Bioavailability of isoflavones and biological activity of major isoflavone metabolites

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The intake of soy isoflavones has been associated with a wide range of beneficial health effects. Since isoflavones are extensively metabolized by the gut microflora and in the liver, such effects may be a consequence of exposure to either the parent compounds or the metabolites. Recent studies show that sugar-conjugation of (iso)flavonoids have an important influence on the absorption and bioavailability of these compounds, but the consequences for the formation of metabolites in the gut and in the liver are unclear. Also little is in known about the biological activity of major relevant metabolites. In this project the bioavailability and the pharmacokinetics of an isoflavone aglycone (daidzein) in comparison to an isoflavone sugar conjugate (malonyl-daidzin) will be determined in a human intervention study with a well controlled cross-over design. A major goal is to establish wether, if differences in the pharmacokinetic behavior have an influence on the metabolism of these compounds. Furthermore, the biological activity of the major relevant metabolites of daidzein and genistein will be investigated by studying the anti- and pro-oxidant capacity, the genotoxic potential as well as the estrogenic potency of the major metabolites ex vivo by using of the isolated metabolites.