European Journal of Clinical Nutrition 1996, 50: 63-71
©1996 Stockton Press. This excerpt is approved by publisher.

Potential Health Effects of the Dietary Flavonol Quercetin

MGL Hertog¹ and PCH Hollman²

1. Department of Chronic Diseases and Environmental Epidemiology, National Institute of Public Health and Environmental Protection, PO Box 1, NL-3720 BA, Bilthoven, the Netherlands; 2DLO State Institute for Quality Control of Agricultural Products, Wageningen, the Netherlands.

Introduction

The flavonol quercetin belongs to the group of flavonoids, one of the large groups of secondary plant metabolites occurring widely throughout the plant kingdom. The role of flavonoids in plant foods, their chemistry, and their distribution in foods has been reviewed periodically in the past forty years (Bate-Smith, 1954; Kühnau, 1976; Herrmann, 1988; Markham, 1989). However, their importance to human health has remained long unclear. Flavonoids are considered to be non-nutrients, i.e. substances without any nutritive value for humans. However, by 1936 Szent-Gyürgyi had shown that two flavonoids derived from citrus fruits decreased capillary fragility and permeability in humans (Rusznyák & Szent-Gyürgyi, 1936). Flavonoids were thus called vitamin P (from permeability) and also vitamin C2, because it was found that some flavonoids had vitamin C sparing activities (Singleton, 1981). However, the claim that flavonoids were vitamins could later not be substantiated, and both terms were dropped around 1950. Following the discovery of the mutagenicity of quercetin, a major food flavonol, in the late seventies, much attention was paid to its potential carcinogenicity, which was however subsequently disproved (reviewed in: MacGregor, 1984; Dunnick & Hailey, 1992). In recent years it was shown that quercetin had potent anticarcinogenic, antioxidative and anti-inflammatory capacities in experimental studies, which attracted the attention on the potential beneficial effects in humans of quercetin and other flavonols such as kaempferol and the flavones apigenin and luteolin. In the present overview the potential health effects of flavonols, e.g. quercetin and flavones will be reviewed with emphasis on the recently Published epidemiologic studies on quercetin consumption and cancer and coronary heart disease risk.

Absorption and metabolism of Flavonoids

The metabolism of flavonoids has been studied well in various animals, and has been reviewed by Griffiths (1982). In the liver the hydroxyl groups of flavonoids are methylated and glucuronidated. In rats, glucuronides are extensively excreted in the bile. Little is known about the biliary excretion of flavonoids in other species. Glycosides are removed and ring fission occurs in the colon by microorganisms, and the resulting phenolic acids are demethylated and dehydroxylated. Three main types of ring scission depending on the subclass of flavonoids have been postulated. Flavonols are metabolized to hydroxylated derivatives of phenylacetic acid and to phloroglucinol derivatives not elucidated so far. A wide range of mammalian species has shown considerable species variation in ring fission products.

Discussion

In the present overview the potential health effects of quercetin and other flavonols and flavones were summarized Experimental studies in animals suggest that dietary quercetin, at relatively high doses, could inhibit the initiation and development of tumors in humans. These results are supported by in vitro studies showing that quercetin inhibited the growth of isolated human tumour cell lines.

In conclusion, the antioxidant quercetin and related flavonoids could lower coronary heart disease risk in humans, but they do not seem to play an important role in cancer prevention. It has to be noted that the health effects of flavonoids currently represents a very rapidly growing field of studies, and that our overview necessarily contains only the work that has been published before the summer of 1995. For instance, on a conference on antioxidants and atherosclerosis and cancer prevention organised in Helsinki in August 1995, preliminary results were presented showing an inverse association between quercetin intake and both cancer and coronary heart disease risk in a Finnish population. New insights and views on the health aspects of flavonoids can therefore be expected in the near future. Nevertheless, several questions need to be resolved before firm conclusions on the health protective effects of quercetin can be drawn. These research issues include amongst many others, epidemiologic studies on quercetin and health in other countries and cultures, studies on the cardiovascular-protective mechanisms of quercetin and (dietary) intervention studies on absorption, metabolism, and biologic effects of quercetin in humans. The work on bioactive dietary components such as quercetin and their relation with human health represents therefore a new and exciting area of research.