Consumption Of Isoflavones Research Articles

Simultaneous determination of soy isoflavone glycosides, daidzin and genistin by monoclonal antibody-based highly sensitive indirect competitive enzyme-linked immunosorbent assay

Soy isoflavones are known as major bioactive compounds in soybean (Glycine max), which is an indispensable food. Despite their utility, the consumption of isoflavones has recently been limited because they exhibit oestrogenic and topoisomerase II inhibitory effects. To assess their intake limitation, accurate, sensitive, and effective quantitative analyses are necessary. In this study, we produced the monoclonal antibody (MAb) against daidzin (DZ) and applied it to an indirect competitive enzyme-linked immunosorbent assay (icELISA) for the simultaneous determination of DZ and genistin (GEN), which are known as two major soy isoflavone glycosides in soy products. Using the DZ-MAb, we developed a sensitive icELISA method, where the limit of detection for DZ and GEN was 1.95ng/ml. Several validation analyses revealed that the icELISA is sufficiently accurate and sensitive to be used to assess the overconsumption of soy isoflavones, which would lead to the safe dietary intake of soy products.

Soy food consumption, cardiometabolic alterations and carotid intima-media thickness in Chinese adults

Background and aimThe associations between soy food consumption, cardiometabolic disturbances and subclinical atherosclerosis remain controversial due to limited evidence. We examined the associations of habitual soy food consumption with cardiometabolic disturbances and carotid intima-media thickness (CIMT). Methods and resultsWe included 2939 subjects (2135 women and 804 men) aged 50–75 years in this community-based cross-sectional study. Dietary data and other covariates were collected using interviewer-administered questionnaires. We determined CIMT in relation to each subject's common carotid artery, internal carotid artery, carotid bifurcation, blood lipids, glucose and urine acid, blood pressure and waist circumference. A logistic regression model was applied to estimate the odd ratios (ORs) and 95% confidence intervals (CIs), and linear regression was used to estimate the regression coefficient and 95% CIs. After adjusting for potential confounders, we found that greater consumption of soy protein (6.1 vs. 0.5 g/d) was inverse associated with the presence of elevated total cholesterol (TC), dyslipidemia, abdominal obesity and hyperuricemia in women, and with abdominal obesity in men, although no significant sex-soy interactions were observed (P: 0.145–0.985). The consumption of soy protein and isoflavones was inversely associated with the number of cardiometabolic disturbances among women, but not men. There were no significant associations of soy protein and isoflavones with CIMT thickening and other cardiometabolic disturbances. ConclusionGreater soy consumption was associated with a lower presence of elevated TC, dyslipidemia, hyperuricemia and less number of cardiometabolic disturbances components in women.

Dietary isoflavone intake is associated with evoked responses to inflammatory cardiometabolic stimuli and improved glucose homeostasis in healthy volunteers

Background and aimsConsumption of foods that modulate inflammatory stress in genetically-prone individuals may influence development of cardiometabolic diseases. Isoflavones in soy-derived foods function as phytoestrogens, have antioxidant and anti-inflammatory activity, inhibit protein-tyrosine kinase activity, and may be atheroprotective. We examined the relationship between soy food consumption and inflammatory responses to endotoxemia, postprandial responses to oral lipid tolerance test (OLTT), and insulin sensitivity from frequently sampled intravenous tolerance tests (FSIGTT). Methods and resultsWe administered low-dose endotoxin (LPS 1 ng/kg) to induce transient endotoxemia in young, healthy volunteers (N = 215) of African (AA), and European (EA) ancestry as part of the GENE Study. We further supported these findings in two independent samples: the MECHE Study and NHANES. Soy food consumption was a significant predictor of peak cytokine response following LPS. Individuals with moderate-high (>1.48 mg/day, N = 65) vs. low-no (<1.48 mg/day, N = 150) isoflavone consumption had significantly higher tumor necrosis factor alpha (TNFα) post-LPS (AUC, P = 0.009). Further, high-isoflavone consumers were protected against inflammation-induced decline in insulin sensitivity (SI) in GENE. We observed significant differences by soy consumption in the interferon gamma (IFNγ) response to OLTT, and the insulin response to OGTT in MECHE, as well as significantly lower fasting insulin, and 2-hour glucose post-OGTT in EA NHANES subjects. ConclusionWe demonstrate that soy consumption may influence inflammatory and metabolic responses. In research of nutritional exposures, measuring evoked phenotypes may be more informative than describing resting characteristics.The GENE Study was registered under NCT00953667 and the MECHE Study under NCT01172951, both at clinicaltrials.gov.

Abstract P317: Serum Soy Isoflavones Are Inversely Associated With Coronary Artery Calcification In A Population-based Sample Of 299 Men In Japan

Objectives: Epidemiological studies in Asia where consumption of soy isoflavones (ISF) are regular and high implicated that isoflavones are protective against coronary heart disease (CHD), especially in post-menopausal women. There is a lack of data on the association of isoflavones with atherosclerosis, especially in men. We aim to determine a cross sectional association of serum ISF with coronary artery calcification (CAC) in men in Japan. Methods: A population-based sample of 299 men aged 40-49 years in Japan was examined for CAC and other risk factors in 2002-06. Electron-beam CT was used to evaluate CAC. Stored serum samples were analyzed for ISF (genistein and daidzein). We defined serum ISFs as the sum of genistein and daidzein. Presence of CAC was defined as coronary calcium score ≥ 10. Because the distribution of serum ISF is skewed, we evaluated quartile of serum ISF and analyzed the association of ISF with the presence of CAC using a general linear model. Findings: The median value (interquartile range) of ISF was 517 (195, 1,147) nM/l. Serum ISF had a significant inverse association with CAC in crude analysis. After adjusting for age, LDL-C, smoking, and BMI, each of which had a significant univariate association with CAC, the inverse association of ISF with CAC remained, with littel change in point estimates. After further adjusting for other risk factors as well as serum levels of long-chain n-3 polyunsaturated fatty acids, the inverse association remained. Conclusions: Serum levels of ISF in Japanese men in Japan had an inverse association of CAC, suggesting that ISF at the levels Japanese in Japan regularly consume have anti-atherogenic properties in men.

Soy food frequency questionnaire does not correlate with baseline isoflavone levels in patients with bladder cancer

The isoflavone genistein, a natural soy product with receptor tyrosine kinase-inhibiting activity, as well as phytoestrogenic and other potential anticarcinogenic effects, is being studied as an anticancer agent. Since isoflavones are commonly consumed in food products containing soy proteins, a method to control for baseline isoflavone consumption is needed. HPLC was used to evaluate baseline plasma and urine concentrations of isoflavone in fifty-four participants with bladder cancer enrolled on a phase II chemoprevention study of G-2535. The soy food frequency questionnaire was used to assess participant's baseline soy intake. The association between baseline isoflavone concentrations and intakes for genistein and daidzein was assessed by the Spearman's rank correlation coefficient. The majority of participants had no detectable genistein or daidzein in plasma at baseline. The median and range of values were 0 (0-1480) nmol/L for genistein, and 0 (0-1260) nmol/L for daidzein. In urine, the median and range of values were 91.0 (0-9030) nmol/L for genistein and 623 (0-100,000) nmol/L for daidzein. The median and range of weekly estimated genistein intake was 0 (0-236) mg/wk; the median and range of weekly estimated daidzein intake was 0 (0-114) mg/wk. There was no relationship to soy intake as measured by the food frequency questionnaire and baseline isoflavone levels in plasma or urine and the Spearman's rank correlation coefficients were not significant. The soy food frequency questionnaire did not correlate with plasma or urine concentrations of either isoflavone. Alternative methods for controlling for soy consumption, including measuring plasma and urine concentrations, in isoflavone chemoprevention trials should be considered.

Cardiovascular Risks in Relation to Daidzein Metabolizing Phenotypes among Chinese Postmenopausal Women

BackgroundStudies suggested that the inter-individual differences in metabolizing isoflavone daidzein to equol or O-desmethylangolensin (ODMA) might explain the inconsistency of the soy/isoflavones efficacy on cardiovascular health.ObjectivesThe study aims to evaluate the relationship between equol and ODMA phenotypes and cardiovascular risks with habitual isoflavone consumption in Chinese postmenopausal women.MethodsThis is a cross-sectional study among 726 prehypertensive postmenopal women who were screened for a randomized controlled trial. 648 women returned a daidzein-challenged urine samples for determination of equol and O-DMA production. 595 attended clinic visits for assessment of cardiovascular risks including body composition, blood pressure (BP), serum lipids, uric acid, high sensitivity C-reactive protein (hs-CRP), fasting glucose and free fatty acid (FFA).ResultsThe prevalences of equol and O-DMA producers were 53.2% and 60.9% respectively. Equol producers had higher fat free mass (p = 0.001), lower systolic (p = 0.01) and diastolic (p = 0.01) BP, serum triglyceride (p = 0.023), hs-CRP (p = 0.015) and FFA (p = 0.001) than non-producers. O-DMA producers had lower body fat% (p = 0.032), SBP (p = 0.02), total cholesterol (p = 0.002) than non-producers. The significant differences remained after further adjustment for potential confounders. The habitual soy isoflavones intake had little relation to cardiovascular risk factors in either equol/O-DMA producer phenotypes.ConclusionEquol/O-DMA producers had more favorable cardiovascular risk profiles than non-producers in prehypertensive postmenopausal women.

Lactobacillus casei Shirota enhances the preventive efficacy of soymilk in chemically induced breast cancer

Soy foods are known to be effective for breast cancer prevention. The habitual consumption of soy isoflavones in combination with the probiotic Lactobacillus casei Shirota (LcS) was shown to decrease the risk of breast cancer occurrence in our previous population-based case-controlled study among Japanese women. The present study aimed to elucidate the cooperative prevention mechanism of soymilk and LcS using an animal carcinogenic model. Female Sprague-Dawley rats received a high-fat, AIN-76A diet containing soymilk, LcS, both soymilk and LcS, or none and were orally exposed to 2-amino-1-methyl-6-penylimidazo[4,5-b]pyridine at a dose of 85 mg/kg bodyweight eight times for 2 weeks. The development of palpable mammary tumors was monitored for 17 weeks. Tumor tissues were immunohistochemically examined for estrogen receptor (ER)-α, Ki-67 and CD34. Compared with the control group, the incidence and multiplicity of mammary tumors were reduced by soymilk alone and soymilk in combination with LcS, while tumor volume was decreased by LcS alone and LcS in combination with soymilk. An immunohistochemical analysis revealed that soymilk in combination with LcS more effectively reduced the numbers of ER-α-positive and Ki-67-positive cells in tumors than soymilk alone and that both soymilk and LcS inhibited tumor angiogenesis. These results demonstrated that soymilk prevents the development of mammary tumors and that LcS suppresses tumor growth, potentially enhancing the preventive efficacy of soymilk. The habitual consumption of LcS in combination with soymilk might be a beneficial dietary style for breast cancer prevention.

Habitual Consumption of Soy Products and Risk of Nasopharyngeal Carcinoma in Chinese Adults: A Case-Control Study

Background and ObjectivesMany studies have shown a negative association between the consumption of soy products and the risk of some cancers, but little is known about the effect of soy consumption on nasopharyngeal carcinoma. We assessed the association between the consumption of soy products on nasopharyngeal carcinoma risk in Chinese individuals.MethodsThis case-control study included 600 (448 males and 152 females) incident cases of nasopharyngeal carcinoma, and an equal number of controls, matched according to gender, age (± 3 y) and household type to the nasopharyngeal carcinoma cases. All subjects were recruited from hospitals in Guangzhou, China. A face-to-face interview was conducted with each study individual to collect general information and habitual dietary intake using a 78-item quantitative food-frequency questionnaire. Odds ratios and their 95% confidence intervals were estimated using conditional logistic regression analyses.ResultsThe median intakes of soy foods (in protein) were 0.5/0.5, 1.4/1.7, 2.7/3.3 and 6.1/7.7 (male/female) g/d in the quartiles 1 to 4. Both univariate and multivariate analyses showed no significant association between the consumption of soy proteins or soy isoflavones and the risk of nasopharyngeal carcinoma. The adjusted odds ratios (95% confidence intervals) between extreme quartiles were 0.97 (0.66-1.45) for soy proteins and 0.97 (0.66-1.42) for total isoflavones. Null associations were also observed between intake of the individual isoflavones daidzein, genistein and glycitein and NPC risk, with adjusted odds ratios for the extreme quartiles ranging between 0.73 and 1.23.ConclusionHabitual consumption of soy products had no significant effect on the risk of nasopharyngeal carcinoma in Chinese adults with a relatively low intake.

Efek Radiasi pada Penurunan Estrogen yang Disertai Konsumsi Isoflavon untuk Mencegah Menopause Dini pada Terapi Radiasi

Radiation effect is one of which is the reduction in estrogen. Gamma rays are ionizing radiation that can lead to cell damage due to free radicals produced when the radiation interacts with cells. The level of cell damage can be minimized by antioxidants. Antioxidants used is the isoflavones of soy milk, so it can be know the effects of radiation on the decline in estrogen that accompanied the consumption of isoflavones to prevent early menopause in radiation therapy. Radiation exposure are given fractionally. The dose was 1,5 Gy in once exposure and given every 3 days up to a maximum dose of the treatment groups. Consumption of soy milk to the mice done orally. Blood was drawn and serum was made. Serum estrogen levels will be tested by using ELISA. The results showed that the ovarium disfunction and stress experienced by mice (Mus musculus) caused by radiation exposure. Maximum results in the consumption of isoflavones on estrogen levels the subject to radiation exposure is 44 mg/day and 131 mg/day of soy milk. This isoflavone dose increase in estrogen levels maximumly. The increase was the response given by the body's immune system of mice due to start reacting and isoflavones are phytoestrogens.

Short-Term Soy Isoflavone Intervention in Patients with Localized Prostate Cancer: A Randomized, Double-Blind, Placebo-Controlled Trial

PurposeWe describe the effects of soy isoflavone consumption on prostate specific antigen (PSA), hormone levels, total cholesterol, and apoptosis in men with localized prostate cancer.Methodology/Principal FindingsWe conducted a double-blinded, randomized, placebo-controlled trial to examine the effect of soy isoflavone capsules (80 mg/d of total isoflavones, 51 mg/d aglucon units) on serum and tissue biomarkers in patients with localized prostate cancer. Eighty-six men were randomized to treatment with isoflavones (n = 42) or placebo (n = 44) for up to six weeks prior to scheduled prostatectomy. We performed microarray analysis using a targeted cell cycle regulation and apoptosis gene chip (GEArrayTM). Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol were analyzed at baseline, mid-point, and at the time of radical prostatectomy. In this preliminary analysis, 12 genes involved in cell cycle control and 9 genes involved in apoptosis were down-regulated in the treatment tumor tissues versus the placebo control. Changes in serum total testosterone, free testosterone, total estrogen, estradiol, PSA, and total cholesterol in the isoflavone-treated group compared to men receiving placebo were not statistically significant.Conclusions/SignificanceThese data suggest that short-term intake of soy isoflavones did not affect serum hormone levels, total cholesterol, or PSA.Trial RegistrationClinicalTrials.gov NCT00255125

Probiotic Beverage with Soy Isoflavone Consumption for Breast Cancer Prevention: A Case-control Study

The purpose of this study is to evaluate how beverages containing Lactobacillus casei Shirota (BLS) and soy isoflavone consumption since adolescence affected the incidence of breast cancer. In a population-based case-control study, three hundred and six cases with breast cancer and 662 controls aged 40 to 55 were matched for age and residential area and included in the analyses. Diet, lifestyle and other breast cancer risk factors were investigated using the self-administered questionnaire and interview. Odds ratios (ORs) of BLS and soy isoflavone consumption for breast cancer incidence were independently and jointly estimated using a conditional logistic regression. The ORs of BLS consumption (≥ four times a week against < four times a week) was 0.65 and statistically significant (p = 0.048). The analysis of association between soy consumption and breast cancer incidence showed the more the isoflavone consumption is, the lower the odds of breast cancer becomes. Adjusted ORs for breast cancer in the second, the third and the fourth quartiles of soy consumption against the first quartile were 0.76, 0.53 and 0.48, respectively (trend test, p = 0.0002). The BLS-isoflavone interaction was not statistically significant; however, a biological interaction was suggested. Regular consumption of BLS and isoflavones since adolescence was inversely associated with the incidence of breast cancer in Japanese women.

Long time exposure to soy/isoflavone-rich diet enhances testicular and prostate health in Long-Evans rats

Soy isoflavone consumption appears to be beneficial for several health parameters. We report the influence of (lifelong exposure to) a high soy/isoflavone (High-Iso) compared to a low soy/isoflavone (Low-Iso) diet on body weight (BW), white adipose tissue (WAT) deposition, prostate weight (PW), testicular weight (TW), and testosterone levels in young adult male Long-Evans rats. WAT deposition and the WAT/BW ratios were significantly less in High-Iso vs. the Low-Iso fed animals. TW and TW/BW ratios were significantly greater in High-Iso vs. Low-Iso fed animals. Sertoli cell area, seminiferous tubule lumens and seminiferous tubule areas were significantly greater in High-Iso vs. Low-Iso animals. These data suggest that consumption of a soy diet high in isoflavone/polyphenolic molecules from conception appear to be beneficial in decreasing PW and WAT deposition while increasing TW, Sertoli cell area and seminiferous tubule volume.

Self-reported menopausal symptoms in a racially diverse population and soy food consumption

ObjectivesEvaluate the association of self-reported vasomotor symptom (VMS) frequency with race/ethnicity among a diverse midlife US population and explore menopause symptom differences by dietary soy isoflavone (genistein+daidzein) consumption. Study designCross-sectional population-based study of peri- and postmenopausal women, ages 45–58. OutcomesRecent VMS frequency, VMS ever; recent symptom bother (hot flashes, night sweats, headache and joint-ache). ResultsOf 18,500 potentially eligible women, 9325 returned questionnaires (50.4% response); 3691 were excluded (premenopausal, missing data, taking hormones). Of 5634 remaining women, 82.1% reported hot flashes ever, 73.1% reported night sweats ever; 48.8% and 38.6% reported recent hot flashes or night sweats, respectively. Compared with White women, Chinese, Japanese, Vietnamese, other Asian (each p<0.001) and Filipino (p<0.01) women less commonly reported ever having hot flashes; Asian women less commonly reported recent VMS bother (p<0.001). Black women more commonly reported hot flashes ever (p<0.05) and recent VMS bother (p<0.05). Compared with non-Hispanic White women, Hispanic women were less likely to report hot flashes (p<0.05) or night sweats (p<0.001) ever. Women were classified by isoflavone consumption: (1) none (n=1819), (2) 0.01–4.30mg/day (n=1931), (3) 4.31–24.99mg/day (n=1347) and (4) ≥25mg/day (n=537). There were no group differences in recent VMS number/day: (1) 7.0 (95% CI 6.5, 7.5); (2) 6.4 (95% CI 6.0, 7.1); (3) 7.0 (95% CI 6.3, 8.2); and (4) 6.8 (95% CI 6.1, 7.7). ConclusionsMenopausal symptoms, independent of isoflavone intake, varied considerably by race/ethnicity and were least common among Asian races.

Dietary isoflavone intake modulates evoked responses to cardiometabolic stimuli in healthy volunteers

Isoflavones, found in high concentrations in soy‐derived foods, function as phytoestrogens, have antioxidant and anti‐inflammatory activity, inhibit protein‐tyrosine kinase activity, and are thought to be atheroprotective. We hypothesized that habitual isoflavone intake modulates response to evoked endotoxemia and oral fat load.In the Genetics of Evoked Responses to Niacin and Endotoxemia (GENE) Study, we administered low dose endotoxin (LPS 1 ng/kg) to induce inflammation in young, healthy volunteers (N=215, 50% female) and administered a separate oral fat tolerance test (OFTT). Data were analyzed using linear regression models adjusted for race, gender, age and BMI.Dietary isoflavone intake was a significant predictor of plasma tumor necrosis factor alpha (TNFα) and interleukin 6 (IL‐6) post LPS. High (&gt;;1.5mg/day, N=64) vs low (&lt;1.5mg/day, N=151) isoflavone consumers had higher peak TNFα (64 vs 45 pg/ml, P=0.015) and peak IL‐6 (210 vs 160 pg/ml, P=0.06). Further, the high isoflavone group had significantly higher β‐hydroxybutyrate levels post‐OFTT (442 vs 332 μmol/L, 2 hours post fat load, P=0.02).Habitual isoflavone consumption may modulate disease development through effects on inflammatory and metabolic responses in humans. For investigating nutritional effects on disease development, measuring evoked phenotypes may be more informative than describing resting characteristics.The GENE Study was supported by NIH Grant UL1TR000003 as well as a NIH‐NHLBI SCCOR Project grant (P50‐HL‐083799) to MPR. JFF is supported by an AHA postdoctoral fellowship grant (12POST11840017).

Isoflavone consumption and risk of breast cancer: a dose-response meta-analysis of observational studies.

Epidemiologic studies that examine whether isoflavone consumption protects against breast cancer have yielded inconsistent results. The controversy focuses on the effects of the menopausal status and exposure dose of isoflavone. We aim to conduct a meta-analysis on the association between isoflavone intake and breast cancer risk by comprehensively assessing isoflavone exposure in the targeted populations. We searched PUBMED and EMBASE databases for case-control and cohort studies that assess the association between isoflavone intake and breast cancer risk. We extracted relative risks (RR) and odds ratios (OR) of different reported categories of isoflavone intake from each study. Fixed- or random-effects models were used to summarize dose-response data. Twenty-two studies were selected for the meta-analysis. Overall, the results showed that isoflavone reduced the breast cancer risk (a combined RR/OR of 0.68, 95% CI: 0.52-0.89) in Asian populations rather than Western populations (a combined RR/OR of 0.98, 95% CI: 0.87, 1.11) for the high-dose category. Further analysis showed that the intake of isoflavone in postmenopausal Asian women 0.46 (95% CI: 0.28-0.78) was better than premenopausal 0.63 (95% CI: 0.50-0.80) but similar in postmenopausal Western women 1.00 (95% CI: 0.98-1.02) and premenopausal 0.99 (95% CI: 0.87-1.12). Exposure to high isoflavone may be associated with a reduced breast cancer risk in Asian populations, especially in postmenopausal women. However, no significant difference in the studies of Western populations may be due to the low intake of isoflavone levels.

2-Heptyl-Formononetin Increases Cholesterol and Induces Hepatic Steatosis in Mice

Consumption of isoflavones may prevent adiposity, hepatic steatosis, and dyslipidaemia. However, studies in the area are few and primarily with genistein. This study investigated the effects of formononetin and its synthetic analogue, 2-heptyl-formononetin (C7F), on lipid and cholesterol metabolism in C57BL/6J mice. The mice were fed a cholesterol-enriched diet for five weeks to induce hypercholesterolemia and were then fed either the cholesterol-enriched diet or the cholesterol-enriched diet-supplemented formononetin or C7F for three weeks. Body weight and composition, glucose homeostasis, and plasma lipids were compared. In another experiment, mice were fed the above diets for five weeks, and hepatic triglyceride accumulation and gene expression and histology of adipose tissue and liver were examined. Supplementation with C7F increased plasma HDL-cholesterol thereby increasing the plasma level of total cholesterol. Supplementation with formononetin did not affect plasma cholesterol but increased plasma triglycerides levels. Supplementation with formononetin and C7F induced hepatic steatosis. However, formononetin decreased markers of inflammation and liver injury. The development of hepatic steatosis was associated with deregulated expression of hepatic genes involved in lipid and lipoprotein metabolism. In conclusion, supplementation with formononetin and C7F to a cholesterol-enriched diet adversely affected lipid and lipoprotein metabolism in C57BL/6J mice.

Evaluation of the Estrogenic Activity of Pueraria (Kudzu) Flower Extract and Its Major Isoflavones Using ER-Binding and Uterotrophic Bioassays

Pueraria flower extract (PFE) is a hot water extract of the Kudzu flower (Pueraria thomsonii). Tea made from dried Kudzu flower is widely used inChina, and PFE is utilized as a nutritional supplement inJapan. PFE contains unique isoflavones such as 6-hydroxygenistein 6,7-di-O-glucoside (6HGDG), tectorigenin 7-O-xylosylglucoside (TGXG), and tectoridin. 6HGDG is known to be metabolized into 6-hydroxygenistein, and TGXG and tectoridin are known to be metabolized into tectorigenin in the digestive tract. Isoflavones typically mimic the effects β-estradiol has on estrogen receptors (ERs) and may influence the female genital system in the case of excessive intake. As a result, the upper limit of safe daily consumption of soy isoflavones has been enforced inJapan. In the present study, ER-binding assays were performed using the EnBio estrogen receptor/cofactor assay system to compare the estrogenic activity of 6-hydroxygenistein and tectorigenin to that of the soy isoflavone genistein. In addition, uterotrophic bioassays were performed to investigate the estrogenic effects of PFE in vivo. The ER-binding assays revealed that the ER-binding affinities of 6-hydroxygenistein and tectorigenin were approximately 0.01 - 0.04 that of genistein. Soy isoflavone products also induced an increase in uterine wet and blotted weight at doses of 500 mg/kg and 1000 mg/kg, whereas PFE did not cause adverse estrogenic effects, even at a dose of 1000 mg/kg. Based on these results, PFE does not appear to contain compounds with strong estrogenic activity or cause adverse estrogenic effects in vivo. Importantly, the results of this study confirm the safety of PFE as a food supplement.

Effects of soybean isoflavones on reproductive parameters in Chinese mini-pig boars.

BackgroundSoybean isoflavones are structurally similar to mammalian estrogens and therefore may act as estrogen agonists or antagonists. However, it has not been determined if they have any negative effects on reproductive parameters in male livestock. Therefore, the objective of this study was to evaluate the effects of soybean isoflavones on male reproduction using Chinese mini-pig boars as a model. Fifty Xiang boars were randomly divided into five groups and fed diets containing 0, 125, 250, or 500 ppm soybean isoflavones or 0.5 ppm diethylstilbestrol for 60 days.ResultsDietary supplementation with 250 ppm of soy isoflavones markedly increased the testis index (P < 0.05), fructose content (P < 0.05), and α-glycosidase content in testicular tissue (P < 0.01), as well as increased the number of viable germ cells (P < 0.01) and the level of Bcl-2 protein (P < 0.01). However, 500 ppm of soybean isoflavones significantly reduced both testis and epididymis indexes (P < 0.05) and lactate dehydrogenase levels (P < 0.01), as well as reduced serum LH and testosterone levels (P < 0.05). High levels of soybean isoflavones also increased malondialdehyde levels (P < 0.05), as well as increased the numbers of early and late apoptotic germ cells (P < 0.01) and the level of Bax proteins (P < 0.05) in the testis.ConclusionsThe results of this study indicate that consumption of soy isoflavones at dietary levels up to 250 ppm did not adversely affect reproductive parameters in Chinese mini-pig boars whereas higher levels of soy isoflavones may adversely affect male reproduction.

Polymorphisms in genes involved in the metabolism and transport of soy isoflavones affect the urinary metabolite profile in premenopausal women following consumption of a commercial soy supplement as a single bolus dose

Genetic variation in relevant enzymes and transporters may contribute to discordant observations concerning health outcomes of dietary isoflavone consumption, so we examined the association of the UGT1A1*28 promoter polymorphism and of other SNPs with isoflavone metabolites in urine. We genotyped prospectively for polymorphisms in UGT1A1 (UGT1A1*28), LPH (666G>A), CBG (1368T>A), ABCG2 (421C>A), and ABCC2 (1249G>A) to select 100 women (18-50 years) to receive a commercial soy supplement as a single dose and collect all urine over 24 h for analysis by RP-HPLC. We observed large differences in isoflavone recovery (mean 39%, eightfold variation) and metabolites. Glucuronides were the major metabolites (72% of total). UGT1A1*28 was associated only with percentage of glycitein as sulphate (positive; p = 0.046), but excluding five participants with both minor alleles of CBG and ABCG2 uncovered additional associations with percentage of glycitein as glucuronide (negative; p = 0.028), combined isoflavones as sulphate (positive; p = 0.035) and sulphate-to-glucuronide ratio for combined isoflavones (positive; p = 0.036). CBG1368T>A, ABCG2 421C>A, and ABCC2 1249G>A were also associated with differences in isoflavone metabolites in urine. Genetic variation in UGT1A1, CBG, ABCG2, and ABCC2 influences isoflavone metabolism so may affect benefits of dietary consumption.

Prevention of Diabetes in db/db Mice by Dietary Soy Is Independent of Isoflavone Levels

Recent evidence points towards the beneficial use of soy proteins and isoflavones to improve glucose control and slow the progression of type 2 diabetes. Here, we used diabetic db/db mice fed a high soy-containing diet (SD) or a casein soy-free diet to investigate the metabolic effects of soy and isoflavones consumption on glucose homeostasis, hepatic glucose production, and pancreatic islet function. Male db/db mice fed with a SD exhibited a robust reduction in hyperglycemia (50%), correlating with a reduction in hepatic glucose production and preserved pancreatic β-cell function. The rapid decrease in fasting glucose levels resulted from an inhibition of gluconeogenesis and an increase in glycolysis in the liver of db/db mice. Soy consumption also prevented the loss of pancreatic β-cell mass and thus improved glucose-stimulated insulin secretion (3-fold), which partly accounted for the overall improvements in glucose homeostasis. Comparison of SD effects on hyperglycemia with differing levels of isoflavones or with purified isoflavones indicate that the beneficial physiological effects of soy are not related to differences in their isoflavone content. Overall, these findings suggest that consumption of soy is beneficial for improving glucose homeostasis and delaying the progression of diabetes in the db/db mice but act independently of isoflavone concentration.