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: 17.81). 07/2007; 146(12):839-47.
Source: PubMed


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. ClinicalTrials.gov 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 · 4.60 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 · 1.95 Impact Factor
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    • "Furthermore, because genistein has been demonstrated to act as a bone-sparing and antiresorptive agent, it has been considered to be a phytoestrogen [15]. This preventive action on bone loss has been reported in various animal and epidemiological studies [16,17]. According to previous in vitro studies, genistein stimulates osteoblastic differentiation and mineralization and inhibits osteoclast formation from pre-osteoclast cells and the bone resorption activity of osteoclasts [18,19]. "
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    ABSTRACT: Genistein, a phytoestrogen, has been demonstrated to have a bone-sparing and antiresorptive effect. Genistein can inhibit the osteoclast formation of receptor activator of nuclear factor-κB ligand (RANKL)-induced RAW 264.7 cells by preventing the translocation of nuclear factor-κB (NF-κB), a redox-sensitive factor, to the nucleus. Therefore, the suppressive effect of genistein on the reactive oxygen species (ROS) level during osteoclast differentiation and the mechanism associated with the control of ROS levels by genistein were investigated. The cellular antioxidant capacity and inhibitory effect of genistein were confirmed. The translation and activation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 1 (Nox1), as well as the disruption of the mitochondrial electron transport chain system were obviously suppressed by genistein in a dose-dependent manner. The induction of phase II antioxidant enzymes, such as superoxide dismutase 1 (SOD1) and heme oxygenase-1 (HO-1), was enhanced by genistein. In addition, the translational induction of nuclear factor erythroid 2-related factor 2 (Nrf2) was notably increased by genistein. These results provide that the inhibitory effects of genistein on RANKL-stimulated osteoclast differentiation is likely to be attributed to the control of ROS generation through suppressing the translation and activation of Nox1 and the disruption of the mitochondrial electron transport chain system, as well as ROS scavenging through the Nrf2-mediated induction of phase II antioxidant enzymes, such as SOD1 and HO-1.
    International Journal of Molecular Sciences 06/2014; 15(6):10605-10621. DOI:10.3390/ijms150610605 · 2.86 Impact Factor
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