Resveratrol supplementation decreases blood glucose without changing the circulating CD14+CD16+ monocytes and inflammatory cytokines in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Resveratrol attenuates inflammation in the rat heart subjected to ischemia-reperfusion: Role of the TLR4/NF-κB signaling pathway. Anti-inflammatory and antioxidant effects of resveratrol in healthy smokers a randomized, double-blind, placebo-controlled, cross-over trial. One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. Anti-Inflammatory Effects of Resveratrol in Patients with Ulcerative Colitis: A Randomized, Double-Blind, Placebo-controlled Pilot Study. Supplementation with Resveratrol and Curcumin Does Not Affect the Inflammatory Response to a High-Fat Meal in Older Adults with Abdominal Obesity: A Randomized, Placebo-Controlled Crossover Trial. Grape Resveratrol Increases Serum Adiponectin and Downregulates Inflammatory Genes in Peripheral Blood Mononuclear Cells: A Triple-Blind, Placebo-Controlled, One-Year Clinical Trial in Patients with Stable Coronary Artery Disease Resveratrol supplementation improves inflammatory biomarkers in patients with nonalcoholic fatty liver disease. Effect of vitamin D supplementation on inflammation: protocol for a systematic review One-year supplementation with a grape extract containing resveratrol modulates inflammatory-related microRNAs and cytokines expression in peripheral blood mononuclear cells of type 2 diabetes and hypertensive patients with coronary artery disease. Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. Effects of Polygonum Cuspidatum Containing Resveratrol on Inflammation in Male Professional Basketball Players Resveratrol levels and all-cause mortality in older community-dwelling adults.
Chronic low- grade inflammation is the hallmark of type 2 diabetes ( T2D ) . Although in vitro and animal studies have shown that resveratrol exerts anti-inflammatory effects , clinical trials addressing these effects in patients with T2D are limited . Therefore , in the present study , we hypothesized that supplementation of resveratrol might improve inflammatory markers in patients with T2D in a r and omized , double-blind , placebo-controlled clinical trial . A total of 45 T2D patients were supplemented with either of 800 mg/d resveratrol or placebo capsules for 8 weeks . Percentage of CD14+CD16 + monocytes , plasma levels of inflammatory cytokines ( tumor necrosis factor α , interleukin [ IL ] 1β , IL-6 , and monocyte chemoattractant protein-1 ) , the expression levels of genes involved in the inflammatory responses ( toll-like receptor 2 , toll-like receptor 4 , and nuclear factor κB ) , lipopolysaccharide-stimulated cytokine ( tumor necrosis factor α , IL-1β , and IL-6 ) secretion from peripheral blood mononuclear cells , and metabolic and anthropometric parameters were assessed at both the baseline level and the end of the study . Compared with the placebo group , we could not detect any significant difference in the percentage of CD14+CD16 + monocytes , lipopolysaccharide-induced cytokine secretion , plasma levels of inflammatory cytokines , and the expression of inflammatory genes in resveratrol group . Moreover , we did not find any significant change in the metabolic and anthropometric parameters except for a significant reduction in fasting blood glucose and blood pressure . In conclusion , 8-week supplementation of resveratrol reduces blood glucose level in patients with T2D without improving their inflammatory markers It has been previously reported that Toll‑like receptor 4 (TLR4)/NF‑κB signaling mediates early inflammation during myocardial ischemia and reperfusion . It has additionally been suggested that resveratrol produces cardioprotective and anti‑inflammatory effects . The aim of the present study was to investigate whether resveratrol could modulate TLR4/NF‑κB signaling , reduce neutrophil accumulation and TNF‑α induction in an ischemia/reperfusion injured rat heart model . Rats were r and omly exposed to a sham operation , myocardial ischemia and reperfusion ( MI/R ) , MI/R + resveratrol or MI/R + resveratrol + L‑NAME . The data showed that following MI/R , the expression of myocardial TLR4 and NF‑κB increased significantly in the area of induced ischemia . As compared with MI/R , resveratrol significantly attenuated the expression of TLR4 and NF‑κB and reduced the levels of myeloperoxidase , serum and myocardial TNF‑α production , myocardial infa rct size and myocardial apoptosis induced by MI/R. All the effects of resveratrol were abolished upon application of L‑NAME , a nitric oxide ( NO ) synthase inhibitor . These data provide evidence that resveratrol inhibits TLR4/NF‑κB signaling in the rat heart subjected to MI/R , and the anti‑inflammatory effect of resveratrol is associated with NO production OBJECTIVE Smokers are characterized by a low- grade systemic inflammatory state and an oxidant-antioxidant imbalance . Few human studies were conducted on the effects of resveratrol , a natural compound with anti-inflammatory and antioxidant properties , and no trial on smokers has been performed to date . We evaluated whether resveratrol has beneficial effects on markers of inflammation and oxidative stress in smokers . METHODS AND RESULTS A r and omized , double- blind , cross-over trial was performed in 50 healthy adult smokers : 25 were r and omly allocated to " resveratrol-first " ( 30-days : 500 mg resveratrol/day , 30-days wash-out , 30-days placebo ) and 25 to " placebo-first " ( 30-days placebo , 30-days wash-out , 30-days 500 mg resveratrol/day ) . Resveratrol significantly reduced C-reactive protein ( CRP ) and triglyceride concentrations , and increased Total Antioxidant Status ( TAS ) values . After analyzing data with general linear models to assess period and carry-over effects , the ratios of the values after resveratrol to those after placebo were respectively : 0.47 ( 95%CI 0.38 - 0.59 ) -CRP- and 0.71 ( 95%CI 0.65 - 0.78 ) -triglycerides- , while TAS increased by 74.2 μmol/L ( 95%CI 60.8 - 87.6 ) . Uric acid , glucose , insulin , cholesterol , liver enzyme concentrations , and weight , waist circumference , and blood pressure values did not significantly change after resveratrol supplementation . CONCLUSIONS Because resveratrol has anti-inflammatory , anti-oxidant , and hypotriglyceridemic effects , its supplementation may beneficially affect the increased cardiovascular risk of healthy smokers The search for complementary treatments in primary prevention of cardiovascular disease ( CVD ) is a high-priority challenge . Grape and wine polyphenol resveratrol confers CV benefits , in part by exerting anti-inflammatory effects . However , the evidence in human long-term clinical trials has yet to be established . We aim ed to investigate the effects of a dietary resveratrol-rich grape supplement on the inflammatory and fibrinolytic status of subjects at high risk of CVD and treated according to current guidelines for primary prevention of CVD . Seventy-five patients undergoing primary prevention of CVD participated in this triple-blinded , r and omized , parallel , dose-response , placebo-controlled , 1-year follow-up trial . Patients , allocated in 3 groups , consumed placebo ( maltodextrin ) , a resveratrol-rich grape supplement ( resveratrol 8 mg ) , or a conventional grape supplement lacking resveratrol , for the first 6 months and a double dose for the next 6 months . In contrast to placebo and conventional grape supplement , the resveratrol-rich grape supplement  significantly decreased high-sensitivity C-reactive protein ( -26 % , p = 0.03 ) , tumor necrosis factor-α ( -19.8 % , p = 0.01 ) , plasminogen activator inhibitor type 1 ( -16.8 % , p = 0.03 ) , and interleukin-6/interleukin-10 ratio ( -24 % , p = 0.04 ) and increased anti-inflammatory interleukin-10 ( 19.8 % , p = 0.00 ) . Adiponectin ( 6.5 % , p = 0.07 ) and soluble intercellular adhesion molecule-1 ( -5.7 % , p = 0.06 ) tended to increase and decrease , respectively . No adverse effects were observed in any patient . In conclusion , 1-year consumption of a resveratrol-rich grape supplement  improved the inflammatory and fibrinolytic status in patients who were on statins for primary prevention of CVD and at high CVD risk ( i.e. , with diabetes or hypercholesterolemia plus ≥1 other CV risk factor ) . Our results show for the first time that a dietary intervention with grape resveratrol could complement the gold st and ard therapy in the primary prevention of CVD BACKGROUND AND AIMS Ulcerative colitis ( UC ) is a chronic idiopathic inflammatory disease in which reducing pro-inflammatory and /or increasing anti-inflammatory molecules is the mainstay of treatment . The aim of this study was to evaluate the effects of supplementation with resveratrol as an antiinflammatory and antioxidant agent on inflammation and quality of life in patients with active UC . METHODS AND RESULTS In this r and omized , double-blind , placebo-controlled study , 50 eligible patients with active mild to moderate UC were supplemented with either a 500-mg resveratrol or placebo capsule for 6 weeks . Serum inflammatory markers , activity of NF-κB in peripheral blood mononuclear cells ( P BMC ) and quality of life were assessed at baseline and at the end of the study . Resveratrol supplementation led to a significant reduction in plasma levels of TNF-α ( 19.70 ± 12.80 to 17.20 ± 10.09 pg/mL ) and hs-CRP ( 4764.25 ± 2260.48 to 2584.50 ± 1792.80 ng/mL ) and activity of NF-κB in P BMC s ( 0.19 ± 0.05 to 0.10 ± 0.04 OD ) ( p < 0.001 ) , whereas there were no significant changes of these factors in placebo group . Also , the score of inflammatory bowel disease question naire -9 ( IBDQ-9 ) increased , whereas the clinical colitis activity index score decreased significantly in the resveratrol group ( 32.72 ± 7.52 to 47.64 ± 8.59 ) ( p < 0.001 ) and when compared with the placebo group ( 35.54 ± 9.50 to 41.08 ± 6.59 ) ( p < 0.001 ) . CONCLUSION Our results indicate that 6 weeks supplementation with 500 mg resveratrol can improve quality of life and disease clinical colitis activity at least partially through inflammation reduction in patients with UC . Whether these effects will be continued in longer duration of treatment remains to be determined Background High-fat meals induce postpr and ial inflammation . Resveratrol is a polyphenol known to prevent comorbidities associated with cardiovascular disease and exerts an anti-inflammatory action . There is also an increasing body of evidence supporting the role of curcumin , a polyphenol from the curcuminoid family , as a modulator of proinflammatory processes . Objective The objectives of this study were to investigate the following : 1 ) the bioavailability of resveratrol consumed in combination with curcumin after consumption of a high-fat meal ; and 2 ) the acute combined effects of this combination on the postpr and ial inflammatory response of subjects with abdominal obesity . Methods In a double blind , crossover , r and omized , placebo-controlled study , 11 men and 11 postmenopausal women [ mean ± SD age : 62 ± 5 y ; mean ± SD body mass index ( in kg/m2 ) : 29 ± 3 ] underwent a 6-h oral fat tolerance test on 2 occasions separated by 1 - 2 wk : once after consumption of a dietary supplement ( 200 mg resveratrol and 100 mg curcumin , Res/Cur ) and once after consumption of a placebo ( cellulose ) . Plasma concentrations of total resveratrol and its major metabolites as well as inflammatory markers , adhesion molecules , and whole blood NFκB1 and PPARA gene expression were measured during both fat tolerance tests . Results Kinetics of resveratrol and identified metabolites revealed rapid absorption patterns but also relatively limited bioavailability based on free resveratrol concentrations . Supplementation with Res/Cur did not modify postpr and ial variations in circulating inflammatory markers ( C-reactive protein , IL-6 , IL-8 , monocyte chemoattractant protein-1 ) and adhesion molecules [ soluble E-selectin , soluble vascular cell adhesion molecule-1 ( sVCAM-1 ) , soluble intercellular adhesion molecule-1 ] compared to placebo ( PTreatment × Time > 0.05 ) . However , Res/Cur significantly decreased the cumulative postpr and ial response of sVCAM-1 , compared to placebo ( incremental area under the curve -4643 % , P = 0.01 ) . Postpr and ial variations of whole-blood PPARA and NFKB1 gene expression were not different between Res/Cur and placebo treatments . Conclusions Acute supplementation with Res/Cur has no impact on the postpr and ial inflammation response to a high-fat meal in abdominally obese older adults . Further studies are warranted to examine how resveratrol and curcumin may alter the vascular response to a high-fat meal . This trial was registered at clinical trials.gov as NCT01964846 Purpose The grape and wine polyphenol resveratrol exerts cardiovascular benefits but evidence from r and omized human clinical trials is very limited . We investigated dose-depending effects of a resveratrol-containing grape supplement on stable patients with coronary artery disease ( CAD ) treated according to currently accepted guidelines for secondary prevention of cardiovascular disease . Methods In a triple-blind , r and omized , placebo-controlled , one-year follow-up , 3-arm pilot clinical trial , 75 stable-CAD patients received 350 mg/day of placebo , resveratrol-containing grape extract ( grape phenolics plus 8 mg resveratrol ) or conventional grape extract lacking resveratrol during 6 months , and a double dose for the following 6 months . Changes in circulating inflammatory and fibrinolytic biomarkers were analyzed . Moreover , the transcriptional profiling of inflammatory genes in peripheral blood mononuclear cells ( P BMC s ) was explored using microarrays and functional gene expression analysis . Results After 1 year , in contrast to the placebo and conventional grape extract groups , the resveratrol-containing grape extract group showed an increase of the anti-inflammatory serum adiponectin ( 9.6 % , p = 0.01 ) and a decrease of the thrombogenic plasminogen activator inhibitor type 1 ( PAI-1 ) ( −18.6 % , p = 0.05 ) . In addition , 6 key inflammation-related transcription factors were predicted to be significantly activated or inhibited , with 27 extracellular-space acting genes involved in inflammation , cell migration and T-cell interaction signals presenting downregulation ( p < 0.05 ) in P BMC s. No adverse effects were detected in relation to the study products . Conclusions Chronic daily consumption of a resveratrol-containing grape nutraceutical could exert cardiovascular benefits in stable-CAD patients treated according to current evidence -based st and ards , by increasing serum adiponectin , preventing PAI-1 increase and inhibiting atherothrombotic signals in P BMC Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in the world . Resveratrol is a polyphenolic compound with antioxidant capacity that shows beneficial effects on down-regulation of inflammatory mediators and metabolic disorders . We hypothesized that supplementation with resveratrol can further improve the efficacy of lifestyle modifications in the management of NAFLD . In this r and omized , double-blinded , controlled clinical trial , 50 NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks . Both groups were advised to follow an energy-balanced diet and received physical activity recommendations  . Serum liver enzymes , inflammatory markers , hepatic steatosis and fibrosis , dietary intake , anthropometric measurements , and physical activity were assessed at both baseline and the end of the study . In both groups , anthropometric measurements ( weight , body mass index , waist circumference ) , liver enzymes , and steatosis grade improved ( P < 005 ) . Resveratrol supplementation was associated with a significant reduction in liver enzyme alanine aminotransferase , inflammatory cytokines , nuclear factor κB activity , serum cytokeratin-18 , and hepatic steatosis grade , as compared with placebo supplementation ( P < .05 ) . For the treatment of NAFLD , our results showed that 12 weeks of supplementation of 500 mg resveratrol , along with lifestyle modification , is superior to lifestyle modification alone . This is at least partially due to the attenuation of inflammatory markers and hepatocellular apoptosis . More studies are needed to confirm and increase the clinical application of the present results Introduction The extraskeletal role of vitamin D is being increasingly recognised . This has important clinical implication s , as vitamin D deficiency has reached epidemic proportions worldwide . Vitamin D has proposed anti-inflammatory properties , yet the role of vitamin D supplementation in reducing inflammation remains largely unknown . The purpose of this review is to investigate the impact of vitamin D supplementation on inflammation , and to identify relevant knowledge gaps in the field . Methods and analysis Medline , CINAHL , EMBASE and All EBM will be systematic ally search ed for r and omised controlled trials ( RCTs ) and systematic review s of RCTs , comparing vitamin D supplementation with placebo , usual care or other pharmacological or non-pharmacological interventions . One review er will assess articles for eligibility according to prespecified selection criteria , after which 2 independent review ers will perform data extraction and quality appraisal . Meta-analyses will be conducted where appropriate . Ethics and dissemination Formal ethical approval is not required as no primary data is collected . This systematic review will identify potential clinical implication s of vitamin D deficiency and supplementation , and will be disseminated through a peer- review ed publication and at conference meetings , to inform future research on the efficacy of vitamin D supplementation for inflammation and inflammatory diseases . PROSPERO registration number CRD42016037104 Numerous studies have shown that resveratrol ( RES ) exerts anti-inflammatory effects but human trials evidencing these effects in vivo are limited . Furthermore , the molecular mechanisms triggered in humans following the oral intake of RES are not yet understood . Therefore , the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells ( P BMC s ) associated to the one-year daily intake of a RES enriched ( 8 mg ) grape extract ( GE-RES ) in hypertensive male patients with type 2 diabetes mellitus ( T2DM ) . We used microarrays and RT-PCR to analyze expression changes in genes and microRNAs ( miRs ) involved in the inflammatory response modulated by the consumption of GE-RES in comparison to a placebo and GE lacking RES . We also examined the changes in several serobiochemical variables , inflammatory and fibrinolytic markers . Our results showed that supplementation with GE or GE-RES did not affect body weight , blood pressure , glucose , HbA1c or lipids , beyond the values regulated by gold st and ard medication in these patients . We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL-6 levels . The expression of the pro-inflammatory cytokines CCL3 , IL-1β and TNF-α was significantly reduced and that of the transcriptional repressor LRRFIP-1 increased in P BMC s from patients taking the GE-RES extract . Also , a group of miRs involved in the regulation of the inflammatory response : miR-21 , miR-181b , miR-663 , miR-30c2 , miR-155 and miR-34a were found to be highly correlated and altered in the group consuming the GE-RES for 12 months . Our results provide preliminary evidence that long-term supplementation with a grape extract containing RES downregulates the expression of key pro-inflammatory cytokines with the involvement of inflammation-related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect in these patients The polyphenol resveratrol is considered to exert many beneficial actions , such as antioxidant , anti-inflammatory , insulin-sensitizer and anticancer effects . Its benefits in patients with type 2 diabetes mellitus ( T2DM ) are controversial . Our aims were to determine whether resveratrol supplementation at two different dosages ( 500 and 40mg/day ) for 6 months i ) reduced the concentrations of C-reactive-protein ( CRP ) and ii ) ameliorated the metabolic pattern of T2DM patients .  In the present double-blind , r and omized , placebo-controlled trial , 192 T2DM patients were r and omized to receive resveratrol 500mg/day ( Resv500arm ) , resveratrol 40mg/day ( Resv40arm ) or placebo for 6-months . At baseline and at the trial end , CRP values , anthropometric , metabolic and liver parameters were determined . No serious adverse event occurred . A dose-dependent , though not significant , CRP decrease of 5.6 % ( Resv40arm ) and 15.9 % ( Resv500arm ) was observed vs placebo . We failed to detect significant differences in weight , BMI , waist circumference , and values of arterial blood pressure , fasting glucose , glycated hemoglobin , insulin , C-peptide , free fatty acids , liver transaminases , uric acid , adiponectin , interleukin-6 , in both the Resv500 and Resv40 arms vs placebo . Total cholesterol and triglycerides slightly increased in the Resv500arm . Subgroup analyses revealed that lower diabetes duration ( in both Resv500 and Resv40arms ) , and , in the Resv500arm , younger age , aspirin use and being a smoker were associated with a significantly higher CRP reduction vs placebo . The supplementations with 40mg/day or 500mg/day resveratrol did neither reduce CRP concentrations , nor improve the metabolic pattern of T2DM patients Background : Exercise can lead to acute oxidative stress , which can result in oxidative damage and induce inflammation . Resveratrol may reduce the levels of inflammatory cytokines . Thus , we investigated the effects of this compound on the plasma levels of tumor necrosis factor-α ( TNF-α ) and interleukin 6 ( IL-6 ) in male professional basketball players . Methods : Twenty healthy male professional basketball players were r and omized into two groups ( 10 each ) . For 6 weeks , they received daily either 200 mg of polygonum cuspidatum extract ( PCE ) st and ardized to contain 20 % trans-resveratrol equivalent to 40 mg trans-resveratrol or placebo . Indices of inflammation were measured before and after 6 weeks of supplementation . Results : There was a significant reduction in plasma levels of TNF-a and IL-6 after 6 weeks of supplementation ; while no change was observed in these markers in the control group . Conclusions : Present study shows that 6 weeks of PCE containing resveratrol supplementation reduces the inflammation in male professional basketball players IMPORTANCE Resveratrol , a polyphenol found in grapes , red wine , chocolate , and certain berries and roots , is considered to have antioxidant , anti-inflammatory , and anticancer effects in humans and is related to longevity in some lower organisms . OBJECTIVE To determine whether resveratrol levels achieved with diet are associated with inflammation , cancer , cardiovascular disease , and mortality in humans . DESIGN Prospect i ve cohort study , the Invecchiare in Chianti ( InCHIANTI ) Study ( " Aging in the Chianti Region " ) , 1998 to 2009 conducted in 2 villages in the Chianti area in a population -based sample of 783 community-dwelling men and women 65 years or older . EXPOSURES Twenty-four-hour urinary resveratrol metabolites . MAIN OUTCOMES AND MEASURES Primary outcome measure was all-cause mortality . Secondary outcomes were markers of inflammation ( serum C-reactive protein [ CRP ] , interleukin [IL]-6 , IL-1β , and tumor necrosis factor [ TNF ] ) and prevalent and incident cancer and cardiovascular disease . RESULTS Mean ( 95 % CI ) log total urinary resveratrol metabolite concentrations were 7.08 ( 6.69 - 7.48 ) nmol/g of creatinine . During 9 years of follow-up , 268 ( 34.3 % ) of the participants died . From the lowest to the highest quartile of baseline total urinary resveratrol metabolites , the proportion of participants who died from all causes was 34.4 % , 31.6 % , 33.5 % , and 37.4 % , respectively ( P = .67 ) . Participants in the lowest quartile had a hazards ratio for mortality of 0.80 ( 95 % CI , 0.54 - 1.17 ) compared with those in the highest quartile of total urinary resveratrol in a multivariable Cox proportional hazards model that adjusted for potential confounders . Resveratrol levels were not significantly associated with serum CRP , IL-6 , IL-1β , TNF , prevalent or incident cardiovascular disease , or cancer . CONCLUSIONS AND RELEVANCE In older community-dwelling adults , total urinary resveratrol metabolite concentration was not associated with inflammatory markers , cardiovascular disease , or cancer or predictive of all-cause mortality . Resveratrol levels achieved with a Western diet did not have a substantial influence on health status and mortality risk of the population in this study
IMPLICATION S Available evidence from RCTs suggests that resveratrol supplementation significantly reduced TNF-α and hs-CRP levels .
Significant improvement in inflammatory markers  support resveratrol as an adjunct to pharmacologic management of metabolic diseases
PURPOSE The evidence has suggested that resveratrol has anti-inflammatory effect ; however , the results are inconsistent and inconclusive .
The aim of this study was to assess the effect of resveratrol supplementation on the levels of inflammatory markers through a systematic review and meta- analysis of available r and omized controlled trials ( RCTs ) .