Isolated isoflavones do not affect the circulating insulin-like growth factor system in men at increased colorectal cancer risk

Epidemiological studies show that increased insulin-like growth factor (IGF)-I concentrations are related to increased colorectal cancer risk. A reduced colorectal cancer risk has been associated with isoflavones, which might affect the IGF-system because of their weak estrogenic activity. We conducted a randomized, placebo-controlled, double-blind crossover study to investigate the effect of an 8-wk isolated isoflavone supplementation (84 mg/d) on serum concentrations of total IGF-I, free IGF-I, total IGF-II, IGF binding protein (BP)-1, IGFBP-2, and IGFBP-3. Additionally, we investigated whether IGF-system component differences were related to concentrations of the more potent estrogenic isoflavone metabolite, equol. Our study population consisted of 37 men with a family history of colorectal cancer or a personal history of colorectal adenomas. Isoflavone supplementation did not significantly affect serum total IGF-I concentrations (relative difference between serum total IGF-I concentrations after isoflavone supplementation and after placebo: -1.3%, 95% CI -8.6 to 6.0%). Neither free IGF-I, nor total IGF-II, IGFBP-1, IGFBP-2, or IGFBP-3 concentrations were significantly altered. Interestingly, the change in serum IGF-I concentrations after isoflavone supplementation was negatively associated with serum equol concentrations (r=-0.49, P=0.002). In conclusion, isolated isoflavones did not affect the circulating IGF-system in a male high-risk population for colorectal cancer. However, to our knowledge, this is the first study that suggests isoflavones might have an IGF-I lowering effect in equol producers only. This underlines the importance of taking into account equol status in future isoflavone intervention studies.     

Urinary isoflavonoid excretion is inversely associated with the ratio of protein to dietary fibre intake in young women

OBJECTIVE: To examine the prevalence of excretion of urinary isoflavonoids in women and determine any relationships with accustomed macronutrient intake. DESIGN: Volunteers in one of two 4-month studies. Study 1 was a randomised crossover study whereby subjects consumed a placebo or isoflavone supplement for 2 months and crossed over. Study 2 was a parallel design in which subjects consumed a placebo for 1 month and an isoflavone supplement for 3 months. SETTING: All subjects were free-living, healthy volunteers. SUBJECTS: A total of 25 (study 1, n=14; study 2, n=11) premenopausal women were recruited through advertisements. INTERVENTIONS: Volunteers were supplemented for 2 months (study 1) or 3 months (study 2) with purified isoflavones (86 mg/day) derived from red clover. Urinary isoflavonoids were measured during the placebo and the second month of isoflavone treatment. Macronutrient intakes were determined from weighed food records. RESULTS: During isoflavone supplementation, the concentration of urinary total isoflavonoids increased by 15-fold (P<0.0001), with 5.4-fold variation between individuals. Multiple linear regression analysis showed that 24% of this variation could be explained by an interaction between dietary fibre and protein (P=0.047), with a highly significant inverse association between total isoflavonoid concentration and the protein to fibre ratio (r=-0.51, P=0.009). CONCLUSIONS: Supplementation with purified isoflavones results in an increase in urinary isoflavonoid excretion and part of the individual variation in response is associated with an interaction between intakes of protein and dietary fibre. Whether manipulation of these macronutrients could enhance efficacy of isoflavone supplements remains to be determined.     

Does genotype and equol-production status affect response to isoflavones? Data from a pan-European study on the effects of isoflavones on cardiovascular risk markers in post-menopausal women

The increase in CVD incidence following the menopause is associated with oestrogen loss. Dietary isoflavones are thought to be cardioprotective via their oestrogenic and oestrogen receptor-independent effects, but evidence to support this role is scarce. Individual variation in response to diet may be considerable and can obscure potential beneficial effects in a sample population; in particular, the response to isoflavone treatment may vary according to genotype and equol-production status. The effects of isoflavone supplementation (50 mg/d) on a range of established and novel biomarkers of CVD, including markers of lipid and glucose metabolism and inflammatory biomarkers, have been investigated in a placebo-controlled 2 x 8-week randomised cross-over study in 117 healthy post-menopausal women. Responsiveness to isoflavone supplementation according to (1) single nucleotide polymorphisms in a range of key CVD genes, including oestrogen receptor (ER) alpha and beta and (2) equol-production status has been examined. Isoflavones supplementation was found to have no effect on markers of lipids and glucose metabolism. Isoflavones improve C-reactive protein concentrations but do not affect other plasma inflammatory markers. There are no differences in response to isoflavones according to equol-production status. However, differences in HDL-cholesterol and vascular cell adhesion molecule 1 response to isoflavones v. placebo are evident with specific ERbeta genotypes. In conclusion, isoflavones have beneficial effects on C-reactive protein, but not other cardiovascular risk markers. However, specific ERbeta gene polymorphic subgroups may benefit from isoflavone supplementation.     

Six months of isoflavone supplement increases fat-free mass in obese-sarcopenic postmenopausal women: a randomized double-blind controlled trial

OBJECTIVE: The aim of this study was to verify if six months of isoflavone supplementation could increase fat-free mass (FFM) and muscle mass index (MMI=appendicular FFM/height(2)) in obese-sarcopenic postmenopausal women. DESIGN: Double-blind randomized study. SUBJECT: Eighteen sarcopenic-obese women completed the study (12 on isoflavones and six on placebo). Body composition was measured by dual-energy X-ray absorptiometry. Subjects ingested 70 mg of isoflavones per day (44 mg of diadzein, 16 mg glycitein and 10 mg genestein) or a placebo for 24 weeks. RESULTS: The isoflavone group increased significantly appendicular (P=0.034), leg (P=0.016) FFM and MMI (P=0.037), but not the placebo group. CONCLUSION: Six months of isoflavone supplementation increased FFM and MMI in obese-sarcopenic postmenopausal women.     

Soy-isoflavone-enriched foods and inflammatory biomarkers of cardiovascular disease risk in postmenopausal women: interactions with genotype and equol production

BACKGROUND: Dietary isoflavones are thought to be cardioprotective because of their structural similarity to estrogen. The reduction of concentrations of circulating inflammatory markers by estrogen may be one of the mechanisms by which premenopausal women are protected against cardiovascular disease. OBJECTIVE: Our aim was to investigate the effects of isolated soy isoflavones on inflammatory biomarkers [von Willebrand factor, intracellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), E-selectin, monocyte chemoattractant protein 1, C-reactive protein (CRP), and endothelin 1 concentrations]. Differences with respect to single-nucleotide polymorphisms in selected genes [estrogen receptor alpha (XbaI and PvuII), estrogen receptor beta [ERbeta (AluI) and ERbeta[cx] (Tsp509I), endothelial nitric oxide synthase (Glu298Asp), apolipoprotein E (Apo E2, E3, and E4), and cholesteryl ester transfer protein (TaqIB)] and equol production were investigated. DESIGN: One hundred seventeen healthy European postmenopausal women participated in this randomized, double-blind, placebo-controlled, crossover dietary intervention trial. Isoflavone-enriched (genistein-to-daidzein ratio of 2:1; 50 mg/d) or placebo cereal bars were consumed for 8 wk, with a washout period of 8 wk between the crossover. Plasma inflammatory factors were measured at 0 and 8 wk of each study arm. RESULTS: Isoflavones improved CRP concentrations [odds ratio (95% CI) for CRP values >1 mg/L for isoflavone compared with placebo: 0.43 (0.27, 0.69)]; no significant effects of isoflavone treatment on other plasma inflammatory markers were observed. No significant differences in the response to isoflavones were observed according to subgroups of equol production. Differences in the VCAM-1 response to isoflavones and to placebo were found with ERbeta AluI genotypes. CONCLUSION: Isoflavones have beneficial effects on CRP concentrations, but not on other inflammatory biomarkers of cardiovascular disease risk in postmenopausal women, and may improve VCAM-1 in an ERbeta gene polymorphic subgroup.     

Insulin-like growth factor-1 and binding protein-3 in a 2-year soya intervention among premenopausal women

Soya foods may protect against the development of breast cancer. Insulin-like growth factor (IGF)-1 is under investigation as a possible link between nutrition and cancer. We examined the effect of soya foods on circulating IGF-1 and IGF binding protein (BP)-3 levels among 196 healthy premenopausal women in a 2-year randomised nutritional trial. The intervention group consumed two daily servings of soya foods including tofu, soya milk, soya nuts and soya protein powder (equivalent to 50 mg isoflavones and 5-22 g soya protein per serving); the controls maintained their regular diet. Five serum samples at baseline, 3, 6, 12, and 24 months were collected in the morning during the luteal phase and analysed for IGF-1 and IGFBP-3 by double-antibody ELISA. We applied mixed models to investigate the intervention effect and predictors of serum levels while considering the repeated measurement design. Adherence with the study regimen was high and dropout rates were acceptable. Randomisation resulted in similar mean IGF-1 and IGFBP-3 levels by group. We did not observe a significant intervention effect on IGF-1, IGFBP-3, and their molar ratio during the entire study period. However, urinary isoflavone excretion during the study period was positively associated with IGF-1 (P=0.04) and the IGF-1:IGFBP-3 ratio (P=0.06). The effect was consistent over time. Adding soya foods to the diet of premenopausal women does not appear to lower serum levels of IGF-1 and IGFBP-3; if anything, the greater protein intake from soya may lead to a small increase in IGF-1 serum levels.     

Effects of supplementation with purified red clover (Trifolium pratense) isoflavones on plasma lipids and insulin resistance in healthy premenopausal women

Consumption of isoflavone-rich soyabean protein is reported to reduce total and LDL-cholesterol, but the specific components responsible are undetermined. In a previous crossover trial we showed that purified isoflavones, derived from red clover (Trifolium pratense), raised HDL3-cholesterol in premenopausal women; however, these findings were inconclusive due to period and carryover effects. In an attempt to overcome this problem, we utilised a parallel study designed to re-examine the effects of purified isoflavones on plasma lipoproteins and markers of insulin resistance in premenopausal women. Twenty-five healthy premenopausal women participated in a double-blind, randomised, parallel study. The treatment group (n 12) consumed a placebo for the first menstrual cycle and an isoflavone supplement (86 mg/d, derived from red clover) for three cycles, while the placebo group (n 13) consumed a placebo supplement for four menstrual cycles. Blood samples were collected weekly during cycles 1, 3 and 4. Supplementation with isoflavones resulted in a 15-fold increase in urinary isoflavone excretion (P<0.0001). There were no significant effects on total cholesterol, LDL- and HDL-cholesterol, HDL subfractions, triacylglycerol, lipoprotein(a), glucose or insulin concentrations. Our present results indicate that purified isoflavones derived from red clover have no effect on cholesterol homeostasis or insulin resistance in premenopausal women, a group which is at low risk of CHD.     

Soy-isoflavone-enriched foods and markers of lipid and glucose metabolism in postmenopausal women: interactions with genotype and equol production

BACKGROUND: The hypocholesterolemic effects of soy foods are well established, and it has been suggested that isoflavones are responsible for this effect. However, beneficial effects of isolated isoflavones on lipid biomarkers of cardiovascular disease risk have not yet been shown. OBJECTIVE: The objective was to investigate the effects of isolated soy isoflavones on metabolic biomarkers of cardiovascular disease risk, including plasma total, HDL, and LDL cholesterol; triacylglycerols; lipoprotein(a); the percentage of small dense LDL; glucose; nonesterified fatty acids; insulin; and the homeostasis model assessment of insulin resistance. Differences with respect to single nucleotide polymorphisms in selected genes [ie, estrogen receptor alpha (XbaI and PvuII), estrogen receptor beta (AluI), and estrogen receptor beta(cx) (Tsp509I), endothelial nitric oxide synthase (Glu298Asp), apolipoprotein E (Apo E2, E3, and E4), cholesteryl ester transfer protein (TaqIB), and leptin receptor (Gln223Arg)] and with respect to equol production were investigated. DESIGN: Healthy postmenopausal women (n = 117) participated in a randomized, double-blind, placebo-controlled, crossover dietary intervention trial. Isoflavone-enriched (genistein-to-daidzein ratio of 2:1; 50 mg/d) or placebo cereal bars were consumed for 8 wk, with a wash-out period of 8 wk before the crossover. RESULTS: Isoflavones did not have a significant beneficial effect on plasma concentrations of lipids, glucose, or insulin. A significant difference between the responses of HDL cholesterol to isoflavones and to placebo was found with estrogen receptor beta(cx) Tsp509I genotype AA, but not GG or GA. CONCLUSIONS: Isoflavone supplementation, when provided in the form and dose used in this study, had no effect on lipid or other metabolic biomarkers of cardiovascular disease risk in postmenopausal women but may increase HDL cholesterol in an estrogen receptor beta gene-polymorphic subgroup.     

Soy proteins and isoflavones reduce interleukin-6 but not serum lipids in older women: a randomized controlled trial

Soy foods contain several components, notably, isoflavones and amino acids, that may improve cardiovascular health. We evaluated the long-term effect of soy protein and/or soy isoflavones supplementation on serum lipids and inflammatory markers using a 1-year randomized, double-blind, placebo-control, clinical trial in 131 healthy ambulatory women older than 60 years. We hypothesized that soy protein, in combination with isoflavones, would have the largest positive effect on coronary heart disease risk factors (serum lipids and inflammatory markers) compared with either intervention alone and that, within groups receiving isoflavones, equol producers would have more positive effects on coronary heart disease risk factors than nonequol producers. After a 1-month baseline period, participants were randomized into 1 of 4 intervention groups: soy protein (18 g/d) and isoflavone tablets (105 mg/d isoflavone aglycone equivalents), soy protein and placebo tablets, control protein and isoflavone tablets, or control protein and placebo tablets. T Tests were used to assess differences between equol and nonequol producers. Ninety-seven women completed the trial. Consumption of protein powder and isoflavone tablets did not differ among groups, and compliance with study powder and tablets was 79% and 90%, respectively. After 1 year, in the entire population, there were either no or little effects on serum lipids and inflammatory markers, regardless of treatment group. Equol producers, when analyzed separately, had significant improvements in total cholesterol/high-density lipoprotein and low-density lipoprotein/high-density lipoprotein ratios (−5.9%, P = .02; −7.2%, P = .04 respectively). Soy protein and isoflavone (either alone or together) did not impact serum lipids or inflammatory markers. Therefore, they should not be considered an effective intervention to prevent cardiovascular disease because of lipid modification in healthy late postmenopausal women lacking the ability to produce equol.     

Beneficial effects of soybean isoflavone supplementation on bone metabolism and serum lipids in postmenopausal japanese women: a four-week study

OBJECTIVE: The aim of this study was to determine the effects of soy isoflavones with weak estrogen-like activities both on bone metabolism and on serum lipids in perimenopausal women. METHODS: Twenty-three healthy perimenopausal women were assigned randomly to either isoflavone or placebo groups. The isoflavone group (n = 12) received daily capsules of soy isoflavone extract (61.8 mg of isoflavones) and the placebo group (n = 11) received daily placebo capsules for four weeks. Urinary excretion of isoflavone was measured at weeks 0, 2 and 4. Urinary excretion of pyridinoline and deoxypyridinoline, bone stiffness and levels of serum cholesterol, triglyceride and cholesterol fractions were measured at weeks 0 and 4. RESULTS: As compared to the placebo group, urinary isoflavone, primarily daidzein, excretion was increased at weeks 2 and 4 in the isoflavone group. Excretion of bone resorption markers was reduced significantly in the isoflavone group. Both total serum cholesterol and LDL cholesterol were decreased significantly in the isoflavone group. Other serum biochemical parameters were not changed in either group. CONCLUSION: Soy isoflavone supplementation for four weeks showed potentially beneficial effects on bone metabolism and on serum lipids in perimenopausal women. These effects could have the potential to reduce the risks of postmenopausal osteoporosis and of cardiovascular diseases in such women.     

Effect of the Intake of Isoflavones on Risk Factors of Breast Cancer—A Systematic Review of Randomized Controlled Intervention Studies

Epidemiological studies suggest that high intake of soy isoflavones may protect against breast cancer, but causal relationships can only be established by experimental trials. Thus, we aimed to provide a systematic review of randomized controlled trials (RCTs) on the effect of an isoflavone intake on risk factors of breast cancer in healthy subjects. After a systematic literature search in PubMed, 18 different RCTs with pre- and/or postmenopausal women were included and investigated for details according to the PRISMA guideline. In these studies, isoflavones were provided by soy food or supplements in amounts between 36.5–235 mg/d for a period of 1–36 months. Breast density, estrogens including precursors, metabolites, estrogen response such as length of menstrual cycle, and markers of proliferation and inflammation were considered. However, in most studies, differences were not detectable between isoflavone and control/placebo treatment despite a good adherence to isoflavone treatment, irrespective of the kind of intervention, the dose of isoflavones used, and the duration of isoflavone treatment. However, the lack of significant changes in most studies does not prove the lack of effects as a sample size calculation was often missing. Taking into account the risk of bias and methodological limitations, there is little evidence that isoflavone treatment modulates risk factors of breast cancer in pre- and postmenopausal women. Future studies should calculate the sample size to detect possible effects and consider methodological details to improve the study quality.     

Consumption of soy isoflavones does not affect plasma total homocysteine or asymmetric dimethylarginine concentrations in healthy postmenopausal women

Postmenopausal women are at increased risk for cardiovascular disease because many risk factors are aggravated by menopause. Phytoestrogens may modulate risk factors favorably, involving mechanisms similar to estrogen. The effect of phytoestrogens on the atherogenic amino acids homocysteine and asymmetric dimethylarginine (ADMA) was investigated in a controlled intervention study in healthy postmenopausal women. A multicenter, double-blind, crossover intervention trial in 89 postmenopausal women from Denmark, Germany, and the UK was performed. Subjects consumed fruit cereal bars with or without soy isoflavones (50 mg/d) for 8 wk each with an 8-wk washout period in between. Urinary phytoestrogens increased significantly after isoflavone intervention (P < 0.001). Isoflavone supplementation did not affect plasma total homocysteine or ADMA. For homocysteine, changes from baseline were 0.32 micromol/L (range: -0.31-0.92; 95% CI 0.13-0.72), and 0.29 micromol/L (range: -0.45-1.09; 95% CI 0.01-0.63, P = 0.286) for isoflavone treatment and placebo, respectively. For ADMA concentrations, changes from baseline were -0.02 micromol/L (range: -0.08-0.03; 95% CI -0.04-0.01, and 0.00 micromol/L (range: -0.05-0.03; 95% CI -0.03-0.01, P = 0.397) for isoflavone treatment and placebo, respectively. There was no association between plasma total homocysteine and ADMA. Changes from baseline in plasma ADMA and folate were negatively correlated (r = -0.18, P = 0.017). These results challenge the overall health effect of isoflavone supplementation in healthy postmenopausal women.     

Soy isoflavone and ascorbic acid supplementation alone or in combination minimally affect plasma lipid peroxides in healthy postmenopausal women

The objective of this study was to assess synergistic antioxidant properties of vitamin C and isoflavones. The design was a placebo-controlled crossover trial: 500 mg vitamin C, 5 mg/kg body weight isoflavones, 500 mg vitamin C plus 5 mg/kg body weight isoflavones, or placebo. Total lipid peroxides, plasma vitamin C, and blood pressure were measured. Eight of 10 healthy postmenopausal women completed the study. A multiple analysis of variance was performed and least-squares difference post-hoc test utilized to determine where differences occurred. Significance was defined as P <.05. There was a significant reduction in total lipid peroxides between baseline and isoflavone treatments (3.22+/-0.72 vs 2.47+/-0.82 nmol/mL, P <.05). Mean systolic blood pressure was higher during isoflavone intervention than placebo (117+/-14 vs 125+/-15 mm Hg, P= .042). Supplementation with vitamin C and isoflavones did not produce a synergistic antioxidant effect. A slight but significant increase in systolic blood pressure occurred with isoflavone supplementation. A larger study should be conducted to fully explore the potential interactions between these antioxidants.     

Effects of soy consumption on gonadotropin secretion and acute pituitary responses to gonadotropin-releasing hormone in women

Soy contains the isoflavone phytoestrogens, genistein and daidzein. These isoflavones are partial estrogen agonists in cell and animal models, but effects from dietary soy in humans are unclear. Experiments were conducted in pre- and postmenopausal women to examine whether dietary isoflavones from soy behave as estrogen agonists, antagonists or have no effect on the estrogen-sensitive pituitary. Pituitary sensitivity to gonadotropin-releasing hormone (GnRH), an estrogen-sensitive endpoint, was measured during GnRH challenge tests administered before, during and after dietary soy consumption. The response to an isoflavone-rich soy food diet was examined in five premenopausal and seven postmenopausal women using transdermal estrogen replacement therapy. Estrogen agonists suppress gonadotropin concentrations and enhance GnRH priming (enhanced gonadotropin secretion in response to repeated doses of GnRH), whereas antagonists elevate gonadotropin concentrations and have no effect on GnRH priming. Each subject consumed 50 g textured soy protein containing 60 mg total isoflavones daily for 10-14 d. Baseline estradiol concentrations were consistent among study periods. In both pre- and postmenopausal women, soy consumption did not affect mean baseline or peak luteinizing hormone (LH) concentrations, indicating a lack of estrogen-like effect at the level of the pituitary. However, in postmenopausal subjects, mean LH secretion decreased after discontinuing soy, suggesting a residual estrogenic effect. In one premenopausal woman, enhanced LH secretion was observed after soy treatment, suggesting there may be subpopulations of women who are highly sensitive to isoflavones.     

Dietary soy containing phytoestrogens does not have detectable estrogenic effects on hepatic protein synthesis in postmenopausal women

BACKGROUND: Dietary phytoestrogens are ligands for the estrogen receptor and may mimic estrogenic effects in vivo. OBJECTIVE: To assess the biological activity of isoflavone phytoestrogens, we analyzed the effect of dietary soy isoflavone supplementation on in vivo bioassays of estrogenicity. DESIGN: Fifty healthy postmenopausal women aged 50-75 y participated in a double-blind, placebo-controlled trial in which they received either soy protein isolate (40 g soy protein, 118 mg isoflavones) or casein placebo. Measurements were made at baseline and at 3 mo. Urinary isoflavone excretion was measured to reflect compliance. The bioassays of estrogenicity included measurement of hepatic proteins and gonadotropin concentrations. RESULTS: Baseline characteristics were not significantly different between the soy and placebo groups. Urinary isoflavone excretion increased in the soy group and at the end of 3 mo was higher in the soy group than in the placebo group. In plasma samples from both groups, C-reactive protein increased significantly over the 3-mo treatment period, whereas sex hormone-binding globulin and thyroid-binding globulin decreased significantly. However, there were no significant differences between the groups in hepatic protein synthesis (change over 3 mo +/- SEM in the soy and placebo groups, respectively): C-reactive protein, 0.42 +/- 0.2 and 0.48 +/- 0.2 U/mL; sex hormone-binding globulin, -6.9 +/- 1.5 and -10.0 +/- 2.1 micro g/mL; thyroid-binding globulin, -16 +/- 8 and -26 +/- 7 nmol/L. Furthermore, gonadotropin and dehydroepiandrosterone sulfate concentrations did not change significantly in either group. CONCLUSIONS: In healthy postmenopausal women, dietary soy isoflavones do not affect in vivo biological indicators of estrogenicity, including hepatic protein synthesis and gonadotropin concentrations. This suggests that soy isoflavones have little biologically relevant estrogenic effect in vivo in postmenopausal women.     

Soya isoflavone-enriched cereal bars affect markers of endothelial function in postmenopausal women

Soya isoflavones are thought to be cardioprotective due to their structural similarity to oestrogen. In order to investigate the effect of soya isoflavones on markers of endothelial function we conducted a randomised, double-blind, placebo-controlled, cross-over study with thirty healthy postmenopausal women. The women consumed cereal bars, with or without soya isoflavones (50 mg/d), for 8 weeks, separated by an 8-week washout period. Systemic arterial compliance (SAC), isobaric arterial compliance (IAC), flow-mediated endothelium-dependent vasodilation (FMD) and nitroglycerine-mediated endothelium-independent vasodilation (NMD) were measured at the beginning of the study and after each intervention period. Blood pressure (BP) and plasma concentrations of nitrite and nitrate (NOx) and endothelin-1 (ET-1) were measured at the beginning and end of each intervention period. NMD was 13.4 (SEM 2.0)% at baseline and 15.5 (SEM 1.1) % after isoflavone treatment compared with 12.4 (SEM 1.0)% after placebo treatment (P=0.03). NOx increased from 27.7 (SEM 2.7) to 31.1 (SEM 3.2) microM after isoflavones treatment compared with 25.4 (SEM 1.5) to 20.4 (SEM 1.1) microM after placebo treatment (P=0.003) and a significant increase in the NOx:ET-1 ratio (P=0.005) was observed after the isoflavone treatment compared with placebo. A significant difference in SAC after the isoflavone and placebo treatment was observed (P=0.04). No significant difference was found in FMD, IAC, BP and ET-1. In conclusion, 8 weeks' consumption of cereals bars enriched with 50 mg soya isoflavones/d increased plasma NOx concentrations and improved endothelium-independent vasodilation in healthy postmenopausal women.     

Soybean isoflavones reduce postmenopausal bone resorption in female Japanese immigrants in Brazil: a ten-week study

OBJECTIVE: Some human studies and animal models of experimental osteoporosis have shown that soy isoflavones may be effective on bone health. In this study, we carried out an intervention study to explore the effects of dietary isoflavone on bone metabolism. METHODS: Forty healthy female postmenopausal Japanese immigrants living in Brazil were divided into two groups: isoflavone-administered (n = 20) or placebo (n = 20). Subjects in the isoflavone-administered group ingested 37.3 mg per day for 10 weeks. The collection of 24-hour urine and the measurement of bone stiffness were performed at 0 and 10 weeks. Urinary excretion of isoflavones and bone resorption markers were analyzed. RESULTS: Urinary isoflavone excretion in the isoflavone-administered group was significantly increased at weeks 3 and 10. Urinary excretion of bone resorption markers was reduced in the isoflavone-administered group, while the placebo group did not show any significant reduction. Differences in levels of urinary isoflavones and bone resorption markers between the two groups were significant. CONCLUSION: This study demonstrated that the bone resorption was associated with the intake of soy isoflavones in postmenopausal women, and continuous dietary intake of isoflavone may inhibit postmenopausal osteoporosis.     

Influence of inulin on plasma isoflavone concentrations in healthy postmenopausal women

BACKGROUND: Bacterial intestinal glucosidases exert an important role in isoflavone absorption. Insoluble dietary fibers such as inulin may stimulate the growth of these bacteria in the colon and, hence, stimulate the absorption of these substances in subjects who may need isoflavone supplementation. OBJECTIVE: The objective was to assess the influence of inulin on plasma isoflavone concentrations after intake of soybean isoflavones in healthy postmenopausal women. DESIGN: Twelve healthy postmenopausal women participated in a randomized, double-blind, crossover study. They consumed 40 mg of a conjugated form of soybean isoflavones (6 mg daidzein and 18 mg genistein as free form) with or without 3.66 g inulin twice daily in two 21-d experimental phases. Blood samples were collected 0, 1, 2, 3, 4, 6, 10, 12, and 24 h after intake of isoflavones with breakfast and dinner at the end of each 21-d experimental phase. Plasma concentrations of isoflavones were assessed by HPLC with an electrochemical detector. RESULTS: Plasma 24-h areas under the curve indicated that the intake of soybean isoflavones with inulin for 21 d was followed by higher plasma concentrations of daidzein and genistein (38% and 91%, respectively) compared with the formulation without inulin. Furthermore, the time for the maximum concentration of daidzein and genistein appeared to be lower after the 21-d intake of soybean isoflavones, with or without inulin. However, the time for the maximum concentration of daidzein and genistein after supplementation with the inulin-containing formulation on day 21 was not significantly different from that after supplementation with the formulation without inulin. CONCLUSIONS: Inulin may increase the apparent plasma concentrations of the soybean isoflavones daidzein and genistein in postmenopausal women. The higher plasma concentrations of the 2 isoflavones suggests that the absorption of each was facilitated by the presence of inulin.     

Soy isoflavones improve plasma lipids in normocholesterolemic and mildly hypercholesterolemic postmenopausal women

BACKGROUND: Soy-protein consumption is known to reduce plasma total and LDL cholesterol concentrations. However, the responsible soy component or components and the magnitude of effects in normocholesterolemic and mildly hypercholesterolemic subjects are unclear. OBJECTIVE: The present study examined the effects of soy isoflavone consumption on plasma concentrations of triacylglycerol, apolipoprotein (apo) A-I, apo B, lipoprotein(a), and total, LDL, and HDL cholesterol and on LDL peak particle diameter in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. DESIGN: In a randomized crossover trial, fasting plasma samples were obtained from 18 postmenopausal women throughout three 93-d periods of daily isolated soy protein (ISP) consumption providing an average of 7.1 +/- 1.1 (control), 65 +/- 11 (low isoflavone), or 132 +/- 22 (high isoflavone) mg isoflavones/d. RESULTS: Compared with values measured during the control diet, the plasma LDL cholesterol concentration was 6.5% lower (P < 0.02) during the high-isoflavone diet and the ratio of LDL to HDL cholesterol was 8.5% and 7.7% lower during the low- and high-isoflavone diets, respectively (P < 0.02). Isoflavone consumption did not significantly affect plasma concentrations of total or HDL cholesterol, triacylglycerol, apo A-I, apo B, or lipoprotein(a) or the LDL peak particle diameter. CONCLUSIONS: Consumption of isoflavones as a constituent of ISP resulted in small but significant improvements in the lipid profile in normocholesterolemic and mildly hypercholesterolemic postmenopausal women. Although the effects were small, it is possible that isoflavones may contribute to a lower risk of coronary heart disease if consumed over many years in conjunction with other lipid-lowering strategies.     

Soybean Isoflavones Reduce Postmenopausal Bone Resorption in Female Japanese Immigrants in Brazil: A Ten-Week Study

Objective: Some human studies and animal models of experimental osteoporosis have shown that soy isoflavones may be effective on bone health. In this study, we carried out an intervention study to explore the effects of dietary isoflavone on bone metabolism.

Methods: Forty healthy female postmenopausal Japanese immigrants living in Brazil were divided into two groups: isoflavone-administered (n = 20) or placebo (n = 20). Subjects in the isoflavone-administered group ingested 37.3 mg per day for 10 weeks. The collection of 24-hour urine and the measurement of bone stiffness were performed at 0 and 10 weeks. Urinary excretion of isoflavones and bone resorption markers were analyzed.

Results: Urinary isoflavone excretion in the isoflavone-administered group was significantly increased at weeks 3 and 10. Urinary excretion of bone resorption markers was reduced in the isoflavone-administered group, while the placebo group did not show any significant reduction. Differences in levels of urinary isoflavones and bone resorption markers between the two groups were significant.

Conclusion: This study demonstrated that the bone resorption was associated with the intake of soy isoflavones in postmenopausal women, and continuous dietary intake of isoflavone may inhibit postmenopausal osteoporosis.