- Isoflavones are a class of phytoestrogens - plant-derived compounds with estrogenic activity. Soybeans and soy products are the richest sources of isoflavones in the human diet. (More information)
- Some health effects of soy may be dependent on one's capacity to convert the isoflavone daidzein to equol during digestion. (More information)
- The results of observational studies suggest that higher intakes of soy foods early in life may decrease the risk of breast cancer in adulthood. There is currently little clinical evidence that taking soy isoflavone supplements decreases the risk of incident and recurrent breast cancer. (More information)
- Current evidence from observational studies and small clinical trials is not robust enough to understand whether soy protein/isoflavone supplements may help prevent or inhibit the progression of prostate cancer. (More information)
- To date, randomized controlled trials examining the effect of soy isoflavones on bone mineral density in postmenopausal women have produced mixed results. Potential benefits of soy isoflavones as an alternative to bone-sparing treatments in women undergoing menopause remain to be determined. (More information)
- Current evidence suggests that whole soy components other than isoflavones may have favorable effects on serum lipid profiles. Yet, two recent meta-analyses of randomized controlled trials indicated that isoflavones might exert cardiovascular benefits by improving vascular function in postmenopausal women. (More information)
- Supplementation with isoflavones appeared to be about 40% less efficient than hormone-replacement therapy in attenuating menopausal hot flashes and required more time to reach its maximum effect. Yet, supplements containing primarily the isoflavone genistein have demonstrated consistent alleviation of menopausal hot flashes. (More information)
- Currently available data suggest that breast cancer survivors should not be further discouraged from consuming soy foods in moderation. Moreover, in a pooled analysis of three large prospective cohort studies, soy isoflavone intake ≥10 mg/day was associated with a 25% reduced risk of tumor recurrence in breast cancer survivors. (More information)
- At present, there is no convincing evidence that infants fed soy-based formula are at greater risk for adverse effects than infants fed cow's milk-based formula. (More information)
Introduction
Isoflavones are polyphenolic compounds that possess both estrogen-agonist and estrogen-antagonist properties (see Biological Activities). For this reason, they are classified as phytoestrogens - plant-derived compounds with estrogenic activity (1). Isoflavones are the major flavonoids found in legumes, particularly soybeans. In soybeans, isoflavones are present as glycosides, i.e., bound to a sugar molecule. Digestion or fermentation of soybeans or soy products results in the release of the sugar molecule from the isoflavone glycoside, leaving an isoflavone aglycone. Soy isoflavone glycosides include genistin, daidzin, and glycitin, while the aglycones are called genistein, daidzein, and glycitein (Figure 1). Unless otherwise indicated, quantities of isoflavones specified in this article refer to aglycones - not glycosides.
Metabolism and Bioavailability
The article on Flavonoids describes some of the factors influencing the absorption, metabolic fate, and bioavailability of flavonoid family members, including isoflavones. Pharmacokinetic studies have indicated that plasma concentrations of daidzein and genistein peaked about six hours after isoflavone intake, preceded by a smaller initial peak one hour post-meal (2, 3). The initial peak reflects isoflavone absorption following the hydrolysis of isoflavone glycosides to aglycones by β-glucosidases in the small intestine, while the second peak corresponds to isoflavone aglycones absorbed after the hydrolysis of glycosides by bacterial β-glucosidases in the colon (2).
The composition of one's colonic microbiota can influence the metabolic fate and biological effects of isoflavones. Indeed, the extent of at least some of the potential health benefits of soy intake are thought to depend on one's capacity to convert isoflavones to key metabolites during digestion. Specifically, some colonic bacteria can convert the soy isoflavone daidzein to equol, a metabolite that has greater estrogenic activity than daidzein, and to other metabolites, such as O-desmethylangolensin [O-DMA], that are less estrogenic (Figure 2) (4, 5). Equol appears in plasma about eight hours after isoflavone intake owing to the transit time of daidzein to the colon and its subsequent conversion to equol by the microbiota. Studies measuring urinary equol excretion after soy consumption indicated that equol was produced by about 25%-30% of the adult population in Western countries compared to 50%-60% of adults living in Asian countries and Western adult vegetarians (4, 6). Note that individuals possessing equol-producing bacteria are called "equol producers" as opposed to "equol non-producers."
Although prolonged soy food consumption has not been associated with the ability to produce equol, the type of soy food consumed might influence the composition of microbiota to include equol-producing bacteria (discussed in 4).
Biological Activities
Estrogenic and anti-estrogenic activities
Soy isoflavones are known to have weak estrogenic or hormone-like activity due to their structural similarity with 17-β-estradiol (Figure 3). Estrogens are signaling molecules that exert their effects by binding to estrogen receptors within cells (Figure 3). The estrogen-receptor complex interacts with DNA to change the expression of estrogen-responsive genes. Estrogen receptors (ER) are present in numerous tissues other than those associated with reproduction, including bone, liver, heart, and brain (7). Soy isoflavones can preferentially bind to and transactivate estrogen receptor-β (ER-β) - rather than ER-α - mimicking the effects of estrogen in some tissues and antagonizing (blocking) the effects of estrogen in others (8). Scientists are interested in the tissue-selective activities of phytoestrogens because anti-estrogenic effects in reproductive tissue could help reduce the risk of hormone-associated cancers (breast, uterine, and prostate), while estrogenic effects in other tissues could help maintain bone mineral density and improve blood lipid profiles (see Disease Prevention). The extent to which soy isoflavones exert estrogenic and anti-estrogenic effects in humans is currently the focus of considerable scientific research.
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