Supplemental Dietary Racemic Equol Has Modest Benefits to Bone but Has Mild Uterotropic Activity in Ovariectomized Rats , ,

Abstract

Soy isoflavones and their metabolites, with estrogenic activity, have been considered candidates for reducing postmenopausal bone loss. In this study, we examined the effect of dietary equol, a bioactive metabolite of the soy isoflavone daidzein, on equol tissue distribution, bone parameters, and reproductive tissue activity using an adult ovariectomized (OVX) rat model. An 8-wk feeding study was conducted to compare 4 dietary treatments of equol (0, 50, 100, 200 mg/kg diet) in 6-mo-old OVX female Sprague-Dawley rats. A dose response increase in tissue equol concentrations was observed for serum, liver, kidney, and heart, and a plateau occurred at 100 mg equol/kg diet for intestine. In OVX rats receiving 200 mg equol/kg diet, femoral calcium concentration was greater than those receiving lower doses but was still less than SHAM (P < 0.05), and other bone measures were not improved. Tibia calcium concentrations were lower in OVX rats receiving 100 and 200 mg equol/kg diet compared with the OVX control rats. Trabecular bone mineral density of tibia was also lower in equol-fed OVX rats. At this dietary equol intake, uterine weight was higher (P < 0.05) than in other OVX groups but lower than the SHAM-operated intact rats. The 200 mg/kg diet dose of dietary equol significantly increased proliferative index in the uterine epithelium. Dietary equol had no stimulatory effect on mammary gland epithelium. We conclude that in OVX rats, a dietary equol dose that had modest effect on bone also exerts mild uterotropic effects.

S-equol and the fermented soy product SE5-OH containing S-equol similarly decrease ovariectomy-induced increase in rat tail skin temperature in an animal model of hot flushes

“…Previous research reported, in contrast to S-equol, that a high-but not a low-dose racemic equol mixture exhibited a mild uterotropic effect on rats. 39,42 S-equol preferentially binds to ER-A, whereas R-equol has a greater affinity for ER->. 3 The latter receptor is abundant in reproductive tissue.…”

Equol: Pharmacokinetics and Biological Actions ,

“…Studies from Japan show more favorable responses in measures of bone loss in those women who are equol-producers (82). Equol in its racemic form has been shown to have modest effects in preventing bone loss in animal models of osteoporosis (83)(84)(85)(86)(87) but has yet to be used in clinical trials. S-(-)equol is also being studied for its effects on reducing the incidence and frequency of menopausal symptoms (88), particularly hot flushes.…”

The pros and cons of phytoestrogens

“…It is not yet clear which enantiomer has more potent bone sparing effects. In OVX rats, daily consumption of 200 mg/kg racemic equol for 8 weeks moderately elevated femoral calcium concentrations but also increased uterine weight [144]. Lower doses also appear to be effective in bone without inducing uterine proliferation, yielding hope that it might be beneficial for human bone without unwanted estrogenic side effects [166].…”