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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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Zinc supplementation is associated with a reduction in serum markers of inflammation and oxidative stress in adults: A systematic review and meta-analysis of randomized controlled trials.
Hosseini, R, Ferns, GA, Sahebkar, A, Mirshekar, MA, Jalali, M
Cytokine. 2021;:155396
Abstract
BACKGROUND Zinc (Zn) is a trace metal that is considered to have an impact on chronic inflammation. However, findings of clinical trials have been inconsistent. The present systematic review and meta-analysis aimed to provide a more robust examination of the evidence on the effectiveness of Zn supplements on markers of inflammation and oxidative stress. METHODS A systematic search in PubMed, Scopus, Web of Science and Cochrane Library was undertaken to identify relevant randomized controlled trials (RCTs) assessing the impact of Zn on inflammation and oxidative stress until 17 August 2020. We applied a random-effects method to obtain effect sizes (ES) and 95% confidence intervals (CIs). Meta-regression was used to detect the potential source of between-study heterogeneity. RESULTS Twenty-one eligible RCTs comprising 1321 participants were included in the meta-analysis. In comparison with the control groups, serum C-reactive protein (CRP) (ES = -0.92 mg/L, 95% CI = [-1.36, -0.48], P < 0.001, I2 = 90.2%), tumor necrosis factor-alpha (TNF-α) (ES = -0.49 pg/mL, 95% CI = [-084, -0.14], P = 0.006, I2 = 34.6%) and malondialdehyde (MDA) (ES = -0.42, 95% CI = [-083, -0.01], P = 0.04, I2 = 76.1%) were significantly reduced in the groups receiving Zn. Serum interleukin 6 (ES = -1.02 pg/mL, 95% CI = [-2.06, 0.02], P = 0.05, I2 = 92.3%) was marginally reduced following Zn supplementation. Moreover, treatment duration was found as the source of inter-study heterogeneity. CONCLUSION This meta-analysis suggests that Zn supplements reduce serum concentrations of markers of inflammation and oxidation: CRP, TNF-α and MDA.
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The effect of exercise intensity on chronic inflammation: A systematic review and meta-analysis.
Rose, GL, Skinner, TL, Mielke, GI, Schaumberg, MA
Journal of science and medicine in sport. 2021;(4):345-351
Abstract
OBJECTIVES Chronic inflammation is independently associated with the incidence and progression of chronic disease. Exercise has been found to reduce chronic inflammation, however the role of exercise intensity (work rate) is unknown. This review aimed to determine the pooled effect of higher- compared to lower-intensity aerobic and resistance exercise on chronic inflammation in adults. DESIGN Systematic review and meta-analysis. METHODS Five electronic databases were searched. Intervention trials that assessed the effect of ≥2 different exercise intensities on peripheral markers of chronic inflammation [c-reactive protein (CRP), interleukin (IL)-6, tumour necrosis factor (TNF)-α and IL-10] in adults were included. Random-effect meta-analyses were conducted to calculate the mean difference in change scores between groups [effect size (ES)]. Sub-group analyses were performed to explore the influence of age, chronic disease, body mass index and intervention duration on inflammation heterogeneity. RESULTS Of 3952 studies identified, 27 were included. There were no significant effects of exercise intensity on IL-6 (ES=-0.039, 95%CI=-0.353-0.275; p=0.806), TNF-α (ES=0.296, 95%CI=-0.184-0.777; p=0.227) and IL-10 (ES=0.007, 95%CI=-0.904-0.919; p=0.987). A significant pooled ES was observed for higher- versus lower-intensity exercise on CRP concentrations, in studies of middle-aged adults (ES=-0.412, 95%CI=-0.821- -0.004, p=0.048) or interventions >9 weeks in duration (ES=-0.520, 95%CI=-0.882--0.159, p=0.005). CONCLUSIONS Exercise intensity did not influence chronic inflammatory response. However, sub-analyses suggest that higher-intensity training may be more efficacious than lower-intensity for middle-aged adults, or when longer duration interventions are implemented (>9 weeks), in the most commonly-reported analyte (CRP).
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The effects of soy supplementation on inflammatory biomarkers: A systematic review and meta-analysis of randomized controlled trials.
Asbaghi, O, Yaghubi, E, Nazarian, B, Kelishadi, MR, Khadem, H, Moodi, V, Naeini, F, Ghaedi, E
Cytokine. 2020;:155282
Abstract
BACKGROUND Soy products contain several compounds with anti-inflammatory properties like genistein and daidzein which reported to act through different pathways. Present study conducted considering the inconsistent results and lack of any comprehensive review regarding randomized controlled trials which assess the effect of soy products on inflammatory markers. METHODS Following electronic databases were searched up to March 2020: PubMed, Scopus, ISI web of science, and Cochrane Library All randomized trials which assessed the effect of soy product supplementation on c-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were included for last analysis. Treatment effects were expressed as mean difference (MD) and the standard deviation (SD) of outcomes. To estimate the overall effect the random-effects model was employed. RESULTS Finally, 51 randomized trial were included for present study. Last analysis showed that soy product supplementation lead to significant reduction in CRP (MD -0.27 mg/L; 95% CI: -0.51, -0.02, p = 0.028) but it did not affect IL-6 (MD 0.0 pg/ml; 95% CI: -0.06, 0.06, p = 0.970) and TNF-α (MD = -0.04 pg/ml; 95% CI: -0.11, 0.03, p = 0.252). Subgroup analysis showed that soy supplementation had a significant impact on decreasing IL-6 and TNF-α levels when studies had a long-term intervention (≥12 weeks) and used low dose isoflavone (<100 mg/day). CONCLUSION In conclusion, present systematic review and meta-analysis found a significant reduction in CRP levels after soy supplementation whiles IL-6 and TNF-α did not affect.
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Effects of TNF-α-308G/A Polymorphism on the Risk of Diabetic Nephropathy and Diabetic Retinopathy: An Updated Meta-Analysis.
Liu, M, Shang, M, Wang, Y, Li, Q, Liu, X, Yang, L, Zhang, Q, Zhang, K, Liu, S, Nie, F, et al
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2020;(10):724-731
Abstract
Diabetic nephropathy (DN) and diabetic retinopathy (DR) are the major factors of morbidity and mortality in the patients with diabetes mellitus (DM). Growing studies have investigated the relationship between the TNF-α-308G/A polymorphism and the susceptibility to DN and DR, without achieving consensus. Thus, we conducted this meta-analysis to reach more comprehensive conclusions for these issues. Eligible studies were retrieved through electronic databases such as PubMed, Embase, Web of Science and China National Knowledge Infrastructure. Summary of odds ratios (OR) and 95% confidence intervals (CIs) were generated to evaluate the intensity of the associations. Statistical analyses were performed by STATA 11.0 and RevMan 5.2. There are fourteen eligible publications involving nineteen studies in this meta-analysis. TNF-α-308G/A polymorphism was significantly related to increasing risk of DN under recessive model (OR=1.37, 95% CI=1.03-1.83) and homozygous model (OR=1.54, 95% CI=1.15-2.06). Moreover, the similar results were also obtained in Asian groups for DN (recessive: OR=1.69, 95% CI=1.18-2.42; homozygous: OR=1.99, 95% CI=1.38-2.86; respectively), and significant association was also detected between TNF-α-308G/A and DN susceptibility in type 2 DM in recessive model (OR=1.39, 95% CI=1.02-1.89). No significant association was observed between TNF-α-308G/A and DR susceptibility in total analyses and subgroup analyses by ethnicity and type of DM. TNF-α-308G/A polymorphism may enhance the susceptibility to diabetic nephropathy, especially in Asian population and in T2DM patients, but not diabetic retinopathy.
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Effect of Propolis Intake on Serum C-Reactive Protein (CRP) and Tumor Necrosis Factor-alpha (TNF-α) Levels in Adults: A Systematic Review and Meta-Analysis of Clinical Trials.
Jalali, M, Ranjbar, T, Mosallanezhad, Z, Mahmoodi, M, Moosavian, SP, Ferns, GA, Jalali, R, Sohrabi, Z
Complementary therapies in medicine. 2020;:102380
Abstract
BACKGROUND Propolis is a natural Product and the antioxidant properties of Propolis appear to be principally responsible for its therapeutic effects. However, several studies have shown the positive effect of Propolis on the reduction the levels of inflammatory markers; some others have revealed non-significant impacts on them. Hence, the present systematic review and meta-analysis aimed to investigate the effects of Propolis intake on C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α). METHODS The systematic search was undertaken in scientific databases that included: PubMed, Embase, Scopus and Web of Science to find studies assessing the effects of Propolis on CRP and TNF-α up to December 2019. Standardized mean difference (SMD) and 95 % confidence intervals (CI) were pooled using a random-effects model. Potential publication bias was tested using Egger's test. RESULTS Six studies comprising 406 participants were included in the meta-analysis. Compared to controls, Propolis intake significantly reduced serum TNF-α (SMD = -0.48, 95 % CI = [-0.69, -0.26], P < 0.0001, I2 = 66.9 %) and CRP (SMD = -0.38, 95 % CI = [-0.68, -0.07], P = 0.01, I2 = 44.4 %) levels. No evidence of publication bias was found in the meta-analyses. CONCLUSION The present study concluded in the statistically and clinically reduction of serum CRP and TNF-α levels following Propolis intake.
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Garlic Supplementation Reduces Circulating C-reactive Protein, Tumor Necrosis Factor, and Interleukin-6 in Adults: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
Darooghegi Mofrad, M, Milajerdi, A, Koohdani, F, Surkan, PJ, Azadbakht, L
The Journal of nutrition. 2019;(4):605-618
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Abstract
BACKGROUND Conflicting findings on the effects of garlic supplementation on inflammatory biomarkers have been observed in randomized clinical trials (RCTs). OBJECTIVES The aim of this study was to summarize study results regarding the effects of garlic supplementation on serum inflammatory biomarkers in adults. METHODS We searched Scopus, PubMed, Google Scholar and Cochrane library databases for relevant papers published until April 2018, using keywords such as "garlic" and "inflammatory biomarker." We included RCTs that 1) were conducted in adults, 2) examined the effects of garlic supplementation on inflammatory biomarkers compared to a control group, and 3) reported sufficient data on inflammatory biomarkers. Results were reported as weighted mean differences (WMD) with 95% CI using random effects models. Cochrane's Q and I-squared (I2) tests were used to determine heterogeneity among studies. Funnel plots and Egger's regression test were used to assess publication bias. RESULTS Sixteen RCTs were included. Garlic doses ranged from 12 to 3600 mg/d, and intervention duration ranged from 2 to 52 wk. Garlic administration significantly reduced serum C-reactive protein (CRP) (n = 13) (WMD: -0.61 mg/L, 95% CI: -1.12, -0.11, P = 0.018, I2 = 76.9%), IL-6 (n = 5) (WMD: -0.73 ng/L, 95% CI: -1.06, -0.40, P < 0.001, I2 = 0%), and TNF (n = 7) (WMD: -0.26 ng/L, 95% CI: -0.41, -0.12, P < 0.001, I2 = 0.0%), compared to controls. However, the effect of garlic supplementation on serum adiponectin (n = 3) (WMD: 0.18 µg/L, 95% CI: -0.21, 0.57, P = 0.35, I2 = 60.7%) and leptin (n = 2) (WMD: -1.25 µg/L, 95% CI: -2.64, 0.14, P = 0.07, I2 = 0.0%) concentrations were not significant. CONCLUSION In this meta-analysis of RCTs, we found that garlic supplementation reduced serum concentrations of CRP, TNF, IL-6, but did not affect serum adiponectin and leptin in adults. More RCTs are needed to test the effects of garlic supplementation on inflammation.
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Can coenzyme Q10 supplementation effectively reduce human tumor necrosis factor-α and interleukin-6 levels in chronic inflammatory diseases? A systematic review and meta-analysis of randomized controlled trials.
Farsi, F, Heshmati, J, Keshtkar, A, Irandoost, P, Alamdari, NM, Akbari, A, Janani, L, Morshedzadeh, N, Vafa, M
Pharmacological research. 2019;:104290
Abstract
BACKGROUND/OBJECTIVE Systematic inflammation plays a major role in all stages of chronic diseases. Recent evidence suggests that Coenzyme Q10 (CoQ10), as an anti-inflammatory agent, has shown beneficial effects on the inflammatory process of various human diseases. However, several trials have examined the effects of CoQ10 on pro-inflammatory cytokines with contrasting results. The objective of this systematic review and meta-analysis of randomized clinical trials (RCTs) was to assess the efficacy of CoQ10 supplementation on tumor necrosis factor- α (TNF-α) and interleukin-6 (IL-6) levels. MATERIALS AND METHODS A systematic literature was performed on databases including PubMed/Medline, EMBASE, Web of Science, SCOPUS, Cochrane Library databases, Clinical Trials.gov and historical search of reference lists from selected studies up to December 2018. Two reviewers independently investigated study eligibility, extracted data, and assessed risk of bias of relevant studies using a standardized protocol. Heterogeneity was measured by the I2 statistic. Data were pooled, using the fix or random-effect model based on the heterogeneity test results and the efficacy of CoQ10 expressed as the standardized mean difference (SMD) with 95% confidence interval (CI). Random-effects meta-regression was done to examine the effect of putative confounders or potential moderators on TNF-α and IL-6 levels. RESULTS Overall, nine RCTs with a total of 509 patients (269 in the CoQ10 arm and 240 in the control arm) provided the inclusion criteria and were included in the analysis. Our meta-analysis indicated that oral CoQ10 supplementation (60-500 mg/day for 8-12 weeks) resulted in significant reduction of TNF-α (SMD: -0.44, 95% CI: [-0.81 to -0.07] mg/dl; I2 = 66.1%, p = 0.00) and IL-6 levels (SMD: -0.37, 95% CI: [-0.65 to -0.09]; I2 = 57.2, p = 0.01), respectively. Subgroup analyses represented a significant reduction of TNF-α and IL-6 levels in patients with BMI < 26. Due to the small number of studies and patients included in each subgroup, these subgroup analyses need to be interpreted cautiously. CONCLUSION This meta-analysis of RCTs reported a significant effect of CoQ10 on some of the inflammatory markers among patients with chronic diseases which could attenuate the inflammatory state. However, well-designed studies with a larger sample size are required. Note that the results should be interpreted with caution because of the evidence of heterogeneity and limited number of studies.
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Tumor necrosis factor-α and diabetic retinopathy: Review and meta-analysis.
Yao, Y, Li, R, Du, J, Li, X, Zhao, L, Long, L, Li, D, Lu, S
Clinica chimica acta; international journal of clinical chemistry. 2018;:210-217
Abstract
BACKGROUND Tumor necrosis factor-alpha (TNF-α) is produced by multinuclear giant cells and acts as local intensification signals in pathological processes associated with chronic eye inflammation. This meta-analysis was performed to provide a better understanding of the relationship between TNF-α and diabetic retinopathy (DR). METHOD Online electric databases were searched to retrieve all relevant articles published before October 2017. The standard mean difference (SMD) and their 95% confidence intervals (CI) were included and then pooled with a random effects model. RESULTS A total of 16 articles with 1286 participants were included in this meta-analysis. No difference in the level of TNF-α was found between DR patients and healthy controls (SMD = 0.39, 95% CI = -0.09 to 0.68, P = 0.01). Subgroup analysis showed that with respect to the level of TNF-α, the association was significant for studies conducted in Europe (SMD: 0.57, 95% CI: 0.11-1.02, P = 0.01), patients with type 1 DM (SMD: 1.06, 95% CI: 0.09-2.04, P = 0.03), studies based on serum samples (SMD: 0.57, 95% CI: 0.12-1.02, P = 0.01) and studies with a sample size >50 (SMD: 0.39, 95% CI: 0.03-0.75, P = 0.04). CONCLUSION The results this meta-analysis indicated that the level of TNF-α in DR patients was significantly different from that in the healthy controls, so TNF-α represents a candidate biomarker for DR.
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Association of Methylation Signals With Incident Coronary Heart Disease in an Epigenome-Wide Assessment of Circulating Tumor Necrosis Factor α.
Aslibekyan, S, Agha, G, Colicino, E, Do, AN, Lahti, J, Ligthart, S, Marioni, RE, Marzi, C, Mendelson, MM, Tanaka, T, et al
JAMA cardiology. 2018;(6):463-472
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Abstract
IMPORTANCE Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine with manifold consequences for mammalian pathophysiology, including cardiovascular disease. A deeper understanding of TNF-α biology may enhance treatment precision. OBJECTIVE To conduct an epigenome-wide analysis of blood-derived DNA methylation and TNF-α levels and to assess the clinical relevance of findings. DESIGN, SETTING, AND PARTICIPANTS This meta-analysis assessed epigenome-wide associations in circulating TNF-α concentrations from 5 cohort studies and 1 interventional trial, with replication in 3 additional cohort studies. Follow-up analyses investigated associations of identified methylation loci with gene expression and incident coronary heart disease; this meta-analysis included 11 461 participants who experienced 1895 coronary events. EXPOSURES Circulating TNF-α concentration. MAIN OUTCOMES AND MEASURES DNA methylation at approximately 450 000 loci, neighboring DNA sequence variation, gene expression, and incident coronary heart disease. RESULTS The discovery cohort included 4794 participants, and the replication study included 816 participants (overall mean [SD] age, 60.7 [8.5] years). In the discovery stage, circulating TNF-α levels were associated with methylation of 7 cytosine-phosphate-guanine (CpG) sites, 3 of which were located in or near DTX3L-PARP9 at cg00959259 (β [SE] = -0.01 [0.003]; P = 7.36 × 10-8), cg08122652 (β [SE] = -0.008 [0.002]; P = 2.24 × 10-7), and cg22930808(β [SE] = -0.01 [0.002]; P = 6.92 × 10-8); NLRC5 at cg16411857 (β [SE] = -0.01 [0.002]; P = 2.14 × 10-13) and cg07839457 (β [SE] = -0.02 [0.003]; P = 6.31 × 10-10); or ABO, at cg13683939 (β [SE] = 0.04 [0.008]; P = 1.42 × 10-7) and cg24267699 (β [SE] = -0.009 [0.002]; P = 1.67 × 10-7), after accounting for multiple testing. Of these, negative associations between TNF-α concentration and methylation of 2 loci in NLRC5 and 1 in DTX3L-14 PARP9 were replicated. Replicated TNF-α-linked CpG sites were associated with 9% to 19% decreased risk of incident coronary heart disease per 10% higher methylation per CpG site (cg16411857: hazard ratio [HR], 0.86; 95% CI, 0.78-1.95; P = .003; cg07839457: HR, 0.89; 95% CI, 0.80-0.94; P = 3.1 × 10-5; cg00959259: HR, 0.91; 95% CI, 0.84-0.97; P = .002; cg08122652: HR, 0.81; 95% CI, 0.74-0.89; P = 2.0 × 10-5). CONCLUSIONS AND RELEVANCE We identified and replicated novel epigenetic correlates of circulating TNF-α concentration in blood samples and linked these loci to coronary heart disease risk, opening opportunities for validation and therapeutic applications.