Alterations in bone turnover by isoflavone aglycone supplementation in relation to estrogen receptor α polymorphism

Soybean isoflavones have structural similarity to estrogen and have attracted much attention due to their prevention of postmenopausal symptoms. It is critical for women to maintain a high bone mineral density (BMD) prior to menopause to prevent osteoporosis. In the present study, the effect of isoflavone aglycone (IA) supplementation on bone turnover was examined in relation to the estrogen receptor α (ERα) polymorphism. Natural isoflavones are glycosides that must be hydrolyzed to aglycones by intestinal microflora to have an effect. To avoid interference by flora, IA (30 mg/day) (but not isoflavones) or a placebo were administered as a supplement for 3 months to a Japanese population consisting of 81 premenopausal women. Due to variations in the intestinal flora, some but not all subjects were able to further metabolize IA into equol. Differences between equol producers and non-producers were also considered. To estimate BMD, the osteo-sono-assessment index (OSI) was determined by measuring bone density at the calcaneus and levels of bone biochemical markers (bone-specific alkaline phosphatase, α-carboxylated osteocalcin, undercarboxylated osteocalcin and deoxypridinoline) before and after supplementation. DNA samples from the subjects were examined for the presence of the XbaI restriction fragment length polymorphism (RFLP) in intron 1. According to univariate analysis, IA had a favorable effect on the OSI of subjects with the X allele, with X designated RFLP undigested by XbaI, although the difference was not statistically significant. Alterations in the levels of bone biochemical markers were also not significant. Thus, a further logistic regression analysis was performed. This indicated that subjects with the XX homozygote administered the IA supplement were less likely to have reduced OSI values. Although equol has been proposed to have the highest phytoestrogen activity, its effect was not apparent. Thus, low-dose IA supplementation is useful for maintaining BMD in premenopausal XX subjects, independent of equol.