Effects of a new flavonoid and Myo-inositol supplement on some biomarkers of cardiovascular risk in postmenopausal women: a randomized trial.

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.

myo-Inositol supplementation and onset of gestational diabetes mellitus in pregnant women with a family history of type 2 diabetes: a prospective, randomized, placebo-controlled study.

OBJECTIVE: To check the hypothesis that myo-inositol supplementation may reduce gestational diabetes mellitus (GDM) onset in pregnant women with a family history of type 2 diabetes. RESEARCH DESIGN AND METHODS: A 2-year, prospective, randomized, open-label, placebo-controlled study was carried out in pregnant outpatients with a parent with type 2 diabetes who were treated from the end of the first trimester with 2 g myo-inositol plus 200 µg folic acid twice a day (n = 110) and in the placebo group (n = 110), who were only treated with 200 µg folic acid twice a day. The main outcome measure was the incidence of GDM in both groups. Secondary outcome measures were as follows: the incidence of fetal macrosomia (>4,000 g), gestational hypertension, preterm delivery, caesarean section, shoulder dystocia, neonatal hypoglycemia, and neonatal distress respiratory syndrome. GDM diagnosis was performed according to the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommendations. RESULTS: Incidence of GDM was significantly reduced in the myo-inositol group compared with the placebo group: 6 vs. 15.3%, respectively (P = 0.04). In the myo-inositol group, a reduction of GDM risk occurrence was highlighted (odds ratio 0.35). A statistically significant reduction of fetal macrosomia in the myo-inositol group was also highlighted together with a significant reduction in mean fetal weight at delivery. In the other secondary outcome measures, there were no differences between groups. CONCLUSIONS: myo-Inositol supplementation in pregnant women with a family history of type 2 diabetes may reduce GDM incidence and the delivery of macrosomia fetuses.

Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 2-year randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate in a 24-month, prospective, randomized, double-blind, placebo-controlled study whether pure administration of the phytoestrogen genistein (54 mg/d) might reduce the number and severity of hot flushes in postmenopausal women, with no adverse effect on the endometrium and vagina. METHODS: A total of 389 participants met the parent study criteria and were randomly assigned to receive the phytoestrogen genistein (n = 198) or placebo (n = 191). About 40% of participants in both groups did not experience hot flushes, and the evaluation was performed in a subgroup of 236 participants (genistein, n = 119; placebo, n = 117). Reductions from the baseline in the frequency and severity of hot flushes were the principal criteria of efficacy. Endometrial thickness was evaluated by ultrasonography. The maturation value was also used to determine hormonal action on the vaginal cells. RESULTS: There were no significant differences in vasomotor symptoms between groups at the baseline (4.4 +/- 0.33 hot flushes per day in the genistein group and 4.2 +/- 0.35 hot flushes per day in the control group). After 12 months of genistein therapy, there was a significant reduction (-56.4%) in the mean number of hot flushes, with a significant difference compared with the control group. After 24 months, there was no further decrease in the number of hot flushes in both groups. No significant difference was found in mean endometrial thickness and the maturation value score between the two groups, either at the baseline or after 24 months. CONCLUSIONS: The phytoestrogen genistein has been shown to be effective on vasomotor symptoms without an adverse effect on the endometrium and vagina, but after the first year, there was no further improvement in the decrease in hot flushes.

Breast safety and efficacy of genistein aglycone for postmenopausal bone loss: a follow-up study.

CONTEXT: Genistein aglycone improves bone metabolism in women. However, questions about the long-term safety of genistein on breast as well as its continued efficacy still remain. OBJECTIVE: We assessed the continued safety profile of genistein aglycone on breast and endometrium and its effects on bone after 3 yr of therapy. DESIGN: The parent study was a randomized, double-blind, placebo-controlled trial involving 389 osteopenic, postmenopausal women for 24-months. Subsequently, a subcohort (138 patients) continued therapy for an additional year. PATIENTS AND INTERVENTIONS: Participants received 54 mg of genistein aglycone daily (n = 71) or placebo (n = 67). Both treatment arms received calcium and vitamin D(3) in therapeutic doses. MAIN OUTCOMES: Mammographic density was assessed at baseline, 24 and 36 months by visual classification scale and digitized quantification. BRCA1 and BRCA2, sister chromatid exchange, and endometrial thickness were also evaluated. Lumbar spine and femoral neck bone mineral density were also assessed. Secondary outcomes were biochemical levels of bone markers. RESULTS: After 36 months, genistein did not significantly change mammographic breast density or endometrial thickness, BRCA1 and BRCA2 expression was preserved, whereas sister chromatid exchange was reduced compared with placebo. Bone mineral density increases were greater with genistein for both femoral neck and lumbar spine compared to placebo. Genistein also significantly reduced pyridinoline, as well as serum carboxy-terminal cross-linking telopeptide and soluble receptor activator of NF-kappaB ligand while increasing bone-specific alkaline phosphatase, IGF-I, and osteoprotegerin levels. There were no differences in discomfort or adverse events between groups. CONCLUSIONS: After 3 yr of treatment, genistein exhibited a promising safety profile with positive effects on bone formation in a cohort of osteopenic, postmenopausal women.

Effects of phytoestrogen genistein on cytogenetic biomarkers in postmenopausal women: 1 year randomized, placebo-controlled study.

To evaluate in a twelve-month, randomized placebo-controlled study whether pure administration of phytoestrogen genistein (54 mg/day) might reduce cytogenetic biomarkers in peripheral lymphocytes of postmenopausal women. A total of 57 postmenopausal women met the criteria and were randomly assigned to receive phytoestrogen genistein (n = 30) or placebo (n = 27). There was no significant difference in age, length of time since menopause or body mass index between the two groups. After one year, plasma genistein level was 0.14 +/- 0.01 micromol/L in the control group and 0.72 +/- 0.08 micromol/L in the genistein group (P < 0.0001). At baseline, sister chromatid exchange rate was 4.97 +/- 2.17 in the control group and 4.96 +/- 1.83 in the genistein group (P = 0.89). After one year, sister chromatid exchange rate was 4.96 +/- 2.16 in the control group and 3.98 +/- 1.14 in the genistein group (P < 0.05). High frequency cells count was 3% in the genistein group and 5% in the control group (P < 0.05) at the end of the study. Chromosomal aberration frequency was 5.55% in the control group at time 0 and 5.75% in the genistein group; after one year, the figures were 5.86% in the control group and 4.5% in the genistein group (P < 0.05). After one year, there was a negative relationship between sister chromatid exchange rate and plasma levels (r = - 0.43; P < 0.05) in the genistein group. Phytoestrogen genistein has been shown in postmenopausal women to be effective in the reduction of cytogenetic biomarkers. The protective effect on genomic damage appears to be a particularly promising tool in reducing the risk of cancer.

OPG and sRANKL serum concentrations in osteopenic, postmenopausal women after 2-year genistein administration.

INTRODUCTION: RANKL and its decoy receptor osteoprotegerin (OPG) constitute a complex physiological mediator system involved in the regulation of bone resorption and may be responsible for the homeostatic mechanism of normal bone remodeling. Genistein, an isoflavone representing 1-5% of total phytoestrogen content in soybean products, may positively regulate cellular bone metabolism, but its mechanism of action on bone is not yet fully understood. MATERIALS AND METHODS: We studied the serum levels of both soluble RANKL (sRANKL) and OPG and the sRANKL/OPG ratio in 389 postmenopausal women (age, 49-67 yr) with a femoral neck BMD <0.795 g/cm(2) and no significant comorbid conditions after 24-mo therapy with genistein, (n = 198; 54 mg/d) or placebo (n = 191). Both intervention and placebo contained calcium and vitamin D(3). All patients received dietary instruction in an isocaloric fat-reduced diet. RESULTS: In comparison with placebo, sRANKL level was lower (p < 0.001 versus placebo) and OPG higher in genistein recipients (p < 0.001 versus placebo) at 1 and 2 yr, respectively. Moreover, at the end of 24 mo, genistein produced a significant reduction in the sRANKL/OPG ratio compared with placebo (genistein = -0.021, 95% CI, -0.020 to -0.022; placebo = +0.004, 95% CI, 0.003-0.005; difference = -0.020, 95% CI, -0.015 to -0.025, p < 0.001). CONCLUSIONS: Our findings suggest that genistein plus calcium and vitamin D(3) as part of a healthy diet is able to positively modulate bone turnover in a cohort of osteopenic, postmenopausal women and improve sRANKL-OPG balance after 24 mo of treatment.

Effects of the phytoestrogen genistein on some predictors of cardiovascular risk in osteopenic, postmenopausal women: a two-year randomized, double-blind, placebo-controlled study.

CONTEXT: Genistein, a soy isoflavone, has received wide attention over the last few years because of its potential preventive role for cardiovascular disease. OBJECTIVE: Our objective was to assess the effects of genistein administration (54 mg/d) on some predictors of cardiovascular risk in osteopenic, postmenopausal women. DESIGN AND SETTING: We conducted a randomized, double-blind, placebo-controlled trial at three Italian university medical centers. INTERVENTION: 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). OUTCOME MEASURES: 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. RESULTS: 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%)]. CONCLUSIONS: 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.

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

BACKGROUND: Observational studies and small trials of short duration suggest that the isoflavone phytoestrogen genistein reduces bone loss, but the evidence is not definitive. OBJECTIVE: To assess the effects of genistein on bone metabolism in osteopenic postmenopausal women. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: 3 university medical centers in Italy. PATIENTS: 389 postmenopausal women with a bone mineral density (BMD) less than 0.795 g/cm2 at the femoral neck and no significant comorbid conditions. INTERVENTION: 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. MEASUREMENTS: 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. RESULTS: 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. CONCLUSION: Twenty-four months of treatment with genistein has positive effects on BMD in osteopenic postmenopausal women. ClinicalTrials.gov registration number: NCT00355953.

Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 1-year randomized, double-blind, placebo-controlled study.

OBJECTIVE: To evaluate in a 12-month, prospective, randomized, double-blind, placebo-controlled study whether pure administration of the phytoestrogen genistein (54 mg/d) might reduce the number and severity of hot flushes in postmenopausal women with no adverse effect on the endometrium. DESIGN: A total of 389 participants met the main study criteria and were randomly assigned to receive the phytoestrogen genistein (n=198) or placebo (n=191). About 40% of participants in both groups did not suffer from hot flushes, and the evaluation was performed in a subgroup of 247 participants (genistein, n=125; placebo, n=122). Reductions from baseline in the frequency and severity of hot flushes were the principal criteria of efficacy. Endometrial thickness was evaluated by ultrasonography. The maturation value was also used to determine hormonal action on the vaginal cells. RESULTS: There were no significant differences in age, time since menopause, body mass index, and vasomotor symptoms between groups at baseline (4.4 +/- 0.33 hot flushes per day in the genistein group and 4.2 +/- 0.35 hot flushes per day in the control group). The effect was already evident in the first month and reached its peak after 12 months of genistein therapy (-56.4% reduction in the mean number of hot flushes). Furthermore, there was a significant difference between the two groups at each evaluation time (1, 3, 6, and 12 months). No significant difference was found in mean endometrial thickness and maturation value score between the two groups, either at baseline or after 12 months. CONCLUSIONS: The phytoestrogen genistein has been shown to be effective on vasomotor symptoms without an adverse effect on endometrium.