Perspective: Isoflavones—Intriguing Molecules but Much Remains to Be Learned about These Soybean Constituents

Isoflavones are naturally occurring compounds found in a wide range of plants, but among commonly consumed foods are especially abundant in soybeans and foods derived from this legume. Much of the substantial amount of research conducted on soy protein and soy foods over the past 30 y is because of their isoflavone content. Research interest in isoflavones increased dramatically beginning in the early 1990s as evidence highlighted their possible role in the prevention of a wide range of cancers, including breast, prostate, and colon cancer. Recognition that isoflavones preferentially bind to estrogen receptor (ER)β in comparison with ERα provided a conceptual basis for classifying these diphenolic molecules as selective ER modulators (SERMs). Isoflavone research soon greatly expanded beyond cancer to include areas such as coronary artery disease, bone health, cognitive function, and vasomotor symptoms of menopause. Nevertheless, safety concerns about isoflavones, based primarily on the results of rodent studies and presumed estrogenic effects, also arose. However, recent work challenges the traditional view of the estrogenicity of isoflavones. Furthermore, safety concerns have largely been refuted by intervention and population studies. On the other hand, investigation of the proposed benefits of isoflavones has produced inconsistent data. The small sample size and short duration common to many intervention trials, combined with marked interindividual differences in isoflavone metabolism, likely contribute to the conflicting findings. Also, many different intervention products have been employed, which vary not only in the total amount, but also in the relative proportion of the 3 soybean isoflavones, and the form in which they are delivered (glycoside compared with aglycone). For those interested in exploring the proposed benefits of isoflavones, studies justify an intake recommendation of ∼50 mg/d, an amount provided by ∼2 servings of traditional Asian soy foods.