Effects of the Phytoestrogen Genistein on Some Predictors of Cardiovascular Risk in Osteopenic, Postmenopausal Women: A Two-Year Randomized, Double-Blind, Placebo-Controlled Study

Department of Internal Medicine, University of Messina, Italy.
Journal of Clinical Endocrinology & Metabolism (Impact Factor: 6.21). 09/2007; 92(8):3068-75. DOI: 10.1210/jc.2006-2295
Source: PubMed


Genistein, a soy isoflavone, has received wide attention over the last few years because of its potential preventive role for cardiovascular disease.
Our objective was to assess the effects of genistein administration (54 mg/d) on some predictors of cardiovascular risk in osteopenic, postmenopausal women.
We conducted a randomized, double-blind, placebo-controlled trial at three Italian university medical centers.
After a 4-wk stabilization on a standard isocaloric, fat-reduced diet, participants were randomly assigned to receive genistein (n = 198) or placebo (n = 191) daily for 24 months. Both intervention and placebo contained calcium and vitamin D(3).
Blood lipid profiles, fasting glucose and insulin, homeostasis model assessment for insulin resistance, fibrinogen, soluble intercellular adhesion molecule-1, soluble vascular cellular adhesion molecule-1, F2-isoprostanes, and osteoprotegerin at baseline and after 12 and 24 months of treatment were measured.
Compared with placebo, genistein significantly reduced fasting glucose and insulin as well as homeostasis model assessment for insulin resistance after both 12 and 24 months of treatment. By contrast, genistein administration did not affect blood lipid levels although fibrinogen, F2-isoprostanes, soluble intercellular adhesion molecule-1, and soluble vascular cellular adhesion molecule-1 decreased significantly compared with placebo after 24 months. Serum osteoprotegerin was higher in the genistein group compared with placebo. At 24 months, the genistein group showed no change in endometrial thickness compared with placebo. Most treatment-related adverse events were moderate and composed of gastrointestinal side effects [genistein, n = 37 (19%); placebo, n = 15 (8%)].
These results suggest that 54 mg genistein plus calcium, vitamin D(3), and a healthy diet was associated with favorable effects on both glycemic control and some cardiovascular risk markers in a cohort of osteopenic, postmenopausal women.

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Available from: Marco Atteritano
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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.
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    • "The frequent consumption of soy products, which are rich in isoflavones, has been shown to be related with a lower prevalence of breast cancer [12]. In addition to providing estrogen-like activity, the high intake of dietary isoflavone also reduced the risks of developing metabolic disorders including cardiovascular diseases, diabetes, and obesity compared to the high intake of animal products [13-16]. In particular, postmenopausal women with type 2 diabetes who received dietary isoflavone supplementation showed significantly reduced fasting insulin levels, indicating improvement in their insulin resistance [17]. "
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    • "Markers of CVD risk were analyzed as previously described (Atteritano et al., 2007; Marini et al., 2010). In brief, both fasting glucose and insulin were measured in serum collected after an overnight fast using routine methods (normal range 65–110 mg/dl and 3–35 μUI/ml, respectively). "
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