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© 2004 The American Society for Nutritional Sciences J. Nutr. 134:2623-2627, October 2004


Nutrient Metabolism

Equol, a Metabolite of Daidzein, Inhibits Bone Loss in Ovariectomized Mice1

Maiko Fujioka, Mariko Uehara*, Jian Wu, Herman Adlercreutz{dagger}, Kazuharu Suzuki*, Kazuki Kanazawa**, Ken Takeda{ddagger}, Kazuhiko Yamada and Yoshiko Ishimi2

Division of Applied Food Research, National Institute of Health and Nutrition, Tokyo, 162-8636, Japan; * Department of Nutritional Science, Tokyo University of Agriculture, Tokyo, 156-8502, Japan; {dagger} Institute for Preventive Medicine, Nutrition and Cancer, Folkhälsan Research Center, and Division of Clinical Chemistry, 00014, University of Helsinki, Helsinki, Finland; ** Department of Life Science, Graduate School of Science and Technology, Kobe University, Kobe, 657-8501, Japan; and {ddagger} School of Pharmacy, Tokyo University of Science, Chiba, 278-8510, Japan

2To whom correspondence should be addressed. E-mail: ishimi{at}nih.go.jp.

Soybean isoflavones have structures similar to that of estrogen and have received attention as alternatives to hormone replacement therapy for the prevention of postmenopausal osteoporosis. Daidzein, a major isoflavone found in soybean, is metabolized to equol by gut microflora, and the metabolite exhibits a stronger estrogenic activity than daidzein. However, there is no direct evidence that equol affects bone metabolism. In this study, we examined the effect of equol on the inhibition of bone loss in ovariectomized (OVX) mice. Female mice (8 wk old) were assigned to 5 groups as follows: sham-operated (sham), OVX, OVX + 0.1 mg/d equol administration (0.1 Eq), OVX + 0.5 mg/d equol administration (0.5 Eq), and OVX + 0.03 µg/d 17ß-estradiol administration (E2). Equol and E2 were administered s.c., using a mini-osmotic pump. At 4 wk after the intervention, uterine weight was less in the OVX mice than in sham-operated mice (P < 0.05). The weight was maintained in the E2 group. In contrast, administration of equol at doses used in this study did not affect uterine atrophy in OVX mice. Bone mineral density (BMD) for the whole body in the OVX group measured by dual-energy X-ray absorptiometry was lower than that in the sham group, whereas administration of 0.5 mg/d Eq as well as E2 maintained the BMD. The BMD of the femur and lumbar spine in the OVX group was also lower than those in the sham group, and treatment with 0.5 mg/d Eq maintained it. Notably, the BMD of the proximal femur in the 0.5 Eq group was the same as that of the sham group. E2 inhibited bone loss from all regions induced by OVX. These results suggest that equol, a major metabolite of daidzein, inhibits bone loss apparently without estrogenic activity in the reproductive organs of OVX mice.


KEY WORDS: • equol • daidzein • postmenopause • osteoporosis




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