Bioavailability of genistein and its glycoside genistin

Genistein belongs to the class of isoflavones. The main sources of isofiavones in food are soybeans and soy-based products. Most isoflavones in plants are bound to sugars such as the glycosides genistin and daidzin. Understanding the various factors that influence absorption and metabolism of isoflavones and especially of their naturally occurring glycosides, is essential to fully elucidate and understand the physiological activity of these dietary ingredients in the human body. It is also essential to fully explore the possible beneficial health effects of the isoflavones, which are considered to be promising as healthy constituents in enriched (novel) foods or supplements. The aim of this thesis is to obtain data on the transport (uptake) and metabolism of the isoflavones genistein and daidzein and their glycosides genistin and diadzin. Special focus is directed to the possible role of SGLTl in the mechanism involved in the transport and absorption of the isoflavonic glycoside genistin. Another objective is to explore, develop, validate and optimise in vitro, in situ and in vivo gastrointestinal model systems for studying the bioavailability and metabolism of genistein, daidzein and their glycosides.

This thesis reveals that in all intestinal models studied genistein is more bioavailable than its glycoside genistin. The major route of absorption of genistin appeared to be deglycosylation of genistin to genistein and the subsequent intestinal metabolism of genistein to genistein glucuronides and sulfates. Mechanistic studies show that the bioavailability of genistin could be improved by the naturally occurring compound phloridzin, present in apples, because phloridzin inhibits the efflux-transporters located at the brush border (apical) membrane of the enterocyte. On the basis the results described in this thesis, it is concluded that the best gastrointestinal model system appears to be freely moving unanaesthetized cannulated rats. However, animal experiments are expensive and time-consuming and should be reduced, refined or replaced whenever feasible also for ethical reasons. The Caco-2 cells provide a good alternative for studying the mechanism of isoflavones absorption, although the hydrolase activity in this cell line should be improved to mimic the human situation to a better extent.

All together the results presented in this thesis provides an insight in the mechanisms underlying the bioavailability of this important class of health beneficial soy based food ingredients and even point at inhibition of apical transporters as a way to improve the bioavailability of genistin and genistein.