from the use of antioxidant supplements on cardiovascular disease or cancer risk, with some trials even suggesting possible harm in certain subgroups. These trials have usually involved the administration of single antioxidant nutrients given at relatively high doses. The results of trials investigating the effect of a balanced combination of antioxidants at levels achievable by diet are awaited. Conclusion: The suggestion that antioxidant supplements can prevent chronic diseases has not been proved or consistently supported by the findings of published intervention trials. Further evidence regarding the efficacy, safety and appropriate dosage of antioxidants in relation to chronic disease is needed. The most prudent public health advice remains to increase the consumption of plant foods, as such dietary patterns are associated with reduced risk of chronic disease.

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A review of the epidemiological evidence for the 'antioxidant hypothesis'.

Recommendations for vitamin C intake are under revision by the Food and Nutrition Board of the National Academy of Sciences. Since 1989 when the last recommended dietary allowance (RDA) of 60 mg was published, exten- sive biochemical, molecular, epidemiologic, and clinical data have become available. New recommendations can be based on the following 9 criteria: dietary availability, steady-state concentrations in plasma in relationship to dose, steady-state concentrations in tissues in relationship to dose, bio- availability, urine excretion, adverse effects, biochemical and molecular func- tion in relationship to vitamin concentration, direct beneficial effects and epidemiologic observations in relationship to dose, and prevention of defi- ciency. We applied these criteria to the Food and Nutrition Board's new guide- lines, the Dietary Reference Intakes, which include 4 reference values. The estimated average requirement (EAR) is the amount of nutrient estimated to meet the requirement of half the healthy individuals in a life-stage and gender group. Based on an EAR of 100 mg/d of vitamin C, the RDA is pro- posed to be 120 mg/d. If the EAR cannot be determined, an adequate intake (AI) amount is recommended instead of an RDA. The AI was estimated to be either 200 mg/d from 5 servings of fruits and vegetables or 100 mg/d of vitamin C to prevent deficiency with a margin of safety. The final classifi- cation, the tolerable upper intake level, is the highest daily level of nutrient intake that does not pose risk or adverse health effects to almost all indi- viduals in the population. This amount is proposed to be less tha n1go f vitamin C daily. Physicians can tell patients that 5 servings of fruits and veg- etables per day may be beneficial in preventing cancer and providing suffi- cient vitamin C intake for healthy people, and tha t1go rmore of vitamin C may have adverse consequences in some people.

N C Flowers

Papers

Leukocyte ascorbic acid and its relationship to coronary artery disease in man