**2. Structure, absorption and bioavailability of soybean phytoestrogens**

Soybeans and its products are the most abundant source of isoflavones in the human diet. Isoflavones are normally taken up with food, absorbed in the gastrointestinal tract, and eliminated via urine. The absorption and bioavailability of isoflavones has been the subject of frequent debates among scientists. One of the main factor influencing the absorption and bioavailability is the chemical structure of the compound (D'Archivio et al., 2010). Structurally, soy isoflavones G, D and Gy are diphenolic compounds, which are present in soy and non-fermented soyfood isoflavones in its glycosylated forms, as glycones genistin, daidzein and glycitin (Setchell, 1999; Fig. 1).

Fig. 1. Structure of soybean phytoestrogens and mammalian 17β – estradiol.

observed beneficial health and weight-lowering effects, high nutritional value makes soy

However, aside from potential beneficial effects (still under intensive investigation and not fully proven), soybean phytoestrogens may also act as endocrine disruptors, by interfering with the function of reproductive system, as well as with other endocrine systems, namely thyroid and adrenal, and may, under some circumstances, increase cancer risk. This is why scientists are intensively trying to precisely evaluate potential benefits versus adverse effects of soy. Due to the importance, the researches are done both in vitro and in vivo, using different experimental approaches, animal models and various human studies. Results obtained so far are highly inconsistent and depend on experimental conditions, applied doses, animals and humans' age and sex, type of diet, presence of other PE sources in the diet, or other factors. Moreover, it remains unclear whether soy extracts, soy concentrate and purified isoflavones have identical effects. This is why the role of soy food in diet became a somewhat confusing topic in recent years. With approximately 2000 soy-related papers published annually, and half of it related to isoflavones (Messina, 2010), it is becoming

Due to the many differences in the chemical composition of soy products, and the fact that two thirds of human population cannot produce equol (Setchell et al., 2002), the authors decided to primarily focus their attention on effects of purified genistein and daidzein. We will evaluate the latest findings, using clear statements from the literature, as well as our own results, focusing on major potential healthful effects while also considering adverse effects of purified soybean phytoestrogens. More important, the authors will try to analyze the data in order to evaluate whether the net beneficial /adverse effect for each targeted

**2. Structure, absorption and bioavailability of soybean phytoestrogens** 

Fig. 1. Structure of soybean phytoestrogens and mammalian 17β – estradiol.

Soybeans and its products are the most abundant source of isoflavones in the human diet. Isoflavones are normally taken up with food, absorbed in the gastrointestinal tract, and eliminated via urine. The absorption and bioavailability of isoflavones has been the subject of frequent debates among scientists. One of the main factor influencing the absorption and bioavailability is the chemical structure of the compound (D'Archivio et al., 2010). Structurally, soy isoflavones G, D and Gy are diphenolic compounds, which are present in soy and non-fermented soyfood isoflavones in its glycosylated forms, as glycones genistin,

probably one of the most strategically important plants.

extremely difficult to compare all of the available data.

organ system depends on sex and age.

daidzein and glycitin (Setchell, 1999; Fig. 1).

As a prerequisite for absorption, the sugar must be removed from the compound at some point during ingestion (Setchell et al., 2002). Soy isoflavone glycosides are hydrolyzed to their aglycones by lactase phloridizin hydrolase in the apical membrane of the lumen of the small intestine, as well as by bacterial intestinal glucosidases (Wilkinson et el., 2003). Aglycones undergo passive diffusion across the small and large intestinal brush border (Larkin et al., 2008). However, some authors claim that glycosides may be absorbed also through the active sodium–dependent glucose transporter (Gee et al., 2000). Results obtained when we examined effects of soy extract on fluidity of erythrocyte membrane, showed that genistein and isoflavone glucosides intercalate and increase the order and rigidity of the outer layer of cellular membrane. Therefore, isoflavone glucosides may be also transported across the cell membrane directly, via entropy-driven flip-flop (Ajdžanović et al., 2010, 2011). Biological significance of this mechanism is unclear.

The absorption and bioavailability of isoflavones depends to some extent on interaction with other food components (Birt et al., 2001). The assumption that isoflavones are absorbed more efficiently from fermented than from non-fermented soy foods was re-examined and then rejected (Maskarinec et al*.*, 2008). Since intestinal microflora is capable of hydrolyzing the isoflavone glycosides from nonfermented soyfood, recommendations favoring fermented soyfood cannot be justified.

Genistein is stronger than daidzein in its agonistic activity for the ERs, as well as in its antioxidative potential. On the other hand, daidzein can be further metabolized into its bacterial metabolite equol, which has stronger estrogenic and antioxidative properties than both genistein and daidzein, or some other isoflavone metabolites (Mitchell et al., 1998). Although it appears that all animals produce equol following soy ingestion, in humans this is the case in approximately 30% of population (Lampe et al., 1998; Setchell et al., 2002). This is thought to be dependent on inter-individual variability in the presence of specific intestinal bacteria (Rowland et al., 2000). Besides the microflora composition, individual differences in gut transit time and redox potential of colon and genetic polymorphisms are likely to contribute to this great variability (Duffy et al., 2007). When evaluating the effects of age on equol production, it was demonstrated that during the first months of life, equol levels in plasma and urine were significantly lower than in adults, which may be due to the immature intestinal flora (Setchell et al. 2002). Lampe et al. (1998) detected no significant differences in the prevalence of equol production between genders.
