Beneficial effects of acute trans-resveratrol supplementation in treated hypertensive patients with endothelial dysfunction The effects of resveratrol supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study. Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Trans-Resveratrol Supplementation and Endothelial Function during the Fasting and Postprandial Phase: A Randomized Placebo-Controlled Trial in Overweight and Slightly Obese Participants 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. The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. A systematic review protocol examining the effect of vitamin D supplementation on endothelial function Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults Resveratrol supplementation decreases blood glucose without changing the circulating CD14+CD16+ monocytes and inflammatory cytokines in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled study. Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus. Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients The effects of chronic trans-resveratrol supplementation on aspects of cognitive function, mood, sleep, health and cerebral blood flow in healthy, young humans. Resveratrol as Add-on Therapy in Subjects With Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial Anti-inflammatory and antioxidant effects of resveratrol in healthy smokers a randomized, double-blind, placebo-controlled, cross-over trial. Resveratrol blunts the positive effects of exercise training on cardiovascular health in aged men. Efficacy and safety of acupuncture for hypertension: An overview of systematic reviews. 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 Effects of Resveratrol on Polycystic Ovary Syndrome: A Double-blind, Randomized, Placebo-controlled Trial. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Resveratrol supplementation improves inflammatory biomarkers in patients with nonalcoholic fatty liver disease. Multispecies Probiotic Supplementation Favorably Affects Vascular Function and Reduces Arterial Stiffness in Obese Postmenopausal Women—A 12-Week Placebo-Controlled and Randomized Clinical Study 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
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 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 BACKGROUND AND AIMS Flow-mediated dilatation of the brachial artery ( FMD ) is a biomarker of endothelial function and cardiovascular health . Impaired FMD is associated with several cardiovascular risk factors including hypertension and obesity . Various food ingredients such as polyphenols have been shown to improve FMD . We investigated whether consuming resveratrol , a polyphenol found in red wine , can enhance FMD acutely and whether there is a dose-response relationship for this effect . METHODS AND RESULTS 19 overweight/obese ( BMI 25 - 35 kg m(-2 ) ) men or post-menopausal women with untreated borderline hypertension ( systolic BP : 130 - 160 mmHg or diastolic BP : 85 - 100 mmHg ) consumed three doses of resveratrol ( resVida ™ 30 , 90 and 270 mg ) and a placebo at weekly intervals in a double-blind , r and omized crossover comparison . One hour after consumption of the supplement , plasma resveratrol and FMD were measured . Data were analyzed by linear regression versus log(10 ) dose of resveratrol . 14 men and 5 women ( age 55 ± 2 years , BMI 28.7 ± 0.5 kg m(-2 ) , BP 141 ± 2/89 ± 1 mmHg ) completed this study . There was a significant dose effect of resveratrol  on plasma resveratrol concentration ( P < 0.001 ) and on FMD ( P < 0.01 ) , which increased from 4.1 ± 0.8 % ( placebo ) to 7.7 ± 1.5 % after 270 mg resveratrol . FMD was also linearly related to log(10 ) plasma resveratrol concentration ( P < 0.01 ) . CONCLUSION Acute resveratrol consumption increased plasma resveratrol concentrations and FMD in a dose-related manner . This effect may contribute to the purported cardiovascular health benefits of grapes and red wine 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 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 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 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 Introduction Vitamin D has potential benefits for extraskeletal health . These could include an anti-inflammatory effect as well as a reduction in endothelial dysfunction . We aim to provide quality evidence for the hypothesis that supplementation with vitamin D will improve endothelial function ( EF ) , possibly through the abrogation of systemic inflammation . Methods and analysis We will conduct a systematic review of all r and omised controlled trials on  vitamin D supplementation and EF lasting 12 weeks or more . The search will cover the period 2000–2015 and include studies that describe direct measures of EF  , markers of endothelial cell ( EC ) activation  and if concurrently reported , indicators of systemic inflammation  . Study selection will follow the Preferred Reporting Items for Systematic Review s and Meta-Analyses ( PRISMA ) guidelines and study quality will be assessed by the Jadad score in addition to an evaluation of allocation concealment and data analysis . If sufficient data are available , a meta- analysis will be conducted . The effect sizes will be generated using Hedges ’ g score , for both fixed and r and om effect models . I2 statistics and Galbraith plots will be used to assess heterogeneity and identify their potential sources . Potential publication and small sample size bias will be assessed by visual inspections of funnel plots and also Egger 's test . Meta-regression analysis ( if feasible ) will be conducted with restricted maximum likelihood ( REML ) estimation method , controlling for potential confounders ( demographics , study methods , location , etc ) . A backward elimination process will be applied in the regression modelling procedure . Subgroup analysis , conditional on number of studies retrieved and their sample size , will be stratified on participant disease category , total dose administered , degree of 25(OH)D change and type of supplement used . Ethics and dissemination Formal ethical approval is not required as primary data will not be collected . The results will be disseminated through a peer- review ed publication , conference presentation and the popular press . Trial registration number International Prospect i ve Register for Systematic Review s ( PROSPERO ) number CRD42014013523 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 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 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 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 Single doses of resveratrol have previously been shown to increase cerebral blood flow ( CBF ) with no clear effect on cognitive function or mood in healthy adults . Chronic resveratrol consumption may increase the poor bioavailability of resveratrol or otherwise potentiate its psychological effects . In this r and omised , double-blind , placebo-controlled , parallel-groups study , a total of sixty adults aged between 18 and 30 years received either placebo or resveratrol for 28 d. On the 1st and 28th day of treatment , the performance of cognitively dem and ing tasks ( serial subtractions , rapid visual information processing and 3-Back ) ( n 41 complete data sets ) was assessed , alongside blood pressure ( n 26 ) and acute ( near-IR spectroscopy ( NIRS ) ) and chronic ( transcranial Doppler ) measures of CBF ( n 46 ) . Subjective mood , sleep quality and health question naires were completed at weekly intervals ( n 53/54 ) . The results showed that the cognitive effects of resveratrol on day 1 were restricted to more accurate but slower serial subtraction task performance . The only cognitive finding on day 28 was a beneficial effect of resveratrol on the accuracy of the 3-Back task before treatment consumption . Subjective ratings of ' fatigue ' were significantly lower across the entire 28 d in the resveratrol condition . Resveratrol also result ed in modulation of CBF parameters on day 1 , as assessed by NIRS , and significantly increased diastolic blood pressure on day 28 . Levels of resveratrol metabolites were significantly higher both before and after the day 's treatment on day 28 , in comparison with day 1 . These results confirm the acute CBF effects of resveratrol and the lack of interpretable cognitive effects 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 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 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 BACKGROUND AND PURPOSE Acupuncture is widely used in the treatment of hypertension , yet its efficacy and safety for hypertension remain controversial . This overview aim ed to summarize the evidence on acupuncture for hypertension . METHODS Eight data bases were search ed . The Assessment of Multiple Systematic Review s ( AMSTAR ) tool and the Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach were performed . RESULTS Fifteen systematic review s ( SRs ) were identified . Method ological quality and quality of evidence were unsatisfactory . Acupuncture combined with Western medicine ( WM ) was superior to WM in systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) , efficacy rate , and traditional Chinese medicine ( TCM ) syndrome .  Acupuncture was more effective in treating SBP and DBP than sham acupuncture plus WM . Evidence regarding the benefit of acupuncture alone for SBP and DBP , efficacy rate and TCM syndrome was inconsistent . No serious adverse effects were identified . CONCLUSION High- quality SRs and r and omized controlled trials ( RCTs ) are required 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 CONTEXT Polycystic ovary syndrome ( PCOS ) is the most common endocrinopathy affecting women of reproductive age . Hyper and rogenism is the central feature of PCOS . Studies on isolated ovarian theca-interstitial cells suggest that resveratrol , a natural polyphenol , reduces and rogen production . OBJECTIVE This study was design ed to evaluate endocrine and metabolic effects of resveratrol on PCOS . DESIGN AND SETTING This was a r and omized ( 1:1 ) double-blind , placebo-controlled trial that evaluated the effects of resveratrol over a period of 3 months in an academic hospital . PATIENTS AND OTHER PARTICIPANTS Subjects with PCOS were identified according to the Rotterdam criteria . Thirty-four subjects were enrolled and 30 subjects completed the trial . Evaluations were performed at baseline and repeated after 3 months of treatment . INTERVENTION Resveratrol ( 1,500 mg p.o . ) or placebo were administered daily . MAIN OUTCOME MEASURE Primary outcome was the change in the serum total T. RESULTS Resveratrol treatment led to a significant decrease of total T by 23.1 % ( P = .01 ) . In parallel , resveratrol induced a 22.2 % decrease of dehydroepi and rosterone sulfate ( P = .01 ) , a decrease of fasting insulin level by 31.8 % ( P = .007 ) and an increase of the Insulin Sensitivity Index ( Matsuda and DeFronzo ) by 66.3 % ( P = .04 ) . Levels of gonadotropins , the lipid profile as well as markers of inflammation and endothelial function were not significantly altered . CONCLUSIONS Resveratrol significantly reduced ovarian and adrenal and rogens . This effect may be , at least in part , related to an improvement of insulin sensitivity and a decline of insulin level 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 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 Obesity in the postmenopausal period is associated with an increased risk of cardiovascular diseases in women . One of the key drivers of cardiovascular risk is endothelial dysfunction ; thus , this is also a crucial point for studies on new therapeutic methods of cardioprotective properties . The aim of the current study was to evaluate the effect of two doses of multispecies probiotic Ecologic ® Barrier supplement on functional ( primary endpoint ) and biochemical parameters ( secondary endpoint ) of endothelial dysfunction in obese postmenopausal women in a 12-week r and omized , placebo-controlled clinical trial . A total of 81 obese Caucasian women participated in the trial . The subjects were r and omly assigned to three groups that received a placebo , a low dose ( LD ) ( 2.5 × 109 colony forming units ( CFU ) per day ) , or a high dose ( HD ) ( 1 × 1010 CFU per day ) of lyophilisate powder containing live multispecies probiotic bacteria . The probiotic supplement was administered each day for 12 weeks in two equal portions . A high dose probiotic supplementation for 12 weeks decreased systolic blood pressure , vascular endothelial growth factor , pulse wave analysis systolic pressure , pulse wave analysis pulse pressure , pulse wave analysis augmentation index , pulse wave velocity , interleukin-6 , tumor necrosis factor alpha , and thrombomodulin . Low doses of probiotic supplementation decreased the systolic blood pressure and interleukin-6 levels . The mean changes in the estimated parameters , compared among the three groups , revealed significant differences in the vascular endothelial growth factor , the pulse wave analysis systolic pressure , the pulse wave analysis augmentation index , the pulse wave velocity , the tumor necrosis factor alpha , and thrombomodulin . The post hoc tests showed significant differences for all parameters between HD and the placebo group , and HD and LD ( besides pulse wave analysis augmentation index ) . We show for the first time that supplementation with multispecies probiotic Ecologic ® Barrier favorably modifies both functional and biochemical markers of vascular dysfunction in obese postmenopausal women 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
Conclusions Resveratrol supplementation significantly increased FMD among patients with MetS and related disorders , but did not affect SBP and DBP .
Introduction There are current trials investigating the effect of resveratrol supplementation on endothelial function and blood pressures among patients with metabolic syndrome ( MetS ) ; however , the findings are controversial .
Aim This systematic review and meta- analysis of r and omized controlled trials ( RCTs ) were carried out to summarize the effects of resveratrol supplementation on endothelial activation and blood pressures among patients with MetS and related disorders .