Isoflavones are substituted derivatives of isoflavone, a type of naturally occurring isoflavonoids, many of which act as phytoestrogens in mammals. Isoflavones are produced almost exclusively by the members of the bean family, Fabaceae (Leguminosae). Although isoflavones and closely related phytoestrogens are sold as dietary supplements, there is little scientific evidence for either the safety of long-term supplementation or of health benefits from these compounds. Some studies have identified potential risks from high intake of isoflavones, such as in women with a history of breast cancer, but this concern has not been substantiated with high-quality clinical research. Organic chemistry and biosynthesis Isoflavone is an isomer of flavone, which is chromone substituted with a phenyl group in the 2-position. In isoflavone, the phenyl group is in the 4-position. Substituted isoflavone derivatives are related to the parent by the replacement of two or three hydrogen atoms with hydroxyl groups. Isoflavone differs from flavone (2-phenyl-4H-1-benzopyr-4-one) in location of the phenyl group. Isoflavones are produced via a branch of the general phenylpropanoid pathway that produces flavonoid compounds in higher plants. Soybeans are the most common source of isoflavones in human food; the major isoflavones in soybean are genistein and daidzein. The phenylpropanoid pathway begins from the amino acid phenylalanine, and an intermediate of the pathway, naringenin, is sequentially converted into the isoflavone genistein by two legume-specific enzymes, isoflavone synthase, and a dehydratase. Similarly, another intermediate naringenin chalcone is converted to the isoflavone daidzein by sequential action of three legume-specific enzymes: chalcone reductase, type II chalcone isomerase, and isoflavone synthase. Plants use isoflavones and their derivatives as phytoalexin compounds to ward off disease-causing pathogenic fungi and other microbes. In addition, soybean uses isoflavones to stimulate soil-microbe rhizobium to form nitrogen-fixing root nodules. Occurrence Most members of the family Fabaceae contain significant quantities of isoflavones. Analysis of levels in various species has found the highest levels of genistein and daidzein in psoralea (Psoralea corylifolia). Various legumes including soybean (Glycine max L.), green bean (Phaseolus vulgaris L.), alfalfa sprout (Medicago sativa L.), mung bean sprout (Vigna radiata L.), cowpea (Vigna unguiculata L.), kudzu root (Pueraria lobata L.), and red clover blossom and red clover sprout (Trifolium pratense L.) have been studied for their estrogenic activity. Highly processed foods made from legumes, such as tofu, retain most of their isoflavone content, and fermented miso, which has increased levels. Soy milk has a much higher concentration of isoflavones than soy