Dietary Flavonoids: Intake, Health Effects and Bioavailability
Introduction
A large number of epidemiological studies show a protective effect of vegetables and fruits against cancer (Block et al., 1992; Steinmetz and Potter, 1991) Although not studied as extensively as for cancer, epidemiological studies also suggest a strong protective effect of vegetables and fruits for stroke, and a weaker protective effect for coronary heart disease (Ness and Powles, 1997). Various hypotheses have been suggested to explain these beneficial effects of an increased consumption of vegetables and fruits. An attractive hypothesis is that vegetables and fruits contain compounds that have a protective effect independent of that of known nutrients and micronutrients. This is supported by in vitro and in vivo studies which show that naturally occurring plant compounds may inhibit various stages in the cancer process (Wattenberg, 1992). Flavonoids, a group of polyphenolic antioxidants, showed inhibitory effects in these models. Reduced risk of cardiovascular disease is possibly associated with high intakes of dietary antioxidants.
Flavonoids are polyphenolic compounds that occur ubiquitously in foods of plant origin. Variations in the heterocyclic ring C give rise to flavonols, flavones, catechins, flavanones, anthocyanidins and isoflavonoids (Fig. 1). In addition, the basic structure of flavonoids allows a multitude of substitution patterns in the benzene rings A and B within each class of flavonoids: phenolic hydroxyls, O-sugars, methoxy groups, sulfates and glucuronides. Over 4000 different naturally occurring flavonoids have been described (Middleton and Kandaswami, 1994). Flavonoids are common substances in the daily diet (Table 1).
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Biological effects of flavonoids
A multitude of in vitro studies has shown that flavonoids can inhibit, and sometimes induce, a large variety of mammalian enzyme systems (Middleton and Kandaswami, 1994). Some of these enzymes are involved in important pathways that regulate cell division and proliferation, platelet aggregation, detoxification, and inflammatory and immune response. Thus, it is not surprising that effects of flavonoids have been found on various stages in the cancer process, on the immune system, and on
Dietary intake of flavonoids
An estimation of the total flavonoid intake is difficult, because only limited data on contents of foods are available. We determined flavonols and flavones of vegetables, fruits and beverages commonly consumed in The Netherlands (Table 2) (Hertog et al., 1992, Hertog et al., 1993b). With these data we were able to calculate the intake of flavonols and flavones in The Netherlands (Hertog et al., 1993a). To our surprise, tea turned out to be the major source in this population (48% of total
Flavonoids in cancer and cardiovascular disease
Reliable data on flavonoid contents of common vegetables and fruits are needed to be able to study the potential role of dietary flavonoids in cancer and coronary heart disease prevention. So far, only data of flavonols and flavones are available (Table 2). These data have been used in a number of prospective cohort studies and in one prospective cross-cultural study on the relation between flavonol and flavone intake and cancer and cardiovascular disease.
Bioavailabilty of flavonoids from foods
These epidemiological data leave room for a role of flavonols as antioxidants in coronary heart disease prevention. However, absorption from the diet is a prerequisite for a causal relation between flavonols and coronary heart disease. In addition, metabolism of flavonols after absorption should not substantially inhibit their antioxidant capacity. The absorption and subsequent distribution, metabolism and excretion of flavonoids in humans has been little studied. Absorption of flavonoids from
Conclusions
Flavonoids are potentially bioactive polyphenols that occur ubiquitously in plant foods. Animal studies and in vitro studies suggest that dietary flavonols could inhibit cancer in humans. However, so far in only one epidemiological study an inverse association with cancer was found. Therefore, flavonols probably do not play an important role in cancer protection.
Flavonoids showed a protective action towards oxidation of LDL in vitro. Quercetin glycosides, the major flavonols in foods, are
Acknowledgements
We thank Professor D. Kromhout, who took the initiative for the epidemiological studies. We are grateful to Dr M.G.L. Hertog, Dr E. Feskens, Professor J.G.A.J. Hautvast and J.H.M. de Vries for valuable discussions, and to John M.P. van Trijp, M.N.C.P. Buysman, D.P. Venema and B.v.d. Putte for technical assistance. This work was supported by grants from the Foundation for Nutrition and Health Research and The Netherlands Heart Foundation (94.128).
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