Estrogenicity of beer: The role of intestinal bacteria in the activation of the beer flavonoid isoxanthohumol

For many centuries, hops (Humulus lupulus L.) have been used as essential ingredient in beers, providing the typical bitterness and hoppy fl avor. However, for the last few years the plant has gained increasing attention as a source of prenylfl avonoids and in 1999, 8-prenylnaringenin was identifi ed as the most potent phytoestrogen known so far. However, despite this high activity, health effects related to the presence of 8-prenylnaringenin in beers were always considered negligible because of the concentrations (< 100 g/l). In this chapter we show that introducing the aspect of bioavailability into the discussion of estrogen exposure after beer consumption can drastically change this vision. Upon ingestion, prenylfl avonoids reach the liver and large intestine, where they can be transformed into metabolites with different biological activity. Special attention is given to isoxanthohumol, the main prenylfl avonoid in beers present in 10-30 higher concentrations than 8-prenylnaringenin, in the role of a potential pro-estrogen by virtue. After all, isoxanthohumol has the potential for a substantial degree of metabolic activation: O-demethylation into 8-prenylnaringenin would increase its relative estrogenic potency from 0.001 to 0.4. Recent work shows that some isoxanthohumol indeed might be activated into 8-prenylnaringenin in the liver. However, the most important activation would occur in the colon. Here, intestinal bacteria can produce 8-prenylnaringenin from isoxanthohumol with high effi ciency. As it was shown that a large fraction of ingested isoxanthohumol reaches the colon, this process could easily 10-fold increase the 8-prenylnaringenin exposure after beer consumption. One drawback is that this process only occurs in one-third of humans due to interindividual differences in intestinal microbiota. Therefore, new strategies are now being developed to increase the 8-prenylnaringenin production in all individuals. In conclusion, these recent fi ndings about increased 8-prenylnaringenin exposure can give new insights in the scientifi c question whether moderate beer consumption can lead to specifi c health outcomes.