Soy Isoflavone Supplementation Research Articles

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.

Effects of 25-hydroxycholecalciferol and soy isoflavones supplementation on bone mineralisation of quail

1. The effects of 25-hydroxycholecalciferol (25-OH-D3) and soy isoflavones supplementation on performance, carcase recovery, bone mineral density, and tibia ash, Ca, P, and serum vitamin D concentrations and alkaline phosphatase activity in the Japanese quail (Coturnix coturnix japonica) exposed to high ambient temperature were evaluated. 2. A total of 270 ten-d-old Japanese quail were randomly assigned to 9 treatment groups, 6 replicates of 5 birds each in a 2 × 3 × 3 factorial arrangement of treatments. Birds were kept in a temperature-controlled room at either 22°C (thermo-neutral) or 34°C (heat stress) for 8 h/d (09:00–17:00 h) and given a basal (control) diet or the basal diet supplemented with one of three levels of 25-OH-D3 (0, 250 and 500 IU/kg of diet) combined with one of three levels of soy isoflavones (0, 400 and 800 mg/kg of diet). 3. Birds kept at 34°C consumed less feed and gained less weight than control birds. An increase in body weight, feed intake (and improvement in feed efficiency and carcase recovery were found in soy isoflavones and 25-OH-D3-supplemented quail reared under heat stress conditions. Bone mineral density, tibia ash, Ca, and P were linearly improved by 25-OH-D3 and soy isoflavones supplementation in both thermoneutral and heat stress groups. Serum vitamin D levels and alkaline phosphatase activity were improved by 25-OH-D3 and soy isoflavones supplementation in both thermoneutral and heat stress groups in quail. 4. In conclusion, a combination of 25-OH-D3 and soy isoflavones supplementation to basal diet significantly improved bone mineralisation in quail.

Soy isoflavone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial

BackgroundIsoflavones are naturally occurring plant estrogens that are abundant in soy. Although purported to protect against bone loss, the efficacy of soy isoflavone supplementation in the prevention of osteoporosis in postmenopausal women remains controversial. ObjectiveOur aim was to test the effect of soy isoflavone supplementation on bone health. DesignA multicenter, randomized, double-blind, placebo-controlled 24-mo trial was conducted to assess the effects of daily supplementation with 80 or 120 mg of soy hypocotyl aglycone isoflavones plus calcium and vitamin D on bone changes in 403 postmenopausal women. Study subjects were tested annually and changes in whole-body and regional bone mineral density (BMD), bone mineral content (BMC), and T scores were assessed. Changes in serum biochemical markers of bone metabolism were also assessed. ResultsAfter study site, soy intake, and pretreatment values were controlled for, subjects receiving a daily supplement with 120 mg soy isoflavones had a statistically significant smaller reduction in whole-body BMD than did the placebo group both at 1 y (P < 0.03) and at 2 y (P < 0.05) of treatment. Smaller decreases in whole-body BMD T score were observed among this group of women at 1 y (P < 0.03) but not at 2 y of treatment. When compared with the placebo, soy isoflavone supplementation had no effect on changes in regional BMD, BMC, T scores, or biochemical markers of bone metabolism. ConclusionDaily supplementation with 120 mg soy hypocotyl isoflavones reduces whole-body bone loss but does not slow bone loss at common fracture sites in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00665860.

The relationship between changes in serum isoflavone concentrations and changes in body fat distribution with soy isoflavone supplementation in postmenopausal women

The relationship between changes in serum isoflavone concentrations and changes in body fat distribution with soy isoflavone supplementation in postmenopausal women

Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis

To determine whether isoflavones exert estrogen-like effects in men by lowering bioavailable T through evaluation of the effects of soy protein or isoflavone intake on T, sex hormone-binding globulin (SHBG), free T, and free androgen index (FAI) in men. PubMed and CAB Abstracts databases were searched through July 1, 2008, with use of controlled vocabulary specific to the databases, such as soy, isoflavones, genistein, phytoestrogens, red clover, androgen, testosterone, and SHBG. Peer-reviewed studies published in English were selected if [1] adult men consumed soy foods, isolated soy protein, or isoflavone extracts (from soy or red clover) and [2] circulating T, SHBG, free T, or calculated FAI was assessed. Data were extracted by two independent reviewers. Isoflavone exposure was abstracted directly from studies. Fifteen placebo-controlled treatment groups with baseline and ending measures were analyzed. In addition, 32 reports involving 36 treatment groups were assessed in simpler models to ascertain the results. No significant effects of soy protein or isoflavone intake on T, SHBG, free T, or FAI were detected regardless of statistical model. The results of this meta-analysis suggest that neither soy foods nor isoflavone supplements alter measures of bioavailable T concentrations in men.

Acute Fish Oil and Soy Isoflavone Supplementation Increase Postprandial Serum (n-3) Polyunsaturated Fatty Acids and Isoflavones but Do Not Affect Triacylglycerols or Biomarkers of Oxidative Stress in Overweight and Obese Hypertriglyceridemic Men

Chronic consumption of fish and fish oil high in (n-3) PUFA reduces triacylglycerols (TG) but may increase oxidative stress, whereas consumption of soy isoflavones may reduce oxidative stress. Elevated serum TG and oxidative stress are considered cardiovascular disease (CVD) risk factors, but the effects of acute (n-3) PUFA and soy isoflavones on these CVD risk factors are unknown. The purpose of the study was to determine the effects of acutely supplementing a high-fat, high-fructose meal with fish oil and isoflavone placebo (FO) and fish oil placebo and soy isoflavones (ISO). In a randomized, double-blind, placebo-controlled, crossover study, 10 overweight or obese men consumed a high-fat, high-fructose meal with 4 dietary supplement combinations: fish oil placebo and isoflavone placebo (placebo); fish oil and isoflavone placebo (FO); fish oil placebo and isoflavones (ISO); and fish oil and isoflavones (FO + ISO). Serum collected at baseline and at 2, 4, and 6 h postprandially was analyzed for fatty acids, isoflavones, TG, and oxidative stress biomarkers (lipid hydroperoxides, oxidized-LDL, total antioxidant status). FO significantly increased serum (n-3) PUFA and ISO increased serum isoflavones. The study meal significantly increased serum total fatty acids and TG without affecting oxidative stress biomarkers. Serum TG and oxidative stress biomarkers did not differ between treatments. The FO and ISO were bioavailable but did not attenuate the postprandial rise in serum TG. Neither the study meal nor the FO or ISO induced significant changes in oxidative stress biomarkers. The current study adds to a limited literature on the acute effects of FO and ISO interventions on postprandial biomarkers of CVD risk.

Multiple mechanisms of soy isoflavones against oxidative stress-induced endothelium injury

Diabetic vascular complications are related to a combination of oxidative stress and hyperglycemia. Here we investigate the effect and mechanism of soy isoflavones on oxidative stress-induced endothelial cell injury. Oxidative stress was modeled in primary cultured human umbilical vein endothelial cells by incubation with H 2O 2 and high glucose. Genistein and daidzein protected the cells against H 2O 2-induced apoptosis and their protective actions were abolished by ICI 182780, an estrogen receptor antagonist. The inhibition of cell proliferation by oxidative stress was prevented by genistein and daidzein under normal glucose conditions, but they were less effective at high glucose levels. Genistein and daidzein upregulated the estrogen receptor ERβ and increased Bcl-2 expression. Silencing of Bcl-2 with siRNA abolished the protection of genistein. Moreover, inhibition of the PI3K and Rho A/Rho kinase pathways by wortmannin and Y-27632 altered the effects of genistein and daidzein on cell survival. We conclude that oxidative stress-induced apoptosis and cell proliferation inhibition can be prevented by soy isoflavones via the regulation of ERβ and Bcl-2/Bax expression and modulation of cell survival signaling, such as the PI3K pathway. These findings imply that multiple mechanisms are involved in the beneficial effects of soy isoflavone supplements for diabetic endothelial injury.

The ethyl acetate extract of alfalfa sprout ameliorates disease severity of autoimmune-prone MRL-lpr/lpr mice

Previous study showed that soy isoflavone supplement alleviates disease severity in autoimmune-prone mice. As the ethyl acetate extract of alfalfa sprout (AS) has selective oestrogenic and anti-inflammatory activity, this study evaluated the effects of alfalfa sprout ethyl acetate extract (ASEA) on disease severity of systemic lupus erythematosus, using autoimmune-prone female MRL-lpr/lpr mice. In Experiment 1, five groups of 12-week-old female mice were per oral treated with vehicle (control), lyophilized AS (550 mg wt/kg BW), ASEA (ASEA, 25 mg/kg BW), coumestrol (CUM, 0.075 mg/kg BW) and tamoxifen (TAM, 0.375 mg/kg BW) as the positive control. The onset of proteinuria was delayed, and the life span was significantly longer in the ASEA and TAM groups but neither in the AS nor in the CUM groups, compared to the control. To examine the changes in the immunological parameters related to disease process, three more groups of MRL-lpr/lpr female mice (control, ASEA and TAM) were fed in a similar manner for 6 weeks in the Experiment 2. Flow cytometric analysis of splenocytes showed a significantly lower percentage of activated T cells in the ASEA and TAM groups. The ex-vivo interferon-gamma and interleukin (IL)-4 production from splenocytes and tumour necrosis factor-alpha and IL-1beta production from peritoneal exudate cells were also significantly lower in the ASEA group compared with the control. The ASEA group also had less severe glomerulonephritis. Thus, ASEA attenuated cytokine and inflammatory responses of self-reactive lymphocytes, decreased the disease severity, increased survival and life span of the autoimmune-prone MRL-lpr/lpr mice, suggesting a potential of ASEA in the treatment of autoimmune diseases.

Inhibition of prostaglandin synthesis and actions by genistein in human prostate cancer cells and by soy isoflavones in prostate cancer patients

Soy and its constituent isoflavone genistein inhibit the development and progression of prostate cancer (PCa). Our study in both cultured cells and PCa patients reveals a novel pathway for the actions of genistein, namely the inhibition of the synthesis and biological actions of prostaglandins (PGs), known stimulators of PCa growth. In the cell culture experiments, genistein decreased cyclooxygenase-2 (COX-2) mRNA and protein expression in both human PCa cell lines (LNCaP and PC-3) and primary prostate epithelial cells and increased 15-hydroxyprostaglandin dehydrogenase (15-PGDH) mRNA levels in primary prostate cells. As a result genistein significantly reduced the secretion of PGE(2) by these cells. EP4 and FP PG receptor mRNA were also reduced by genistein, providing an additional mechanism for the suppression of PG biological effects. Further, the growth stimulatory effects of both exogenous PGs and endogenous PGs derived from precursor arachidonic acid were attenuated by genistein. We also performed a pilot randomised double blind clinical study in which placebo or soy isoflavone supplements were given to PCa patients in the neo-adjuvant setting for 2 weeks before prostatectomy. Gene expression changes were measured in the prostatectomy specimens. In PCa patients ingesting isoflavones, we observed significant decreases in prostate COX-2 mRNA and increases in p21 mRNA. There were significant correlations between COX-2 mRNA suppression, p21 mRNA stimulation and serum isoflavone levels. We propose that the inhibition of the PG pathway contributes to the beneficial effect of soy isoflavones in PCa chemoprevention and/or treatment.

Effect of long-term intervention of soy isoflavones on bone mineral density in women: A meta-analysis of randomized controlled trials

IntroductionA number of RCTs have examined the role of soy isoflavones on bone mineral density (BMD) and yielded inconsistent results. This meta-analyses aims to assess the overall effect of soy isoflavones on BMD. MethodsWe searched for all articles published in English from January 1990 to March, 2008. We included RCTs of soy isoflavone supplementation in women of at least one year duration. The main outcomes were BMD changes from baseline at the lumbar spine, total hip and femoral neck. ResultsWe identified 10 eligible RCTs containing 896 women. A mean dose of 87 mg soy isoflavones for at least one year did not significantly affect BMD changes. The mean (95%CI) differences in BMD changes (in mg/cm2/year) were 4.1 (−1.6, 9.8) (0.4%) at the lumbar spine, −1.5 (−7.2, 4.3) (−0.3%) at the femoral neck under random-effects model, and 2.5 (−0.5, 5.4) (0.2%) at the total hip by fix-effects model, respectively. Similar results were obtained in subgroup analyses by isoflavone sources (soy protein vs. isoflavone extract), ethnic differences (Asian vs. Western). Larger dose (≥80 mg/d), but not lower dose (<80 mg/d), of isoflavone intervention tended to have a weak beneficial effect on spine BMD (p=0.08 vs. p=0.94). ConclusionsSoy isoflavone supplementation is unlikely to have significant favorable on BMD at the lumbar spine and hip in women.

The effects of soy isoflavone on insulin sensitivity and adipocytokines in insulin resistant rats administered with high-fat diet

The effects of soy isoflavone (SIF) on insulin sensitivity and adipocytokines in high-fat-diet-induced insulin resistant (IR) rats were studied. Male Sprague Dawley rats (n = 80) were randomly assigned into a basal diet fed group and high-fat diet fed group. The high-fat-diet-induced IR rats were assigned into IR model control group and three SIF-treated groups with different dosages. Thirty days later, the fasting blood glucose, insulin and adipocytokines in serum and mRNA expressions of adipocytokines in perirenal white adipose tissue were measured. The Homeostasis Model Assessment of IR was calculated. The administration of 450 mg kg−1 d−1 SIF decreased the body weights and depositions of visceral adipose tissue as well as improved insulin resistance in high-fat-diet-induced IR rats. The mechanisms were associated with SIF regulating the expression of adipocytokines, including adiponectin, leptin, resistin and TNF-α. SIF supplements may have favourable effects on insulin resistance in high-fat-diet-induced IR rats.

A preliminary study of the safety, feasibility and cognitive efficacy of soy isoflavone supplements in older men and women

a small number of reports exist on the cognitive effects of soy isoflavones, the findings from which are mixed. Isoflavone efficacy is dependent upon conversion of glycosides contained in soy foods and supplements to the biologically active aglycons. Of particular interest is the production of the metabolite, equol, which is dependent upon intestinal microflora and an integrous digestive system, both being altered by age and age-associated conditions. Unfortunately, few studies enrolled adults over the age of 70, and none included older men. we examined safety, feasibility and cognitive efficacy of soy isoflavone administration in older nondemented men and women (age 62-89 years). in this randomised, placebo-controlled, double-blind pilot study, subjects ingested either 100 mg/day soy isoflavones (glycoside weight) or matching placebo tablets for 6 months. active and placebo-treated subjects exhibited a comparable side-effect profile. Plasma levels of genistein and daidzein (P < 0.001), but not equol, increased with isoflavone administration. While similar at baseline, the two groups differed across 6 months of treatment on 8 of 11 cognitive tests administered. Isoflavone-treated subjects improved on tests of visual-spatial memory (P < 0.01) and construction (P = 0.01), verbal fluency (P < 0.01) and speeded dexterity (P = 0.04). Placebo-treated participants were faster than isoflavone-treated subjects on two tests of executive function (P < 0.05). these data suggest that administration of 100 mg/day of isoflavones was well tolerated. Plasma genistein and daidzein levels, but not equol, increased with isoflavone administration. Finally, data support the potential cognitive effects of soy isoflavones in older adults.

Lack of effects of isoflavones on the lipid profile of Brazilian postmenopausal women

Objective To evaluate the effects of soy isoflavone supplementation on profile lipid and endogenous hormone levels. Methods In this double-blind, placebo-controlled study, 47 postmenopausal women 47–66 y of age received 40 mg of isoflavone ( n = 25) or 40 mg of casein placebo ( n = 22). Cardiovascular risk factors were assessed by evaluating lipid profile at baseline and after 6 mo of treatment. To examine the effects of this regime on endogenous hormone levels, follicle-stimulating hormone and β-estradiol were measured. Urinary isoflavone concentrations (genistein and daidzein) were measured as markers of both compliance and absorption using high performance liquid chromatography. Baseline characteristics were compared by the unpaired Student's t-test. Within-group changes were determined by paired Student's t-test and comparison between the isoflavone and casein placebo groups were determined by analysis of variance. Results Lipid levels (low-density lipoprotein and total cholesterol) similarly decreased in both groups. High-density lipoprotein increased significantly in both groups and cannot thus be attributable to treatment; the reason for such variation is unknown and can be attributed to chance or to bias (even that of a real placebo effect in both groups or perhaps in spontaneous changes in exercise and dietary habits of patients after their inclusion). Furthermore, in both groups very low-density lipoprotein and triacylglycerol levels increased in a non-significant manner. Conclusion The results of the present study do not support any biologically significant estrogenic effects of isoflavone on the parameters assessed. Further research will be necessary to definitively assess the safety and efficacy of isoflavone.

Soy isoflavones supplementation alleviates disease severity in autoimmune-prone MRL-lpr/lpr mice

Soy isoflavones supplements, which are phyto-oestrogens widely used as alternatives to alleviate menopausal syndromes or prevent chronic diseases, may exert oestrogenic and anti-oestrogenic activities. This study aimed to investigate the effects of soy isoflavones supplement on oestrogen-related autoimmune disease, such as systemic lupus erythematosus, using autoimmune-prone female MRL-lpr/lpr mice. Eighty mice of 8 weeks were divided into five groups: 0 (Control), 2 (Isf 2), 10 (Isf 10) and 20 (Isf 20) mg/kg BW/day Phyto Soya isoflavones or 0.375 mg/kg BW/day tamoxifen (TAM) as the positive control, by tube-feeding. Some mice were killed at age 15 weeks for cellular cytokine secretion. The data suggested that the Isf 20 and TAM groups had higher weight gain and survival compared with the control group. At age 22 weeks, the Isf 20 group still had 75% survival comparable to mice treated with TAM. At age 14 weeks, the TAM group showed significantly lower serum anti-double-stranded (ds) DNA IgG and anti-cardiolipin IgG. The mice in the Isf 10 and Isf 20 groups also had lower anti-dsDNA IgG and anti-cardiolipin IgG. The interferon (IFN)-gamma secretion from mitogen-stimulated T cells in the Isf 20 and TAM groups were significantly lower than those of control mice. Furthermore, the oestrogenic activity of the methanol extracts of soy isoflavones for oestrogen receptor (ER)beta, but not ERalpha, significantly increased, suggesting that soy isoflavones have a selective modulation of ER activation. Thus, soy isoflavone supplementation did not aggravate murine lupus, but apparently ameliorated the disease.

Soy isoflavones in the management of postmenopausal osteoporosis

This is a review article designed to address the effects of soy isoflavones on bone metabolism in postmenopausal women and their place in the prevention and treatment of postmenopausal osteoporosis. Soy isoflavones are natural products that could be used as an alternative to menopausal hormone therapy because they are structurally and functionally related to 17beta-estradiol. In vitro and animal studies have shown that they act in multiple ways to exert their bone-supporting effects. They act on both osteoblasts and osteoclasts through genomic and nongenomic pathways. Epidemiological studies and clinical trials suggest that soy isoflavones have beneficial effects on bone mineral density, bone turnover markers, and bone mechanical strength in postmenopausal women. However, there are conflicting results related to differences in study design, estrogen status of the body, metabolism of isoflavones among individuals, and other dietary factors. The long-term safety of soy isoflavone supplements remains to be demonstrated.

The Key Importance of Soy Isoflavone Bioavailability to Understanding Health Benefits

Research over the past two decades has provided significant epidemiological and other evidence for the health benefits of the consumption of soy-based foods. A large number of dietary intervention studies have examined the effects of soy isoflavones on risk factors for cardiovascular disease and hormone-dependent cancers. However, these report large variability in outcome measures, very limited reproducibility between studies, and in some cases, controversy between the results of clinical trials using dietary soy or soy protein and isoflavone supplementation. This highlights a major gap in our understanding of soy isoflavone uptake, metabolism, distribution, and overall bioavailability. There are many potential factors that may influence bioavailability and a better knowledge is necessary to rationalize the inconsistencies in the intervention and clinical studies. This review focuses attention on our current state of knowledge in this area and highlights the importance of metabolism of the parent soy isoflavones and the critical role of gut microbiota on the bioavailability of these compounds and their metabolites.

Development of techniques for the analysis of isoflavones in soy foods and nutraceuticals

For over 20 years, soy isoflavones have been investigated for their ability to prevent a wide range of cancers and cardiovascular problems, and numerous other disease states. This research is underpinned by the ability of researchers to analyse isoflavones in various forms in a range of raw materials and biological fluids. This review summarizes the techniques recently used in their analysis. The speed of high performance liquid chromatography analysis has been improved, allowing analysis of more samples, and increasing the sensitivity of detection techniques allows quantification of isoflavones down to nanomoles per litre levels in biological fluids. The combination of high-performance liquid chromatography with immunoassay has allowed identification and estimation of low-level soy isoflavones. The use of soy isoflavone supplements has shown an increase in their circulating levels in plasma and urine, aiding investigation of their biological effects. The significance of the metabolite equol has spurned research into new areas, and recently the specific enantiomers have been studied. High-performance liquid chromatography, capillary electrophoresis and gas chromatography are widely used with a range of detection systems. Increasingly, immunoassay is being used because of its high sensitivity and low cost.

Soy isoflavone (IF) supplementation appears safe after a two‐year randomized controlled trial (RCT)

Although RCTs quantifying a benefit for menopausal soy IF supplementation abound, few studies have considered the safety of long‐term soy IF intake, particularly when exposure levels are in the form of a tablet, as opposed to food. To evaluate the effect of soy IF on bone loss, 403 early postmenopausal women (54.0±4.0 y) were enrolled in a multi‐site, 2‐year, double‐blind RCT with 1/3 on placebo, 1/3 on 80 mg/d IF and 1/3 on 120 mg/d IF. Baseline characteristics were similar in all groups. The study design focused on safety as a secondary outcome measure and included serum electrolytes, lipids, liver and renal functions, complete blood counts, reproductive and thyroid hormones and cancer (CA) screening. In the supplement groups versus placebo, there was a decrease in free thyroxine (T4) (p=0.024) and an increase in blood urea nitrogen (BUN) (p=0.048), but not thyroid stimulating hormone (p=0.264) or creatinine (p=0.145) after 2 years. Absolute changes in free T4 and BUN were neither outside the normal range nor clinically significant. Major adverse events included one subject with endometrial CA and one with breast CA, which were fewer than predicted in this study population. Soy IF supplementation up to 120 mg/d has no measurable deleterious effect over a 2‐year interval. Supported by Initiative for Future Agriculture and Food Systems Grant 2001‐52102‐11255 USDA CSREES.

Effect of Soy Isoflavone Supplementation on Menopausal Quality of Life

Recent clinical trials have found an increased risk of health problems in women using menopausal hormone therapy. As a result, women are in search of alternative strategies to improve their quality of life. The purpose of this study was to assess the effect of soy isoflavone supplementation on quality of life in postmenopausal women. 403 healthy postmenopausal women (54.0+4.0 yrs) were enrolled in a 2 year multicenter, randomized, controlled trial designed to evaluate the effect of soy isoflavone supplementiation on the prevention of osteoporosis. Quality of life was assessed as a secondary outcome and was measured using the validated Menopause‐Specific Quality of Life Questionnaire (MENQOL) administered at baseline and at annual intervals. Participants were randomly assigned to receive soy isoflavones 80 mg/d, soy isoflavones 120 mg/d, or placebo. Data were analyzed using an analysis of variance (ANOVA). Baseline characteristics were similar among the three groups. There was a non‐significant decrease i.e. improvement, in the vasomotor domain score at one and two years compared to baseline in all three groups. However, there were no differences among groups. In conclusion, soy isoflavones provide no added benefit over placebo in terms of qualifty of life as measured by the MENQOL. Supported by IFAFS 2001‐52102‐11255 USDA CSREES.

Osteoporosis prevention using soy: the OPUS study

Soy isoflavones are believed to have anti‐osteoporotic properties. To evaluate the effect of soy isoflavones on bone loss, 403 early postmenopausal women (54.0±4.0 y) were enrolled in an intent‐to‐treat, multi‐site, 2‐year follow‐up, randomized, double‐blind study with 1/3 on placebo, 1/3 on 80 mg/d of isoflavones, and 1/3 on 120 mg/d of isoflavones along with 1,000 mg/d of CaCO3 and a daily multivitamin with 400 IU of vitamin D. Bone mineral density (BMD) of the whole body (WB), hip and spine and serum bone turnover markers (osteocalcin, bone specific alkaline phosphatase, and cross‐linked N‐telopeptides of type 1 collagen) were measured at baseline and annual intervals. Baseline characteristics were similar in the three groups. A significant protective effect on the decrease in WB BMD was observed with 120 mg/d of soy isoflavones vs. placebo after 1 y (p = 0.027) and 2 y (p = 0.048) of supplementation. No differences were observed in regional BMD measurements or in bone turnover markers. In conclusion, soy isoflavone supplementation reduces the loss of WB BMD at the highest supplementation level, but was not protective at the regional sites. Supported by Initiative for Future Agriculture and Food Systems Grant no. 2001‐52102‐11255 from the USDA CSREES.