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1.
The efficacy of soy isoflavones combined with soy protein on serum concentration of interleukin-6 and tumour necrosis factor-α among post-menopausal women? A systematic review and meta-analysis of randomized controlled trials.
Gholami, A, Mollanoroozy, E, Reza Baradaran, H, Hariri, M
Clinical and experimental pharmacology & physiology. 2022;(1):10-24
Abstract
The post-menopausal stage in women's life is associated with the enhancement of inflammation that may be reduced using soy isoflavones or soy protein. The present study aimed to summarize the effect of soy isoflavones plus soy protein on circulating interleukin-6 (IL-6) and tumour necrosis factor-α (TNF-α) in post-menopausal women. The English-language articles were identified from the databases such as Cochrane Library, clinicaltrials.gov, Web of Science, PubMed, and Scopus until December 2020. The mean change from baseline and its standard deviation (SD) for intervention and comparison groups were used to calculate the effect size. The statistical heterogeneity of the intervention effects was computing by Cochran's Q test and I2 statistic. Nine and seven studies were selected for systematic review and meta-analysis, respectively. The results of our meta-analysis indicated a non-significant effect on the serum concentrations of IL-6 and TNF-α (weighted mean differences [WMD] = 0.07 pg/mL; 95% confidence interval [CI] = -0.03, 0.17 pg/mL; P = 0.190; WMD =0.05 pg/mL; 95% CI = -0.01, 0.12 pg/mL; P = 0.092; respectively). In subgroup analysis, soy isoflavones plus soy protein could increase the serum concentration of IL-6 in studies with soy isoflavones dose ≤87 mg/days, cross-over design, weak quality, and studies on participants who had health risk factors or diseases. The serum concentration of TNF-α increased in studies with cross-over design, intervention duration ≤56 days, and body mass index (BMI) >27, and in studies that were conducted on at-risk or sick participants. In conclusion, our meta-analysis did not confirm any significant effect on serum concentration of IL-6 and TNF-α among post-menopausal women.
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2.
Evaluation of Clinical Meaningfulness of Red Clover (Trifolium pratense L.) Extract to Relieve Hot Flushes and Menopausal Symptoms in Peri- and Post-Menopausal Women: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Kanadys, W, Barańska, A, Błaszczuk, A, Polz-Dacewicz, M, Drop, B, Kanecki, K, Malm, M
Nutrients. 2021;(4)
Abstract
The meta-analysis presented in this article covered the efficacy of red clover isoflavones in relieving hot flushes and menopausal symptoms in perimenopausal and postmenopausal women. Studies were identified by MEDLINE (PubMed), Embase, and the Cochrane Library searches. The quality of the studies was evaluated according to Cochrane criteria. A meta-analysis of eight trials (ten comparisons) demonstrated a statistically significant reduction in the daily incidence of hot flushes in women receiving red clover compared to those receiving placebo: weighted mean difference (WMD-weighted mean difference) -1.73 hot flushes per day, 95% CI (confidence interval) -3.28 to -0.18; p = 0.0292. Due to 87.34% homogeneity, the performed analysis showed substantive difference in comparisons of postmenopausal women with ≥5 hot flushes per day, when the follow-up period was 12 weeks, with an isoflavone dose of ≥80 mg/day, and when the formulations contained a higher proportion of biochanin A. The meta-analysis of included studies assessing the effect of red clover isoflavone extract on menopausal symptoms showed a statistically moderate relationship with the reduction in the daily frequency of hot flushes. However, further well-designed studies are required to confirm the present findings and to finally determine the effects of red clover on the relief of flushing episodes.
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3.
Effects of soy isoflavone supplementation on patients with diabetic nephropathy: a systematic review and meta-analysis of randomized controlled trials.
Wang, X, Liang, QF, Zeng, X, Huang, GX, Xin, GZ, Xu, YH, Wang, SM, Tang, D
Food & function. 2021;(17):7607-7618
Abstract
Diabetic nephropathy (DN) is a microvascular complication that is becoming a worldwide public health concern. The aim of this study was to assess the effects of dietary soy isoflavone intervention on renal function and metabolic syndrome markers in DN patients. Seven databases including Medline, the Cochrane Central Register of Controlled Trials, Science Direct, Web of Science, Embase, China National Knowledge Infrastructure, and WanFang were searched for controlled trials that assessed the effects of soy isoflavone treatment in DN patients. Finally, a total of 141 patients from 7 randomized controlled trials were included. The meta-analysis showed that dietary soy isoflavones significantly decreased 24-hour urine protein, C-reactive protein (CRP), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and fasting blood glucose (FBG) in DN patients. The standard mean difference was -2.58 (95% CI: -3.94, -1.22; P = 0.0002) for 24-hour urine protein, -0.67 (95% CI: -0.94, -0.41; P < 0.00001) for BUN, -6.16 (95% CI: -9.02, -3.31; P < 0.0001) for CRP, -0.58 (95% CI: -0.83, -0.33; P < 0.00001) for TC, -0.41 (95% CI: -0.66, -0.16; P < 0.00001) for TG, -0.68 (95% CI: -0.94, -0.42; P < 0.00001) for LDL-C, and -0.39 (95% CI: -0.68, -0.10; P = 0.008) for FBG. Therefore, soy isoflavones may ameliorate DN by significantly decreasing 24-hour urine protein, BUN, CRP, TC, TG, LDL-C, and FBG.
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4.
The effects of soy isoflavones on total testosterone and follicle-stimulating hormone levels in women with polycystic ovary syndrome: a systematic review and meta-analysis.
Zilaee, M, Mansoori, A, Ahmad, HS, Mohaghegh, SM, Asadi, M, Hormoznejad, R
The European journal of contraception & reproductive health care : the official journal of the European Society of Contraception. 2020;(4):305-310
Abstract
OBJECTIVES The aims of this systematic review and meta-analysis were to evaluate the effectiveness of soy isoflavones on serum levels of total testosterone (TT) and follicle-stimulating hormone (FSH) in women with polycystic ovary syndrome (PCOS). METHODS A meta-analysis was performed by searching for relevant randomised controlled trials (RCTs) in several databases. Of the four trials found, the eligibility criteria to evaluate the efficacy of soy isoflavones on serum levels of FSH were met by three trials and of TT by four trials. The Cochrane scale was used to evaluate the risk of bias. Fixed-effects and random-effects models were used to evaluate overall effect. The χ 2 test (Cochran's Q test) and the I 2 index were used to assess the heterogeneity of RCTs. RESULTS Our results showed that soy isoflavones significantly decreased TT (weighted mean difference [WMD] - 0.14; 95% confidence interval [CI] - 0.2, -0.02; p = 0.016; I 2 = 89%, p < 0.001) but had no significant effect on FSH levels (WMD -0.25; 95% CI -0.54, 0.02; p = 0.06; I 2 = 0%, p = 0.85). CONCLUSION Although the results of this meta-analysis showed that soy isoflavones in women with PCOS decreased TT and had no significant effect on FSH, better and more valid studies are needed to confirm these results.
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5.
Effects of red clover (Trifolium pratense) isoflavones on the lipid profile of perimenopausal and postmenopausal women-A systematic review and meta-analysis.
Kanadys, W, Baranska, A, Jedrych, M, Religioni, U, Janiszewska, M
Maturitas. 2020;:7-16
Abstract
AIM: The aim of this systematic review and meta-analysis was to clarify the effect of a specific standardised extract of red clover (Trifolium pratense) on the lipid profile of perimenopausal and postmenopausal women. METHODS Medline (PubMed), EMBASE, and Cochrane Library electronic databases were searched for papers in English reporting randomized controlled trials published up to 2017. Reference lists from those papers were checked for further relevant publications. Studies were identified and reviewed for their eligibility for inclusion in this review. The changes from baseline in the levels of individual components of the lipid profiles were used to assess differences between the active treatment and placebo groups. Weighted mean differences and 95 % confidence intervals were calculated for continuous data using a random-effects model. RESULTS Ten eligible studies (twelve comparisons) with 910 peri- and postmenopausal women were selected for systematic review. The meta-analysis showed changes in serum levels: total cholesterol, -0.29 (95 % CI: -0.53 to -0.06) mmol/L [-11.21 (95 % CI: -20.49 to -13.92) mg/dL], p = 0.0136; LDL-cholesterol, -0.13 (95 % CI: -0.35 to 0.09) mmol/L [-5.02 (95 % CI: -13.53 to 3.48) mg/dL], p = 0.2418; triglycerides, -0.15 (95 % CI: -0.32 to 0.01) mmol/L [-13.28 (95 % CI: -28.34 to 0.88) mg/dL], p = 0.0592; and HDL-cholesterol, 0.14 (95 % CI: -0.08 to 0.36) mmol/L [5.41 (95 % CI: -3.09-13.92) mg/dL], p = 0.2103. TheI2 statistic ranged from 87.95%-98.30 %, indicating significant heterogeneity. CONCLUSIONS The results suggest that a red clover extract is efficacious in reducing the concentrations of total cholesterol; however, changes in HDL-C, LDL-C and triglycerides are not as pronounced. Potentially, this means that women takingTrifolium pratense for menopausal symptoms can derive additional benefits from the plant's specific effect that corrects abnormal cholesterol levels. Additional studies are needed to assess its effects on post-menopausal women.
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6.
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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7.
Soy, Soy Isoflavones, and Protein Intake in Relation to Mortality from All Causes, Cancers, and Cardiovascular Diseases: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies.
Nachvak, SM, Moradi, S, Anjom-Shoae, J, Rahmani, J, Nasiri, M, Maleki, V, Sadeghi, O
Journal of the Academy of Nutrition and Dietetics. 2019;(9):1483-1500.e17
Abstract
OBJECTIVE We conducted a systematic review and dose-response meta-analysis of prospective studies to summarize findings on the associations between intakes of soy, soy isoflavones, and soy protein and risk of mortality from all causes, cancers, and cardiovascular diseases. METHODS Online databases were systematically searched to identify relevant articles published earlier than May 2018. We applied restricted cubic splines using random-effects analysis to assess dose-response associations. Between-study heterogeneity was assessed by I2 value and Cochrane Q test. Potential publication bias was assessed by visual inspection of funnel plots and Begg regression test. RESULTS In total, 23 prospective studies with an overall sample size of 330,826 participants were included in the current systematic review and the meta-analysis. Soy/soy products consumption was inversely associated with deaths from cancers (pooled relative risk 0.88, 95% CI 0.79 to 0.99; P=0.03; I2=47.1%, 95% CI 0.0% to 75.4%) and cardiovascular diseases (pooled effect size: 0.85, 95% CI 0.72 to 0.99; P=0.04; I2=50.0%, 95% CI 0.0% to 77.6%). Such significant associations were also observed for all-cause mortality in some subgroups of the included studies, particularly those with higher quality. In addition, higher intake of soy was associated with decreased risk of mortality from gastric, colorectal, and lung cancers as well as ischemic cardiovascular diseases. Participants in the highest category of dietary soy isoflavones intake had a 10% lower risk of all-cause mortality compared with those in the lowest category. We also found that a 10-mg/day increase in intake of soy isoflavones was associated with 7% and 9% decreased risk of mortality from all cancers and also breast cancer respectively. Furthermore, a 12% reduction in breast cancer death was indicated for each 5-g/day increase in consumption of soy protein. However, intake of soy protein was not significantly associated with all-cause and cardiovascular diseases mortality. CONCLUSIONS Soy and its isoflavones may favorably influence risk of mortality. In addition, soy protein intake was associated with a decreased risk in the mortality of breast cancer. Our findings may support the current recommendations to increase intake of soy for greater longevity.
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8.
Soy and isoflavones consumption and breast cancer survival and recurrence: a systematic review and meta-analysis.
Qiu, S, Jiang, C
European journal of nutrition. 2019;(8):3079-3090
Abstract
BACKGROUND Some studies have investigated the association between soy and isoflavones consumption and breast cancer survival, but the results are far from conclusive. Accordingly, we performed a systematic review and meta-analysis to explore this issue. METHODS We performed a comprehensive search of Web of Science, PubMed, and Embase from inception to January 2018. The summary hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using a random effects model. RESULTS A total of 12 articles were included, which reported overall survival (OS), breast cancer specific survival (BCSS), and recurrence in 5770, 2386, and 1500 cases, respectively, among 37,275 women with breast cancer. The summary HR (95% CI) for the association (highest vs. lowest) of pre-diagnosis soy and isoflavones consumption with OS and BCSS was 0.84 (0.71-0.98) and 0.89 (0.74-1.07), respectively. Stratified analyses suggested that the reduced OS was more easily detected in studies that focused on post-menopausal patients. No significant association was found between post-diagnosis soy and isoflavones consumption with OS and BCSS, with summary HRs (95% CIs) of 0.80 (0.62-1.04) and 0.83 (0.64-1.07), respectively. Pre- and post-diagnosis soy isoflavones consumption were associated with reduced risk of recurrence. CONCLUSION This study provides limited evidence that pre-diagnosis soy and isoflavones intake is associated with a small reduction in post-menopausal breast cancer OS.
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9.
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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10.
Effect of soy isoflavone supplementation on plasma lipoprotein(a) concentrations: A meta-analysis.
Simental-Mendía, LE, Gotto, AM, Atkin, SL, Banach, M, Pirro, M, Sahebkar, A
Journal of clinical lipidology. 2018;(1):16-24
Abstract
BACKGROUND Soy supplementation has been shown to reduce total and low-density lipoprotein cholesterol, while increasing high-density lipoprotein cholesterol. However, contradictory effects of soy isoflavone supplementation on lipoprotein(a) [Lp(a)] have been reported suggesting the need for a meta-analysis to be undertaken. OBJECTIVE The aim of the study was to investigate the impact of supplementation with soy isoflavones on plasma Lp(a) levels through a systematic review and meta-analysis of eligible randomized placebo-controlled trials. METHODS The search included PubMed-Medline, Scopus, ISI Web of Knowledge, and Google Scholar databases (by March 26, 2017), and quality of studies was evaluated according to Cochrane criteria. Quantitative data synthesis was performed using a random-effects model, with standardized mean difference and 95% confidence interval as summary statistics. Meta-regression and leave-one-out sensitivity analysis were performed to assess the modifiers of treatment response. RESULTS Ten eligible studies comprising 11 treatment arms with 973 subjects were selected for the meta-analysis. Meta-analysis did not suggest any significant alteration of plasma Lp(a) levels after supplementation with soy isoflavones (standardized mean difference: 0.08, 95% confidence interval: -0.05, 0.20, P = .228). The effect size was robust in the leave-one-out sensitivity analysis. In meta-regression analysis, neither dose nor duration of supplementation with soy isoflavones was significantly associated with the effect size. CONCLUSION This meta-analysis of the 10 available randomized placebo-controlled trials revealed no significant effect of soy isoflavones treatment on plasma Lp(a) concentrations.