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Can soy isoflavones plus soy protein change serum levels of interlukin-6? A systematic review and meta-analysis of randomized controlled trials.
Gholami, A, Baradaran, HR, Hariri, M
Phytotherapy research : PTR. 2021;(3):1147-1162
Abstract
In the present review, we aimed to summarize the effect of soy isoflavones plus soy protein on circulating interlukin-6 (IL-6) in adult participants. Databases including ISI Web of Science, PubMed, Scopus, Cochrane Library, and clinicaltrials.gov were searched up to 23 March 2020. The mean change from baseline of IL-6 concentrations and its SD for intervention and comparison groups were used to calculate the effect size. If the heterogeneity test was statistically significant, DerSimonian and Laird random effects model was used. Cochran's Q test and I-squared statistic were also used to compute the statistical heterogeneity of the intervention's effects. Eighteen studies were known to be eligible for systematic review and 14 studies were selected for meta-analysis. Our meta-analysis results indicated a non-significant effect in serum IL-6 concentrations compared to the comparison group (WMD = 0.03 pg/ml, 95% CI: -0.06, 0.12; p = .459). In subgroup analysis, based on soy isoflavones dosage, it was observed that this combination could reduce IL-6 levels in studies that used isoflavones with dose >84 mg/day (WMD = -0.12 pg/ml 95% CI: -0.24, -0.004; p = .042, I2 = 82.7%) and in articles with a good quality (WMD = -0.15 pg/ml 95% CI: -0.24, -0.05; p = .003, I2 = 62.3%). Performing well-designed intervention studies using a high dose of soy isoflavones is recommended to confirm the beneficial effects of soy ingredients on IL-6.
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Effects of soy isoflavones on cognitive function: a systematic review and meta-analysis of randomized controlled trials.
Cui, C, Birru, RL, Snitz, BE, Ihara, M, Kakuta, C, Lopresti, BJ, Aizenstein, HJ, Lopez, OL, Mathis, CA, Miyamoto, Y, et al
Nutrition reviews. 2020;(2):134-144
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Abstract
CONTEXT The results of preclinical and observational studies support the beneficial effect of soy isoflavones on cognition. OBJECTIVE This review aimed to evaluate the effects of soy isoflavones on cognition in adults. DATA SOURCES The PUBMED, EMBASE, Ovid Medline, Cochrane Library, and clinicaltrials.gov databases were searched. STUDY SELECTION Two researchers independently screened 1955 records, using the PICOS criteria: participants were adults; intervention was dietary sources with soy isoflavones or isolated soy isoflavones; comparator was any comparator; outcome was cognitive function; study type was randomized controlled trials (RCTs). A third researcher was consulted to resolve any discrepancies. Sixteen RCTs were included and their quality assessed. DATA EXTRACTION Information on study design, characteristics of participants, and outcomes was extracted. PRISMA guidelines were followed. DATA ANALYSIS A random-effects meta-analysis was used to pool estimates across studies. In the 16 RCTs (1386 participants, mean age = 60 y), soy isoflavones were found to improve overall cognitive function (standardized mean difference [SMD], 0.19; 95% confidence interval [CI], 0.07-0.32) and memory (SMD, 0.15; 95%CI, 0.03-0.26). CONCLUSION The results showed that soy isoflavones may improve cognitive function in adults. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration no. CRD42018082070.
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Legume and soy intake and risk of type 2 diabetes: a systematic review and meta-analysis of prospective cohort studies.
Tang, J, Wan, Y, Zhao, M, Zhong, H, Zheng, JS, Feng, F
The American journal of clinical nutrition. 2020;(3):677-688
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Abstract
BACKGROUND Previous findings on the associations of legume and soy intake with the risk of type 2 diabetes are conflicting. OBJECTIVE We aimed to summarize the longitudinal associations between legume and soy intake and risk of type 2 diabetes. METHODS We searched for relevant prospective cohort studies in PubMed, EMBASE, and Ovid up to August 2019. Study-specific, multivariable-adjusted RRs and 95% CIs were pooled by random-effects models. RESULTS We identified 15 unique cohorts including 565,810 individuals and 32,093 incident cases. The summary RRs (95% CIs) of incident type 2 diabetes were 0.95 (0.79, 1.14; NS) for total legumes, 0.83 (0.68, 1.01; NS) for total soy, 0.89 (0.71, 1.11; NS) for soy milk, 0.92 (0.84, 0.99) for tofu, 0.84 (0.75, 0.95) for soy protein, and 0.88 (0.81, 0.96) for soy isoflavones, respectively. High heterogeneity was found for total legumes (I2 = 84.8%), total soy (I2 = 90.8%), and soy milk (I2 = 91.7%). Potential sources of heterogeneity were not evident for total legumes or soy milk, whereas for total soy, geographic location (Asia, United States; P = 0.04) and study quality (high, moderate, or low; P = 0.02) significantly predicted heterogeneity. In dose-response analysis, significant linear inverse associations were observed for tofu, soy protein, and soy isoflavones (all P < 0.05). Overall quality of evidence was rated as moderate for total legumes and low for total soy and soy subtypes. CONCLUSIONS Dietary intakes of tofu, soy protein, and soy isoflavones, but not total legumes or total soy, are inversely associated with incident type 2 diabetes. Our findings support recommendations to increase intakes of certain soy products for the prevention of type 2 diabetes. However, the overall quality of evidence was low and more high-quality evidence from prospective studies is needed. This trial was registered as PROSPERO CRD42019126403 (https://www.crd.york.ac.uk/PROSPERO).
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Soy isoflavones prevent bone resorption and loss, a systematic review and meta-analysis of randomized controlled trials.
Akhlaghi, M, Ghasemi Nasab, M, Riasatian, M, Sadeghi, F
Critical reviews in food science and nutrition. 2020;(14):2327-2341
Abstract
BACKGROUND Osteoporosis is a common bone disease characterized by reduced bone mass resulting from continuous bone resorption. METHODS PubMed, Scopus, and Embase were searched to find published trials on the effect of soy isoflavones on bone mineral density (BMD) and bone turnover markers (bone-specific alkaline phosphatase, osteocalcin, osteoprotegerin, pyridinoline, deoxypyridinoline, C-telopeptide, and N-telopeptide). Random-effects inverse-variance model was used to calculate the pooled effects. RESULTS A total of 5313 articles were found, screened, and assessed for eligibility, and finally 52 trials were included in the meta-analysis. Consumption of soy isoflavones caused significant improvement in BMD of lumbar spine (mean difference (MD) = 0.76%; 95% CI: 0.09, 1.42%; p = 0.03), hip (MD = 0.22%; 95% CI: 0.02, 0.42%; p = 0.04), and femoral neck (MD = 2.27%; 95% CI: 1.22, 3.31%; p < 0.001). Subgroup analysis showed that in all 3 sites, the improvement was significant in normal weight subjects and interventions longer than a year, although trial location and dosage were also factors influencing isoflavones' impact on BMD. Among markers of bone turnover, osteoprotegerin (MD = 5.79; 95% CI: 3.08, 8.51 pg/ml; p < 0.001), pyridinoline (MD = -5.13; 95% CI: -7.76, -2.50 nmol/mmol; p < 0.001), and C-telopeptides (MD = -0.08; 95% CI: -0.16, -0.00 ng/ml; p = 0.04) were favorably affected by isoflavones while osteocalcin and bone alkaline phosphatase did not change. Subgroup analysis of bone markers showed that in overweight/obese individuals and dosages <90 mg/day, isoflavones are more effective. CONCLUSIONS Soy isoflavones prevent osteoporosis-related bone loss in any weight status or treatment duration. They increase BMD in normal weight subjects and diminish bone resorption in overweight/obese individuals. Although bone resorption may be decelerated over short-term isoflavone consumption, periods longer than a year are probably needed to affect BMD. Isoflavones also appear benefits on bone in any dose or subjects' ethnicity.
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High soy isoflavone or soy-based food intake during infancy and in adulthood is associated with an increased risk of uterine fibroids in premenopausal women: a meta-analysis.
Qin, H, Lin, Z, Vásquez, E, Luan, X, Guo, F, Xu, L
Nutrition research (New York, N.Y.). 2019;:30-42
Abstract
Numerous studies have examined the association of soy isoflavones or soy-based food intake with the risk of uterine fibroids (UF), but the results are inconsistent. The purpose of this meta-analysis was to quantitatively assess whether high soy isoflavones intake is associated with an increased risk of UF. PUBMED and EMBASE databases were reviewed to screen for relevant published studies up to December 2018. Using key words of uterine fibroid and isoflavone, we identified 4 studies focusing on infancy intake and 7 studies evaluating intake during adulthood. The pooled odds ratio (OR) and corresponding 95% confidence interval (95% CI) were calculated using a random-effect model. In addition, subgroup analyses and 2-stage random-effect dose-response were also performed. When comparing high vs low intake of soy isoflavones, we found that there were positive associations of UF among patients being fed soy formula during infancy (OR, 1.19; 95% CI, 0.99-1.43; P = .06) and with high consumption of soy-based foods in adulthood (OR, 2.50; 95% CI, 1.09-5.74; P = .03), respectively. Additionally, dose-response analysis showed the pooled ORs (95% CIs) of UF risk for low, moderate, and high intake of soy isoflavones were 1.00 (0.87-1.14), 1.08 (0.94-1.24), and 1.23 (0.99-1.53) when compared to occasional intake, respectively. Our findings suggest that high soy isoflavones or soy-based food intake during infancy and in adulthood is associated with an increased risk of uterine fibroids in premenopausal women. There is a need for large-scale prospective cohort studies using more accurate measurements of soy isoflavones to further ascertain our study findings.
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Equol Decreases Hot Flashes in Postmenopausal Women: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.
Daily, JW, Ko, BS, Ryuk, J, Liu, M, Zhang, W, Park, S
Journal of medicinal food. 2019;(2):127-139
Abstract
Soy isoflavones may benefit some, but not all, menopausal women, and the ability of the women to produce equol may be the major determinant of effectiveness. We assessed the efficacy of soy isoflavones and equol for alleviating menopausal symptoms, especially vasomotor symptoms, in postmenopausal women who were equol producers and nonproducers by using systematic review and meta-analysis of randomized clinical trials (RCTs). We searched 12 English, Korean, and Chinese language scientific and medical databases. We selected all available RCTs that assessed the effect of equol, either equol itself or soy isoflavone in equol producers, on menopausal symptoms in peri- or postmenopausal women. The primary outcome was the effect on hot flashes. The severity of hot flashes was determined by the scores, and sensitivity and risk of bias analyses were conducted. Other outcomes of the review, but not meta-analysis, included depression and adverse events. Six studies (779 total subjects) met all criteria for the systematic review, 5 of those could be included in the meta-analysis (728 total subjects). Two studies included in the meta-analysis reported no statistically significant benefits of equol; the other three did report significant benefits of equol. Meta-analysis revealed a significant benefit of equol for lowering hot flash scores and revealed a generally low risk of bias. In conclusion, this study found that supplementing equol to equol nonproducers significantly lowered the incidence and/or severity of hot flashes in menopausal women.
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Systematic Review and Meta-Analysis of the Effects of Soy on Glucose Metabolism in Patients with Type 2 Diabetes.
Soltanipour, S, Hasandokht, T, Soleimani, R, Mahdavi-Roshan, M, Jalali, MM
The review of diabetic studies : RDS. 2019;:60-70
Abstract
OBJECTIVE This study aimed to assess the effects of soy consumption on glucose metabolism in patients with type 2 diabetes. METHODS A systematic review was performed in accordance with the Preferred Reporting Items for Systematic Review (PRISMA) principles. Literature published between 1990 and 2019 was searched. Primary outcomes were the effect of soy on fasting plasma glucose (FPG), insulin, and HbA1c. The data were pooled using random effects models. Heterogeneity was assessed using Cochran's Q and I2 statistics. Also, the Cochrane Collaboration's tool for assessing risk of bias was used, and sensitivity analysis and meta-regression were conducted. Publication bias was evaluated using Egger and Begg tests. RESULTS Sixteen randomized clinical trials (RCTs) with a total of 471 participants were regarded as eligible and included in the study. Soy consumption had no significant effects on FPG, insulin, and HbA1c. After the "trim-and-fill" method was applied, soy revealed a significant effect size on FPG (adjusted Cohen's d: -0.18; p = 0.03). Also, subgroup analyses using studies with parallel design showed a significant improvement (moderate effect size) in FPG and insulin. Sensitivity analysis indicated the robustness of our findings. Among secondary outcomes, the results showed a significant effect of soy on HOMA-IR and total cholesterol levels. CONCLUSIONS Although this systematic review and meta-analysis indicated no beneficial effects of soy consumption on FPG, insulin, and HbA1c in patients with type 2 diabetes, pooling of parallel studies showed different results from crossover studies. The quality of evidence revealed low levels of confidence for primary outcomes. Therefore, further research is recommended.
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Association between Dietary Isoflavones in Soy and Legumes and Endometrial Cancer: A Systematic Review and Meta-Analysis.
Zhong, XS, Ge, J, Chen, SW, Xiong, YQ, Ma, SJ, Chen, Q
Journal of the Academy of Nutrition and Dietetics. 2018;(4):637-651
Abstract
BACKGROUND Epidemiologic studies have reported conflicting findings between soy- and legume-derived dietary isoflavones and risk of endometrial cancer. OBJECTIVE The aim of the present meta-analysis was to quantitatively investigate the association between daily intake of soy- and legume-derived isoflavones and risk of endometrial cancer. DESIGN A broad search was conducted in the following electronic databases: PubMed, EMBASE, Google Scholar, the Cochrane Library, the China Knowledge Resource Integrated Database, and the Chinese Biomedical Database based on combinations of the key words endometrial cancer, isoflavone, soy, and legume for epidemiologic studies that focused on relationships between dietary isoflavones and endometrial cancer risk. A fixed-effect or random-effect model was used to pool study-specific risk estimates. RESULTS A total of 13 epidemiologic studies were included in the present meta-analysis, consisting of three prospective cohort studies and 10 population-based case-control studies. The final results indicated that higher dietary isoflavone levels from soy products and legumes were associated with a reduced risk of endometrial cancer (odds ratio [OR] 0.81, 95% CI 0.74 to 0.89). Low heterogeneous bias was observed (I2=11.7%; P=0.327). Subgroup analyses were conducted based on study design, source of dietary isoflavones, and study region. When restricted to study design, dietary isoflavones from soy and legumes played a role in prevention of endometrial cancer in case-control studies (OR 0.81, 95% CI 0.73 to 0.90). However, there did not appear to be an association between dietary isoflavones and endometrial cancer in cohort studies (OR 0.81, 95% CI 0.66 to 1.00). Significant associations were found between dietary isoflavones from soy products (OR 0.82, 95% CI 0.72 to 0.92) and legumes (OR 0.84, 95% CI 0.74 to 0.96) and endometrial cancer. Dietary isoflavones were associated with reduced incidence of endometrial cancer, both in Asian countries (OR 0.78, 95% CI 0.66 to 0.93) and non-Asian countries (OR 0.82, 95% CI 0.73 to 0.92). CONCLUSIONS The findings suggest a weak inverse association between higher consumption of dietary isoflavones from soy products and legumes and endometrial cancer risk. However, there is still a need for large, prospective epidemiologic studies that provide a higher level of evidence to verify these findings.
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Meta-analysis and transcriptome profiling reveal hub genes for soybean seed storage composition during seed development.
Qi, Z, Zhang, Z, Wang, Z, Yu, J, Qin, H, Mao, X, Jiang, H, Xin, D, Yin, Z, Zhu, R, et al
Plant, cell & environment. 2018;(9):2109-2127
Abstract
Soybean is an important crop providing edible oil and protein source. Soybean oil and protein contents are quantitatively inherited and significantly affected by environmental factors. In this study, meta-analysis was conducted based on soybean physical maps to integrate quantitative trait loci (QTLs) from multiple experiments in different environments. Meta-QTLs for seed oil, fatty acid composition, and protein were identified. Of them, 11 meta-QTLs were located on hot regions for both seed oil and protein. Next, we selected 4 chromosome segment substitution lines with different seed oil and protein contents to characterize their 3 years of phenotype selection in the field. Using strand-specific RNA-sequencing analysis, we profile the time-course transcriptome patterns of soybean seeds at early maturity, middle maturity, and dry seed stages. Pairwise comparison and K-means clustering analysis revealed 7,482 differentially expressed genes and 45 expression patterns clusters. Weighted gene coexpression network analysis uncovered 46 modules of gene expression patterns. The 2 most significant coexpression networks were visualized, and 7 hub genes were identified that were involved in soybean oil and seed storage protein accumulation processes. Our results provided a transcriptome dataset for soybean seed development, and the candidate hub genes represent a foundation for further research.
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Effect of Soy and Soy Isoflavones on Obesity-Related Anthropometric Measures: A Systematic Review and Meta-analysis of Randomized Controlled Clinical Trials.
Akhlaghi, M, Zare, M, Nouripour, F
Advances in nutrition (Bethesda, Md.). 2017;(5):705-717
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Soy may be a suitable food for anti-obesity efforts because of its high protein and isoflavone content. We conducted this meta-analysis to evaluate potential effects of soy and soy isoflavones on weight, waist circumference, and fat mass. PubMed, MEDLINE, Scopus, EMBASE, and Cochrane databases were searched. Twenty-four trials with soy and 17 trials with isoflavones passed the eligibility stage. According to the results, soy showed no overall statistically significant effect on weight, waist circumference, or fat mass, but a significant increasing effect on weight was observed in some circumstances: for instance, in obese subjects [mean difference (MD): 0.80 kg; 95% CI: 0.15, 1.45 kg; P = 0.02], with ingestions of ≥40 g soy protein/d (MD: 0.94 kg; 95% CI: 0.11, 1.77 kg; P = 0.03), with short-term applications (1-3 mo) (MD: 0.45 kg; 95% CI: 0.05, 0.86 kg; P = 0.03), and when soy was compared with meat (MD: 0.36 kg; 95% CI: 0.09, 0.64 kg; P = 0.03) and whey protein (MD: 1.53 kg; 95% CI: 0.10, 2.96 kg; P = 0.04). In contrast to the effects of soy on weight, soy significantly decreased waist circumference in older ages (MD: -0.36 cm; 95% CI: -0.71, -0.01 cm; P = 0.04), in women (MD: -0.32 cm; 95% CI: -0.57, -0.08 cm; P = 0.01), and at doses of <40 g soy protein/d (MD: -0.31 cm; 95% CI: -0.57, -0.05 cm; P = 0.02). Isoflavone studies, conducted only in women, showed that isoflavones may reduce body mass index (BMI; in kg/m2) (MD: -0.26; 95% CI: -0.55, 0.04; P = 0.085), especially in dosages <100 mg/d (MD: -0.48; 95% CI: -0.90, -0.06; P = 0.02) and in intervention periods of 2-6 mo (MD: -0.28; 95% CI: -0.56, 0.00; P = 0.053), but no effect was observed in higher doses or longer intervention periods. Also, a trend for reduced BMI after consumption of isoflavones was observed in Caucasians (MD: -0.35; 95% CI: -0.74, 0.04; P = 0.08). Overall, results showed that, although soy is the major source of isoflavones, soy and isoflavones may have different impacts on weight status.