Resveratrol as Add-on Therapy in Subjects With Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial Beneficial effects of acute trans-resveratrol supplementation in treated hypertensive patients with endothelial dysfunction 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. 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. Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. 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 The effects of chronic trans-resveratrol supplementation on aspects of cognitive function, mood, sleep, health and cerebral blood flow in healthy, young humans. 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 Supplementation in Schizophrenia Patients: A Randomized Clinical Trial Evaluating Serum Glucose and Cardiovascular Risk Factors 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 on cerebral blood flow variables and cognitive performance in humans: a double-blind, placebo-controlled, crossover investigation. Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus. Acute Resveratrol Consumption Improves Neurovascular Coupling Capacity in Adults with Type 2 Diabetes Mellitus
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 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 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 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 : 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 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 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 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 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 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 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 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 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 The many putative beneficial effects of the polyphenol resveratrol include an ability to bolster endogenous antioxidant defenses , modulate nitric oxide synthesis , and promote vasodilation , which thereby improves blood flow . Resveratrol may therefore modulate aspects of brain function in humans . OBJECTIVE The current study assessed the effects of oral resveratrol on cognitive performance and localized cerebral blood flow variables in healthy human adults . DESIGN In this r and omized , double-blind , placebo-controlled , crossover study , 22 healthy adults received placebo and 2 doses ( 250 and 500 mg ) of trans-resveratrol in counterbalanced order on separate days . After a 45-min resting absorption period , the participants performed a selection of cognitive tasks that activate the frontal cortex for an additional 36 min . Cerebral blood flow and hemodynamics , as indexed by concentration changes in oxygenated and deoxygenated hemoglobin , were assessed in the frontal cortex throughout the posttreatment period with the use of near-infrared spectroscopy . The presence of resveratrol and its conjugates in plasma was confirmed by HPLC after the same doses in a separate cohort ( n = 9 ) . RESULTS Resveratrol administration result ed in dose-dependent increases in cerebral blood flow during task performance , as indexed by total concentrations of hemoglobin . There was also an increase in deoxyhemoglobin after both doses of resveratrol , which suggested enhanced oxygen extraction , that became apparent toward the end of the 45-min absorption phase and was sustained throughout task performance . Cognitive function was not affected . Resveratrol metabolites were present in plasma throughout the cognitive task period . CONCLUSION These results showed that single doses of orally administered resveratrol can modulate cerebral blood flow variables 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 Background : Poor cerebral perfusion may contribute to cognitive impairment in type 2 diabetes mellitus ( T2DM ) . We conducted a r and omized controlled trial to test the hypothesis that resveratrol can enhance cerebral vasodilator function and thereby alleviate the cognitive deficits in T2DM . We have already reported that acute resveratrol consumption improved cerebrovascular responsiveness ( CVR ) to hypercapnia . We now report the effects of resveratrol on neurovascular coupling capacity ( CVR to cognitive stimuli ) , cognitive performance and correlations with plasma resveratrol concentrations . Methods : Thirty-six T2DM adults aged 40–80 years were r and omized to consume single doses of resveratrol ( 0 , 75 , 150 and 300 mg ) at weekly intervals . Transcranial Doppler ultrasound was used to monitor changes in blood flow velocity ( BFV ) during a cognitive test battery . The battery consisted of dual-tasking ( finger tapping with both Trail Making task and Serial Subtraction 3 task ) and a computerized multi-tasking test that required attending to four tasks simultaneously . CVR to cognitive tasks was calculated as the per cent increase in BFV from pre-test basal to peak mean blood flow velocity and also as the area under the curve for BFV . Results : Compared to placebo , 75 mg resveratrol significantly improved neurovascular coupling capacity , which correlated with plasma total resveratrol levels . Enhanced performance on the multi-tasking test battery was also evident following 75 mg and 300 mg of resveratrol . Conclusion : a single 75 mg dose of resveratrol was able to improve neurovascular coupling and cognitive performance in T2DM . Evaluation of benefits of chronic resveratrol supplementation is now warranted
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 .