title: Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Weight loss, exercise, or both and physical function in obese older adults. The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial Effects of resveratrol on memory performance, hippocampus connectivity and microstructure in older adults – A randomized controlled trial Effects of resveratrol supplementation on liver fat content in overweight and insulin‐resistant subjects: A randomized, double‐blind, placebo‐controlled clinical trial Resveratrol supplementation improves inflammatory biomarkers in patients with nonalcoholic fatty liver disease. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Resveratrol Supplementation in Schizophrenia Patients: A Randomized Clinical Trial Evaluating Serum Glucose and Cardiovascular Risk Factors Melinjo (Gnetum gnemon L.) Seed Extract Decreases Serum Uric Acid Levels in Nonobese Japanese Males: A Randomized Controlled Study Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus. 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 Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. 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. One-year consumption of a grape nutraceutical containing resveratrol improves the inflammatory and fibrinolytic status of patients in primary prevention of cardiovascular disease. 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. An antiinflammatory and reactive oxygen species suppressive effects of an extract of Polygonum cuspidatum containing resveratrol. Efficacy of an orlistat-resveratrol combination for weight loss in subjects with obesity: A randomized controlled trial. 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. Serum concentrations and gene expression of sirtuin 1 in healthy and slightly overweight subjects after caloric restriction or resveratrol supplementation: A randomized trial. Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults 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.
abstract: Although resveratrol has widely been studied for its potential health benefits , little is known about its metabolic effects in humans . Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action . After an initial general examination ( including blood chemistry ) , nineteen patients enrolled in the 4-week-long double-blind study were r and omly assigned into two groups : a resveratrol group receiving oral 2 × 5 mg resveratrol and a control group receiving placebo . Before and after the second and fourth weeks of the trial , insulin resistance/sensitivity , creatinine-normalised ortho-tyrosine level in urine sample s ( as a measure of oxidative stress ) , incretin levels and phosphorylated protein kinase B (pAkt):protein kinase B ( Akt ) ratio in platelets were assessed and statistically analysed . After the fourth week , resveratrol  significantly decreased insulin resistance ( homeostasis model of assessment for insulin resistance ) and urinary ortho-tyrosine excretion , while it increased the pAkt : Akt ratio in platelets . On the other h and , it had no effect on parameters that relate to β-cell function ( i.e. homeostasis model of assessment of β-cell function ) . The present study shows for the first time that resveratrol  improves insulin sensitivity in humans , which might be due to a resveratrol-induced  decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway BACKGROUND Obesity exacerbates the age-related decline in physical function and causes frailty in older adults ; however , the appropriate treatment for obese older adults is controversial . METHODS In this 1-year , r and omized , controlled trial , we evaluated the independent and combined effects of weight loss and exercise in 107 adults who were 65 years of age or older and obese . Participants were r and omly assigned to a control group , a weight-management ( diet ) group , an exercise group , or a weight-management-plus-exercise ( diet-exercise ) group . The primary outcome was the change in score on the modified Physical Performance Test . Secondary outcomes included other measures of frailty , body composition , bone mineral density , specific physical functions , and quality of life . RESULTS A total of 93 participants ( 87 % ) completed the study . In the intention-to-treat analysis , the score on the Physical Performance Test , in which higher scores indicate better physical status , increased more in the diet-exercise group than in the diet group or the exercise group ( increases from baseline of 21 % vs. 12 % and 15 % , respectively ) ; the scores in all three of those groups increased more than the scores in the control group ( in which the score increased by 1 % ) ( P<0.001 for the between-group differences ) . Moreover , the peak oxygen consumption improved more in the diet-exercise group than in the diet group or the exercise group ( increases of 17 % vs. 10 % and 8 % , respectively ; P<0.001 ) ; the score on the Functional Status Question naire , in which higher scores indicate better physical function , increased more in the diet-exercise group than in the diet group ( increase of 10 % vs. 4 % , P<0.001 ) . Body weight decreased by 10 % in the diet group and by 9 % in the diet-exercise group , but did not decrease in the exercise group or the control group ( P<0.001 ) . Lean body mass and bone mineral density at the hip decreased less in the diet-exercise group than in the diet group ( reductions of 3 % and 1 % , respectively , in the diet-exercise group vs. reductions of 5 % and 3 % , respectively , in the diet group ; P<0.05 for both comparisons ) . Strength , balance , and gait improved consistently in the diet-exercise group ( P<0.05 for all comparisons ) . Adverse events included a small number of exercise-associated musculoskeletal injuries . CONCLUSIONS These findings suggest that a combination of weight loss and exercise provides greater improvement in physical function than either intervention alone . ( Funded by the National Institutes of Health ; Clinical Trials.gov number , NCT00146107 . ) 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 Introduction : The polyphenol resveratrol has been suggested to exert beneficial effects on memory and the aging hippocampus due to calorie‐restriction mimicking effects . However , the evidence based on human interventional studies is scarce . We therefore aim ed to determine the effects of resveratrol on memory performance , and to identify potential underlying mechanisms using a broad array of blood‐based biomarkers as well as hippocampus connectivity and microstructure assessed with ultra‐high field magnetic resonance imaging ( UHF‐MRI ) . Methods : In this double‐blind , r and omized controlled trial , 60 elderly participants ( 60–79 years ) with a wide body‐mass index ( BMI ) range of 21–37 kg/m2 were r and omized to receive either resveratrol ( 200mg/day ) or placebo for 26 weeks ( registered at Clinical Trials.gov : NCT02621554 ) . Baseline and follow‐up assessment s included the California Verbal Learning Task ( CVLT , main outcome ) , the ModBent task , anthropometry , markers of glucose and lipid metabolism , inflammation and neurotrophins derived from fasting blood , multimodal neuroimaging at 3 and 7 T , and question naires to assess confounding factors . Results : Multivariate repeated‐ measures ANOVA did not detect significant time by group effects for CVLT performance . There was a trend for preserved pattern recognition memory after resveratrol , while performance decreased in the placebo group ( n.s . , p=0.07 ) . Further exploratory analyses showed increases in both groups over time in body fat , cholesterol , fasting glucose , interleukin 6 , high sensitive C‐reactive protein , tumor necrosis factor alpha and in mean diffusivity of the subiculum and presubiculum , as well as decreases in physical activity , brain‐derived neurotrophic factor and insulin‐like growth factor 1at follow‐up , which were partly more pronounced after resveratrol . Discussion : This interventional study failed to show significant improvements in verbal memory after 6 months of resveratrol in healthy elderly with a wide BMI range . A non‐significant trend emerged for positive effects on pattern recognition memory , while possible confounding effects of unfavorable changes in lifestyle behavior , neurotrophins and inflammatory markers occurred . Our findings also indicate the feasibility to detect (un)healthy aging‐related changes in measures of hippocampus microstructure after 6 months using 7 T diffusion MRI . More studies incorporating a longer duration and larger sample size are needed to determine if resveratrol  enhances memory performance in healthy older adults . HIGHLIGHTSIn this r and omized clinical trial , 6 months resveratrol supplementation showed no significant effects on verbal memory  compared to placebo . Unfavorable changes in lifestyle factors at follow‐up might have introduced confounding . Secondary analyses showed a trend towards preserved pattern recognition . We used multimodal ultra high field MRI to detect subtle changes in microstructure of hippocampus subfields 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 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 Ageing is thought to be associated with decreased vascular function partly due to oxidative stress . Resveratrol is a polyphenol , which in animal studies has been shown to decrease atherosclerosis , and improve cardiovascular health and physical capacity , in part through its effects on Sirtuin 1 signalling and through an improved antioxidant capacity . We tested the hypothesis that resveratrol supplementation enhances training-induced improvements in cardiovascular health parameters in aged men . Twenty-seven healthy physically inactive aged men ( age : 65 ± 1 years ; body mass index : 25.4 ± 0.7 kg m(-2 ) ; mean arterial pressure ( MAP ) : 95.8 ± 2.2 mmHg ; maximal oxygen uptake : 2488 ± 72 ml O2 min(-1 ) ) were r and omized into 8 weeks of either daily intake of either 250 mg trans-resveratrol ( n = 14 ) or of placebo ( n = 13 ) concomitant with high-intensity exercise training . Exercise training led to a 45 % greater ( P < 0.05 ) increase in maximal oxygen uptake in the placebo group than in the resveratrol group and to a decrease in MAP in the placebo group only ( -4.8 ± 1.7 mmHg ; P < 0.05 ) . The interstitial level of vasodilator prostacyclin was lower in the resveratrol than in the placebo group after training ( 980 ± 90 vs. 1174 ± 121 pg ml(-1 ) ; P < 0.02 ) and muscle thromboxane synthase was higher in the resveratrol group after training ( P < 0.05 ) . Resveratrol administration also abolished the positive effects of exercise on low-density lipoprotein , total cholesterol/high-density lipoprotein ratio and triglyceride concentrations in blood ( P < 0.05 ) . Resveratrol did not alter the effect of exercise training on the atherosclerosis marker vascular cell adhesion molecule 1 ( VCAM-1 ) . Sirtuin 1 protein levels were not affected by resveratrol supplementation . These findings indicate that , whereas exercise training effectively improves several cardiovascular health parameters in aged men , concomitant resveratrol supplementation can blunt these effects 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 : Patients with schizophrenia ( SZ ) are generally overweight or obese and have several metabolic disorders . Additionally , such patients have a lower life expectancy and the main cause of their increased mortality is cardiovascular disease ( CVD ) . The objective of this study was to determine the efficacy of resveratrol supplementation on serum glucose and CVD risk factors in individuals with SZ . Methods and Results : This is a four-week r and omized , double-blind controlled trial ( registration No. : NCT 02062190 ) in which 19 men with a diagnosis of SZ , aged 18 to 65 , were assigned to either a resveratrol supplement group ( 200 mg/day ) or a placebo group ( 200 mg/day ) . In short , we did not observe significant changes after resveratrol supplementation . In the placebo group , we found a significant increase in total cholesterol levels ( p = 0.024 ) and in LDL-cholesterol ( p = 0.002 ) , as well as a decrease in body fat percentage ( p = 0.038 ) . The placebo group also showed an increase in triglycerides ( 9.19 % ) and a reduction in HDL-cholesterol ( 4.88 % ) . In the resveratrol group , triglycerides decreased ( 7.64 % ) . Conclusion : In summary , oral resveratrol in reasonably low dosages ( 200 mg daily ) brought no differences to body weight , waist circumference , glucose , and total cholesterol . It was possible to note that the lipid profile in the placebo group worsened and , although no significant differences were found , we can assume that resveratrol might prevent lipid profile damage and that the intervention affected the lipoprotein metabolism at various levels Melinjo ( Gnetum gnemon L. ) seed extract ( MSE ) containing trans-resveratrol ( 3,5,4′-trihydroxy-trans-stilbene ) and other derivatives exerts various beneficial effects . However , its mechanism of action in humans remains unknown . In this study , we aim ed to investigate beneficial effects of MSE in healthy adult males . In this double-blind , r and omized controlled study , 30 males aged 35–70 years with ≤10 % flow-mediated dilatation received placebo or 750 mg MSE powder for 8 weeks , and twenty-nine males ( 45.1 ± 8.8 years old ) completed the trial . There was a significant difference in the melinjo and placebo groups . Compared with the placebo control , MSE significantly reduced serum uric acid at 4 weeks and 8 weeks ( n = 14 and 15 , resp . ) . HDL cholesterol was significantly increased in the melinjo group . To clarify the mechanism of MSE for reducing uric acid , we investigated xanthine oxidase inhibitory activity , angiotensin II type 1 ( AT1 ) receptor binding inhibition rate , and agonistic activities for PPARα and PPARγ  . MSE , trans-resveratrol , and a resveratrol dimer , gnetin C ( GC ) , significantly inhibit AT1 receptor binding and exhibit mild agonistic activities for PPARα and PPARγ . In conclusion , MSE may decrease serum uric acid regardless of insulin resistance and may improve lipid metabolism by increasing HDL cholesterol 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 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 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 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 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 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 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 BACKGROUND Resveratrol have been shown to exert an antiinflammatory and antiaging effects in vitro and in animal models . OBJECTIVE The objective of the study was to investigate the effect of a Polygonum cuspidatum extract ( PCE ) containing resveratrol on oxidative and inflammatory stress in normal subjects . RESEARCH DESIGN AND METHODS Two groups ( 10 each ) of normal-weight healthy subjects were r and omized to placebo or PCE containing 40 mg resveratrol daily for 6 wk . Fasting blood sample s were obtained prior to and after treatment at 1 , 3 , and 6 wk . Mononuclear cells were prepared for reactive oxygen species generation , RNA isolation , nuclear extract , and total cell homogenate preparation . Indices of oxidative and inflammatory stress , suppressor of cytokine signaling-3 , phosphotyrosine phosphatase-1B , jun-N-terminal kinase-1 , and inhibitor of kappaB-kinase-beta were measured by RT-PCR and Western blotting . RESULTS The extract induced a significant reduction in reactive oxygen species generation , the expression of p47(phox ) , intranuclear nuclear factor-kappaB binding , and the expression of jun-N-terminal kinase-1 , inhibitor of kappaB-kinase-beta , phosphotyrosine phosphatase-1B , and suppressor of cytokine signaling-3 in mononuclear cells when compared with the baseline and the placebo . PCE intake also suppressed plasma concentrations of TNF-alpha , IL-6 , and C-reactive protein . There was no change in these indices in the control group given placebo . CONCLUSIONS The PCE-containing resveratrol has a comprehensive suppressive effect on oxidative and inflammatory stress 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 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 BACKGROUND Sirtuin 1 ( Sirt1 ) plays an important role in vascular biology , and influences aspects of age-dependent atherosclerosis . In animals , the sirtuin system is strongly influenced by resveratrol and caloric restriction , but its expression in humans is controversial . This study investigated the effects of resveratrol and caloric restriction on Sirt1 serum concentrations and vascular biomarkers in a healthy human population . METHODS AND RESULTS Forty-eight healthy participants ( 24 women ) aged 55 - 65years were r and omized to either 30days of resveratrol administration ( 500mg/day ) or caloric restriction ( 1000cal/day ) . Blood was collected at baseline and day 30 . Laboratory data analyzed were triglycerides , total cholesterol , HDL , VLDL , LDL , apolipoprotein A1 , apolipoprotein B , lipoprotein ( a ) , non-esterified fatty acids ( NEFA ) , glucose , insulin , oxidative stress , C-reactive protein , and Sirt1 . Expression of the Sirt1 gene was analyzed using real-time PCR . Caloric restriction diminished the abdominal circumference and improved the lipid profile , but not resveratrol intervention . Resveratrol and caloric restriction increased serum concentrations of Sirt1 , from 1.06±0.71 to 5.75±2.98ng/mL ; p<0.0001 , and from 1.65±1.81 to 5.80±2.23ng/mL ; p<0.0001 , respectively . Sirt1 increased in women and men in both interventions . On the other h and expression of Sirt1 mRNA was not different after caloric restriction and resveratrol treatment . CONCLUSIONS Caloric restriction and resveratrol significantly increased plasma concentrations of Sirt1 . The long-term impact of these interventions on atherosclerosis should be assessed Background : We have previously demonstrated acute dose-dependent increases of flow-mediated dilatation ( FMD ) in the brachial artery after resveratrol consumption in mildly hypertensive , overweight/obese adults .  Resveratrol supplementation has also been shown to increase cerebral blood flow acutely , without affecting cognition . Objectives : To evaluate the effects of chronic resveratrol supplementation on both FMD and cognitive performance . Method : Twenty-eight obese but otherwise healthy adults ( BMI : 33.3 ± 0.6 kg/m2 ) were r and omized to take a single 75 mg capsule of trans-resveratrol ( Resvida ) or placebo daily for 6 weeks each in a double-blind crossover supplementation trial . Blood pressure , arterial compliance , FMD , and performance on the Stroop Color-Word Test were assessed at the end of each 6-week intervention period while fasted and at least 18 h after taking the last daily capsule . An additional capsule of the same supplement was then taken . FMD assessment was repeated 1 h later . Results : Chronic resveratrol supplementation for 6 weeks was well tolerated and result ed in a 23 % increase in FMD  compared with placebo ( P = 0.021 , paired t-test ) . The extent of increase correlated negatively with baseline FMD ( r = −0.47 , P = 0.01 ) . A single dose of resveratrol ( 75 mg ) following chronic resveratrol supplementation result ed in a 35 % greater acute FMD response than the equivalent placebo supplementation . These FMD improvements remained significant after adjusting for baseline FMD . Blood pressure , arterial compliance , and all components of the Stroop Color-Word Test were unaffected by chronic resveratrol supplementation . Conclusion : Daily resveratrol consumption was well tolerated and has the potential to maintain healthy circulatory function in obese adults 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
target: Overall , the current meta- analysis demonstrated that resveratrol intake significantly reduced weight , BMI , WC and fat mass , and significantly increased lean mass , but did not affect leptin and adiponectin levels
background: Abstract This systematic review and meta- analysis of r and omized controlled trials ( RCTs ) was conducted to summarize the effect of resveratrol intake on weight loss .