Thousands of biologically active phytochemicals have been identified in plant foods, eg, grains, nuts, legumes, vegetables, and fruit. Of these plant food groups, vegetables and fruit are the most botanically diverse. In a Western diet alone, vegetables and fruit include roots, leaves, stems, fruit, and seeds from >40 botanical families. Thus, they have the potential to contribute significant variety and complexity to the human diet.

A diet rich in vegetables and fruit may provide protection against cardiovascular disease (1), several common cancers (2), and other chronic diseases. The associative evidence comes from case-control and cohort studies as well as ecologic studies. Analytic, epidemiologic studies also contribute evidence of a possible causal relation; however, in some cases, these studies may provide more evidence that a dietary or lifestyle pattern, rather than an individual constituent, plays a role in disease prevention. For example, Serdula et al (3) showed that the frequency of intake of fresh fruit and vegetables increased as the level of physical activity increased, and that consumption of fruit and vegetables was lower in those who reported that they were sedentary, heavy smokers, or heavy drinkers. Human intervention studies with disease as the endpoint would be the ideal test of causality, but we do not have the luxury of conducting placebo-controlled, randomized trials to examine the effect of endless doses and permutations of phytochemicals and dietary factors on disease outcomes.

Extensive study of phytochemicals in cell-culture systems and animal models has provided a wealth of information on the mechanisms by which a diet high in fruit and vegetables may lower the risk of chronic disease in humans. However, it is not always clear whether the effects in animals, often observed with high doses of single compounds, can be readily extrapolated to humans. It is not clear whether the biology that appears to influence disease risk in animals fed compounds, often at high levels, is functional to the same degree or in the same manner in humans consuming realistic doses as part of a habitual diet. Furthermore, studies in cell culture are often conducted before it is known how the phytochemicals are processed in vivo, how they are absorbed and metabolized in the body, or whether they are even available to tissues of interest. For example, some phytochemicals are fermented by colonic bacteria so that the compound absorbed from the gut and circulating in the blood is different from what was consumed (4) and the original phytochemical may not even be detectable in the blood.