Background:No published studies have directly examined the effect of soy protein with isoflavones on bone or bone turnover in perimenopausal women. Objective: Our objective was to determine the effects of 24 wk of consumption of soy protein isolate with isoflavones (80.4 mg/d) in attenuating bone loss during the menopausal transition. Design: Perimenopausal subjects were randomly assigned, double blind, to treatment: isoflavone-rich soy (SPI+; n = 24), isoflavone-poor soy (SPIϪ; n = 24), or whey (control; n = 21) protein. At baseline and posttreatment, lumbar spine bone mineral density (BMD) and bone mineral content (BMC) were measured by using dual-energy X-ray absorptiometry. At baseline, midtreatment, and posttreatment, urinary N-telopeptides and serum bonespecific alkaline phosphatase (BAP) were measured. Results: The percentage change in lumbar spine BMD and BMC, respectively, did not differ from zero in the SPI+ or SPIϪ groups, but loss occurred in the control group (Ϫ1.28%, P = 0.0041; Ϫ1.73%, P = 0.0037). By regression analysis, SPI+ treatment had a positive effect on change in BMD (5.6%; P = 0.023) and BMC (10.1%; P = 0.0032). Baseline BMD and BMC (P ≤ 0.0001) negatively affected the percentage change in their respective models; baseline body weight (P = 0.0036) and bone-free lean weight (P = 0.016) contributed positively to percentage change in BMD and BMC, respectively. Serum BAP posttreatment was negatively related to percentage change in BMD (P = 0.0016) and BMC (P = 0.019). Contrast coding using analyses of covariance with BMD or BMC as the outcome showed that isoflavones, not soy protein, exerted the effect. Conclusion: Soy isoflavones attenuated bone loss from the lumbar spine in perimenopausal women.Am J Clin Nutr 2000; 72:844-52. KEY WORDSSoy, isoflavones, bone density, lumbar vertebrae, biochemical markers, menopause, bone mineral content, perimenopausal women INTRODUCTIONCurrent therapies for treating osteoporosis include estrogen and hormone replacement therapies (ERT and HRT), bisphosphonates, calcitonin, and raloxifene. Because of possible contraindications of ERT and HRT, such as breast cancer, endometrial adenocarcinoma, and undesirable side effects (1), compliance with hormonal therapy is poor (2), leading to loss of treatment efficacy (3). Continued uterine bleeding and other adverse side effects of HRT cause women to search for alternatives to traditional therapy. Isoflavone-containing soy may be a potential alternative for preventing bone loss during the menopausal transition.Isoflavones, found predominantly in soy products, are estrogen-like substances structurally and functionally similar to 17 ␤-estradiol (4). On the basis of evidence primarily from animal and in vitro studies, isoflavones are thought to exert both estrogenic and antiestrogenic effects, depending on the tissue in which they act (5). Isoflavones may exert a weak antagonistic effect on the estrogen receptor (5), thereby having an antiestrogenic effect on uterine and breast tissue (6), where excess estrogen ...

Adlercreutzia equolifaciens gen. nov., sp. nov., an equol-producing bacterium isolated from human faeces, and emended description of the genus Eggerthella Nine strains capable of metabolizing isoflavones to equol were isolated from human faeces. Four of the strains were characterized by determining phenotypic and biochemical features and their phylogenetic position based on 16S rRNA gene sequence analysis. These strains were related to Eggerthella sinensis HKU14 T with about 93 % 16S rRNA gene sequence similarity; they were asaccharolytic, obligately anaerobic, non-spore-forming, non-motile and Gram-positive coccobacilli. In enzyme activity tests, arginine dihydrolase, arginine and leucine arylamidases were positive but nitrate reduction, urease and b-glucosidase were negative. The major menaquinone was DMMK-6 (dimethylmenaquinone-6), while that of members of the genus Eggerthella was MMK-6 (methylmenaquinone-6). Furthermore, the cell-wall peptidoglycan type of these strains was A1c, while that of members of the genus Eggerthella was A4c. On the basis of these data, a new genus, Adlercreutzia gen. nov., is proposed with one species, Adlercreutzia equolifaciens sp. , 2006). We isolated nine strains capable of metabolizing isoflavones to equol from human faeces. Seven of these strains could metabolize daidzein via dihydrodaidzein to equol, while the other two isolates could metabolize only dihydrodaidzein to equol. These strains were divided into four groups by 16S rRNA gene sequence analysis. Representative strains selected from each group were asaccharolytic, obligately anaerobic, non-spore-forming, non-motile and Gram-positive coccobacilli. Although these strains were genetically related to the genus Eggerthella, they did not belong to the genera Eggerthella, Slackia or Denitrobacterium from 16S rRNA gene sequence analysis.The presence of dimethylmenaquinone-6 (DMMK-6) as the predominant menaquinone of these strains is unique. Furthermore, the cell-wall peptidoglycan type of these strains was A1c, while that of members of the genus Eggerthella was A4c.Strains FJC-A10, FJC-A161, FJC-B9 T , FJC-B12, FJC-B15, FJC-B19, FJC-B20, FJC-D47 and FJC-D53 were cultivated for 3 days at 37 u C on BL agar (Nissui) with 5 % (v/v) horse blood. Coriobacterium glomerans JCM 10262 T was cultivated for 2 days at 30 u C on GAM agar (Nissui). Detailed menaquinone and fatty acid profiles of representative strains and related type strains and minimum-evolution and maximumparsimony 16S rRNA gene sequence-based trees are available as supplementary material with the online version of this paper.

The combined intervention of isoflavone intake and walking exercise over 1 year in postmenopausal Japanese women exhibited a trend for a greater effect on prevention of bone loss at the total hip and Ward's triangle regions. Introduction:The additive effects of isoflavones and exercise on bone and lipid metabolism have been shown in estrogen-deficient animals. In this study, we determined the effects of isoflavone intake, walking exercise, and their interaction on bone, fat mass, and lipid metabolism over 1 year in postmenopausal Japanese women. Materials and Methods: A total of 136 postmenopausal women at <5 years after the onset of menopause were randomly assigned to four groups: (1) placebo, (2) walking (45 minutes/day, 3 days/week) with placebo, (3) isoflavone intake (75 mg of isoflavone conjugates/day), and (4) combination of isoflavone plus walking. BMD, fat mass, serum lipid, and serum and urinary isoflavone concentrations were assessed. Results: A significant main effect of isoflavone on the reduction in trunk fat mass was obtained at 12 months. Significant main effects of walking on the reduction in fat mass in the whole body and the trunk were observed at 3, 6, and 12 months and that in the legs and arms at 6 and 12 months. Serum high-density lipoprotein (HDL)-cholesterol concentration significantly increased by 12 months after the walking and the combined intervention. After 12 months, a significant main effect of isoflavone on BMD was observed only at Ward's triangle. Walking prevented bone loss at the total hip and the Ward's triangle to significant degrees. The effect of the combined intervention on BMD at total hip and Ward's triangle regions was greater than that of either alone. No significant interaction was observed between isoflavone and walking in any measurements recorded during the study. Conclusions: Our study suggest that combined intervention of 75 mg/day of isoflavone intake and walking exercise 3 times/week for 1 year showed a trend for a greater effect on BMD at total hip and Ward's triangle regions than either alone. Intervention with isoflavone in postmenopausal Japanese women showed a modest effect on BMD compared with those in Westerners. Further studies over longer treatment duration that include assessment of BMD at various regions are necessary to ascertain the clinical significance of the combined intervention of isoflavone plus walking in postmenopausal women.

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The effects of the plant isoflavones, daidzin and genistin, on bone loss in ovariectomized (ovx) rats fed a calcium-deficient diet were investigated. Daidzin and genistin were orally administered to ovx rats for 4 weeks. The femurs of these rats showed significantly lower density, strength (breaking forces), ash weight and calcium and phosphorus content (p<0.01) in comparison with those of sham-operated rats. These changes were largely prevented in animals receiving oral daidzin or genistin for 4 weeks at a dose of 50 mg/kg/d and in animals receiving subcutaneous estrone (7.5 microg/kg/d) as a positive control. Ovariectomy caused atrophy of the uterus and increased the ratio of the urinary excretion of pyridinoline and deoxypyridinoline to endogenous creatinine excretion. This was prevented by administration of daidzin or estrone, but, interestingly, not genistin. The preventive effect of daidzin treatment on bone loss in ovariectomized rats appears to be due to suppression of bone turnover. Genistin has a different mechanism of action from daidzin.