Effects Of Soy Isoflavones Research Articles

The effect of soy-derived isoflavones over hot flushes, menopausal symptoms and mood in climacteric women with increased body mass index

Background. Risk-benefit issues raised after the WHI have significantly increased the use of alternative treatments for the menopause. Despite this, data regarding the effect of soy isoflavones over mood and menopausal symptoms in high risk populations is still lacking.Objective. To evaluate the effect of soy derived isoflavones over hot flushes, menopausal symptoms and mood in climacteric women with increased body mass index (BMI).Methods. Fifty symptomatic climacteric women aged 40 to 59 with increased BMI (≥25) were recruited to receive oral 100 mg/day of soy derived isoflavones (Climasoy®) for 3 months. Hot flushes (frequency/intensity), menopausal symptoms (Menopause Rating Scale [MRS]) and mood (Hamilton Depressive Rating Scale [HDRS]) were evaluated at baseline and at 90 days.Results. A total of 45 women completed the study. After 3 months of soy isoflavone supplementation hot flushes significantly decreased in percentage, number and severity (100% to 31.1%; 3.9 ± 2.3 to 0.4 ± 0.8 and 2.6 ± 0.9 to 0.4 ± 0.8, respectively, p < 0.001). MRS scores (total and for subscales) reflecting general menopausal symptoms also significantly decreased compared to baseline. Regarding mood, after three months total HDRS scores and the rate of women presenting depressed mood (scores ≥ 8) significantly decreased (16.3 ± 5.4 to 6.9 ± 5.2 and 93.3% to 28.9%, respectively, p < 0.05). There was no effect on blood pressure levels or BMI values after treatment.Conclusion. In this high risk climacteric population, soy derived isoflavone treatment improved mood as well as vasomotor and general menopausal symptoms. More research is required to determine if the positive effect over mood is a direct or an indirect one through hot flush alleviation.

Effects of soy isoflavone supplements on bone turnover markers in menopausal women: Systematic review and meta-analysis of randomized controlled trials

Introduction Effects of soy isoflavone supplements on bone turnover markers remain unclear. This up-to-date systematic review and meta-analysis of randomized controlled trials (RCTs) was performed primarily to more completely and precisely clarify the effects on urinary deoxypyridinoline (DPD) and serum bone alkaline phosphatase (BAP) and secondarily to evaluate the effects on other bone turnover markers, compared with placebo in menopausal women. Methods PubMed, CENTRAL, ICHUSHI, and CNKI were searched in June 2009 for relevant studies of RCTs. Data on study design, participants, interventions, and outcomes were extracted and methodological quality of each included trial was assessed. Results From 3740 identified relevant articles, 10 (887 participants), 10 (1210 participants), and 8 (380 participants) RCTs were selected for meta-analysis of effects on DPD, BAP, and serum osteocalcin (OC), respectively, using Review Manager 5.0.22. Daily ingestion of an average 56 mg soy isoflavones (aglycone equivalents) for 10 weeks to 12 months significantly decreased DPD by 14.1% (95% CI: − 26.8% to − 1.5%; P = 0.03) compared to baseline (heterogeneity: P < 0.00001; I 2 = 93%; random effects model). The overall effect of soy isoflavones on DPD compared with placebo was a significant decrease of − 18.0% (95% CI: − 28.4% to − 7.7%, P = 0.0007; heterogeneity: P = 0.0001; I 2 = 73%; random effects model). Subgroup analyses and meta-regressions revealed that isoflavone dose and intervention duration did not significantly relate to the variable effects on DPD. Daily supplementation of about 84 mg and 73 mg of soy isoflavones for up to 12 months insignificantly increased BAP by 8.0% (95% CI: − 4.2% to 20.2%, P = 0.20; heterogeneity: P < 0.00001; I 2 = 98%) and OC by 10.3% (95% CI: − 3.1% to 23.7%, P = 0.13; heterogeneity: P = 0.002; I 2 = 69%) compared with placebo (random effects model), respectively. Conclusions Soy isoflavone supplements moderately decreased the bone resorption marker DPD, but did not affect bone formation markers BAP and OC in menopausal women. The effects varied between studies, and further studies are needed to address factors relating to the observed effects of soy isoflavones on DPD and to verify effects on other bone turnover markers.

Abstract 912: Soy isoflavone intake, MDM2 gene polymorphism and breast cancer risk among Chinese women in Singapore

Abstract Epidemiologic studies among populations that consume moderate to high amount of soy have shown that soy isoflavones may reduce breast cancer risk, and the chemopreventive effects are postulated to be related to the anti-estrogenic properties of soy isoflavones. Recently, experimental studies have revealed that dietary isoflavones may also down-regulate the expression of the MDM2 oncogene, and the inhibition of the expression of the MDM2 oncoprotein has in turn been associated with antitumor activities in breast cancer models. Furthermore, a polymorphism in the promoter region of MDM2 SNP309 (T&amp;gt;G change at nucleotide 309 in the first intron; rs2279744) leads to increased expression of the oncogene and has been associated with earlier onset of breast cancer. We have previously shown that postmenopausal women with a higher than median intake of soy have a reduced risk of breast cancer compared with those with a lower intake. If down-regulation of the MDM2 oncogene is one of the mechanistic pathways for the chemopreventive effects of soy isoflavones in breast cancer, we postulate that the protective effect of soy isoflavones on breast cancer will be stronger in those possessing the high-activity MDM2 genotype. To confirm this hypothesis, we conducted a nested case-control study among 281 incident, postmenopausal breast cancer cases and 462 postmenopausal control subjects within the Singapore Chinese Health Study Cohort. Overall, there was no significant association between MDM2 gene polymorphism and breast cancer risk. Postmenopausal women who had a higher than median intake of soy had a reduced risk of breast cancer [odds ratio (OR), 0.76; 95% confidence interval (CI), 0.56-1.03]. This inverse association was principally noted among women homozygous for the high activity MDM2 allele (GG genotype). There was a statistically significant, roughly 50% reduction in breast cancer risk between above versus below median level of soy consumption in this subgroup of women (OR, 0.52; 95% confidence interval, 0.28-0.98). On the other hand, a much weaker, and statistically nonsignificant association was noted among women possessing the lower-activity MDM2 genotypes (OR, 0.86, 95% CI, 0.59-1.24). Our findings suggest that the ability of soy isoflavones to down-regulate the MDM2 oncoprotein may be one etiologic mechanism through which the intake of soy is associated with breast cancer protection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 912.

Abstract 2886: Differential effects of soy isoflavones on Akt and vimentin expression in human prostate cancer cells and mouse xenograft tumors

Abstract Studies have reported that soy isoflavones inhibit growth in a number of carcinoma cell lines. The overexpression of Akt, a prosurvival pathway, and vimentin, a mesenchymal marker, in urological carcinomas has been associated with tumor progression and poor prognosis. Our study investigated the effects of a soy isoflavone concentrate (ISF) on the expression of Akt and vimentin in a) cultured human prostate cancer cells and b) xenograft tumors in mice. METHODS: Human prostate cancer PC-3 cells, which are androgen-insensitive and do not express p53 or PTEN, were grown in culture. Hypoxia exposure was at 1% oxygen vs room air for 48 hours. Akt, phosphorylated-Akt (phosAkt), carbonic anhydrase IX (CAIX) and vimentin expression in cells was measured by Western immunoblot analysis. Male nude mice on a soy-free control diet were injected with PC-3 cells into the hind flank. On day 5, half the mice were placed on a diet containing 0.5% soy isoflavone concentrate (ISF). Tumor size was monitored biweekly. Resected tumors were fixed in formalin and paraffin-embedded. Immunohistochemical (IHC) analysis of tumors used antibodies against PCNA, TUNEL, CAIX, Akt, phosAkt, and vimentin. RESULTS: In culture, PC-3 cells constitutively express high levels of Akt and vimentin proteins, which is not altered by hypoxia; in contrast, phosAkt and CAIX proteins are highly expressed only under hypoxic conditions. ISF caused dose-dependent inhibition of DNA synthesis and cell viability without evidence of apoptotic cell death. In culture, ISF decreased the constitutive expression of vimentin, as well as the hypoxia-mediated induction of pAkt and CAIX. In mice, the soy ISF diet significantly inhibited xenograft tumor growth. At 39 days, median tumor size was 862 mm3 in soy-free controls, and 520 mm3 in mice on the ISF diet (p=0.02). IHC analysis of tumors shows that ISF decreased the expression of nuclear PCNA, while TUNEL positive apoptotic cells was increased 4-fold. The ISF diet markedly suppressed levels of total Akt and activated phosAkt. In contrast, staining for CAIX protein was not different in control vs ISF-tumors. Vimentin was clearly expressed in PC-3 tumors and was increased by exposure to irradiation (IR, 2Gy). Interestingly, ISF suppressed IR-induced vimentin expression. Thus, soy ISF treatment inhibited PC-3 cell proliferation both in vitro and in vivo, but different mechanisms are involved in the regulation of expression of the dominant Akt prosurvival signaling pathway, as well as a major mesenchymal marker vimentin. CONCLUSIONS: Together, data indicate that a soy ISF diet strongly inhibits the growth of prostate xenograft tumors which is mediated by differential effects on hypoxia-regulated genes in the tumor microenvironment. (Supported by NIH CA102386 and the Maren Foundation) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2886.

Abstract 1766: Effect of soy isoflavones on prostate cancer cell cycle regulation and apoptosis

Abstract Background: As many as one-third of all cancer deaths in the United States can be linked to diet. Significant epidemiological evidence suggests a role of a variety of dietary factors including the amount of dietary soy. In Asian countries where the average diet consists of 10 times the amount of soy products consumed compared to the average American diet there is a significantly lower incidence of prostate and breast cancer. Further supporting a dietary and environmental influence is the finding that Asian immigrants who have moved to the United States and adopt a Western diet have a prostate cancer incidence that approaches U.S. born males. These findings have been supported by other studies and, again, suggest that environmental factors such as dietary soy intake may be responsible for these differences in geographic incidence. Although there is this preclinical and epidemiological data suggesting that soy isoflavones decrease the risk of developing prostate cancer (PC), there is limited information regarding the in vivo effects of soy supplementation on human PC and benign prostate tissue. Methods: The primary objective of this study was to evaluate the molecular effects of soy isoflavones on human PC cell cycle regulation and apoptosis. Patients with histologically confirmed PC who had chosen radical prostatectomy (RRP) for treatment (without any other primary therapy) were randomized in double blind fashion to receive either soy supplementation or placebo. The patients in the treatment group received 4 capsules of a commercially available pure soy tablet (240 mg of total isoflavones) from time of enrollment until RRP. At the time of surgery, fresh tissue was collected from the tumor and adjacent normal tissue. Using these samples, we evaluated the status of genes essential for cell cycle regulation and apoptosis using cDNA microarray analyses. Results: In this preliminary analysis, multiple cell cycle and apoptotic genes were either down regulated or up regulated in the treatment samples compared to the placebo treated samples, including BAX, BCL-2, and Caspase-7. This effect was present in both tumor and adjacent normal tissue. Using samples from an additional four patients, we then further characterized these changes in gene expression using Western Blots analysis. Cleaved caspase-7 was up regulated in soy treated tumor and adjacent normal samples when compared to placebo, suggesting that soy mediates apoptosis though Caspace-7. The expression of BCL2L1 was down regulated in the treated compared to placebo tissue with this change being most marked in the adjacent normal samples. Conclusion: In total, our results suggest that soy isoflavones may exert a prostate cancer protective effect via a beneficial effect on cell cycle regulation and apoptosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1766.

Soy isoflavones increase bone mineral density without altering markers of whole body vitamin D or calcium metabolism in mice

The soy isoflavone genistein enhances the biological activity of the vitamin D (VD) metabolite 1,25 dihydroxyvitamin D (1,25D) in cultured cells by inhibiting CYP24‐mediated degradation of the hormone. We examined if similar effects can be recapitulated in vivo to improve calcium and bone metabolism. Weanling male B6D2F1 mice were fed AIN‐93G diets containing 50 or 400 IU VD with, or without, Novasoy® 400 soy isoflavone concentrate (added to provide 250 mg genistein/kg diet) until 13 weeks of age. Bone mineral density (BMD) was measured by DEXA. Serum VD metabolites were measured by RIA. Gene expression in duodenum and kidney was measured by RT‐PCR. Higher dietary VD intake increased serum 25 hydroxyvitamin D (25D) from levels viewed as adequate (61 ± 6 nM) to optimal (164 ± 10 nM) for human health but this had no impact on either BMD or molecular indices of calcium metabolism. In contrast, isoflavones increased both serum 25D and femur BMD by 15% (p &lt; 0.01). However, neither serum 1,25D nor tissue gene expression (e.g. duodenal calbindin D9K, TRPV6; renal calbindin D9K or D28K, TRPV5) was influenced by isoflavones. Our data show that the beneficial effect of soy isoflavones on bone that we observed is independent of their ability to modulate whole body VD or calcium metabolism and suggest a direct effect of isoflavones on bone formation or turnover. We thank ADM for Novasoy® 400. Funding: Purdue‐UAB Botanicals Center Pilot Grant.Grant Funding Source: Purdue‐UAB Botanicals Center Pilot Grant

Soy isoflavones for three years exert modest effects on pQCT bone measures in postmenopausal women

We examined the effect of soy isoflavones on bone density and strength in healthy postmenopausal women (45.8–65.0 y). Peripheral quantitative computed tomography (pQCT) measured 3 y change in cortical bone mineral density (CtBMD), cortical thickness (CtThk), periosteal circumference (PC), endosteal circumference (EC), and strength‐strain index (SSI) at the 1/3 midshaft femur (N=165) and trabecular density (TbBMD), PC, and SSI at the 4% distal tibia (N=162) in response to soy protein‐extracted isoflavones (120 or 80 mg/d) or placebo. We report no treatment effect for femur CtThk, PC, or EC, or tibia PC. The 120 mg/d dose protected TbBMD, but high urinary phosphorus (UrP) (p&lt;0.05) lessened this effect. High UrP negatively affected tibia SSI (p&lt;0.05) in the 120 mg/d group. Also, the 120 mg/d dose protected femur CtBMD as time since last menstrual period increased (p&lt;0.01) and the 80 mg/d dose protected femur SSI as bone turnover increased (p&lt;0.05). Hence, soy isoflavones may exert a modest protective effect on pQCT measured bone parameters in postmenopausal women, but high UrP lessened this potential benefit. Supported by NIAMS/NIH (AR046922); NWRC, ISU; USDA/ARS, WHNRC; Clinical &amp; Translational Science Center, CRC, UCD (1M01RR19975‐01); National Center for Medical Research (UL1 RR024146).

Combination of Genistin and Fructooligosaccharides Prevents Bone Loss in Ovarian Hormone Deficiency

We have reported that soy isoflavones are capable of preventing loss of bone mineral density (BMD) in rats due to ovariectomy. The intestinal microflora is important in rendering soy isoflavones bioavailability by facilitating their conversion to equol. Hence, substances that can modulate the intestinal microflora could affect the bioavailability of isoflavones. The purpose of this study was to examine whether combination of genistin and fructooligosaccharides (FOS), a prebiotic, can enhance the effects of soy isoflavones on bone in ovariectomized (OVX) female rats. Forty-eight 90-day-old female Sprague-Dawley rats were either sham-operated (Sham; one group) or Ovx (three groups) and were placed on dietary treatment for 50 days. The Sham and one Ovx group received a control diet, and the remaining Ovx groups received genistin-rich isoflavones diet (Ovx+G) or genistin-rich isoflavones and FOS diet (Ovx+G+FOS). After 50 days, blood and bone specimens were collected for analysis. The genistin-rich isoflavones diet was able to significantly increase the whole-body, right femur, and fourth lumbar BMD by 1.6%, 1.48%, and 1.3%, respectively in comparison with the Ovx control. The combination of genistin-rich isoflavones diet and 5% FOS further increased whole-body, right femur, and fourth lumbar BMD more compared to the genistin-rich isoflavones diet. Our findings suggest that although a genistin-rich isoflavones diet can increase the BMD in rats with Ovx-induced bone loss, combination of genistin-rich isoflavones and FOS had greater effect in preventing bone loss in this rat model.

Combined inhibitory effects of soy isoflavones and curcumin on the production of prostate‐specific antigen

Sustained chronic inflammation in the prostate promotes prostate carcinogenesis. Since an elevated level of prostate-specific antigen (PSA) per se reflects the presence of inflammation in the prostate, intervention to improve the PSA value might potentially have beneficial effects for the prevention of the development of prostate cancer. Isoflavones and curcumin have anti-inflammatory and anti-oxidant properties. We examined the biological effects of soy isoflavones and curcumin on LNCaP cells. After that, we conducted a clinical trial for men who received prostate biopsies, but were not found to have prostate cancer, to evaluate the effects of soy isoflavones and curcumin on serum PSA levels. The expression of androgen receptor and PSA were examined in LNCaP cells before and after treatment of isoflavones and/or curcumin. Eighty-five participants were randomized to take a supplement containing isoflavones and curcumin or placebo daily in a double-blind study. Subjects were subdivided by the cut-off of their baseline PSA value at 10 microg/ml. We evaluated values of PSA before and 6 months after treatment. The production of PSA were markedly decreased by the combined treatment of isoflavones and curcumin in prostate cancer cell line, LNCaP. The expression of the androgen receptor was also suppressed by the treatment. In clinical trials, PSA levels decreased in the patients group with PSA >or= 10 treated with supplement containing isoflavones and curcumin (P = 0.01). Our results indicated that isoflavones and curcumin could modulate serum PSA levels. Curcumin presumably synergizes with isoflavones to suppress PSA production in prostate cells through the anti-androgen effects.

Design and baseline characteristics of the Soy Phytoestrogens As Replacement Estrogen (SPARE) study — A clinical trial of the effects of soy isoflavones in menopausal women

Following the results of the Women's Health Initiative, many women now decline estrogen replacement at the time of menopause and seek natural remedies that would treat menopausal symptoms and prevent bone loss and other long-term consequences of estrogen deficiency, but without adverse effects on the breast, uterus, and cardiovascular system. The results of most soy studies in this population have had limitations because of poor design, small sample size, or short duration. This report describes the study rationale, design, and procedures of the Soy Phytoestrogens As Replacement Estrogen (SPARE) study, which was designed to determine the efficacy of soy isoflavones in preventing spinal bone loss and menopausal symptoms in the initial years of menopause. Women ages 45 to 60 without osteoporosis and within 5 years from menopause were randomized to receive soy isoflavones 200 mg daily or placebo for 2 years. Participants have yearly measurements of spine and hip bone density, urinary phytoestrogens, and serum lipids, thyroid stimulating hormone, and estradiol. Menopausal symptoms, mood changes, depression, and quality of life are assessed annually. The SPARE study recruited 283 women, 66.1% were Hispanic white. With a large cohort, long duration, and large isoflavone dose, this trial will provide important, relevant, and currently unavailable information on the benefits of purified soy isoflavones in the prevention of bone loss and menopausal symptoms in the first 5 years of menopause. Given the high proportion of Hispanics participating in the study, the results of this trial will also be applicable to this minority group.

INTERVENSI ISOFLAVON KEDELAI TIDAK BERPENGARUH TERHADAP STATUS INFLAMASI DAN IMUNITAS PADA REMAJA DENGAN KEGEMUKAN

&lt;p class="MsoNormal" style="margin: 0cm 12.8pt .0001pt 14.2pt; text-align: justify; text-indent: 21.8pt;"&gt;&lt;span style="font-size: 10pt;"&gt;Overweight/obesity is a condition that has been proven to be interrelated with chronic inflammation and compromised immune system due to disregulation of adipocytokine. The aim of the present study was to evaluate the effect of soy isoflavone on the markers of inflammation and immunity of overweight or obese teenagers. Eighteen overweight or obese teenagers, 9 boys and 9 girls each sex were randomized to one of three intervention groups; 0 ml, 150 ml and 300 ml soy milk, equal to 0 g, 25 g and 50 mg isoflavone everyday for 30 days. The data collected were food consumption, plasma isoflavone concentration, plasma IL6 as indicator of inflammation, and lymphocyte and NK cell count as indicator of immunity. The study showed that nutrient intake of samples were still relatively low. The soy milk intervention significantly increased plasma isoflavone concentration, but not significantly had contribution to the plasma IL6 concentration and lymphocyte and NK cell count. Several kind of food consumed by samples had contribution to the plasma isoflavone concentration, and lymphocyte count. Based on the results, it was suggested that soy isoflavone intervention does not affect the inflammation status and immunity of overweight/obese teenagers.&lt;/span&gt;&lt;/p&gt;

Soy Isoflavone and Its Effect to Regulate Hypothalamus and Peripheral Orexigenic Gene Expression in Ovariectomized Rats Fed on A High-Fat Diet

To explore the effect of soy isoflavone on obesity in the light of hypothalamus and peripheral orexigenic gene regulation. Fifty-four female rats were randomly assigned to 6 groups: one sham-operated group (SHAM), one ovariectomized (OVX) control group, three OVX groups fed with 400 ppm (L-SI), 1200 ppm (M-SI) and 3600 ppm (H-SI) isoflavone respectively, and one OVX group receiving 0.45 ppm diethylstilbestrol (EC). All rats were allowed to take high-fat diet for 4 weeks. Some neuropeptides were measured by RT-PCR. These neuropeptides included NPY, pro-opiomelanocortin (POMC), cocaine and amphetamine regulated transcript (CART), orexin, melanin-concentrating hormone (MCH), melanin-concentrating hormone precursor (P-MCH), ghrelin, and leptin. Compared with the OVX control group, the body weight and food intake in the H-SI group were reduced significantly and there was a significant dose-dependent manner in the 3 isoflavone groups. The results of RT-PCR showed that the NPY level in the 3 isoflavone groups was significantly increased and the POMC/CART gene expression decreased significantly in rats' hypothalamus compared with that in the OVX control group. However, the expression of orexin, MCH and P-MCH had no change. The peripheral grelin mRNA expression was higher in the 3 isoflavone groups, while leptin gene expression in the fat was not consistent. This research showed that isoflavone could prevent obesity induced by high-fat diet and ovariectomy through regulating hypothalamus and peripheral orexigenic gene expressions associated with food intake.

Estrogen Receptor-β Mediates the Inhibition of DLD-1 Human Colon Adenocarcinoma Cells by Soy Isoflavones

To understand the relationship between the role of soy isoflavones and estrogen receptor (ER)-β in colon tumorigenesis, we investigated the cellular effects of soy isoflavones (composed of genistein, daidzein, and glycitein) in DLD-1 human colon adenocarcinoma cells with or without ER-β gene silencing by RNA interference (RNAi). Soy isoflavones decreased the expression of proliferating cell nuclear antigen (PCNA), extracellular signal-regulated kinase (ERK)-1/2, AKT, and nuclear factor (NF)-κB. Soy isoflavones dose-dependently caused G2/M cell cycle arrest and downregulated the expression of cyclin A. This was associated with inhibition of cyclin dependent kinase (CDK)-4 and up-regulation of its inhibitor p21cip1 expressions. ER-β gene silencing lowered soy isoflavone-mediated suppression of cell viability and proliferation. ERK-1/2 and AKT expressions were unaltered and NF-κB was modestly upregulated by soy isoflavones after transient knockdown of ER-β expression. Soy isoflavone-mediated arrest of cells at G2/M phase and upregulation of p21cip1 expression were not observed when ER-β gene was silenced. These findings suggest that maintaining the expression of ER-β is crucial in mediating the growth-suppressive effects of soy isoflavones against colon tumors. Thus upregulation of ER-β status by specific food-borne ER-ligands such as soy isoflavones could potentially be a dietary prevention or therapeutic strategy for colon cancer.

A Phase IIb Trial of Soy Isoflavone Supplementation To Decrease Breast Cell Proliferation in High Risk Women.

Abstract Background: epidemiologic data suggest that consumption of soy isoflavones confers protection against the development of breast cancer. Some recent animal data have conflicted with this. We conducted a Phase IIB trial of soy isoflavone supplementation with the goal of examining the effect of supplementation on breast cell proliferation in healthy women at high risk for breast cancer.Methods: 150 women with an elevated breast cancer risk estimate (Gail or Claus), or a prior history of completely treated unilateral breast cancer, were randomly assigned to a mixed soy isoflavone supplement (PTIG-2535, Unconjugated Isoflavones-70, containing genistein 150mg, daidzein 74 mg, glycitein 11 mg) or placebo, stratified by menopausal status, and by ER status of prior breast cancer if present. A random fine needle aspiration (rFNA) of a previously unaffected breast/s was performed at study entry and repeated after six months of study intervention. Women were excluded if estimated epithelial cell yield was ≤ 4000 cells. Cells were immunostained for Ki-67 (primary endpoint), examined for cytomorphology, and by spectral imaging. Plasma samples were obtained for determination of genistein and equol concentrations, for compliance monitoring. Sex hormone-binding globulin (SHBG) and follicle-stimulating hormone (FSH) assays were included to monitor the presence of a systemic estrogenic effect of soy isoflavones. The trial was powered to detect a 50% decrease in Ki-67 labeling, from 2% at baseline to 1% following active intervention.Results: A total of 99 randomized women were evaluable for the primary endpoint of Ki-67 labeling index (LI). Fifty were in the treatment group and 49 in the placebo group; 57 were premenopausal, 42 were postmenopausal. Twelve postmenopausal and 13 premenopausal women had a prior history of breast cancer (10 ER neg, 15 ER pos). The overall median Ki-67 LI at study entry was 1.08, and following intervention was 1.04. In the treated women, the entry and post-intervention Ki-67 LI was 1.18 and 1.12 respectively, whereas in the placebo group it was 0.97 and 0.92 (between group 2-sided Wilcoxon rank-sum p=0.32). There was no significant difference in the change in Ki-67 LI when menopausal strata were examined separately (Wilcoxon rank-sum p=0.33 for premenopausal and 0.42 for postmenopausal groups). The median Masood scores for cytomorphologic features pre- and post-intervention were 14 vs. 14 in the soy and 13 vs. 14 in the placebo groups. There was no significant change in SHBG (p=.347) or FSH values (p=.465 for premenopausal and .297 for postmenopausal women). Compliance assessment is ongoing and will be completed shortly. Spectral imaging analysis of cellular material is also underway.Conclusions: A six-month intervention of mixed soy isoflavones does not appear to cause a significant change in breast epithelial cell proliferation in healthy high risk women. These results argue against the efficacy of soy isoflavone supplementation of the adult western diet for purposes of breast cancer prevention, but also do not suggest an adverse effect on the breast. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1049.

Effect of genistein therapy on plasma levels of asymmetric dimethylarginine in healthy postmenopausal women: a randomized, placebo-controlled study

The aim of this study was to investigate the effects of pure genistein therapy on asymmetric dimethylarginine in healthy postmenopausal women. Healthy postmenopausal women received pure genistein (n=21) or placebo (n=17) for 6 months, and no statistically significant effects on plasma asymmetric dimethylarginine levels were found with pure genistein treatment.

Effects of soy isoflavones on the uterus and urethra of ovariectomized rats

To evaluate the effect of soy isoflavone extract (SIE) on the uterus and urethra of castrated female rats. Ovariectomized adult virgin Wistar rats (n = 45) received, for 30 days: placebo (GI); SIE from day 5 of castration (GII); or day 28 of castration (GIII). A standardized SIE was administered by gavage at 125 microg genistein/g body weight/day, with a soy-free diet. Average numbers of nuclei (NU), blood vessels (BV) and collagen fibers (CF) in uterus and mid-urethra sections were compared using Dunnett and Tukey tests (95% CI). Uterus: GII and GIII differed from GI in all respects; GII vs. GIII, no differences. Urethra: GIII vs. GI: no differences; GII vs. GI, differences in NU and CF; GII vs. GIII, differences in NU and CF. Early oral administration of SIE to ovariectomized rats reversed uterine/urethral effects of castration.

The effect of soy isoflavones on ATP binding cassette A1 expression level in rats without ovaries with atherosclerotic plaque

To study the effect of soy isoflavones (SI) on ATP binding cassette A1 (ABCA1) expression in rats without ovary with atherosclerosis. After they were raised for a week by given basic feed, the ovaries of 50 12-week old SPF rats were removed. The rats were randomly divided into groups by weight. Ten rats were selected as the basic control group (A) that basic feed was given all through the research. The other 40 rats were given high-fat diets and at the end of 4 weeks, these rats were randomly divided into four groups by blood lipid level: atherosclerotic model group (B) that was given high-fat diets through the research, low isoflavones group (C) that was given high-fat diets plus 30 mg/kg SI, middle isoflavones group (D) that was given high-fat diets plus 90 mg/kg SI, and high isoflavones group (E) that was given high-fat diets plus 270 mg/kg SI. After 22 weeks, all rats were executed to measure morphological change on the aorta wall, assessing the ABCA1 gene expression in aorta wall by real-time PCR and protein expression by Western blotting in aorta wall, small intestine and liver. Serum lipid level of A, B, C, D, E groups: TC levels were (6.82 +/- 0.22), (15.73 +/- 1.51), (10.77 +/- 1.12), (9.95 +/- 1.18), (9.11 +/- 1.12) mmol/L respectively (F = 72.882, P < 0.01); TG levels were: (2.49 +/- 0.24), (0.78 +/- 0.13), (0.39 +/- 0.08), (0.29 +/- 0.09), (0.24 +/- 0.09) mmol/L respectively (F = 378.515, P < 0.01); LDL-C levels were (1.29 +/- 0.08), (14.76 +/- 1.23), (8.18 +/- 0.80), (7.85 +/- 0.72), (7.16 +/- 0.64)mmol/L respectively (F = 320.936, P < 0.01); HDL-C levels were (1.94 +/- 0.18), (1.04 +/- 0.10), (1.55 +/- 0.14), (1.88 +/- 0.17), (2.11 +/- 0.22) mmol/L respectively (F = 49.450, P < 0.01). ABCA1 protein expression in intestine, liver and aorta: for A, B, C, E groups in intestine were 96.577 +/- 9.743, 5.218 +/- 2.048, 18.060 +/- 5.179, 54.725 +/- 8.960, respectively (F = 172.272, P < 0.01); ABCA1 protein expression in liver of groups of A, B, C, E were: 13.657 +/- 2.397, 1.361 +/- 0.266, 7.069 +/- 2.264, 11.793 +/- 2.515 respectively (F = 37.383, P < 0.01); ABCA1 protein expression in aorta of groups A, B, C, E were: 6.756 +/- 1.310, 0.027 +/- 0.006, 0.035 +/- 0.002 and 7.479 +/- 1.520 respectively (F = 91.999, P < 0.01). Compared to basic control group, atherosclerotic plaque could be observed in atherosclerotic model group, and it could be partially reversed by isoflavones addition. Soy isoflavones treatment might inhibit atherosclerotic progression by lowering the level of blood lipid and increasing ABCA1 expression.

Combined inhibitory effects of soy isoflavones and curcumin on the production of Prostate-specific antigen (PSA)

Combined inhibitory effects of soy isoflavones and curcumin on the production of Prostate-specific antigen (PSA)

Isoflavones and Bone Health

Osteoporosis is a highly-prevalent chronic disease that affects postmenopausal women who are clinically asymptomatic until complications, such as fractures, appear. Although the incidence of osteoporotic fractures is increasing in many parts of Asia, rates are still lower than those reported in Western countries. It has been postulated that soy intake, a major source of isoflavones, may have potentially-beneficial effects on bone health. In vitro and animal studies have shown that isoflavones exert their bone- supporting effects in multiple ways. Experimental data show that they act on both osteoblasts and osteoclasts through genomic and nongenomic pathways. Retrospective and prospective studies (case-control and cohort studies) have showed a conflicting effect of isoflavones on bone health. A small number of randomized controlled trials on the effects of soy isoflavones on bone mineral density and bone remodeling markers have been carried out. Only the Shanghai Womens Health Study has evaluated the association between soy consumption and the risk of fracture. The aim of this review was to evaluate the possible role of isoflavones in the prevention of osteoporotic fractures in postmenopausal women as demonstrated in high quality studies. Keywords: Osteoporosis, soy, isoflavones, fractures, bone mineral density, women

Soy Isoflavones Mitigate Long-Term Femoral and Lumbar Vertebral Bone Loss in Middle-Aged Ovariectomized Mice

We evaluated the protective effects of soy isoflavones (SIF) against osteoporosis in middle-aged ovariectomized (OVX) mice. SIF (30 mg/kg or 60 mg/kg) or 17beta-estradiol (E(2)) was administered to OVX mice for 4 months after bilateral ovariectomy. We observed the biochemical markers of bone turnover, e.g., alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP), in serum. We also observed the bone mineral density (BMD) in femurs and lumbar vertebrae. In addition, we examined trabecular bone and interstitial cells in the femur using hematoxylin and eosin staining. The decrease in ALP levels and the increase in TRAP levels normally resulting from ovariectomy were suppressed by administration of 60 mg/kg SIF or E(2). Administration of 60 mg/kg SIF or E(2) also maintained the BMD, trabecular bone, and interstitial cells in OVX mice compared to those in pre-OVX mice. These results suggest that 60 mg/kg SIF effectively mitigates ovariectomy-induced osteoporosis in middle-aged mice.