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 Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. Resveratrol shows neuronal and vascular-protective effects in older, obese, streptozotocin-induced diabetic rats. Acute Resveratrol Consumption Improves Neurovascular Coupling Capacity in Adults with Type 2 Diabetes Mellitus The Impact of Resveratrol Supplementation on Blood Glucose, Insulin, Insulin Resistance, Triglyceride, and Periodontal Markers in Type 2 Diabetic Patients with Chronic Periodontitis Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus. The effects of chronic trans-resveratrol supplementation on aspects of cognitive function, mood, sleep, health and cerebral blood flow in healthy, young humans. 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 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 Effects of chronic resveratrol supplementation in military firefighters undergo a physical fitness test--a placebo-controlled, double blind study. Resveratrol supplementation improves glycemic control in type 2 diabetes mellitus. Oral resveratrol and calcium fructoborate supplementation in subjects with stable angina pectoris: effects on lipid profiles, inflammation markers, and quality of life. Are Observational Studies More Informative Than Randomized Controlled Trials in Hypertension?: Con Side of the Argument
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 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 objective of this study was to examine the effectiveness of resveratrol in lowering blood glucose in the presence of st and ard antidiabetic treatment in patients with type 2 diabetes , in a r and omized placebo-controlled double-blinded parallel clinical trial . A total of 66 subjects with type 2 diabetes were enrolled in this study and r and omly assigned to intervention group which was supplemented with resveratrol at a dose 1 g/day for 45 days and control group which received placebo tablets .  Body weight , blood pressure , fasting blood glucose , haemoglobin A1c , insulin , homeostatic assessment s for insulin resistance , triglycerides , total cholesterol , low density lipoprotein , high density lipoprotein , and markers of liver and kidney damage were measured at baseline and after 45 days of resveratrol or placebo supplementation . Resveratrol treatment significantly decreased systolic blood pressure , fasting blood glucose , haemoglobin A1c , insulin , and insulin resistance , while HDL was significantly increased , when compared to their baseline levels . On the other h and , the placebo group had slightly increased fasting glucose and LDL when compared to their baseline levels . Liver and kidney function markers were unchanged in the intervention group . Overall , this study showed that resveratrol supplementation exerted strong antidiabetic effects in patients with type 2 diabetes BACKGROUND 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 Diabetes-induced CVD is the most significant complication of prolonged hyperglycaemia . The aim of this study was to determine whether resveratrol , a polyphenol antioxidant compound , when administered at a dose that can be reasonably obtained through supplementation could prevent the development of cardiovascular complications in older , obese , diabetic rats . Diabetes was induced in 6-month old , obese , male Wistar rats via a single intravenous dose of streptozotocin ( 65 mg/kg ) . R and omly selected animals were administered resveratrol ( 2 mg/kg ) via oral gavage daily for 8 weeks . Body weights , blood glucose levels , food intake and water consumption were monitored , and assessment s of vascular reactivity , tactile allodynia and left ventricular function were performed . Resveratrol therapy significantly improved tactile allodynia and vascular contractile functionality in diabetic rats ( P<0·05 ) . There were no significant changes in st and ardised vasorelaxation responses , plasma glucose concentrations , water consumption , body weight , left ventricular hypertrophy , kidney hypertrophy , heart rate or left ventricular compliance with resveratrol administration . Resveratrol-mediated improvements in vascular and nerve function in old , obese , diabetic rats were associated with its reported antioxidant effects . Resveratrol did not improve cardiac function nor mitigate the classic clinical symptoms of diabetes mellitus ( i.e. hyperglycaemia , polydypsia and a failure to thrive ) . This suggests that supplementation with resveratrol at a dose achievable with commercially available supplements would not produce significant cardioprotective effects in people with diabetes mellitus 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 The aim of this study was to investigate the impact of resveratrol supplementation along with non-surgical periodontal treatment on blood glucose , insulin , insulin resistance , triglyceride ( TG ) , and periodontal markers in patients with type 2 diabetes with periodontal disease . In this double-blind clinical trial study , 43 patients with diabetes with chronic periodontitis were participated . Subjects were r and omly allocated to intervention and control groups . The intervention and control groups received either 480 mg/day of resveratrol or placebo capsules ( two pills ) for 4 weeks . Fasting blood glucose , insulin , insulin resistance ( homeostasis model assessment of insulin resistance ) , TGs , and pocket depth were measured in all subjects ' pre-intervention and post-intervention . The mean serum levels of fasting insulin and insulin resistance ( homeostasis model assessment of insulin resistance ) were significantly lower in the intervention group compared with control group ( 10.42 ± 0.28 and 10.92 ± 0.9 ; 3.66 ± 0.97 and 4.49 ± 1.56 , respectively ) . There was a significant difference in the mean pocket depth between intervention and control groups ( 2.35 ± 0.6 and 3.38 ± 0.5 , respectively ) following intervention . No significant differences were observed in the mean levels of fasting blood glucose and TGs between two groups ' post-intervention . It is recommended that resveratrol supplementation may be beneficial as adjuvant therapy along with non-surgical periodontal treatment in insulin resistance and improving periodontal status among patients with diabetes with periodontal disease . Copyright © 2016 John Wiley & Sons , 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 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 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 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 PURPOSE The purpose of this study was to determine the plasma metabolic response and certain indicators of oxidative stress ( antioxidant system and oxidative stress biomarkers ) in plasma and erythrocytes of Brazilian military firefighters supplemented or not with resveratrol ( RES ) for 90 days ( 100 mg/day ) . The analyses were performed before and after a typical physical fitness test ( FT ) used to induce oxidative stress . METHODS / RESULTS In this placebo-controlled double-blinded study , we observed that RES supplementation did not present hepatic consequences compared with the placebo group following analysis of AST , ALT and GGT plasma activities . Plasma glucose and triglycerides levels were increased after the FT in firefighters supplemented with RES but were not elevated at baseline . Neither total nor cholesterol fractions were modified by RES supplementation . CK levels were increased after the firefighters performed the FT ; however , no differences were determined between the placebo and RES groups . Ferric-reducing ability of plasma as well as uric acid was increased after the FT , but was not modified by RES supplementation . Plasma oxidative stress biomarkers , such as thiol content , 8-isoprostane and 8OHdG , showed no modifications , while IL-6 and TNF-α were decreased in the RES group after the FT . Among antioxidant enzyme activities determined in erythrocytes from the firefighters , only GPx activity was reduced by RES supplementation both before and after the FT . CONCLUSION In summary , the most pronounced effect of RES supplementation is its anti-inflammatory effect , which reduced IL-6 and TNF-α level . The FT applied to Brazilian military firefighters was not sufficient to challenge the antioxidant defense systems , and , therefore , 100 mg of RES for three months did not induce significant effects Resveratrol is a naturally occurring polyphenolic compound . Numerous animal studies have been reported on its wide-ranging beneficial effects in the biological system including diabetes mellitus ( DM ) . We hypothesized , therefore , that oral supplementation of resveratrol would improve the glycemic control and the associated risk factors in patients with type 2 diabetes mellitus ( T2DM ) . The present clinical study was therefore carried out to test the hypothesis . Sixty-two patients with T2DM were enrolled from Government Headquarters Hospital , Ootacamund , India , in a prospect i ve , open-label , r and omized , controlled trial . Patients were r and omized into control and intervention groups . The control group received only oral hypoglycemic agents , whereas the intervention group received resveratrol ( 250 mg/d ) along with their oral hypoglycemic agents for a period of 3 months . Hemoglobin A(1c ) , lipid profile , urea nitrogen , creatinine , and protein were measured at the baseline and at the end of 3 months . The results reveal that supplementation of resveratrol for 3 months significantly improves the mean hemoglobin A(1c ) ( means ± SD , 9.99 ± 1.50 vs 9.65 ± 1.54 ; P < .05 ) , systolic blood pressure ( mean ± SD , 139.71 ± 16.10 vs 127.92 ± 15.37 ; P < .05 ) , total cholesterol ( mean ± SD , 4.70 ± 0.90 vs 4.33 ± 0.76 ; P < .05 ) , and total protein ( mean ± SD , 75.6 ± 4.6 vs 72.3 ± 6.2 ; P < .05 ) in T2DM . No significant changes in body weight and high-density lipoprotein and low-density lipoprotein cholesterols were observed . Oral supplementation of resveratrol is thus found to be effective in improving glycemic control and may possibly provide a potential adjuvant for the treatment and management of diabetes 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 The very first rigorously design ed , r and omized controlled trial ( RCT ) in the history of modern medicine was published in 1948 . The study , design ed and carried out by the Streptomycin in Tuberculosis Trials Committee of the Medical Research Council , demonstrated the efficacy of streptomycin in treating pulmonary tuberculosis on top of bed rest , which was the best available treatment at that time.1 In the field of hypertension treatment and cardiovascular prevention , the history of event-based RCTs began in 1967 , when the cardiovascular benefits and risks of antihypertensive drug treatment were evaluated in the setting of the Veterans Administration Cooperative Study in Hypertension.2 In that trial , 143 patients with severe hypertension were r and omized to receive blood pressure (BP)–lowering drug treatment or matched placebo for 11 months . A major morbid or fatal event was observed in 26 of 70 patients who received placebo ( 37 % ) and in only 1 of 73 patients under active treatment ( 1 % ) . The amazing results of this l and mark trial established beyond any doubt the striking cardiovascular benefits of antihypertensive drug treatment of hypertension at a time when controversy still persisted regarding the supposedly deleterious effects of BP reduction on organ perfusion.3 Ever since , RCTs have represented a formidable tool for evaluating risks and benefits of hypertension treatment . Over the past 50 years , the remarkable progress in treatment and control of high BP , one of the most outst and ing achievements of modern medicine , has been driven by the results of many large , event-based RCTs . The influential position of RCTs in clinical and therapeutic research as opposed to real-world observational studies ( surveys , registries , and retrospective analyses of existing data bases ) originates from their high internal validity ( ie , the power to address clinical questions with a low level of internal bias ) . A list of strengths and weaknesses of RCTs and observational studies is
Conclusion : The favourable effect of resveratrol emerging from the current meta- analysis suggests the possible use of this nutraceutical as active compound in order to promote cardiovascular health , mostly when used in high daily dose ( ≥300 mg/day ) and in diabetic patients
ABSTRACT Introduction : Results of previous clinical trials evaluating the effect of  resveratrol supplementation on blood pressure ( BP )  are controversial .
Purpose : We aim ed to assess the impact of resveratrol on BP through systematic review of literature and meta- analysis of available r and omized , controlled clinical trials ( RCTs ) .