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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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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.
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Effects of Coenzyme Q10 on Markers of Inflammation: A Systematic Review and Meta-Analysis.
Zhai, J, Bo, Y, Lu, Y, Liu, C, Zhang, L
PloS one. 2017;(1):e0170172
Abstract
BACKGROUND/OBJECTIVE Chronic inflammation contributes to the onset and development of metabolic diseases. Clinical evidence has suggested that coenzyme Q10 (CoQ10) has some effects on inflammatory markers. However, these results are equivocal. The aim of this systematic review was to assess the effects of CoQ10 on serum levels of inflammatory markers in people with metabolic diseases. METHODS Electronic databases were searched up to February 2016 for randomized controlled trials (RCTs). The outcome parameters were related to inflammatory factors, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and C reactive protein (CRP). RevMan software was used for meta-analysis. Meta-regression analysis, Egger line regression test and Begg rank correlation test were performed by STATA software. RESULTS Nine trials involving 428 subjects were included in this meta-analysis. The results showed that compared with control group, CoQ10 supplementation has significantly improved the serum level of CoQ10 by 1.17μg/ml [MD = 1.17, 95% CI (0.47 to 1.87) μg/ml, I2 = 94%]. Meanwhile, it has significantly decreased TNF-α by 0.45 pg/ml [MD = -0.45, 95% CI (-0.67 to -0.24) pg/ml, I2 = 0%]. No significant difference was observed between CoQ10 and placebo with regard to CRP [MD = -0.21, 95% CI (-0.60 to 0.17) mg/L, I2 = 21%] and IL-6 [MD = -0.89, 95% CI (-1.95 to 0.16) pg/ml, I2 = 84%]. CONCLUSIONS CoQ10 supplementation may partly improve the process of inflammatory state. The effects of CoQ10 on inflammation should be further investigated by conducting larger sample size and well-defined trials of long enough duration.
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Can coenzyme Q10 supplementation effectively reduce human tumour necrosis factor-α and interleukin-6 levels in chronic diseases? Protocol for a systematic review and meta-analysis of randomised controlled trials.
Farsi, F, Heshmati, J, Janani, L, Irandoost, P, Mesri Alamdari, N, Keshtkar, A, Akbari, A, Vafa, M
BMJ open. 2017;(10):e016841
Abstract
INTRODUCTION Inflammation, as a critical factor, can cause numerous chronic diseases by creating various proinflammatory cytokines. Coenzyme Q10 (CoQ10) can potentially exert an anti-inflammatory agent; in turn, this agent can reduce the systemic inflammatory response. The aims of this study are to conduct a comprehensive systematic review and a meta-analysis for the determination of the CoQ10 efficacy on the changes in serum interleukin-6 (IL-6) and the tumour necrosis factor-α (TNF-α) levels in unhealthy subjects. METHOD AND ANALYSIS We will conduct an electronic search for articles published between January 1990 and January 2017 using a prespecified search strategy in MEDLINE, SCOPUS, EMBASE, CENTRAL and Web of Science.Our search will focus only on randomised controlled clinical trials in unhealthy subjects that employ either a parallel or a crossover design; this search will involve concurrent control groups. The primary outcomes of the literature are to determine the CoQ10 efficacy on the changes in the serum IL-6 and the TNF-α levels in unhealthy subjects. Secondary outcomes such as body mass index, serum adiponectin and high-sensitivity C-reactive protein levels, lipid profile and the heterogeneity assessment of the primary studies will be evaluated. The stages of screen articles, the extracts of relevant data and the assessment of study quality using the Cochrane risk of bias tool will be conducted independently by the two reviewers. Any disagreement will be resolved by discussion with a third person. If the number of eligible studies is sufficient, we will carry out a meta-analysis according to both outcomes. ETHICS AND DISSEMINATION This study is the protocol for a systematic review and no ethics approval is needed. The findings from the full systematic review will be published in a peer-reviewed journal, and they will also be exhibited at national/international academic and clinical conferences. TRIAL REGISTRATION NUMBER CRD42016052200.
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TNF-α -308 G > A (rs1800629) Polymorphism is Associated with Celiac Disease: A Meta-analysis of 11 Case-Control Studies.
Khan, S, Mandal, RK, Jawed, A, Dar, SA, Wahid, M, Panda, AK, Areeshi, MY, Ahmed Khan, ME, Haque, S
Scientific reports. 2016;:32677
Abstract
Celiac disease (CD) remains one of the most significant autoimmune diseases worldwide. The pathogenesis of CD is not clearly understood and is probably attributed to genomic variations and host genetic make-up. Case-control and cohort studies of the association between the TNF-α -308 G > A (rs1800629) polymorphism and CD susceptibility have yielded inconsistent results. In this study, PubMed, EMBASE, and Google Scholar web-databases were searched for pertinent reports showing association of TNF-α -308 G > A gene with CD risk. A total of eleven reports involving 1774 controls and 1147 CD cases were included. Significant associations in four genetic models, viz. variant allele (A vs. G: p = 0.001; OR = 2.051, 95% CI = 1.452-2.895), variant homozygous (AA vs. GG: p = 0.001; OR = 6.626, 95% CI = 3.569-12.300), recessive (AA vs. GG + AG: p = 0.001; OR = 4.766, 95% CI = 3.177-7.152) and dominant (AA + AG vs. GG: p = 0.008; OR = 1.910, 95% CI = 1.181-3.088) were found in comparison with wild type homozygous GG genotype. However, heterozygous genetic model did not show any association. Sensitivity analysis revealed stable and statistically robust results. Our results suggest that TNF-α -308 G > A gene polymorphism significantly contributes to CD susceptibility.
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Tumor necrosis factor-alpha g308α gene polymorphism and essential hypertension: a meta-analysis involving 2244 participants.
Li, YY
PloS one. 2012;(4):e35408
Abstract
BACKGROUND The tumor necrosis factor-alpha (TNFα) G308A gene polymorphism has been implicated in susceptibility to essential hypertension (EH), but study results are still controversial. OBJECTIVE AND METHODS The present meta-analysis is performed to investigate the relationship between the TNFα G308A gene polymorphism and EH. Electronic databases were searched and seven separate studies on the association of the TNF α G308A gene polymorphism with EH were analyzed. The meta-analysis involved 1092 EH patients and 1152 controls. The pooled odds ratios (ORs) and their corresponding 95% confidence interval (CI) were calculated by a fixed or random effect model. RESULTS A significant relationship between the TNFα G308A gene polymorphism and EH was found in an allelic genetic model (OR: 1.45, 95% CI: 1.17 to 1.80, P = 0.0008), a recessive genetic model (OR: 3.181, 95% CI: 1.204 to 8.408, P = 0.02), and a homozygote model (OR: 3.454, 95% CI: 1.286 to 9.278, P = 0.014). No significant association between them was detected in both a dominant genetic model (OR: 1.55, 95% CI: 0.99 to 2.42, P = 0.06) or a heterozygote genetic model (OR: 1.45, 95% CI: 0.90 to 2.33, P = 0.13). CONCLUSION The TNFα G308A gene polymorphism is associated with EH susceptibility.
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Meta-analysis of TNF 308 G/A polymorphism and type 2 diabetes mellitus.
Feng, RN, Zhao, C, Sun, CH, Li, Y
PloS one. 2011;(4):e18480
Abstract
BACKGROUND AND OBJECTIVES Many investigations have focused the association between TNF 308 G/A polymorphism and risk for type 2 diabetes mellitus (T2DM). However, the sample sizes of most of the studies were small. The aim of this study is to evaluate the precise association between this variant and risk for T2DM in a large-scale meta-analysis. METHODS All publications were searched on the association between TNF 308 G/A polymorphism and T2DM. The key words were as follows: diabetes, tumor necrosis factor and polymorphism/variant/genotype. This meta-analysis was assessed by Review manager 5.0. RESULTS There were 18 studies identified. The odds ratios (ORs) and 95% confidence intervals (CI) for GA+AA versus GG genotype of TNF 308 G/A polymorphism were 1.03 (0.95-1.12), 1.03 (0.94-1.13) and 1.03 (0.78-1.36) in overall, Caucasian and Asian populations, respectively. The sensitivity analysis further strengthened the validity of this association. No publication bias or heterogeneity was observed in this study. CONCLUSION In summary, there was no significant association detected between the TNF 308 G/A polymorphism and risk for T2DM.