The indigenous intestinal microflora are involved in a variety of processes within the human body, and are important for maintaining host health. As such, interindividual differences in the ability to harbor certain intestinal bacteria might be associated with interindividual differences in health and/or disease susceptibility. In the last decade there has been considerable interest in phytoestrogen intakes in relation to human health. Daidzein, an isoflavone phytoestrogen found in soy, is metabolized to equol and O-desmethylangolensin (O-DMA) by intestinal bacteria. The specific bacterium/bacteria responsible for equol and O-DMA production in humans have yet to be identified definitively, but in vitro and animal studies have suggested that equol and O-DMA are more biologically active than their precursor daidzein. Interestingly, substantial interindividual differences in daidzein metabolism exist; following soy or daidzein consumption, approximately 30%-50% of the human population produce equol, and approximately 80%-90% produce O-DMA. Observational and intervention studies in humans have suggested that the ability to produce equol and O-DMA may be associated with reduced risk of certain diseases including breast and prostate cancers. However, relatively few studies have been conducted to date. In this review, we discuss the available evidence for a relationship between daidzeinmetabolizing phenotypes and human health, and suggest potential mechanisms for some of the reported relationships.

Phyto-oestrogens have emerged from their esoteric role in animal husbandry following the hypothesis that the human Western diet is relatively deficient in these substances compared with societies where large amounts of plant foods and legumes are eaten. Evidence is beginning to accrue that they may begin to offer protection against a wide range of human conditions, including breast, bowel, prostate and other cancers, cardiovascular disease, brain function, alcohol abuse, osteoporosis and menopausal symptoms. Of the two main classes of these weak oestrogens, the isoflavones are under intensive investigation due to their high levels in soyabean. Like the ‘anti-oestrogen’ Tamoxifen, these seem to have oestrogenic effects in human subjects in the cardiovascular system and bone. Although previously only available from food, isoflavones are now being marketed in health-food supplements or drinks, and tablets may soon be available over the counter as ‘natural’ hormone-replacement therapy. In cancer, anti-oestrogenic effects are thought to be important, although genistein especially has been shown to induce wide-ranging anti-cancer effects in cell lines independent of any hormone-related influence. There are few indications of harmful effects at present, although possible proliferative effects have been reported. In infants, the effects of high levels in soya milk formulas are uncertain. The second group, lignans, have been less investigated despite their known anti-oestrogenic effects and more widespread occurrence in foods. Investigation of the possible benefits ofphyto-oestrogensis hampered by lack of analytical standards and, hence, inadequate methods for the measurement of low levels in most foods. This problem may prove to be a major dilemma for regulatory authorities, clinicians and others wishing to advise the general public on whether these compounds really do have the health benefits attributed to them.

Background: Isoflavone phytoestrogen therapy has been proposed as a natural alternative to hormone replacement therapy (HRT). HRT has a beneficial effect on bone, but few trials in humans have investigated the effects of isoflavones on bone. Objective: The objective of the study was to determine the effect on bone density of a red clover-derived isoflavone supplement that provided a daily dose of 26 mg biochanin A, 16 mg formononetin, 1 mg genistein, and 0.5 mg daidzein for 1 y. Effects on biochemical markers of bone turnover and body composition were also studied. Design: Women aged 49-65 y (n ϭ 205) were enrolled in a double-blind, randomized, placebo-controlled trial; 177 completed the trial. Bone density, body composition, bone turnover markers, and diet were measured at baseline and after 12 mo. Results: Loss of lumbar spine bone mineral content and bone mineral density was significantly (P ϭ 0.04 and P ϭ 0.03, respectively) lower in the women taking the isoflavone supplement than in those taking the placebo. There were no significant treatment effects on hip bone mineral content or bone mineral density, markers of bone resorption, or body composition, but bone formation markers were significantly increased (P ϭ 0.04 and P ϭ 0.01 for bone-specific alkaline phosphatase and N-propeptide of collagen type I, respectively) in the intervention group compared with placebo in postmenopausal women. Interactions between treatment group and menopausal status with respect to changes in other outcomes were not significant. Conclusion: These data suggest that, through attenuation of bone loss, isoflavones have a potentially protective effect on the lumbar spine in women.