Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med

Azienda Ospedaliera Universitaria Policlinico G. Martino, University of Messina, Messina, Italy.
Annals of internal medicine (Impact Factor: 16.1). 07/2007; 146(12):839-47.
Source: PubMed

ABSTRACT Observational studies and small trials of short duration suggest that the isoflavone phytoestrogen genistein reduces bone loss, but the evidence is not definitive.
To assess the effects of genistein on bone metabolism in osteopenic postmenopausal women.
Randomized, double-blind, placebo-controlled trial.
3 university medical centers in Italy.
389 postmenopausal women with a bone mineral density (BMD) less than 0.795 g/cm2 at the femoral neck and no significant comorbid conditions.
After a 4-week stabilization period during which participants received a low-soy, reduced-fat diet, participants were randomly assigned to receive placebo (n = 191) or 54 mg of genistein (n = 198) daily for 24 months. Both the genistein and placebo tablets contained calcium and vitamin D.
The primary outcome was BMD at the anteroposterior lumbar spine and femoral neck at 24 months. Secondary outcomes were serum levels of bone-specific alkaline phosphatase and insulin-like growth factor I, urinary excretion of pyridinoline and deoxypyridinoline, and endometrial thickness. Data on adverse events were also collected.
At 24 months, BMD had increased in genistein recipients and decreased in placebo recipients at the anteroposterior lumbar spine (change, 0.049 g/cm2 [95% CI, 0.035 to 0.059] vs. -0.053 g/cm2 [CI, -0.058 to -0.035]; difference, 0.10 g/cm2 [CI, 0.08 to 0.12]; P < 0.001) and the femoral neck (change, 0.035 g/cm2 [CI, 0.025 to 0.042] vs. -0.037 g/cm2 [CI, -0.044 to -0.027]; difference, 0.062 g/cm2 [CI, 0.049 to 0.073]; P < 0.001). Genistein statistically significantly decreased urinary excretion of pyridinoline and deoxypyridinoline, increased levels of bone-specific alkaline phosphatase and insulin-like growth factor I, and did not change endometrial thickness compared with placebo. More genistein recipients than placebo recipients experienced gastrointestinal side effects (19% vs. 8%; P = 0.002) and discontinued the study. Limitations: The study did not measure fractures and had limited power to evaluate adverse effects.
Twenty-four months of treatment with genistein has positive effects on BMD in osteopenic postmenopausal women. registration number: NCT00355953.

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Available from: Marco Atteritano, May 17, 2014
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    • "Moreover, some studies showed that the aglycone forms of isoflavones had a faster and more efficient absorption than the glycoside and mixed forms [20] [21]. Weaver et al. reported that genistein and daidzein (the two main components of soy isoflavones) may be resistant to each other [22], and previous intervention studies suggested that isolated genistein or daidzein was more effective in the improvement of bone health than mixed isoflavones [22] [23] [24]. Therefore, the effect of soy foods or isoflavones on diabetes remains inconclusive, and further studies are needed to determine the effects of isolated genistein and daidzein on the risk of diabetes or glycemic control in humans. "
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    ABSTRACT: ScopeThis randomized, double-blind, and placebo-controlled trial evaluated the effect of isolated daidzein and genistein on glycemic control and insulin sensitivity in 165 Chinese women aged 30-70 with impaired glucose regulation (IGR).Methods and resultsParticipants were randomly assigned to one of three groups with a daily dose of 10 g of soy protein plus (i) no addition, (ii) 50 mg of daidzein, or (iii) 50 mg of genistein for 24 wk. Fasting glucose (FG), insulin, and glycosylated hemoglobin (HbA1c), and glucose concentrations at 30, 60, 120, and 180 min and insulin concentrations at 30, 60, and 120 min after an oral 75-g glucose tolerance test were assessed at baseline and at 12 and 24 wk postintervention. a total of 158 and 151 subjects completed the measures at wk 12 and 24, respectively. There were no significant differences in the changes (%) of FG and the 2-h glucose, HbA1c, fasting, and 2-h insulin or the area under the curve of glucose and insulin between the three treatment groups at wk 12 or 24 (all p > 0.05).Conclusion Neither isolated daidzein nor genistein has a significant effect on glycemic control and insulin sensitivity in Chinese women with IGR over a 6-month supplementation period.
    Molecular Nutrition & Food Research 02/2015; 59(2). DOI:10.1002/mnfr.201400390 · 4.91 Impact Factor
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    • "Inositol is a polyol which may be considered a second messenger of insulin [12], and myo-inositol is one of its nine isomers, capable of reducing insulin resistance, blood pressure, and improving lipid profile in a small cohort of postmenopausal women affected by metabolic syndrome [10] [11]. The soy-derived isoflavone genistein acting as a natural selective estrogen receptor modulator (SERM) has a proven efficacy on markers of CVD risk [9] and in reducing bone loss in postmenopausal women [13]. Very recently, genistein has shown to reduce insulin resistance, blood pressure, and homocysteine and it improved lipid profile in a cohort of women with metabolic syndrome [14]. "
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    ABSTRACT: Background and Aim. Cardiovascular risk is increased in women with menopause and metabolic syndrome. Aim of this study was to test the effect of a new supplement formula, combining cocoa polyphenols, myo-inositol, and soy isoflavones, on some biomarkers of cardiovascular risk in postmenopausal women with metabolic syndrome. Methods and Results. A total of 60 women were enrolled and randomly assigned (n = 30 per group) to receive the supplement (NRT: 30 mg of cocoa polyphenols, 80 mg of soy isoflavones, and 2 gr of myo-inositol), or placebo for 6 months. The study protocol included three visits (baseline, 6, and 12 months) for the evaluation of glucose, triglycerides, and HDL-cholesterol (HDL-C), adiponectin, visfatin, resistin, and bone-specific alkaline phosphatase (bone-ALP). At 6 months, a significant difference between NRT and placebo was found for glucose (96 ± 7 versus 108 ± 10 mg/dL), triglycerides (145 ± 14 versus 165 ± 18 mg/dL), visfatin (2.8 ± 0.8 versus 3.7 ± 1.1 ng/mL), resistin (27 ± 7 versus 32 ± 8 µg/L), and b-ALP (19 ± 7 versus 15 ± 5 µg/mL). No difference in HDL-C concentrations nor in adiponectin levels between groups was reported at 6 months. Conclusions. The supplement used in this study improves most of the biomarkers linked to metabolic syndrome. This Trial is registered with NCT01400724.
    International Journal of Endocrinology 08/2014; 2014:653561. DOI:10.1155/2014/653561 · 1.52 Impact Factor
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    • "In this study, 389 osteopenic postmenopausal women participated in the trial for 24 months and a subcohort (138 patients) continued for an additional year. After 36 months, genistein continued to enhance femoral neck and lumbar spine BMD and did not bring any significant adverse effects on breast and uterus (Marini et al., 2008), which was consistent with the previously reports (Morabito et al., 2002; Li and Yu, 2003; Migliaccio and Anderson, 2003; Marini et al., 2007). This long-term clinical trial of genistein indicates that genistein appears to be one of the most effective but safe isoflavone in preserving bone health, although further clinical studies are still needed to make recommendations for its clinical application. "
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    ABSTRACT: Increasingly natural products particularly flavonoids are being explored for their therapeutic potentials in reducing bone loss and maintaining bone health. This article has reviewed previous studies on the two better known flavonoids, genistein and icariin, their structures, functions, action mechanisms, relative potency, and potential application in regulating bone remodeling and preventing bone loss. Genistein, an isoflavone abundant in soy, has dual functions on bone cells, able to inhibit bone resorption activity of osteoclasts and stimulate osteogenic differentiation and maturation of bone marrow stromal progenitor cells (BMSCs) and osteoblasts. Genistein is an estrogen receptor (ER)-selective binding phytoestrogen, with a greater affinity to ERβ. Genistein inhibits tyrosine kinases and inhibits DNA topoisomerases I and II, and may act as an antioxidant. Genistein enhances osteoblastic differentiation and maturation by activation of ER, p38MAPK-Runx2 and NO/cGMP pathways, and it inhibits osteoclast formation and bone resorption through inducing osteoclastogenic inhibitor osteoprotegerin (OPG) and blocking NF-κB signalling. Icariin, a prenylated flavonol glycoside isolated from Epimedium herb, stimulates osteogenic differentiation of BMSCs and inhibits bone resorption activity of osteoclasts. Icariin, whose metabolites include icariside I, icariside II, icaritin and desmethylicaritin, has no estrogenic activity. However, icariin is more potent than genistein in promoting osteogenic differentiation and maturation of osteoblasts. The existence of a prenyl group on C-8 of icariin molecular structure has been suggested to be the reason why icariin is more potent than genistein in osteogenic activity. Thus, the prenylflavonoids may represent a class of flavonoids with a higher osteogenic activity. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc.
    Journal of Cellular Physiology 03/2013; 228(3). DOI:10.1002/jcp.24158 · 3.87 Impact Factor
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