Effect of resveratrol supplementation on lipid profile in subjects with dyslipidemia: A randomized double-blind, placebo-controlled trial. Resveratrol Supplementation in Schizophrenia Patients: A Randomized Clinical Trial Evaluating Serum Glucose and Cardiovascular Risk Factors Oral resveratrol and calcium fructoborate supplementation in subjects with stable angina pectoris: effects on lipid profiles, inflammation markers, and quality of life. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. Beneficial effects of acute trans-resveratrol supplementation in treated hypertensive patients with endothelial dysfunction Serum concentrations and gene expression of sirtuin 1 in healthy and slightly overweight subjects after caloric restriction or resveratrol supplementation: A randomized trial. 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 The effects of 30 days resveratrol supplementation on adipose tissue morphology and gene expression patterns in obese men Resveratrol as Add-on Therapy in Subjects With Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus. The effects of resveratrol supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study. Effects of resveratrol alone or in combination with piperine on cerebral blood flow parameters and cognitive performance in human subjects: a randomised, double-blind, placebo-controlled, cross-over investigation. Resveratrol attenuates oxidative stress and prevents steatosis and hypertension in obese rats programmed by early weaning. Consumption of a grape extract supplement containing resveratrol decreases oxidized LDL and ApoB in patients undergoing primary prevention of cardiovascular disease: a triple-blind, 6-month follow-up, placebo-controlled, randomized trial. Anti-inflammatory and antioxidant effects of resveratrol in healthy smokers a randomized, double-blind, placebo-controlled, cross-over trial. The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial 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 Trans-Resveratrol Supplementation and Endothelial Function during the Fasting and Postprandial Phase: A Randomized Placebo-Controlled Trial in Overweight and Slightly Obese Participants Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults
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 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 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 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 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 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 ABSTRACT Endothelial dysfunction is a surrogate marker of cardiovascular risk . Resveratrol is known to improve endothelial function in animals , however , clinical trials are limited . We hypothesized that the acute trans-resveratrol supplementation improves endothelial function in treated hypertensive patients with endothelial dysfunction . Twenty-four hypertensive patients between 45 and 65 years-old with baseline endothelial dysfunction were enrolled in a r and omized , cross-over , double-blind , placebo-controlled trial . Individuals received either a single dose of trans-resveratrol ( 300 mg ) or placebo and were crossed-over after a one-week washout  period . Blood pressure ( BP ) measurements , aortic systolic blood pressure ( SBP ) and brachial flow-mediated dilation ( FMD ) were performed before and 1.5 hours after the intervention . FMD was significantly increased in women ( 4.2 ± 0.5 vs 7.1 ± 1.3 % , p = 0.026 ) but not in men ( 4.4 ± 0.9 vs 4.9 ± 0.8 % , p = 0.588 ) in the trans-resveratrol group . There was no statistical difference between baseline and final values of brachial BP and also no changes in aortic SBP . Patients with higher low-density lipoprotein  ( LDL ) cholesterol had better FMD response  to trans-resveratrol than patients with lower LDL cholesterol ( 7.4 ± 1.2 vs 4.3 ± 1.0 % , p = 0.004 ) . Our study demonstrated that the acute supplementation of trans-resveratrol promoted an improvement in endothelial function , especially in women and those with higher LDL-cholesterol , despite no changes in BP . List of Abbreviation : Aix : augmentation index ; AP : augmentation pressure ; BP : blood pressure ; BMI : body Mass Index ; CVD : cardiovascular disease ; FMD : flow-mediated dilation ; FRS : Framingham Risk Score ; HDL : high-density lipoprotein ; LDL : low-density lipoprotein ; NO : nitric oxide ; SPSS : Statistical Package for Social Sciences ; ROS : reactive oxygen species ; SBP : systolic blood pressure ; TG : triglycerides 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 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 Polyphenolic compounds , such as resveratrol , have recently received widespread interest because of their ability to mimic effects of calorie restriction . The objective of the present study was to gain more insight into the effects of 30 days resveratrol supplementation on adipose tissue morphology and underlying processes . Eleven healthy obese men were supplemented with placebo and resveratrol for 30 days ( 150 mg per day ) , separated by a 4-week washout period in a double-blind r and omized crossover design . A postpr and ial abdominal subcutaneous adipose tissue biopsy was collected to assess adipose tissue morphology and gene expression using microarray analysis . Resveratrol significantly decreased adipocyte size , with a shift toward a reduction in the proportion of large and very-large adipocytes and an increase in small adipocytes . Microarray analysis revealed downregulation of Wnt and Notch signaling pathways and upregulation of pathways involved in cell cycle regulation after resveratrol supplementation , suggesting enhanced adipogenesis . Furthermore , lysosomal/phagosomal pathway and transcription factor EB were upregulated reflecting an alternative pathway of lipid breakdown by autophagy . Further research is necessary to investigate whether resveratrol improves adipose tissue function OBJECTIVE To determine whether resveratrol supplementation can improve insulin sensitivity and promote overall metabolic health on top of st and ard diabetes care . RESEARCH DESIGN AND METHODS Seventeen subjects with well-controlled type 2 diabetes ( T2D ) were treated with placebo and 150 mg/day resveratrol ( resVida ) in a r and omized double-blind crossover study for 30 days . The main outcome measure was insulin sensitivity by the hyperinsulinemic-euglycemic clamp technique . RESULTS Hepatic and peripheral insulin sensitivity were not affected by resveratrol treatment . Intrahepatic lipid content also remained unaffected by resveratrol ; however , the change in intrahepatic lipid content correlated negatively with plasma resveratrol levels ( R = −0.68 , P = 0.03 ) . Intramyocellular lipid content increased in type 2 muscle fibers ( P = 0.03 ) , and systolic blood pressure tended to decrease ( P = 0.09 ) upon resveratrol treatment . In addition , resveratrol significantly improved ex vivo mitochondrial function ( state 3 and state U respiration upon malate with octanoyl-carnitine , P < 0.005 ) . Intriguingly , a correlation was found between plasma levels of a metabolite of resveratrol  ( dihydroresveratrol ) and the metformin dose used by the patients ( R = 0.66 , P = 0.005 ) , suggesting an interaction between metformin and resveratrol . It could be speculated that the lack of a  resveratrol-induced insulin-sensitizing effect is caused by this interaction . CONCLUSIONS Resveratrol supplementation does not improve hepatic or peripheral insulin sensitivity . Our results question the generalized value of resveratrol as an add-on therapy in the treatment of T2D and emphasize the need to perform studies in drug-naive patients with T2D or subjects with prediabetes 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 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 Previous research has shown that resveratrol can increase cerebral blood flow ( CBF ) in the absence of improved cognitive performance in healthy , young human subjects during the performance of cognitively dem and ing tasks . This lack of cognitive effects may be due to low bioavailability and , in turn , reduced bioefficacy of resveratrol in vivo . Piperine can alter polyphenol pharmacokinetics , but previous studies have not investigated whether this affects the efficacy of the target compound . Therefore , the objective of the present study was to ascertain whether co-supplementation of piperine with resveratrol affects the bioavailability and efficacy of resveratrol  with regard to cognition and CBF . The present study utilised a r and omised , double-blind , placebo-controlled , within-subjects design , where twenty-three adults were given placebo , trans-resveratrol ( 250 mg ) and trans-resveratrol with 20 mg piperine on separate days at least a week apart . After a 40 min rest/absorption period , the participants performed a selection of cognitive tasks and CBF was assessed throughout the period , in the frontal cortex , using near-IR spectroscopy . The presence of resveratrol and its conjugates in the plasma was confirmed by liquid chromatography-MS analysis carried out following the administration of the same doses in a separate cohort ( n 6 ) . The results indicated that when co-supplemented , piperine and resveratrol significantly augmented CBF during task performance in comparison with placebo and resveratrol alone . Cognitive function , mood and blood pressure were not affected . The plasma concentrations of resveratrol and its metabolites were not significantly different between the treatments , which indicates that co-supplementation of piperine with resveratrol enhances the bioefficacy of resveratrol with regard to CBF effects , but not cognitive performance , and does this without altering bioavailability We hypothesized that resveratrol , a natural phytoalexin found in grapes , can prevent oxidative stress , obesity and its related disturbances in obese rats programmed by early weaning . Lactating Wistar rats were separated into two groups : early weaning ( EW ) - dams who were wrapped with a b and age to interrupt the lactation in the last 3 days of lactation ; control - dams whose pups had free access to milk during all lactation . At the 150th day , EW offspring were r and omly subdivided into EW+resveratrol ( EW+Res ) - resveratrol ( 30 mg/kg/day ) ; EW+vehicle ( EW ) - rats that received 0.5 % ( w/v ) aqueous methylcellulose . The control group received vehicle . Rats were treated by gavage daily for 30 days . EW offspring developed hyperphagia , higher body weight , visceral obesity , higher systolic ( SBP ) and diastolic blood pressure ( DBP ) ( + 15 % and + 20 % , respectively ; P<.05 ) and higher serum triglycerides ( TG ) and low-density lipoprotein but lower high-density lipoprotein ( + 55 % , + 33 % and -13 % , respectively ; P<.05 ) . Resveratrol normalized food intake , SBP and DBP and prevented obesity and dyslipidemia in EW+Res . EW rats had higher plasma and liver thiobarbituric-acid-reactive substances ( TBARS ) and lower plasma superoxide dismutase ( SOD ) and liver glutathione peroxidase activities ( + 51 % , + 18 % , -58 % , -31 % , respectively ; P<.05 ) , and resveratrol normalized both plasma and liver TBARS and increased the activity of SOD and catalase in plasma . EW rats presented liver steatosis and higher liver TG , and resveratrol prevented these hepatic alterations . In conclusion , this study demonstrated a potential therapeutic use of resveratrol in preventing obesity and oxidative stress and reducing the risk of hypertension , dyslipidemia and steatosis in adult rats programmed by early weaning SCOPE The cardioprotective role of resveratrol as part of the human diet is not yet clear . Our aim was to investigate the effect of a grape supplement containing 8 mg resveratrol in oxidized LDL ( LDLox ) , apolipoprotein-B ( ApoB ) , and serum lipids on statin-treated patients in primary cardiovascular disease prevention ( PCP ) . METHODS AND RESULTS A triple-blind , r and omized , placebo-controlled trial was conducted . Seventy-five patients ( three parallel arms ) consumed one capsule ( 350 mg ) daily for 6 months containing resveratrol-enriched grape extract ( GE-RES , Stilvid ® ) , grape extract ( GE , similar polyphenolic content but no resveratrol ) , or placebo ( maltodextrin ) . After 6 months , no changes were observed in the placebo group and only LDL cholesterol ( LDLc ) decreased by 2.9 % ( p = 0.013 ) in the GE group . In contrast , LDLc ( -4.5 % , p = 0.04 ) , ApoB ( -9.8 % , p = 0.014 ) , LDLox ( -20 % , p = 0.001 ) , and LDLox/ApoB ( -12.5 % , p = 0.000 ) decreased in the Stilvid ® group , whereas the ratio non-HDLc ( total atherogenic cholesterol load)/ApoB increased ( 8.5 % , p = 0.046 ) . No changes were observed in hepatic , thyroid , and renal function . No adverse effects were observed in any of the patients . CONCLUSION This GE-RES reduced atherogenic markers and might exert additional cardioprotection beyond the gold-st and ard medication in patients from PCP . The presence of resveratrol in the GE was necessary to achieve these effects OBJECTIVE Smokers are characterized by a low- grade systemic inflammatory state and an oxidant-antioxidant imbalance . Few human studies were conducted on the effects of resveratrol , a natural compound with anti-inflammatory and antioxidant properties , and no trial on smokers has been performed to date . We evaluated whether resveratrol has beneficial effects on markers of inflammation and oxidative stress in smokers . METHODS AND RESULTS A r and omized , double- blind , cross-over trial was performed in 50 healthy adult smokers : 25 were r and omly allocated to " resveratrol-first " ( 30-days : 500 mg resveratrol/day , 30-days wash-out , 30-days placebo ) and 25 to " placebo-first " ( 30-days placebo , 30-days wash-out , 30-days 500 mg resveratrol/day ) . Resveratrol significantly reduced C-reactive protein ( CRP ) and triglyceride concentrations , and increased Total Antioxidant Status ( TAS ) values . After analyzing data with general linear models to assess period and carry-over effects , the ratios of the values after resveratrol to those after placebo were respectively : 0.47 ( 95%CI 0.38 - 0.59 ) -CRP- and 0.71 ( 95%CI 0.65 - 0.78 ) -triglycerides- , while TAS increased by 74.2 μmol/L ( 95%CI 60.8 - 87.6 ) . Uric acid , glucose , insulin , cholesterol , liver enzyme concentrations , and weight , waist circumference , and blood pressure values did not significantly change after resveratrol supplementation . CONCLUSIONS Because resveratrol has anti-inflammatory , anti-oxidant , and hypotriglyceridemic effects , its supplementation may beneficially affect the increased cardiovascular risk of healthy smokers 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 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 Studies on the effects of the long-term intake of trans-resveratrol on vascular function are conflicting . In addition , postpr and ial effects of long-term trans-resveratrol intake on endothelial function are not known . We therefore supplemented 45 overweight and slightly obese volunteers ( 25 men and 20 women ) with a mean ( ±SD ) age of 61 ± 7 years and body mass index of 28.3 ± 3.2 kg/m2 in r and om  order trans-resveratrol ( 2 × 75 mg/day ) or placebo capsules for 4 weeks , separated by a washout period of at least 4 weeks . At the end of each intervention period , brachial artery flow-mediated vasodilation ( FMD ) was measured before and after meal consumption . Plasma biomarkers for endothelial function , inflammation , and glucose and lipid metabolism were also determined . Compared with the placebo , trans-resveratrol did not affect fasting FMD ( 2.9 ± 1.4 % vs. 3.0 ± 1.9 % ; p = 0.69 ) . After the postpr and ial test , changes in FMD ( −0.7 ± 2.3 % vs. 0.2 ± 2.6 % ; p = 0.13 ) were also not significantly different . Postpr and ial changes in biomarkers were also comparable . In conclusion , for overweight and slightly obese volunteers , a daily intake of 150 mg of trans-resveratrol for 4 weeks does not change plasma biomarkers of endothelial function or inflammation in the fasting state or postpr and ial phase 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 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 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
We conclude that resveratrol does not change lipid profile concentration .
A : Meta‐ analysis of the effect of resveratrol supplementation on total cholesterol .
B : Meta‐ analysis of the effect of resveratrol supplementation on low‐density lipoprotein .
C : Meta‐ analysis of the effect of resveratrol supplementation on high‐density lipoprotein .
D : Meta‐ analysis of the effect of resveratrol supplementation on triglyceride after removing the study by Zortea et al. & NA ; Despite the notion that resveratrol can significantly reduce plasma lipids , the result of r and omized clinical trials ( RCTs ) on resveratrol effect and the serum lipid profile are contradictory .
Our objective was to conduct a systematic review and meta‐ analysis on r and omized clinical trials ( RCTs ) and assess the effect of resveratrol on lipids .