Association of dietary soy genistein intake with lung function and asthma control: a post-hoc analysis of patients enrolled in a prospective multicentre clinical trial.
ABSTRACT: Broad dietary patterns have been linked to asthma but the relative contribution of specific nutrients is unclear. Soy genistein has important anti-inflammatory and other biological effects that might be beneficial in asthma. A positive association was previously reported between soy genistein intake and lung function but not with asthma exacerbations.To conduct a post-hoc analysis of patients with inadequately controlled asthma enrolled in a prospective multicentre clinical trial to replicate this association.A total of 300 study participants were included in the analysis. Dietary soy genistein intake was measured using the Block Soy Foods Screener. The level of soy genistein intake (little or no intake, moderate intake, or high intake) was compared with baseline lung function (pre-bronchodilator forced expiratory volume in 1 second (FEV(1))) and asthma control (proportion of participants with an episode of poor asthma control (EPAC) and annualised rates of EPACs over a 6-month follow-up period.Participants with little or no genistein intake had a lower baseline FEV(1) than those with a moderate or high intake (2.26 L vs. 2.53 L and 2.47 L, respectively; p=0.01). EPACs were more common among those with no genistein intake than in those with a moderate or high intake (54% vs. 35% vs. 40%, respectively; p<0.001). These findings remained significant after adjustment for patient demographics and body mass index.In patients with asthma, consumption of a diet with moderate to high amounts of soy genistein is associated with better lung function and better asthma control.
Project description:Soy isoflavone supplements are used to treat several chronic diseases, although the data supporting their use are limited. Some data suggest that supplementation with soy isoflavone may be an effective treatment for patients with poor asthma control.To determine whether a soy isoflavone supplement improves asthma control in adolescent and adult patients with poorly controlled disease.Multicenter, randomized, double-blind, placebo-controlled trial conducted between May 2010 and August 2012 at 19 adult and pediatric pulmonary and allergy centers in the American Lung Association Asthma Clinical Research Centers network. Three hundred eighty-six adults and children aged 12 years or older with symptomatic asthma while taking a controller medicine and low dietary soy intake were randomized, and 345 (89%) completed spirometry at week 24.Participants were randomly assigned to receive soy isoflavone supplement containing 100 mg of total isoflavones (n=193) or matching placebo (n=193) in 2 divided doses administered daily for 24 weeks.The primary outcome measure was change in forced expiratory volume in the first second (FEV1) at 24 weeks. Secondary outcome measures were symptoms, episodes of poor asthma control, Asthma Control Test score (range, 5-25; higher scores indicate better control), and systemic and airway biomarkers of inflammation.Mean changes in prebronchodilator FEV1 over 24 weeks were 0.03 L (95% CI, -0.01 to 0.08 L) in the placebo group and 0.01 L (95% CI, -0.07 to 0.07 L) in the soy isoflavone group, which were not significantly different (P?=?.36). Mean changes in symptom scores on the Asthma Control Test (placebo, 1.98 [95% CI, 1.42-2.54] vs soy isoflavones, 2.20 [95% CI, 1.53-2.87]; positive values indicate a reduction in symptoms), number of episodes of poor asthma control (placebo, 3.3 [95% CI, 2.7-4.1] vs soy isoflavones, 3.0 [95% CI, 2.4-3.7]), and changes in exhaled nitric oxide (placebo, -3.48 ppb [95% CI, -5.99 to -0.97 ppb] vs soy isoflavones, 1.39 ppb [95% CI, -1.73 to 4.51 ppb]) did not significantly improve more with the soy isoflavone supplement than with placebo. Mean plasma genistein level increased from 4.87 ng/mL to 37.67 ng/mL (P?<?.001) in participants receiving the supplement.Among adults and children aged 12 years or older with poorly controlled asthma while taking a controller medication, use of a soy isoflavone supplement, compared with placebo, did not result in improved lung function or clinical outcomes. These findings suggest that this supplement should not be used for patients with poorly controlled asthma.clinicaltrials.gov Identifier: NCT01052116.
Project description:BACKGROUND:The 4G4G genotype of plasminogen activator inhibitor 1 (PAI-1) is associated with increased plasma PAI-1 levels and poor asthma control. Previous studies suggest that soy isoflavones can reduce PAI-1 levels. OBJECTIVE:We sought to investigate PAI-1 genotype-specific differences of the soy isoflavone response in asthma outcomes. METHODS:A PAI-1 functional polymorphism (rs1799768, 4G5G) was characterized in subjects with poorly controlled asthma enrolled in a randomized clinical trial of soy isoflavones (n = 265). Genotype-specific treatment responses on asthma outcomes were compared between soy isoflavones and placebo. Normal human bronchial epithelial cells were cultured with or without TGF-?1, genistein, or both, and PAI-1 levels were measured. RESULTS:The 4G4G/4G5G genotype was associated with a greater risk for allergy-related worsened asthma symptoms and eczema at baseline compared with the 5G5G genotype. There was a significant interaction between the genotype and soy isoflavone intervention on oral corticosteroid use for asthma exacerbation (P = .005). In a subgroup analysis soy isoflavones significantly reduced the use of oral corticosteroids (number of events/person-year) by 4-fold compared with placebo in the 4G4G/4G5G genotype (0.2 vs 0.8; relative risk, 0.28; P < .001) but not in the 5G5G genotype. Soy isoflavones reduced plasma PAI-1 levels compared with placebo. Genistein treatment reduced TGF-?1-induced PAI-1 production in normal human bronchial epithelial cells. CONCLUSIONS:This study demonstrates that soy isoflavone treatment provides a significant benefit in reducing the number of severe asthma exacerbations in asthmatic patients with the high PAI-1-producing genotype. PAI-1 polymorphisms can be used as a genetic biomarker for soy isoflavone-responsive patients with asthma.
Project description:There is a growing interest in assessing dietary intake more accurately across different population groups, and biomarkers have emerged as a complementary tool to replace traditional dietary assessment methods. The purpose of this study was to conduct a systematic review of the literature available and evaluate the applicability and validity of biomarkers of legume intake reported across various observational and intervention studies. A systematic search in PubMed, Scopus, and ISI Web of Knowledge identified 44 studies which met the inclusion criteria for the review. Results from observational studies focused on soy or soy-based foods and demonstrated positive correlations between soy intake and urinary, plasma or serum isoflavonoid levels in different population groups. Similarly, intervention studies demonstrated increased genistein and daidzein levels in urine and plasma following soy intake. Both genistein and daidzein exhibited dose-response relationships. Other isoflavonoid levels such as O-desmethylangolensin (O-DMA) and equol were also reported to increase following soy consumption. Using a developed scoring system, genistein and daidzein can be considered as promising candidate markers for soy consumption. Furthermore, genistein and daidzein also served as good estimates of soy intake as evidenced from long-term exposure studies marking their status as validated biomarkers. On the contrary, only few studies indicated proposed biomarkers for pulses intake, with pipecolic acid and S-methylcysteine reported as markers reflecting dry bean consumption, unsaturated aliphatic, hydroxyl-dicarboxylic acid related to green beans intake and trigonelline reported as marker of peas consumption. However, data regarding criteria such as specificity, dose-response and time-response relationship, reliability, and feasibility to evaluate the validity of these markers is lacking. In conclusion, despite many studies suggesting proposed biomarkers for soy, there is a lack of information on markers of other different subtypes of legumes. Further discovery and validation studies are needed in order to identify reliable biomarkers of legume intake.
Project description:Kawasaki disease (KD) is an acute vasculitis affecting children. Incidence of KD varies according to ethnicity and is highest in Asian populations. Although genetic differences may explain this variation, dietary or environmental factors could also be responsible. The objectives of this study were to determine dietary soy and isoflavone consumption in a cohort of KD children just before disease onset and their mothers' intake during pregnancy and nursing. We tested the hypothesis that soy isoflavone consumption is associated with risk of KD in US children, potentially explaining some of the ethnic-cultural variation in incidence. We evaluated soy food intake and isoflavone consumption in nearly 200 US KD cases and 200 age-matched controls using a food frequency questionnaire for children and in their mothers. We used a logistic regression model to test the association of isoflavones and KD. Maternal surveys on soy intake during pregnancy and nursing showed no significant differences in isoflavone consumption between groups. However, we identified significantly increased KD risk in children for total isoflavone (odds ratio [OR], 2.33; 95% confidence interval [CI], 1.37-3.96) and genistein (OR, 2.46; 95% CI, 1.46-4.16) intakes, when comparing high soy consumers vs nonconsumers. In addition, significantly increased KD risk occurred in Asian-American children with the highest consumption (total isoflavones: OR, 7.29; 95% CI, 1.73-30.75; genistein: OR, 8.33; 95% CI, 1.92-36.24) compared to whites. These findings indicate that childhood dietary isoflavone consumption, but not maternal isoflavone intake during pregnancy and nursing, relates to KD risk in an ethnically diverse US population.
Project description:The red flour beetle Tribolium castaneum is a known pest of various grains and stored-products such as wheat flours; however, T. castaneum feeds on and infests soybean and soy products. For more than 60 years, soy flour has been suggested to be unstable food for Tribolium spp. because it causes larval development failure. However, it remains unknown whether soy flour affects adult beetles. The objective of the present study was to examine the effects of soy flour and its related isoflavones against T. castaneum using an artificial dietary intake assay. Beetles were fed gypsum (a non-digestible compound) mixed with either water (control) or soy flour. Significantly fewer beetles survived after being fed the soy flour treatment. Although the soy isoflavone genistein, a defensive agent and secondary metabolite, decreased the T. castaneum adult survival, it required a long time to have a lethal effect. Therefore, the cytotoxic effects of soy flour, i.e., the rapid biological responses following isoflavone addition, were also examined using a cultured cell line derived from T. castaneum. Both genistin and genistein significantly affected the survival of the cultured cells, although genistein had a stronger lethal effect. This study demonstrated the toxicity of genistein found in soybean against T. castaneum cultured cells within 24 h period. Genistein may be used as an oral toxin biopesticide against T. castaneum.
Project description:Systemic inflammation has been associated with reduced lung function. Adhesion molecules, such as intercellular adhesion molecule (ICAM)-1 and P-selectin, figure importantly in initiating the inflammatory response. We studied the association between ICAM-1 and P-selectin concentrations and lung function in the Coronary Artery Risk Development in Young Adults study.Spirometry testing was conducted at years 5, 10, and 20. ICAM-1 and P-selectin were assayed at year 15.Complete data were obtained from 2,455 participants. We first predicted year-20 lung function from year-15 ICAM-1 concentration data. After controlling for race, gender, height, age, physical activity, smoking status, alcohol intake, BMI, and asthma status, all taken at year 15, the year-20 FVC was 164 mL higher (p < 0.0001) and FEV(1) was 164 mL higher (p = 0.0003) in the lowest ICAM-1 concentration quartile than the highest ICAM-1 quartile, whereas the FEV(1)/FVC ratio showed no association (p = 0.25). We then predicted the year-15 ICAM-1 concentration from year-5 lung function and change in lung function (year 10 - year 5). The year-15 ICAM-1 concentration was about 13 ng/mL higher in the lowest vs highest quartile of either the year-5 FVC (p = 0.01) or year-5 FEV(1) (p = 0.005). Year-15 ICAM-1 concentration was unrelated to year-5 FEV(1)/FVC ratio. Greater loss in FVC and FEV(1) (year 10 - year 5) also was associated with higher year-15 ICAM-1 concentrations. Associations between P-selectin and lung function followed a similar but weaker pattern to that observed for ICAM-1.These data suggest a bidirectional association between circulating adhesion molecules, such as ICAM-1 and P-selectin, and pattern of lung function change in adults.
Project description:To investigate the effects soy isoflavones in established cancers, the role of genistein, daidzein, and combined soy isoflavones was studied on progression of subcutaneous tumors in nude mice created from green fluorescent protein (GFP) tagged-MDA-MB-435 cells. Following tumor establishment, mice were gavaged with vehicle or genistein or daidzein at 10 mg/kg body weight (BW) or a combination of genistein (10 mg/kg BW), daidzein (9 mg/kg BW), and glycitein (1 mg/kg BW) three times per week. Tumor progression was quantified by whole body fluorescence image analysis followed by microscopic image analysis of excised organs for metastases. Results show that daidzein increased while genistein decreased mammary tumor growth by 38 and 33% respectively, compared to vehicle. Daidzein increased lung and heart metastases while genistein decreased bone and liver metastases. Combined soy isoflavones did not affect primary tumor growth but increased metastasis to all organs tested, which include lung, liver, heart, kidney, and bones. Phosphoinositide-3-kinase (PI3-K) pathway real time PCR array analysis and western blotting of excised tumors demonstrate that genistein significantly downregulated 10/84 genes, including the Rho GTPases RHOA, RAC1, and CDC42 and their effector PAK1. Daidzein significantly upregulated 9/84 genes that regulate proliferation and protein synthesis including EIF4G1, eIF4E, and survivin protein levels. Combined soy treatment significantly increased gene and protein levels of EIF4E and decreased TIRAP gene expression. Differential regulation of Rho GTPases, initiation factors, and survivin may account for the disparate responses of breast cancers to genistein and daidzein diets. This study indicates that consumption of soy foods may increase metastasis.
Project description:A published meta-analysis pooled individual studies by using the study-specific odds ratio (OR) or relative risk (RR) for the highest vs. lowest category of soy or isoflavone intake from each study, but it should be problematic to make comparison between studies/populations for lung cancer risk as the quantiles are so different from different studies/populations. Therefore, we conducted a meta-analysis to explore the association between exposure of estimated daily soy protein intake in grams and lung cancer risk. We extracted ORs or RRs and 95% confidence intervals (CIs), converted them to the estimated ones for daily soy protein intake and pooled them using fixed or random effects models from 11 epidemiologic studies. Overall, the inverse association between daily grams of soy protein intake and risk of lung cancer was borderline statistically significant (OR = 0.98, 95% CI = 0.96 to 1.00); the inverse association was statistically significant in nonsmokers (OR = 0.96; 95% CI = 0.93 to 0.99) and stronger than in smokers (P for difference <0.05). No statistical significance for the associations was observed between genders, the origin of the participants, study design and types of soy intake. This study suggests a borderline reduction in risk of lung cancer with daily soy protein intake in grams, and a significant inverse association in nonsmokers.
Project description:The study relates the present evaluation of exposure to estrogenic isoflavones of French consumers through two approaches: (1) identification of the isoflavone sources in the French food offering, (2) a consumption-survey on premenopausal women. For the foodstuff approach 150 food-items were analysed for genistein and daidzein. Additionally, 12,707 labels of processed-foods from French supermarket websites and a restaurant-supplier website were screened, and 1616 foodstuffs of interest were retained. The sources of phytoestrogens considered were soy, pea, broad bean and lupine. A price analysis was performed. A total of 270 premenopausal women from the French metropolitan territory were interviewed for their global diet habits and soy consumption and perception. In supermarkets, there were significantly less selected foodstuffs containing soy than in restaurant (11.76% vs. 25.71%, p < 0.01). There was significantly more soy in low price-foodstuff in supermarket (p < 0.01). Isoflavone levels ranged from 81 to 123,871 µg per portion of the analyzed soy containing foodstuff. Among the women inquired 46.3% claimed to have soy regularly. Isoflavone intake >45 mg/day is associated to vegan-diet (p < 0.01). In total, 11.9% of soy-consumers had a calculated isoflavone intake >50 mg/day. This dose can lengthen the menstrual cycles. The actual exposure to phytoestrogen is likely to have an effect in a part of the French population.
Project description:There are conflicting reports on the impact of soy on breast carcinogenesis. This study examines the effects of soy supplementation on breast cancer-related genes and pathways.Women (n = 140) with early-stage breast cancer were randomly assigned to soy protein supplementation (n = 70) or placebo (n = 70) for 7 to 30 days, from diagnosis until surgery. Adherence was determined by plasma isoflavones: genistein and daidzein. Gene expression changes were evaluated by NanoString in pre- and posttreatment tumor tissue. Genome-wide expression analysis was performed on posttreatment tissue. Proliferation (Ki67) and apoptosis (Cas3) were assessed by immunohistochemistry.Plasma isoflavones rose in the soy group (two-sided Wilcoxon rank-sum test, P < .001) and did not change in the placebo group. In paired analysis of pre- and posttreatment samples, 21 genes (out of 202) showed altered expression (two-sided Student's t-test, P < .05). Several genes including FANCC and UGT2A1 revealed different magnitude and direction of expression changes between the two groups (two-sided Student's t-test, P < .05). A high-genistein signature consisting of 126 differentially expressed genes was identified from microarray analysis of tumors. This signature was characterized by overexpression (>2-fold) of cell cycle transcripts, including those that promote cell proliferation, such as FGFR2, E2F5, BUB1, CCNB2, MYBL2, CDK1, and CDC20 (P < .01). Soy intake did not result in statistically significant changes in Ki67 or Cas3.Gene expression associated with soy intake and high plasma genistein defines a signature characterized by overexpression of FGFR2 and genes that drive cell cycle and proliferation pathways. These findings raise the concerns that in a subset of women soy could adversely affect gene expression in breast cancer.