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Soy isoflavones reduce asthma exacerbation in asthmatic patients with high PAI-1-producing genotypes.

ABSTRACT: 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.

SUBMITTER: Cho SH

PROVIDER: S-EPMC6612283 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Soy isoflavones reduce asthma exacerbation in asthmatic patients with high PAI-1-producing genotypes.

Cho Seong H SH Jo Ara A Casale Thomas T Jeong Su J SJ Hong Seung-Jae SJ Cho Joong K JK Holbrook Janet T JT Kumar Rajesh R Smith Lewis J LJ

The Journal of allergy and clinical immunology 20190129 1

<h4>Background</h4>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.<h4>Objective</h4>We sought to investigate PAI-1 genotype-specific differences of the soy isoflavone response in asthma outcomes.<h4>Methods</h4>A PAI-1 functional polymorphism (rs1799768, 4G5G) was characterized in subjects with poorly controlled asthma enrolled in a rando ...[more]

PMID: 30707970

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Project description:Background and aimsAssociations between soy intake and risk of cancer have been evaluated in prospective observational studies with inconsistent results. Whether the potential anticancer effects offered by soy were attributed to soy isoflavones and soy protein still needs to be elucidated. This study aimed to comprehensively quantify the association of soy, soy isoflavones and soy protein intake with risk of cancer incidence and cancer mortality by conducting a meta-analysis of all available studies.MethodsPubMed, Embase, Web of Science, and Cochrane Library databases were searched up to 16 September 2021. Prospective cohort studies that examined the effect of soy, soy isoflavones and soy protein on cancer incidence and cancer mortality were identified. Random-effects models were used to pool the multivariable-adjusted relative risks (RRs) and corresponding 95% confidence intervals (CIs). The potential dose-response relations were explored by using generalized least-squares trend estimation.ResultsEighty one prospective cohort studies were included in the meta-analysis. A higher intake of soy was significantly associated with a 10% reduced risk of cancer incidence (RR, 0.90; 95% CI, 0.83-0.96). Each additional 25 g/d soy intake decreased the risk of cancer incidence by 4%. Intake of soy isoflavones was inversely associated with risk of cancer incidence (RR, 0.94; 95% CI, 0.89-0.99), whereas no significant association was observed for soy protein. The risk of cancer incidence was reduced by 4% with each 10 mg/d increment of soy isoflavones intake. Similar inverse associations were also found for soy in relation to site-specific cancers, particularly lung cancer (RR, 0.67; 95%CI, 0.52-0.86) and prostate cancer (RR, 0.88; 95%CI, 0.78-0.99). However, high intake of soy, soy isoflavones and soy protein were not associated with cancer mortality.ConclusionsHigher intake of soy and soy isoflavones were inversely associated with risk of cancer incidence, which suggested that the beneficial role of soy against cancer might be primarily attributed to soy isoflavones. These findings support recommendations to include soy as part of a healthy dietary pattern for the prevention of cancer.

Project description: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.

Project description:Porcine reproductive and respiratory syndrome virus (PRRSV) is an economically important disease, and ingestion of soy isoflavones (ISF) may benefit PRRSV-infected pigs due to demonstrated anti-inflammatory and antiviral properties. The objective of this experiment was to recreate immunological effects previously observed in young pigs infected with PRRSV receiving ISF and determine how those effects influence growth performance during the entire growth period from weaning to market. In total, 96 weaned barrows were group housed in a biosafety level-2 containment facility and allotted to 1 of 3 experimental treatments that were maintained throughout the study: noninfected pigs received an ISF-devoid control diet (NEG, n = 24), and infected pigs received either the control diet (POS, n = 36) or that supplemented with total ISF in excess of 1,600 mg/kg (ISF, n = 36). Following a 7-d adaptation, weanling pigs were inoculated intranasally with either a sham-control (PBS) or live PRRSV (1 × 105 TCID50/mL, strain NADC20). After inoculation, individual blood samples (n = 8 to 12/treatment) were routinely collected to monitor viral clearance and hematological parameters, including serum neutralizing anti-PRRSV antibody production. Pen-based oral fluids were used to monitor PRRSV clearance at later growth stages. A 1- or 2-way ANOVA was performed to compare experimental treatments depending on whether the outcome was repeatedly measured. In general, PRRSV infection decreased performance during early growth phases, resulting in 5.4% lower final BW for POS vs. NEG pigs (P < 0.05). Dietary ISF elicited inconsistent effects on growth performance, increased (P < 0.05) neutrophil cell counts and the relative proportion of memory T-cells, and decreased (P < 0.05) the time to full PRRSV clearance from oral fluids. Dietary ISF also elicited earlier, more robust anti-PRRSV neutralizing antibody production when compared with POS pigs. Additionally, and most notably, POS pigs experienced ~50% greater infection-related mortality rate vs. ISF pigs (P < 0.05), which may have significant economic implications for producers. Overall, dietary ISF ingestion supported immune responses and reduced mortality in PRRSV-infected pigs when fed to growing pigs though the biological mechanism of these effects remains unclear.

Dataset Information

Soy isoflavones reduce asthma exacerbation in asthmatic patients with high PAI-1-producing genotypes.

Publications

Soy isoflavones reduce asthma exacerbation in asthmatic patients with high PAI-1-producing genotypes.

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