The Observational View of Dietary Antioxidants

Cancer and cardiovascular disease (CVD) are the two leading causes of death worldwide, diabetes mellitus is reaching epidemic proportions, and dementia and maculopathy are largely untreatable irreversible disorders that are increasingly common in our aging population. The prevalence and standardized mortality rates of these diseases vary considerably between and within populations. Mortality from CVD varies more than 10-fold amongst different populations, and incidences of specific cancers vary 20-fold or more across the globe. This enormous variation highlights the multiple factors at play in the etiology of chronic age-related diseases. These factors include smoking habit, socioeconomic status, exposure to infectious agents, cholesterol levels, certain genetic factors, and diet. Dietary factors have long been known to play an important role in determining disease risk. Indeed, 30-40% of overall cancer risk is reported to be diet-related, and there is a wealth of compelling observational evidence that a lower risk of cancer, CVD, diabetes, and other chronic age-related disorders is associated with diets that are rich in antioxidants.

In terms of dietary antioxidants, the major research focus to date has been on the water-soluble vitamin C (ascorbic acid) and the lipophilic vitamin E. 'Vitamin E' is a group of eight lipid-soluble toco-pherols and tocotrienols; however, the most widely studied form to date is a-tocopherol because it is the most abundant form in human plasma. Neither vitamin C nor vitamin E can be synthesized by humans, so they must be obtained in the diet, most coming from plant-based foods and oils. Deficiency of either of these vitamins is rare and can be prevented by the daily intake of a few milligrams of each. However, an adequate intake to prevent simple deficiency is unlikely to be sufficient for optimal health. Based on observational findings and experimental evidence that vitamin C and vitamin E protect key biological sites from oxidative damage in vitro, it has been suggested that there is a threshold of intake or plasma concentration for these antioxidants that confers minimum disease risk and promotes optimal health. The strength of the data supporting the health benefits of increased intakes of these vitamins was acknowledged in the US Food and Nutrition Board recommendation in 2000 to increase the daily intake of vitamin C to 75 mg day-1 for women and 90mgday-1 for men and to increase that of vitamin E to 15mgday-1 for both men and women. However, whether these new recommended intakes are 'optimal' is a contentious issue.

Supplementation trials with vitamin C or vitamin E have not to date shown the expected health benefits. The reasons for this mismatch between observational and supplementation data are not yet known, but some suggested reasons are outlined in Table 1. Nonetheless, despite the apparent lack of effect in supplementation trials, the variety and strength of observational findings, backed by a solid body of in vitro biochemical data, keep dietary antioxidants in the research spotlight, and in recent years attention has focused on the influence of 'non-nutrient' dietary antioxidants, such as polyphenolic compounds, in addition to the effects of vitamin C and vitamin E. The current evidence for vitamin C, vitamin E, and non-nutrient dietary antioxidants in relation to the major causes of morbidity and mortality in developed countries is discussed briefly below.

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