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. 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 the inflammatory reaction induced by ischemia/reperfusion in the rat heart. Anti-Inflammatory Effects of Resveratrol in Patients with Ulcerative Colitis: A Randomized, Double-Blind, Placebo-controlled Pilot Study. Resveratrol attenuates inflammation and oxidative stress induced by myocardial ischemia-reperfusion injury: role of Nrf2/ARE pathway. 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 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. Resveratrol supplementation improves inflammatory biomarkers in patients with nonalcoholic fatty liver disease. One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. Oral resveratrol and calcium fructoborate supplementation in subjects with stable angina pectoris: effects on lipid profiles, inflammation markers, and quality of life. 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. The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial Effect of resveratrol on exercise capacity: a randomized placebo-controlled crossover pilot study. Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. Resveratrol as Add-on Therapy in Subjects With Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial Effects of chronic resveratrol supplementation in military firefighters undergo a physical fitness test--a placebo-controlled, double blind study.
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 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 The role of resveratrol ( Res ) in inflammation induced by ischemia/reperfusion is not well understood . The aim of the present study was to investigate whether Res modulates neutrophil accumulation and tumor necrosis factor-α ( TNF-α ) induction in an ischemia/reperfusion-injured rat heart model . The rats were r and omly exposed to sham surgery , myocardial ischemia/reperfusion ( MI/R ) alone , MI/R + Res , MI/R + Res + L-NG-nitroarginine methyl ester ( L-NAME ) and MI/R + Res + methylene blue ( MB ) . The results demonstrated that compared with MI/R , Res reduced the myocardial infa rct area , myocardial myeloperoxidase levels , serum creatinine kinase and lactate dehydrogenase levels , and serum and myocardial TNF-α production . All the effects of Res demonstrated were inhibited by L-NAME ( a nitric oxide ( NO ) synthase inhibitor ) and MB [ a cyclic guanosine monophosphate ( cGMP ) inhibitor ] . Thus , Res  produces cardioprotective and anti-inflammatory effects . These effects may be associated with an increase in NO production , the inhibition of neutrophil accumulation , TNF-α induction and cGMP signaling pathways in myocardium subjected to 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 The protective role of resveratrol in myocardial ischemia/reperfusion is not well understood . The aim of this study was to investigate whether resveratrol modulates inflammation and oxidative stress and the possible role of nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element ( ARE ) pathway in an ischemia/reperfusion injured rat heart model . Rats were r and omly exposed to sham operation , myocardial ischemia/reperfusion ( MI/R ) alone , and MI/R + resveratrol . The results demonstrated that compared to MI/R , resveratrol improved cardiac function , reduced myocardial infa rct ion area , myocardial myeloperoxidase ( MPO ) levels , serum creatinine kinase ( CK ) and lactate dehydrogenase ( LDH ) levels .  Resveratrol also markedly enhanced the activities of antioxidant enzymes superoxide dismutase ( SOD ) and glutathione peroxidase ( GSH-PX ) , and reduced the level of malondialdehyde ( MDA ) in MI/R rats . Resveratrol also enhanced levels of Nrf2 and heme oxygenase-1 . In summary , these results demonstrated that resveratrol exerted significant antioxidant and cardioprotective effects following myocardial ischemia , possibly through the activation of the Nrf2/ARE signaling pathway 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 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 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 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 OBJECTIVE This study aim ed to evaluate the effects of short-term ( 60-d ) oral supplementation with calcium fructoborate , resveratrol , and their combination on the clinical and biological statuses of subjects with stable angina pectoris . METHODS A r and omized , double-blinded , active-controlled , parallel clinical trial was conducted in three groups of subjects . Of the total number of subjects included in study ( n = 166 ) , 87 completed the 60-d test treatment study period and 29 followed in parallel their usual medical care and treatment . The primary outcomes were inflammation biomarkers ( high-sensitivity C-reactive protein ) , left ventricular function markers ( N-terminal prohormone of brain natriuretic peptide ) , and lipid markers ( total cholesterol , low-density lipoprotein cholesterol , high-density lipoprotein cholesterol , and triacylglycerols ) . Quality of life was assessed by the Canadian Cardiovascular Society angina class and the number of angina attacks per week . RESULTS There was a significant decrease of high-sensitivity C-reactive protein in all groups at the 30-d and 60-d visits . This decrease was greater ( 39.7 % at 60 d ) for group 3 ( calcium fructoborate ) , followed by group 2 ( resveratrol plus calcium fructoborate , 30.3 % at 60 d ) . The N-terminal prohormone of brain natriuretic peptide was significantly lowered by resveratrol ( group 1 , 59.7 % at 60 d ) and by calcium fructoborate ( group 3 , 52.6 % at 60 d ) . However , their combination ( group 2 ) was the most effective and induced a decrease of 65.5 % . Lipid markers showed slight changes from baseline in all groups . The improvement in the quality of life was best observed for subjects who received the resveratrol and calcium fructoborate mixture ( group 2 ) . CONCLUSION The results indicate that the combination of resveratrol and calcium fructoborate has beneficial effects in patients with 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 Abstract Aims Oxidative stress plays a pivotal role in the pathogenesis of type 2 diabetes ( T2D ) . In vitro and animal studies have shown that resveratrol exerts an antioxidant effect , but clinical trials addressing this effect in patients with T2D are limited . The aim of this study was to determine whether resveratrol supplementation affects oxidative stress markers in a r and omized , placebo-controlled , double-blind clinical trial . Methods A total of 48 patients with T2D r and omly were assigned to receive 800 mg/day resveratrol or placebo for 2 months . Plasma total antioxidant capacity , malondialdehyde concentration , protein carbonyl and total thiol contents , intracellular superoxide anion ( O2− · ) and hydrogen peroxide ( H2O2 ) in P BMC s , the expression of genes involved in oxidative stress responses ( Nrf2 , SOD , Cat , HO-1 , RAGE , NOS ) in P BMC s , and metabolic and anthropometric parameters were measured at the baseline and at the trial end . Results Compared with the placebo group , resveratrol reduced plasma protein carbonyl content and P BMC s O2− · level and significantly increased plasma total antioxidant capacity and total thiol content . Furthermore , the expression of Nrf2 and SOD was significantly increased after resveratrol consumption . Resveratrol had no significant effects on the metabolic and anthropometric parameters except for a significant reduction in weight , BMI , and blood pressure levels . Resveratrol was well tolerated , and no serious adverse event was occurred . Conclusions Our study demonstrated that 8 weeks of supplementation with 800 mg/day resveratrol has an antioxidant effect in the blood and P BMC s of patients with T2D . Clinical Trial Registry number and website I RCT registration number : I RCT 2015072523336N1 and http://en . search .i rct .ir/view/24752 To assess the effect on exercise capacity and tolerability of resveratrol , 13 healthy , sedentary adult volunteers were enrolled in a r and omized crossover study comparing resveratrol and placebo over two 4-week periods , with a 2-week time between periods when subjects received no treatment . No significant changes in exercise duration or aerobic capacity ( peak oxygen uptake ) were observed . Gastrointestinal side effects were more common during resveratrol treatment ( 77 % vs. 15 % , p = 0.0048 ) . A small reduction in fasting glucose and small but statistically significant increases in liver enzymes , total cholesterol , and triglycerides were observed , although mean results remained within normal limits . There was no change in complete blood count , inflammatory markers , renal function , or other measures of liver function 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 OBJECTIVE To determine whether resveratrol supplementation can improve insulin sensitivity and promote overall metabolic health on top of st and ard diabetes care . RESEARCH DESIGN AND METHODS Seventeen subjects with well-controlled type 2 diabetes ( T2D ) were treated with placebo and 150 mg/day resveratrol ( resVida ) in a r and omized double-blind crossover study for 30 days . The main outcome measure was insulin sensitivity by the hyperinsulinemic-euglycemic clamp technique . RESULTS Hepatic and peripheral insulin sensitivity were not affected by resveratrol treatment . Intrahepatic lipid content also remained unaffected by resveratrol ; however , the change in intrahepatic lipid content correlated negatively with plasma resveratrol levels ( R = −0.68 , P = 0.03 ) . Intramyocellular lipid content increased in type 2 muscle fibers ( P = 0.03 ) , and systolic blood pressure tended to decrease ( P = 0.09 ) upon resveratrol treatment . In addition , resveratrol significantly improved ex vivo mitochondrial function ( state 3 and state U respiration upon malate with octanoyl-carnitine , P < 0.005 ) . Intriguingly , a correlation was found between plasma levels of a metabolite of resveratrol  ( dihydroresveratrol ) and the metformin dose used by the patients ( R = 0.66 , P = 0.005 ) , suggesting an interaction between metformin and resveratrol . It could be speculated that the lack of a  resveratrol-induced insulin-sensitizing effect is caused by this interaction . CONCLUSIONS Resveratrol supplementation does not improve hepatic or peripheral insulin sensitivity . Our results question the generalized value of resveratrol as an add-on therapy in the treatment of T2D and emphasize the need to perform studies in drug-naive patients with T2D or subjects with prediabetes PURPOSE The purpose of this study was to determine the plasma metabolic response and certain indicators of oxidative stress ( antioxidant system and oxidative stress biomarkers ) in plasma and erythrocytes of Brazilian military firefighters supplemented or not with resveratrol ( RES ) for 90 days ( 100 mg/day ) . The analyses were performed before and after a typical physical fitness test ( FT ) used to induce oxidative stress . METHODS / RESULTS In this placebo-controlled double-blinded study , we observed that RES supplementation did not present hepatic consequences compared with the placebo group following analysis of AST , ALT and GGT plasma activities . Plasma glucose and triglycerides levels were increased after the FT in firefighters supplemented with RES but were not elevated at baseline . Neither total nor cholesterol fractions were modified by RES supplementation . CK levels were increased after the firefighters performed the FT ; however , no differences were determined between the placebo and RES groups . Ferric-reducing ability of plasma as well as uric acid was increased after the FT , but was not modified by RES supplementation . Plasma oxidative stress biomarkers , such as thiol content , 8-isoprostane and 8OHdG , showed no modifications , while IL-6 and TNF-α were decreased in the RES group after the FT . Among antioxidant enzyme activities determined in erythrocytes from the firefighters , only GPx activity was reduced by RES supplementation both before and after the FT . CONCLUSION In summary , the most pronounced effect of RES supplementation is its anti-inflammatory effect , which reduced IL-6 and TNF-α level . The FT applied to Brazilian military firefighters was not sufficient to challenge the antioxidant defense systems , and , therefore , 100 mg of RES for three months did not induce significant effects
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 ) .