title: Curcumin downregulates human tumor necrosis factor-α levels: A systematic review and meta-analysis ofrandomized controlled trials.
abstract: Tumor necrosis factor-α (TNF-α) is a key inflammatory mediator and its reduction is a therapeutic target in several inflammatory diseases. Curcumin, a bioactive polyphenol from turmeric, has been shown in several preclinical studies to block TNF-α effectively. However, clinical evidence has not been fully conclusive.
  
  
  
  The aim of the present meta-analysis was to evaluate the efficacy of curcumin supplementation on circulating levels of TNF-α in randomized controlled trials (RCTs).
  
  
  
  The search included PubMed-Medline, Scopus, Web of Science and Google Scholar databases by up to September 21, 2015, to identify RCTs investigating the impact of curcumin on circulating TNF-α concentration. Quantitative data synthesis was performed using a random-effects model, with weighed mean difference (WMD) and 95% confidence interval (CI) as summary statistics. Meta-regression and leave-one-out sensitivity analyses were performed to assess the modifiers of treatment response.
  
  
  
  Eight RCTs comprising nine treatment arms were finally selected for the meta-analysis. There was a significant reduction of circulating TNF-α concentrations following curcumin supplementation (WMD: -4.69pg/mL, 95% CI: -7.10, -2.28, p<0.001). This effect size was robust in sensitivity analysis. Meta-regression did not suggest any significant association between the circulating TNF-α-lowering effects of curcumin with either dose or duration (slope: 0.197; 95% CI: -1.73, 2.12; p=0.841) of treatment.
  
  
  
  This meta-analysis of RCTs suggested a significant effect of curcumin in lowering circulating TNF-α concentration.
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Metabolic Research Centre, Royal Perth Hospital, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia.
authors.forename: Amirhossein
authors.initials: A
authors.lastname: Sahebkar
authors.affiliation: Medicine and Surgery Sciences Dept.,University of Bologna, Italy. Electronic address: arrigo.cicero@unibo.it.
authors.forename: Arrigo F G
authors.initials: AFG
authors.lastname: Cicero
authors.affiliation: Biomedical Research Unit, Mexican Social Security Institute, Durango, Mexico.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Simental-Mendía
authors.affiliation: Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX USA.
authors.forename: Bharat B
authors.initials: BB
authors.lastname: Aggarwal
authors.affiliation: Department of Biochemistry, Faculty of Science, Banaras Hindu University, Varanasi, India.
authors.forename: Subash C
authors.initials: SC
authors.lastname: Gupta
mesh_terms: D000818:Animals; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D003474:Curcumin
keywords: Curcuma longa; Curcumin; Inflammation; Meta-analysis; Randomized controlled trial; TNF-α