title: Effect of flavonoids on circulating levels of TNF-α and IL-6 in humans: a systematic review and meta-analysis.
abstract: Epidemiological or in vitro evidence suggests a potential role for flavonoids as anti-inflammatory agents; we investigated the effect of flavonoids-rich foods or supplements on tumor necrosis factor- alpha (TNF-α) and interleukin-6 (IL-6) in long-term placebo-controlled human intervention trials. From 110 human intervention studies selected (MEDLINE, EMBASE, CHORANE, and FSTA databases), 32 long-term placebo-controlled trials were suitable for meta-analysis. After sensitivity analysis, seven studies imputed of bias were excluded and 25 studies were analyzed (TNF-α, n = 2404; IL-6, n = 2174). Levels of TNF-α decreased after flavonoid consumption in the fixed model only (mean difference (MD) (95% CI): -0.098 (-0.188, -0.009), p = 0.032), but metaregression results showed that neither higher dose, nor a longer duration of intervention were associated with a greater effect size. Subgroup analysis did not reveal any significant effect for quercetin and soy, but other sources (red wine, pomegranate, and tea extracts) showed a significant effect size both in fixed (MD (95% CI): TNF-α -0.449 (-0.619, -0.280), p < 0.001; IL-6 -0.346 (-0.612, -0.079), p = 0.011) and random (MD (95% CI): TNF-α -0.783 (-1.476, -0.090), p = 0.027; IL-6, -0.556 (-1.062, -0.050), p = 0.031) effect models. High-quality placebo-controlled trials are needed in order to identify flavonoids as the active ingredients.
authors.affiliation: Agricultural Research Council (CRA), Ex National Institute for Food and Nutrition Research (INRAN), Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Peluso
authors.forename: Anna
authors.initials: A
authors.lastname: Raguzzini
authors.forename: Mauro
authors.initials: M
authors.lastname: Serafini
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016208:Databases, Factual; D019587:Dietary Supplements; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D016032:Randomized Controlled Trials as Topic; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha