Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women

Steinberg, Francene M.; Murray, Michael J.; Lewis, Richard D.; Cramer, Margaret A.; Amato, Paula; Young, Ronald L.; Barnes, Stephen; Konzelmann, Karen L; Fischer, Joan G.; Ellis, Kenneth J.; Shypailo, Roman J.; Fraley, J. Kennard; Smith, E. O’Brian; Wong, William W.

doi:10.3945/ajcn.110.008359

Cited by 64 publications

(73 citation statements)

References 53 publications

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“…42 mg/kg b.wt per day in a range from 30 to 55 mg/kg/ day. Such a dose is relatively high-a human equivalent dosage [25] can only be reached by dietary supplements using a dose, which is three to four times higher than the maximum dose commonly used for treatment of postmenopausal complaints [74][75][76][77][78].…”

Section: Genisteinmentioning

confidence: 99%

Effects of estradiol, estrogen receptor subtype-selective agonists and genistein on glucose metabolism in leptin resistant female Zucker diabetic fatty (ZDF) rats

Weigt

Hertrampf

Flenker

et al. 2015

The Journal of Steroid Biochemistry and Molecular Biology

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Section: Genisteinmentioning

confidence: 99%

Effects of estradiol, estrogen receptor subtype-selective agonists and genistein on glucose metabolism in leptin resistant female Zucker diabetic fatty (ZDF) rats

Weigt

Hertrampf

Flenker

et al. 2015

The Journal of Steroid Biochemistry and Molecular Biology

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“…Peri-and post-menopausal women with a family history of breast cancer are a sub-population in Western society that increasingly is considered vulnerable for unregulated and selfadministrated consumption of dietary soy supplements (BfR, 2007;Doerge et al, 2000;Maskarinec, 2013). Despite their beneficial effects for human health and large societal acceptance by consumers, potential adverse effects as suggested in in vitro and in vivo experiments, and in clinical trials, raise questions about the safety of high dosages of phytoestrogens (Andres et al, 2011;Haines et al, 2012;Rietjens et al, 2013;Steinberg et al, 2011). However, most of the in vitro estrogenicity experiments used biologically active aglycones, which generally make up <1-2% of the total isoflavone levels present in blood (Gu et al, 2006;Hosoda et al, 2010;Sesink et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Deconjugation of soy isoflavone glucuronides needed for estrogenic activity

Islam

Bekele

Berg

et al. 2015

Toxicology in Vitro

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Soy isoflavones (SIF) are present in the systemic circulation as conjugated forms of which the estrogenic potency is not yet clear. The present study provides evidence that the major SIF glucuronide metabolites in blood, genistein-7-O-glucuronide (GG) and daidzein-7-O-glucuronide (DG), only become estrogenic after deconjugation. The estrogenic potencies of genistein (Ge), daidzein (Da), GG and DG were determined using stably transfected U2OS-ERα, U2OS-ERβ reporter gene cells and proliferation was tested in T47D-ERβ cells mimicking the ERα/ERβ ratio of healthy breast cells and inT47D breast cancer cells. In all assays applied, the estrogenic potency of the aglycones was significantly higher than that of their corresponding glucuronides. UPLC analysis revealed that in U2OS and T47D cells, 0.2-1.6% of the glucuronides were deconjugated to their corresponding aglycones. The resulting aglycone concentrations can account for the estrogenicity observed upon glucuronide exposure. Interestingly, under similar experimental conditions, rat breast tissue S9 fraction was about 30 times more potent in deconjugating these glucuronides than human breast tissue S9 fraction. Our study confirms that SIF glucuronides are not estrogenic as such, and that the small % of deconjugation in the cell is enough to explain the slight bioactivity observed for the SIF-glucuronides. Species differences in deconjugation capacity should be taken into account when basing risk-benefit assessment of these SIF for the human population on animal data.

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“…Although hormone replacement therapy (HRT) can help to prevent and treat the menopausal syndromes, the side effects of HRT, such an increased risk of developing breast and endometrial cancer, prevent the acceptance of HRT [4,5] . Recently, reliable evidence has indicated that phytoestrogens offer the www.chinaphar.com Ma HR et al Acta Pharmacologica Sinica npg best potential therapy for menopausal women because they are safe and have a high compliance rate [6,7] . Increasing numbers of women are using phytoestrogens as an alternative therapy for menopausal syndromes.…”

Section: Introductionmentioning

confidence: 99%

Assessment of the estrogenic activities of chickpea (Cicer arietinum L) sprout isoflavone extract in ovariectomized rats

Hai

Wang

et al. 2013

Acta Pharmacol Sin

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Aim: Chickpea (Cicer arietinum L) is a traditional Uighur herb. In this study we investigated the estrogenic activities of the isoflavones extracted from chickpea sprouts (ICS) in ovariectomized rats. Methods: Ten-week-old virgin Sprague-Dawley female rats were ovariectomized (OVX). The rats were administered via intragastric gavage 3 different doses of ICS (20, 50, or 100 mg·kg -1 ·d -1 ) for 5 weeks. Their uterine weight and serum levels of 17β-estradiol (E 2 ), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were measured. The epithelial height, number of glands in the uterus, and number of osteoclasts in the femur were histologically quantified, and the expression of proliferating cell nuclear antigen (PCNA) was assessed immunohistochemically. Bone structural parameters, including bone mineral density (BMD), bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular separation (Tb.Sp) were measured using Micro-CT scanning. Results: Treatments of OVX rats with ICS (50 or 100 mg·kg -1 ·d -1 ) produced significant estrogenic effects on the uteruses, including the increases in uterine weight, epithelial height and gland number, as well as in the expression of the cell proliferation marker PCNA. The treatments changed the secretory profile of ovarian hormones and pituitary gonadotropins: serum E 2 level was significantly increased, while serum LH and FSH levels were decreased compared with the vehicle-treated OVX rats. Furthermore, the treatments significantly attenuated the bone loss, increased BMD, BV/TV and Tb.Th and decreased Tb.Sp and the number of osteoclasts. Treatment of OVX rats with the positive control drug E 2 (0.25 mg·kg -1 ·d -1 ) produced similar, but more prominent effects.Conclusion: ICS exhibits moderate estrogenic activities as compared to E 2 in ovariectomized rats, suggesting the potential use of ICS for the treatment of menopausal symptoms and osteoporosis caused by estrogen deficiency.

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Clinical outcomes of a 2-y soy isoflavone supplementation in menopausal women

Abstract: Daily supplementation for 2 y with 80-120 mg soy hypocotyl isoflavones has minimal risk in healthy menopausal women. This trial was registered at clinicaltrials.gov as NCT00665860.

Cited by 64 publications

References 53 publications

Effects of estradiol, estrogen receptor subtype-selective agonists and genistein on glucose metabolism in leptin resistant female Zucker diabetic fatty (ZDF) rats

Effects of estradiol, estrogen receptor subtype-selective agonists and genistein on glucose metabolism in leptin resistant female Zucker diabetic fatty (ZDF) rats

Deconjugation of soy isoflavone glucuronides needed for estrogenic activity

Assessment of the estrogenic activities of chickpea (Cicer arietinum L) sprout isoflavone extract in ovariectomized rats

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