Over 4000 flavonoids from plant sources have been identified (Kandaswami and Middleton, 1994), in addition to countless non-flavonoid compounds with antioxidant capacities. Indeed, in the 1930s investigators suggested that flavones might be essential to the human diet and they were termed vitamin P (Rusznyak and Szent-Gyorgyi, 1936). The substances that make up this bewildering variety of compounds differ widely in their antioxidant activities and their ability to affect both enzyme function and blood clotting activities. Synergistic effects of a balanced mixture of different antioxidants obtained from the diet may be required by the body for optimal health maintenance.
About half of the plasma antioxidant capacity comes from albumin and urate, the remainder represents the antioxidant gap (Miller and Rice-Evans, 1996). This gap is filled by the activities of single molecules, for example the vitamins a-tocopherol and ascorbate, flavonoids such as quercetin, isoflavonoids such as diadzein, and by the activity of antioxidant enzymes including superoxide dismutase and peroxidase. Furthermore, within the antioxidant system constant recycling of antioxidants such as a-tocopherol also occurs (Bieri, 1972). The importance of whole-food antioxidants in terms of promoting antioxidant recycling in the body is poorly understood.
Supplementation of diets with any single molecule showing in vitro antioxidant capacity does not necessarily promote health improvement. Recent studies of p-carotene have revealed that there may be risks associated with antioxidant supplementation. In the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (1994) and the CARET study (Omenn et al., 1996) the risk ratio for lung cancer in smokers receiving p-carotene increased. Protective effects of a diet rich in fruit and vegetable have recently been shown to reduce lung cancer independently of the effects of single-vitamin supplements (Yong et al., 1997).
Problems with single supplements have also been observed in animal models. Resveratrol is a polyphenolic compound from red wine with an antioxidant capacity in vitro (Siemann and Creasy, 1992) and has received much attention. Resveratrol may inhibit cancer in mice (Jang et al., 1997), however dietary supplementation with it is not associated with reduced lipid peroxidation in rats (Turrens et al., 1997) and may even be associated with increased atherogenesis (Wilson et al., 1996).
Part of the reason for these confusing results may be related to the fact that supplementation studies often use antioxidant amounts that are larger than could be encountered in a normal diet. Occasionally, when very high concentrations of antioxidants are reached, an antioxidant can promote oxidation; this observation has been called a pro-oxidant effect (Otero et al., 1997; Podmore et al., 1998). The popularity of antioxidant neutraceuticals coupled with a 'more is better' mentality may make pro-oxidant considerations important.
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