Sources of isoflavones.   Unlike the ubiquitously occurring lignans, another class of phytoestrogens considered important to human health (Setchell et al. 1980[] ), isoflavones are found almost exclusively in legumes. The soybean, in particular, provides the most abundant source of isoflavones, and therefore most soy foods will provide a significant dietary source of these bioactive nonnutrients (Coward et al. 1993[] , Murphy 1982[] , Reinli and Block 1996[] ). Isoflavones occur predominantly as glycosides in plants and consequently are highly polar (water-soluble) compounds (Walz 1931[] ). Comprehensive analyses of the isoflavone content of numerous soy foods have been reported and generally indicate that most contain 0.1–3.0 mg/g of total isoflavone (Coward et al. 1993[] , Murphy 1982[] ). Soy germ products derived from the hypocotyledon provide one of the most concentrated (>20 mg/g) sources of isoflavones. Numerous commercial soy supplements, many of which are made from concentrated extracts of the soybean, are now available, circumventing the need for nutrition as a source of isoflavones. The clinical effects of isoflavone supplements, however, have yet to be fully evaluated, and there are obvious concerns regarding the potentially adverse effects that could result from megadosing with these bioactive compounds, a practice all too common in the supplement area (Setchell et al. 1997[] ). Although a high proportion of foods contain soy products, these are mostly soy oils and soy lecithin; these soy products are devoid of isoflavones, and the average daily dietary intake of isoflavones in Western populations is typically negligible (<1 mg/d). Isoflavones migrate with the protein fraction of the soybean during its processing, and because soy protein is rarely a normal component of the average Western diet, this accounts for the low daily intake. The rapidly changing eating trends in Japan or China now make it difficult to make an accurate determination of the intake of isoflavones in these countries in which soy is traditionally a staple. Recent estimates indicate intakes of 20–50 mg/d (Nagata et al. 1998[] ), but this may vary between urban and rural areas, and with generational and other lifestyle factors.    Absorption and metabolism. The chemical form in which isoflavones occur is an important consideration because it may influence the biological activity, the bioavailability, and therefore the physiologic effects of these dietary constituents. We showed almost two decades ago that intestinal microflora play a key role in the metabolism and bioavailability of both lignans and isoflavones (Borriello et al. 1985[] , Setchell et al. 1984[] ). After ingestion, soybean isoflavones are hydrolyzed by intestinal glucosidases, which release the aglycones, daidzein, genistein and glycitein (Fig. 3[] ).These may be absorbed or further metabolized to many specific metabolites including, equol and p-ethylphenol (Axelson et al. 1984[] , Bannwart et al. 1984[] , Joannou et al. 1995[] , Kelly et al. 1993[] ). The extent of this metabolism appears to be highly variable among individuals and is influenced by other components of the diet (Setchell et al. 1984[] ). A high carbohydrate milieu, which causes increased intestinal fermentation, results in more extensive biotransformation of phytoestrogens, with greatly increased formation of equol ,a mammalian isoflavone metabolite of daidzein (Cassidy 1991[] ). This metabolic pathway may be clinically relevant to the efficacy of soybean isoflavones because the estrogenic potency of equol is an order of magnitude higher than its precursor, daidzein (Shutt and Cox 1972[] ). The importance of the microflora in the metabolic handling of phytoestrogens is illustrated from observations that antibiotic administration blocks metabolism, germfree animals do not excrete the metabolites and infants fed soy infant formulas in the first 4 mo of life, when gut microflora are underdeveloped, cannot form appreciable amounts of equol (Axelson and Setchell 1981[] , Cruz et al. 1994[] , Setchell et al. 1997 and 1998[] [] ). We have determined the plasma half-life of daidzein and genistein, measured from their plasma appearance and disappearance curves, to be 7.9 h in adults; peak concentrations occur 6–8 h after administration of the pure compounds (Setchell 1998 ). Consequently, adherence to a soy-containing diet will ultimately lead to high steady-state plasma concentrations. Knowledge of the pharmacokinetics of the isoflavones in soy foods (or supplements) is essential in making recommendations regarding longer-term efficacy in clinical studies. Clearly, maintenance of steady-state plasma concentrations should be achieved; on the basis of our data for clearance rates, this is best accomplished by divided doses of the soy food or supplements, rather than by single daily intakes. The pharmacokinetic behavior of phytoestrogens contrasts with that of the environmental xenoestrogens which, because of their very long half-lives, bioaccumulate and persist in fat tissues for years. It is this difference that may explain in part the potential dangers of synthetic xenoestrogens as endocrine disruptors (Safe 1995 ). Plasma concentrations of 50–800 ng/mL are achieved for daidzein, genistein and equol in adults consuming modest quantities of soy foods containing ~50 mg/d of total isoflavones. These values are similar to the plasma concentrations of Japanese consuming their traditional diet (Adlercreutz et al. 1993b ). In infants fed soy formulas and ingesting similar daily intakes, plasma concentrations are even higher (Setchell et al. 1997 ). Overall, when soy is consumed on a regular basis, plasma isoflavone levels far exceed normal plasma estradiol concentrations, which in men and women generally range between 40 and 80 pg/mL. It was this early observation that led us to hypothesize that with such disproportional levels one could anticipate hormonal effects from phytoestrogens (Setchell et al. 1984 ); these were subsequently established in premenopausal women adhering to a diet of soy protein (Cassidy et al. 1994 and 1995 ). This comes as no surprise because there are well-documented examples, mostly deleterious, of hormonal effects in several animal species resulting from ingesting phytoestrogens (Bennetts et al. 1946 , Setchell et al. 1987a ). Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. 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