title: 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 red yeast rice combined with antioxidants on lipid pattern, hs-CRP level, and endothelial function in moderately hypercholesterolemic subjects Effects of resveratrol supplementation on liver fat content in overweight and insulin‐resistant subjects: A randomized, double‐blind, placebo‐controlled clinical trial Causal relationship of hepatic fat with liver damage and insulin resistance in nonalcoholic fatty liver Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease Resveratrol supplementation improves inflammatory biomarkers in patients with nonalcoholic fatty liver disease. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Small, dense low-density lipoprotein particles as a predictor of the risk of ischemic heart disease in men. Prospective results from the Québec Cardiovascular Study. Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus. Resveratrol improves ex vivo mitochondrial function but does not affect insulin sensitivity or brown adipose tissue in first degree relatives of patients with type 2 diabetes Resveratrol Promotes Foot Ulcer Size Reduction in Type 2 Diabetes Patients Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial. Oral resveratrol and calcium fructoborate supplementation in subjects with stable angina pectoris: effects on lipid profiles, inflammation markers, and quality of life. The effects of resveratrol supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study. The effects of polyphenol supplementation on adipose tissue morphology and gene expression in overweight and obese humans Resveratrol does not benefit patients with nonalcoholic fatty liver disease. The Impact of Resveratrol Supplementation on Blood Glucose, Insulin, Insulin Resistance, Triglyceride, and Periodontal Markers in Type 2 Diabetic Patients with Chronic Periodontitis Efficacy of an orlistat-resveratrol combination for weight loss in subjects with obesity: A randomized controlled trial. Effects of resveratrol in patients with type 2 diabetes mellitus on skeletal muscle SIRT1 expression and energy expenditure. 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. Effects of Pharmacologic Dose of Resveratrol Supplementation on Oxidative/Antioxidative Status Biomarkers in Nonalcoholic Fatty Liver Disease Patients: A Randomized, Double-Blind, Placebo-Controlled Trial Effect of resveratrol supplementation on lipid profile in subjects with dyslipidemia: A randomized double-blind, placebo-controlled trial.
abstract: 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 Our aim was to test , through a crossover , double-blind , placebo-controlled r and omized clinical trial , if a short-term treatment with 10 mg monacolins combined with antioxidants could improve lipid pattern , high-sensitivity C-reactive protein ( hs-CRP ) , and endothelial function in a small cohort of moderately hypercholesterolemic subjects . Thus , 25 healthy , moderately hypercholesterolemic subjects were consecutively enrolled and , after 4 weeks of stabilization diet , were r and omized to the sequence placebo followed by a washout , monacolins or monacolins followed by a washout , placebo , with each period being 4 weeks long . At each study step , a complete lipid pattern , safety parameters , hs-CRP , and endothelial function have been measured . When compared to the placebo phase , during monacolin treatment , patients experienced a more favorable percentage change in total cholesterol ( TC ) ( TC after monacolin treatment , −18.35 % ; TC after placebo treatment , −5.39 % ) , low-density lipoprotein cholesterol ( LDL-C ) ( LDL after monacolin treatment , −22.36 % ; LDL after placebo treatment , −1.38 % ) , non-high-density lipoprotein cholesterol ( HDL-C ) ( non-HDL after monacolin treatment , −22.83 % ; non-HDL after placebo treatment : −7.15 % ) , hs-CRP ( hs-CRP after monacolin treatment : −2.33 % ; hs-CRP after placebo treatment , 2.11 % ) , and endothelial function ( pulse volume displacement after monacolin treatment , 18.59 % ; pulse volume displacement after placebo treatment , −6.69 % ) . No significant difference was observed with regard to triglycerides , HDL-cholesterol , and safety parameters . On the basis of our data , we could demonstrate that a 10 mg monacolin nutraceutical treatment appears to safely reduce cholesterolemia , hs-CRP , and markers of vascular remodeling in moderately hypercholesterolemic subjects . These results need to be confirmed in larger patient sample s and in studies with longer duration We performed the largest r and omized , placebo‐controlled clinical trial to date ( N = 112 , 12‐week intervention ) to investigate the effects and safety of resveratrol supplementation on liver fat content and cardiometabolic risk parameters in overweight and obese and insulin‐resistant subjects . At baseline the variability in liver fat content was very large , ranging from 0.09 % to 37.55 % ( median , 7.12 % ; interquartile range , 3.85%‐12.94 % ) . Mean ( SD ) liver fat content was 9.22 ( 6.85 ) % in the placebo group and 9.91 ( 7.76 ) % in the resveratrol group . During the study liver fat content decreased in the placebo group ( −0.7 % ) but not in the resveratrol group ( −0.03 % ) ( differences between groups : P = .018 for the intention‐to‐treat [ ITT ] population ; N = 54 , resveratrol , N = 54 , placebo and P = .0077 for the per protocol [ PP ] population ) . No effects  of resveratrol supplementation on cardiometabolic risk parameters were observed . Resveratrol supplementation was well tolerated and safe Abstract Background and Aims Nonalcoholic fatty liver disease is epidemiologically associated with hepatic and metabolic disorders . The aim of this study was to examine whether hepatic fat accumulation has a causal role in determining liver damage and insulin resistance . Methods We performed a Mendelian r and omization analysis using risk alleles in PNPLA3 , TM6SF2 , GCKR and MBOAT7 , and a polygenic risk score for hepatic fat , as instruments . We evaluated complementary cohorts of at‐risk individuals and individuals from the general population : 1515 from the liver biopsy cohort ( LBC ) , 3329 from the Swedish Obese Subjects Study ( SOS ) and 4570 from the population ‐based Dallas Heart Study ( DHS ) . Results Hepatic fat was epidemiologically associated with liver damage , insulin resistance , dyslipidemia and hypertension . The impact of genetic variants on liver damage was proportional to their effect on hepatic fat accumulation . Genetically determined hepatic fat was associated with aminotransferases , and with inflammation , ballooning and fibrosis in the LBC . Furthermore , in the LBC , the causal association between hepatic fat and fibrosis was independent of disease activity , suggesting that a causal effect of long‐term liver fat accumulation on liver disease is independent of inflammation . Genetically determined hepatic steatosis was associated with insulin resistance in the LBC and SOS . However , this association was dependent on liver damage severity . Genetically determined hepatic steatosis was associated with liver fibrosis/cirrhosis and with a small increase in risk of type 2 diabetes in publicly available data bases . Conclusion These data suggest that long‐term hepatic fat accumulation plays a causal role in the development of chronic liver disease ABSTRACT Objective “ The obesity epidemic ” has led to an increase in obesity-related conditions including non-alcoholic fatty liver disease ( NAFLD ) , for which effective treatments are in dem and . The polyphenol resveratrol prevents the development of experimental NAFLD through modulation of cellular pathways involved in calorie restriction . We aim ed to test the hypothesis that resveratrol alleviates NAFLD in a r and omised , clinical trial . Material s and methods A total of 28 overweight patients with transaminasemia and histological NAFLD were r and omised 1:1 to placebo or resveratrol 1.5 g daily for 6 months . Twenty-six participants completed the trial and underwent repeated clinical investigation , blood work , MR spectroscopy ; and 19 participants agreed to a repeat liver biopsy . Results Resveratrol treatment was generally not superior to placebo in improving plasma markers of liver injury ( primary outcome : alanine transaminase , p = 0.51 ) . Resveratrol-treated patients showed a 3.8 % decrease in liver lipid content ( p = 0.03 ) , with no difference between the two treatment arms ( p = 0.38 ) and no improvement of histological features .  Resveratrol treatment was not associated with improvements in insulin sensitivity or markers of the metabolic syndrome , except for a transient decrease in systolic BP . Microarray analysis and qRT-PCR revealed no major changes in expression profile . Also , we report a serious adverse event in a patient who developed fever and bicytopenia . Conclusions In this placebo-controlled , high-dose and long-term study , resveratrol treatment had no consistent therapeutic effect in alleviating clinical or histological NAFLD , though there may be a small ameliorating effect on liver function tests and liver fat accumulation 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 Resveratrol is a naturally occurring polyphenolic compound . Numerous animal studies have been reported on its wide-ranging beneficial effects in the biological system including diabetes mellitus ( DM ) . We hypothesized , therefore , that oral supplementation of resveratrol would improve the glycemic control and the associated risk factors in patients with type 2 diabetes mellitus ( T2DM ) . The present clinical study was therefore carried out to test the hypothesis . Sixty-two patients with T2DM were enrolled from Government Headquarters Hospital , Ootacamund , India , in a prospect i ve , open-label , r and omized , controlled trial . Patients were r and omized into control and intervention groups . The control group received only oral hypoglycemic agents , whereas the intervention group received resveratrol ( 250 mg/d ) along with their oral hypoglycemic agents for a period of 3 months . Hemoglobin A(1c ) , lipid profile , urea nitrogen , creatinine , and protein were measured at the baseline and at the end of 3 months . The results reveal that supplementation of resveratrol for 3 months significantly improves the mean hemoglobin A(1c ) ( means ± SD , 9.99 ± 1.50 vs 9.65 ± 1.54 ; P < .05 ) , systolic blood pressure ( mean ± SD , 139.71 ± 16.10 vs 127.92 ± 15.37 ; P < .05 ) , total cholesterol ( mean ± SD , 4.70 ± 0.90 vs 4.33 ± 0.76 ; P < .05 ) , and total protein ( mean ± SD , 75.6 ± 4.6 vs 72.3 ± 6.2 ; P < .05 ) in T2DM . No significant changes in body weight and high-density lipoprotein and low-density lipoprotein cholesterols were observed . Oral supplementation of resveratrol is thus found to be effective in improving glycemic control and may possibly provide a potential adjuvant for the treatment and management of diabetes BACKGROUND Case-control studies have reported that patients with ischemic heart disease ( IHD ) have a higher proportion of small , dense LDL particles than do healthy control subjects . The extent to which the risk attributed to small LDL particles may be independent of concomitant variations in plasma lipoprotein-lipid concentrations remains to be clearly determined , however , particularly through prospect i ve studies . METHODS AND RESULTS Baseline characteristics were obtained in 2103 men initially free of IHD , among whom 114 developed IHD during a 5-year follow-up period . These 114 case patients were matched with healthy control subjects for age , body mass index , smoking habits , and alcohol intake . LDL peak particle diameter ( PPD ) was measured a posteriori in 103 case-control pairs by nondenaturing gradient gel electrophoresis of whole plasma . Conditional logistic regression analysis of the case-control status revealed that men in the first tertile of the control LDL-PPD distribution ( LDL-PPD < or = 25.64 nm ) had a 3.6-fold increase in the risk of IHD ( 95 % CI , 1.5 to 8.8 ) compared with those in the third tertile ( LDL-PPD > 26.05 nm ) . Statistical adjustment for concomitant variations in LDL cholesterol , triglycerides , HDL cholesterol , and apolipoprotein B concentrations had virtually no impact on the relationship between small LDL particles and the risk of IHD . CONCLUSIONS These results represent the first prospect i ve evidence suggesting that the presence of small , dense LDL particles may be associated with an increased risk of subsequently developing IHD in men . Results also suggest that the risk attributed to small LDL particles may be partly independent of the concomitant variation in plasma lipoprotein-lipid concentrations Resveratrol has been reported to have potent anti-atherosclerotic effects in animal studies . However , there are few interventional studies in human patients with atherosclerogenic diseases . The cardio-ankle vascular index ( CAVI ) reflects arterial stiffness and is a clinical surrogate marker of atherosclerosis . The aim of the present study was to investigate the effect of resveratrol on arterial stiffness assessed by CAVI in patients with type 2 diabetes mellitus (T2DM).In this double-blind , r and omized , placebo-controlled study , 50 patients with T2DM received supplement of a 100 mg resveratrol tablet ( total resveratrol : oligo-stilbene 27.97 mg/100 mg/day ) or placebo daily for 12 weeks . CAVI was assessed at baseline and the end of study . Body weight ( BW ) , blood pressure ( BP ) , glucose and lipid metabolic parameters , and diacron-reactive oxygen metabolites ( d-ROMs ; an oxidative stress marker ) were also measured . Resveratrol supplementation decreased systolic BP ( -5.5 ± 13.0 mmHg ) , d-ROMs ( -25.6 ± 41.8 U.CARR ) , and CAVI ( -0.4 ± 0.7 ) significantly ( P < 0.05 ) and decreased BW ( -0.8 ± 2.1 kg , P = 0.083 ) and body mass index ( -0.5 ± 0.8 kg/m2 , P = 0.092 ) slightly compared to baseline , while there were no significant changes in the placebo group . Decreases in CAVI and d-ROMs were significantly greater in the resveratrol group than in the placebo group . Multivariate logistic regression analysis identified resveratrol supplementation as an independent predictor for a CAVI decrease of more than 0.5.In conclusion , 12-week resveratrol supplementation may improve arterial stiffness and reduce oxidative stress in patients with T2DM . Resveratrol may be beneficial in preventing the development of atherosclerosis induced by diabetes . However , a large-scale cohort study is required to vali date the present findings Objective Resveratrol supplementation improves metabolic health in healthy obese men , but not in patients with type 2 diabetes ( T2D ) when given as add-on therapy . Therefore , we examined whether resveratrol can enhance metabolic health in men at risk of developing T2D . Additionally , we examined if resveratrol can stimulate brown adipose tissue ( BAT ) . Methods Thirteen male first degree relatives ( FDR ) of patients with T2D received resveratrol ( 150 mg/day ) and placebo for 30 days in a r and omized , placebo controlled , cross-over trial . Results Resveratrol significantly improved ex vivo muscle mitochondrial function on a fatty acid-derived substrate . However , resveratrol did not improve insulin sensitivity , expressed as the rate of glucose disposal during a two-step hyperinsulinemic-euglycemic clamp . Also , intrahepatic and intramyocellular lipid content , substrate utilization , energy metabolism , and cold-stimulated 18F-FDG glucose uptake in BAT ( n = 8) remained unaffected by resveratrol . In vitro experiments in adipocytes derived from human BAT confirmed the lack of effect on BAT . Conclusions Resveratrol stimulates muscle mitochondrial function in FDR males , which is in concordance with previous results . However , no other metabolic benefits of resveratrol were found in this group . This could be attributed to subject characteristics causing alterations in metabolism of resveratrol and thereby affecting resveratrol 's effectiveness . Clinical Trials.gov ID NCT02129595 Objective . The effect of a proprietary formulation of trans-resveratrol ( t-RSV ) on manifestations of diabetic foot syndrome ( DFS ) was studied in type 2 diabetic patients with newly diagnosed diabetic foot ulcers . Method . Placebo-controlled , examiner-blinded , parallel-group r and omized controlled pilot clinical trial ( ACTRN Clinical Trial Registry number 12610000629033 ) involving 24 patients with DFS ( 15 males and 9 females , average age of 56.4 ± 9.1 years ) divided into the  placebo and RSV-treatment groups was performed . 50 mg of t-RSV or placebo capsules was given to each patient twice a day over a 60-day time period . Results . Reduction in the parameters reflecting diabetic ulcer size was more profound in the RSV group as compared to placebo . RSV-treated patients also had a marginally improved performance in the foot pressure test . A statistically significant decline in the plasma fibrinogen level , but not CRP , was also found in the RSV-treated patients . Some improvement in the plasma lipid profile and fasting glucose levels were not related to RSV-treatment , since they have been seen on both the RSV and placebo groups , revealing the effectiveness of medical supervision and education in the newly diagnosed patients with DFS . Conclusion . t-RSV supplementation promotes reduction of the foot ulcer size and reduces plasma fibrinogen level in type 2 diabetic patients The objective of this study was to examine the effectiveness of resveratrol in lowering blood glucose in the presence of st and ard antidiabetic treatment in patients with type 2 diabetes , in a r and omized placebo-controlled double-blinded parallel clinical trial . A total of 66 subjects with type 2 diabetes were enrolled in this study and r and omly assigned to intervention group which was supplemented with resveratrol at a dose 1 g/day for 45 days and control group which received placebo tablets .  Body weight , blood pressure , fasting blood glucose , haemoglobin A1c , insulin , homeostatic assessment s for insulin resistance , triglycerides , total cholesterol , low density lipoprotein , high density lipoprotein , and markers of liver and kidney damage were measured at baseline and after 45 days of resveratrol or placebo supplementation . Resveratrol treatment significantly decreased systolic blood pressure , fasting blood glucose , haemoglobin A1c , insulin , and insulin resistance , while HDL was significantly increased , when compared to their baseline levels . On the other h and , the placebo group had slightly increased fasting glucose and LDL when compared to their baseline levels . Liver and kidney function markers were unchanged in the intervention group . Overall , this study showed that resveratrol supplementation exerted strong antidiabetic effects in patients with type 2 diabetes BACKGROUND The obese insulin-resistant state is characterized by impairments in lipid metabolism . We previously showed that 3-d supplementation of combined epigallocatechin-3-gallate and resveratrol ( EGCG+RES ) increased energy expenditure and improved the capacity to switch from fat toward carbohydrate oxidation with a high-fat mixed meal ( HFMM ) test in men . OBJECTIVE The present study aim ed to investigate the longer-term effect of EGCG+RES supplementation on metabolic profile , mitochondrial capacity , fat oxidation , lipolysis , and tissue-specific insulin sensitivity . DESIGN In this r and omized double-blind study , 38 overweight and obese subjects [ 18 men ; aged 38 ± 2 y ; body mass index ( kg/m(2 ) ) : 29.7 ± 0.5 ] received either EGCG+RES ( 282 and 80 mg/d , respectively ) or placebo for 12 wk . Before and after the intervention , oxidative capacity and gene expression were assessed in skeletal muscle . Fasting and postpr and ial ( HFMM ) lipid metabolism was assessed by using indirect calorimetry , blood sampling , and microdialysis . Tissue-specific insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp with [6,6-(2)H2]-glucose infusion . RESULTS EGCG+RES supplementation did not affect the fasting plasma metabolic profile . Although whole-body fat mass was not affected , visceral adipose tissue mass tended to decrease after the intervention compared with placebo ( P-time × treatment = 0.09 ) . EGCG+RES supplementation significantly increased oxidative capacity in permeabilized muscle fibers ( P-time × treatment < 0.05 , P-EGCG+RES < 0.05 ) . Moreover , EGCG+RES  reduced fasting ( P-time × treatment = 0.03 ) and postpr and ial respiratory quotient ( P-time × treatment = 0.01 ) compared with placebo . Fasting and postpr and ial fat oxidation was not significantly affected by EGCG+RES ( P-EGCG+RES = 0.46 and 0.38 , respectively ) but declined after placebo ( P-placebo = 0.05 and 0.03 , respectively ) . Energy expenditure was not altered ( P-time × treatment = 0.96 ) . Furthermore , EGCG+RES supplementation attenuated the increase in plasma triacylglycerol concentrations during the HFMM test that was observed after placebo ( P-time × treatment = 0.04 , P-placebo = 0.01 ) . Finally , EGCG+RES had no effect on insulin-stimulated glucose disposal , suppression of endogenous glucose production , or lipolysis . CONCLUSION Twelve weeks of EGCG+RES supplementation increased mitochondrial capacity and stimulated fat oxidation compared with placebo , but this did not translate into increased tissue-specific insulin sensitivity in overweight and obese subjects . This trial was registered at clinical trials.gov as NCT02381145 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 Non-alcoholic fatty liver disease ( NAFLD ) is usually associated with insulin resistance , central obesity , reduced glucose tolerance , type 2 diabetes mellitus and hypertriacylglycerolaemia . The beneficial effects of resveratrol on metabolic disorders have been shown previously . The aim of this study was to evaluate the effects of resveratrol supplementation on cardiovascular risk factors in patients with NAFLD . In this r and omised double-blinded placebo-controlled clinical trial , fifty 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 physical activity recommendations . resveratrol supplementation reduced alanine aminotransferase ( ALT ) and hepatic steatosis significantly more than placebo ( P0·05 ) . There were no significant changes in blood pressure , insulin resistance markers and TAG in either group ( P>0·05 ) . Our data have shown that 12-week supplementation of 500 mg resveratrol does not have any beneficial effect on anthropometric measurements , insulin resistance markers , lipid profile and blood pressure ; however , it reduced ALT and hepatic steatosis in patients with NAFLD ABSTRACT Dietary polyphenols have beneficial effects on adipose tissue mass and function in rodents , but human studies are scarce . In a r and omized , placebo-controlled study , 25 ( 10 women ) overweight and obese humans received a combination of the polyphenols epigallocatechin-gallate and resveratrol ( 282 mg/d , 80 mg/d , respectively , EGCG+RES , n = 11 ) or placebo ( PLA , n = 14 ) supplementation for 12 weeks . Abdominal subcutaneous adipose tissue ( SAT ) biopsies were collected for assessment of adipocyte morphology and micro-array analysis . EGCG+RES had no effects on adipocyte size and distribution compared with PLA . However , we identified pathways contributing to adipogenesis , cell cycle and apoptosis were significantly downregulated by EGCG+RES versus PLA . Furthermore , EGCG+RES significantly decreased expression of pathways related to energy metabolism , oxidative stress , inflammation , and immune defense as compared with PLA . In conclusion , the SAT gene expression profile indicates a reduced cell turnover after 12-week EGCG+RES in overweight-obese subjects . It remains to be eluci date d whether these alterations translate into long-term metabolic effects BACKGROUND & AIMS Nonalcoholic fatty liver disease ( NAFLD ) , characterized by accumulation of hepatic triglycerides ( steatosis ) , is associated with abdominal obesity , insulin resistance , and inflammation . Although weight loss via calorie restriction reduces features of NAFLD , there is no pharmacologic therapy . Resveratrol is a polyphenol that prevents high-energy diet-induced steatosis and insulin resistance in animals by up-regulating pathways that regulate energy metabolism . We performed a placebo-controlled trial to assess the effects of resveratrol in patients with NAFLD . METHODS Overweight or obese men diagnosed with NAFLD were recruited from hepatology outpatient clinics in Brisbane , Australia from 2011 through 2012 . They were r and omly assigned to groups given 3000 mg resveratrol ( n = 10 ) or placebo ( n = 10 ) daily for 8 weeks . Outcomes included insulin resistance ( assessed by the euglycemic-hyperinsulinemic clamp ) , hepatic steatosis , and abdominal fat distribution ( assessed by magnetic resonance spectroscopy and imaging ) . Plasma markers of inflammation , as well as metabolic , hepatic , and antioxidant function , were measured ; transcription of target genes was measured in peripheral blood mononuclear cells .  Resveratrol pharmacokinetics and safety were assessed . RESULTS Eight-week administration of resveratrol did not reduce insulin resistance , steatosis , or abdominal fat distribution when compared with baseline . No change was observed in plasma lipids or antioxidant activity . Levels of alanine and aspartate aminotransferases increased significantly among patients in the resveratrol group until week 6 when compared with the placebo group . Resveratrol did not significantly alter transcription of NQO1 , PTP1B , IL6 , or HO1 in peripheral blood mononuclear cells . Resveratrol was well-tolerated . CONCLUSIONS Eight weeks administration of resveratrol did not significantly improve any features of NAFLD , compared with placebo , but it increased hepatic stress , based on observed increases in levels of liver enzymes . Further studies are needed to determine whether agents that are purported to mimic calorie restriction , such as resveratrol , are safe and effective for complications of obesity . Clinical trials registration no : ACTRN12612001135808 The aim of this study was to investigate the impact of resveratrol supplementation along with non-surgical periodontal treatment on blood glucose , insulin , insulin resistance , triglyceride ( TG ) , and periodontal markers in patients with type 2 diabetes with periodontal disease . In this double-blind clinical trial study , 43 patients with diabetes with chronic periodontitis were participated . Subjects were r and omly allocated to intervention and control groups . The intervention and control groups received either 480 mg/day of resveratrol or placebo capsules ( two pills ) for 4 weeks . Fasting blood glucose , insulin , insulin resistance ( homeostasis model assessment of insulin resistance ) , TGs , and pocket depth were measured in all subjects ' pre-intervention and post-intervention . The mean serum levels of fasting insulin and insulin resistance ( homeostasis model assessment of insulin resistance ) were significantly lower in the intervention group compared with control group ( 10.42 ± 0.28 and 10.92 ± 0.9 ; 3.66 ± 0.97 and 4.49 ± 1.56 , respectively ) . There was a significant difference in the mean pocket depth between intervention and control groups ( 2.35 ± 0.6 and 3.38 ± 0.5 , respectively ) following intervention . No significant differences were observed in the mean levels of fasting blood glucose and TGs between two groups ' post-intervention . It is recommended that resveratrol supplementation may be beneficial as adjuvant therapy along with non-surgical periodontal treatment in insulin resistance and improving periodontal status among patients with diabetes with periodontal disease . Copyright © 2016 John Wiley & Sons , OBJECTIVE To evaluate the efficacy of an orlistat-resveratrol ( O-R ) combination in subjects with obesity over a 6-month period . METHODS This study was a double-blind , parallel , r and omized controlled clinical trial . Patients fulfilling the selection criteria ( age from 20 to 60 years and body mass index ( BMI ) ≥30 and ≤39.9 kg/m(2 ) ) consumed an energy-reduced diet with 500 fewer calories than their usual diet for 2 weeks . Then the participants were r and omly assigned to four groups , placebo , resveratrol , orlistat , or O-R , and they consumed the energy-reduced diet for 6 months . The study consisted of seven visits . During each visit , a 24-h recall was performed , along with measurements of anthropometric and serum biochemical parameters . RESULTS A total of 161 participants were selected . Of these , 84 participants completed the study . A significant weight loss of -6.82 kg ( 95 % CI -8.37 to -5.26 ) was observed in the O-R group compared with -3.50 kg ( -5.05 to -1.95 , P = 0.021 ) in the placebo group . In contrast , the -6.02 kg ( -7.68 to -4.36 ) orlistat and -4.68 kg ( -6.64 to -2.71 ) resveratrol monotherapy losses did not significantly differ from the placebo . Significant decreases in BMI , waist circumference , fat mass , triglycerides , leptin , and leptin/adiponectin ratio were observed with the O-R combination . CONCLUSIONS The O-R combination was the most effective weight loss treatment OBJECTIVES The primary aims of the study were to examine the effect of resveratrol on skeletal muscle SIRT1 expression and energy expenditure in subjects with Type 2 diabetes mellitus ( T2DM ) . BACKGROUND Animal and in vivo studies indicate that resveratrol increases SIRT1 expression that stimulates PGC1α activity . Subsequent upregulation of AMPK and GLUT4 expression are associated with improved insulin sensitivity in peripheral tissues . METHODS Ten subjects with T2DM were r and omized in a double-blind fashion to receive 3 g resveratrol or placebo daily for 12 weeks . Secondary outcomes include measures of AMPK , p-AMPK and GLUT4 expression levels , energy expenditure , physical activity levels , distribution of abdominal adipose tissue and skeletal muscle fiber type composition , body weight , HbA1c , plasma lipid subfraction , adiponectin levels , and insulin sensitivity . RESULTS There was a significant increase in both SIRT1 expression ( 2.01 vs. 0.86 arbitrary units [ AU ] , p = .016 ) and p-AMPK to AMPK expression ratio ( 2.04 vs. 0.79 AU , p = .032 ) in the resveratrol group compared with the placebo group . Although the percentage of absolute change ( 8.6 vs. -13.9 % , p = .033 ) and percentage of predicted resting metabolic rate ( RMR ; 7.8 vs. -13.9 % , p = .013 ) were increased following resveratrol , there was a significant reduction in average daily activity ( -38 vs. 43.2 % , p = .028 ) and step counts ( -39.5 vs. 11.8 % , p = .047 ) when compared with placebo . CONCLUSIONS In patients with T2DM , treatment with resveratrol regulates energy expenditure through increased skeletal muscle SIRT1 and AMPK expression . These findings indicate that resveratrol may have beneficial exercise-mimetic effects in patients with T2DM 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 Purpose : Despite a proposed role for oxidative stress in the pathogenesis of nonalcoholic fatty liver disease ( NAFLD ) , antioxidant approaches have not been sufficiently investigated in human NAFLD management . Resveratrol has been reported to possess a wide range of biological functions , including antioxidant activities . This study aim ed to evaluate the effects of resveratrol supplementation on oxidative/anti-oxidative status in patients with NAFLD . Methods : This r and omized , double-blind , placebo-controlled clinical trial was conducted on 60 patients with NAFLD ( males and females ) aged 20 to 60 years , and body mass index ( BMI ) of 25 - 35 kg/m2 . Subjects were r and omly assigned to receive a daily dose of 600 mg resveratrol ( 2 × 300 mg pure trans-resveratrol capsules ; n=30 ) or placebo capsules ( n=30 ) for 12 wk . Fasting blood sample s , anthropometric measurements , and dietary intakes were collected for all patients at baseline and at the end of the trial . Oxidative stress was evaluated by measurement of serum malondialdehyde ( MDA ) , oxidized low-density lipoprotein ( ox-LDL ) , total antioxidant capacity ( TAC ) , and erythrocyte superoxide dismutase ( SOD ) as well as glutathione peroxidase ( GSH-Px ) activities . Changes in the outcomes were analyzed using analysis of covariance ( ANCOVA ) . Results : Resveratrol supplementation did not significantly affect neither serum MDA , ox-LDL , and TAC levels , nor erythrocyte SOD and GSH-Px activities , compared to placebo group ( All P>0.05 ) . Moreover , changes in serum levels of liver enzymes ( ALT , AST , GGT , and ALP ) were not significant in neither of the study groups ( All P>0.05 ) . Conclusion : Resveratrol supplementation did not modify oxidative/anti-oxidative status in patients with NAFLD OBJECTIVES The aim of this study was to explore the effect of resveratrol supplementation on lipid profile in individuals with dyslipidemia . METHODS Apparently healthy men and non-pregnant women 20 to 65 y of age with new diagnosis of dyslipidemia were enrolled in a r and omized double-blind , placebo-controlled trial and r and omly allocated to receive either resveratrol 100 mg/d or placebo ( sucrose 0.5 g/d ) for 2 mo . Smoking , alcohol intake , diabetes , acute or chronic renal or hepatic diseases , malignancy , cardiovascular disease , serum triacylglycerol levels ≥400 mg/dL , low-density lipoprotein cholesterol levels ≥190 mg/dL , and consumption of lipid-lowering drugs or supplements containing resveratrol were exclusion criteria . RESULTS Seventy-one individuals with new diagnosis of dyslipidemia were enrolled and r and omly allocated to the resveratrol ( n = 35 ) or placebo groups ( n = 36 ) . At baseline , there were no significant differences between the study groups . After intervention period , individuals in the resveratrol group showed a significant decrease in total cholesterol ( 201.4 ± 34.4 versus 220.6 ± 37.4 , P = 0.04 ) and triacylglycerol ( 133.4 ± 55.3 versus 166.7 ± 68.5 , P = 0.04 ) concentrations compared with the placebo group , without significant statistical differences for high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels . CONCLUSION The results suggest that resveratrol supplementation significantly reduces total cholesterol and triacylglycerol concentrations in individuals with dyslipidemia
target: This meta- analysis demonstrated that resveratrol supplementation among patients with MetS and related disorders  significantly reduced total cholesterol and increased GGT concentrations , but did not affect triglycerides , LDL- , HDL-cholesterol , ALT , and AST concentrations .
  This data suggests that resveratrol may have a potential cardio-protective effect in patients with MetS and related disorders
background: There are current trials investigating the effect of resveratrol supplementation on lipid profiles and liver enzymes among patients with metabolic syndrome ( MetS ) and related disorders ; however , their findings are controversial .
  This systematic review and meta- analysis were aim ed to determine the effects of resveratrol supplementation on lipid profiles and liver enzymes among patients with MetS and related disorders .