Table 3.

Human intervention trials suggesting health benefits of polyphenol intake with respect to IBD—an overview.

Aspects studied	Dosing and time	Effects found	Mechanism proposed and critics	Reference
Effect of curcumin on CD patients in a RCT study	89 patients with UC, 45 given 2 g curcumin/d for 6 months	Curcumin improved both clinical activity index & endoscopic index	Curcumin suppressed morbidity associated with UC	[75]
Effect of different dietary interventions, prospective trial	22 CD subjects receiving semivegetarian versus omnivorous diet for 2 y	Semivegetarian diet more successful in maintaining remission over 2 y versus omnivorous diet (94 versus 33%)	Effects of fiber & polyphenols?	[76]
Effect of cacao drink on gut bacteria	22 healthy adults receiving 494 mg or (n = 23) cocoa flavanols/d for 4 weeks	Significant reductions in plasma TG & CRP in group receiving high flavonol drink	Flavonol rich drink sign. increased Bifidobacteria & Lactobacilli populations, sign. decreasing Clostridia counts	[77]
Effect of pycnogenol in subjects with CD	15 children with CD receiving 2 mg/kg bw. for 12 weeks. 15 control children with no intervention	Compared to baseline, improved lipoperoxides, improved SOD, reduced AOPP	Oxidative stress related markers improved following PP consumption	[78]
Effect of red wine consumption on plasma LPS & gut bacteria	10 volunteers, 20 d, 272 mL of red wine (RW) with/without alcohol (DRW), or 100 mL gin	No significant differences in the change in LPS or LBP conc. between chronic RW, DRW, & gin consumption	Bifidobacterium & Prevotella amounts were significantly increased by RW & correlated negatively with LPS concentrations	[79]
Effect of blueberry beverage (bb) on healthy subjects	20 subjects, either consuming bb (375 mg ACNs & 128 mg CA) for 6 weeks versus placebo	Bb enhanced Bifidobacteria counts compared to placebo	Prebiotic effect of polyphenols	[80]
Effect of apple products on inflammation & gut microbiota	5 × 4 weeks crossover, whole apples (550 g/d), apple pomace (22 g/d), clear & cloudy apple juices (500 mL/d), none, n = 23 healthy adults, 75–240 mg PP/d	No effect on HDL-cholesterol, TAG, weight, waist-to-hip ratio, blood pressure, CRP, gut microbiota, insulin, IGF1, lower serum LDL for whole apples & pomace	Too high variation of bacterial changes such as Bifidobacteria, already health subjects, too short intervention period?	[81]
Effect of red wine on fecal markers of inflammation	34 healthy subjects drinking RW (1.76 g/L PP) for 4 weeks	In a subgroup of 6 subjects, TNF-α, IL-6, & IFN-γ in feces were sign. reduced	Reduced inflammation via NF-κB?	[82]
Effect of red wine PP on gut bacteria of obese subjects	10 obese & 10 normal subjects receiving 272 mL RW over 30 d	PP sign. increased fecal Bifidobacteria & Lactobacillus & butyrate producers (Faecalibacterium prausnitzii & Roseburia) at expense of undesired bacteria, for example, LPS producers (E. coli & Enterobacter cloacae)	Intestinal barrier protection & SCFA production	[83]

ACNs: anthocyanins; AMPK: adenosine monophosphate kinase; AOPP: advanced oxidation protein end-products; Bcl-xl: B-cell lymphoma-extra large; bcrp: breast cancer cell resistance protein; bw: body weight; CA: chlorogenic acid; CAT: catalase; ccl2: chemokine (C-C motif) ligand 2; CINC1: cytokine-induced neutrophil chemoattractant-1; CYP1A1: cytochrome P450, family 1, member 1A1; CD: Crohn's disease; COX-2: cyclooxygenase 2; CRP: c-reactive protein; CXCL1: chemokine (C-X-C motif) ligand, neutrophil activating; DAI: disease activity index; DSS: dextran sodium sulphate; DRW: dealcoholized wine; EA: ellagic acid; EGCG: epigallocatechin gallate; EP: evening primrose (Oenothera paradoxa) pomace; GAE: gallic acid equivalents; GM-CSF: granulocyte macrophage colony stimulating factor; FRAP: ferric reducing antioxidant power assay; GR: glutathione reductase; Gred: reduced glutathione; GrTP: green tea extract; GPx: glutathione peroxidase; GSH: glutathione (reduced); GSP: grape seed polyphenols; GSTT2: glutathione-S-transferase theta 2; ICAM: Intercellular adhesion molecule 1; IFN: interferon; IL: interleukin; iNOS: inducible nitric oxide synthase; LBP: LPS binding protein; LPS: lipopolysaccharides; Mcp-1: monocyte chemoattractant protein-1; Mdr1a (−/−): multidrug resistance targeted mutation; MDA: malondialdehyde; MPO: myeloperoxidase; MIP2: macrophage inflammatory protein 2; MRP: multidrug resistance protein; OHdG: 8-hydroxy-2′-deoxyguanosine; NF-κB: nuclear factor kappa B; Nrf-2: nuclear factor (erythroid-derived 2)-like 2; NQO1: NAD(P)H dehydrogenase [quinone-1] 1; PCAM-1: platelet endothelial cell adhesion molecule; PGE2: prostaglandin-E2; P-gp: P-glycoprotein; PP: polyphenols; PRDX-6: peroxiredoxin-6; PPAR: peroxisome proliferator-activated receptor; RCT: randomized control trial; RW: red wine; SAA: serum amyloid α; SAPK: stress activated protein kinase; SCFAs: short chain fatty acids; SOD: superoxide dismutase; STAT1: signal transducer and activator of transcription 1; TAC: total antioxidant capacity; TBNS: 2,4,6-trinitrobenzenesulfonic acid; TBARS: thiobarbituric acid reactive substances; TG: triglycerides; TNF-α: tumor necrosis factor alpha; TXNRD-1: thioredoxin reductase-1; UGT1A1: UDP-glucuronosyltransferase family 1 member A1; UTR: untranslated; VCAM-1: vascular cell adhesion protein 1; WB: Western blot.