Summary and Research Needs

Strong evidence from a variety of sources indicates that a high intake of vitamin C or something very closely associated with it in the diet is protective against cancer and CVD, the major causes of disability and death in our aging communities. Indeed, it may be that plasma ascorbic-acid concentration can predict overall mortality risk. This interesting concept remains to be confirmed. The evidence for the benefits of a high intake of vitamin E is also strong, but research is needed into which member(s) of the vitamin E family are most important. The evidence for the benefits of carotenoids and flavo-noids stems largely from observational studies that show a decreased risk of disease in association with a high intake of foods or beverages rich in these non-nutrient antioxidants rather than the agents themselves. However, individuals who take these foods in large quantities are often more health conscious, take fewer total calories, do not smoke, exercise more, and eat less red meat and saturated fat. The relationship between diet and health is clear, but diet is complex and dynamic, the underlying mechanisms of chronic diseases are uncertain, and the influence of individual dietary antioxidants is difficult to discern within the heterogeneous framework of the human diet and lifestyle. Antioxi-dants do appear to play a role in protecting key biological sites, but further study is needed to establish which, how, and where and to establish the doses needed to achieve optimal effect. To date there is no evidence that high intakes of antioxidants in the diet are harmful. It is not yet known, however, whether intake above a threshold level brings additional benefit or whether the benefit of increased intake is limited to those with initially poor or marginal antioxidant status. Furthermore, antioxidants are likely to act within a coordinated system, and more of one may require more of others for beneficial effects to be achieved. Achieving 'target thresholds' of several antioxidants may be critical to achieving the optimal effect of each, and threshold plasma concentrations of 50 mmol l-1 and 30 mmol l-1 for vitamin C and vitamin E, respectively, with a ratio of more than 1.3, have been proposed for minimizing the risk of CHD.

To establish cause and effect and to make firm recommendations about the type and dose of anti-oxidants needed to achieve optimal health requires much in the way of further study. Of particular interest and value in such study is the growing field of orthomolecular nutrition, in which advances in genomics and proteomics are used to determine gene-nutrient interaction and the influence of diet on epigenetic phenomena. Such molecular-based studies, guided by epidemiological data and incorporated into future supplementation trials, will help answer the questions about the mechanisms of action and which, if any, antioxidants are important, how much, and for whom. However, while many questions relating to dietary antioxidants and health remain unanswered, to understand how to obtain a mixture of antioxidants and promote health we need look only at the macro level of food rather than at the micro level of specific constituents or molecular level of response. Fruits, vegetables, teas, herbs, wines, juices, and some types of chocolate are rich in antioxidants. It is known that diets rich in a variety of such foods are beneficial to health. The results of molecular-based experimental studies will determine whether these two truths are linked in a cause-and-effect relationship.

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