Phytoestrogens and brain health

Phytoestrogens are a diverse group of naturally occurring polyphenolic compounds that structurally resemble mammalian estrogens although they are distributed in plants.¹ Due to their structural similarities, phytoestrogens can bind to mammalian estrogen receptors (ERs); some of them have a binding preference to ERβ, but, overall, they have weaker binding afnities when compared with the female endogenous estrogen 17β-estradiol. In the mammalian system, through their interactions with ERs, phytoestrogens can moderately interfere with the endogenous estrogen-responsive signaling and result in either estrogenic or antiestrogenic bioactivities, depending on the status of the endogenous estrogens and the distribution of two ER subtypes, ERa and ERβ.^2,3 Three major subclasses of phytoestrogens have been identied and chemically dened as isoavones, lignans, and coumestans (see Table 3.1).¹ Isoavones are predominantly enriched in red clover and legumes, such as soybeans; lignans are largely distributed in oilseeds, such as axseeds; and coumestans are widely distributed in plant sprouts, such as red clover sprouts and alfalfa sprouts. Mature red clover leaf is the known richest source of total isoavones, mainly biochanin A and formononetin, along with lesser amounts of genistein and daidzein. Biochanin A and formononetin are O-methylated precursor molecules of genistein and daidzein, respectively, and are enzymatically converted to genistein and daidzein once ingested in mammalians.⁴ Soy is the richest source of genistein, rich in daidzein, and the known exclusive source of glycitein. Besides red clover and soy, kudzu root is another major botanical source for isoavones, serving as the richest source of daidzein among all plants.⁵ Flaxseed provides the richest dietary source of lignans, with a large amount of secoisolariciresinol and a lesser amount of matairesinol.⁶ Once ingested, these plant lignans are enzymatically converted to mammalian lignans-secoisolariciresinol to enterodiol, and matairesinol to enterolactone. Coumestrol is a major coumestan, with a structure quite different from that of isoavones while highly estrogenic due to the presence of two phenol groups at both ends, which allows it to bind strongly to ERs as does genistein. Only a small trace amount of coumestrol exists in human diets.⁶.