Beneficial effects of acute trans-resveratrol supplementation in treated hypertensive patients with endothelial dysfunction Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus. Resting blood pressure reductions following isometric handgrip exercise training and the impact of age and sex: protocol for a systematic review Acute resveratrol supplementation improves flow-mediated dilatation in overweight/obese individuals with mildly elevated blood pressure. The effects of resveratrol on markers of oxidative stress in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled clinical trial Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease 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 supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study. Chronic resveratrol consumption improves brachial flow-mediated dilatation in healthy obese adults Effect of vitamin D supplementation on inflammation: protocol for a systematic review Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. Effects of 6 months of resveratrol versus placebo on pentraxin 3 in patients with type 2 diabetes mellitus: a double-blind randomized controlled trial The blood pressure sensitivity to changes in sodium intake is similar in Asians, Blacks and Whites. An analysis of 92 randomized controlled trials Antihyperglycemic Effects of Short Term Resveratrol Supplementation in Type 2 Diabetic Patients 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 Proposed trial: safety and efficacy of resveratrol for the treatment of non-alcoholic fatty liver disease (NAFLD) and associated insulin resistance in adolescents who are overweight or obese adolescents - rationale and protocol. Outcome Measures of Chinese Herbal Medicine for Hypertension: An Overview of Systematic Reviews 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. Serum concentrations and gene expression of sirtuin 1 in healthy and slightly overweight subjects after caloric restriction or resveratrol supplementation: A randomized trial. Review: E-health interventions improve blood pressure level and control in hypertension Sources of evidence for systematic reviews of interventions in diabetes. The Impact of Resveratrol Supplementation on Blood Glucose, Insulin, Insulin Resistance, Triglyceride, and Periodontal Markers in Type 2 Diabetic Patients with Chronic Periodontitis The effects of chronic trans-resveratrol supplementation on aspects of cognitive function, mood, sleep, health and cerebral blood flow in healthy, young humans.
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 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 The risk of developing cardiovascular disease is directly correlated to one ’s resting blood pressure ( BP ) , age , and biological sex . Resting BP can be reduced using h and grip exercise training , but the impact of age and sex on the effectiveness of training is not well documented . Methods / design A systematic search of the literature will be conducted for all experimental studies ( including r and omized controlled trials and prospect i ve experiments ) that report the influence of isometric h and grip exercise training on resting systolic blood pressure . The data bases Medline , Embase , Cochrane Review s , Cumulative Index to Nursing and Allied Health Literature ( CINAHL ) , SPORTD iscus , Web of Science , Allied and Complementary Medicine ( AMED ) , PubMed , and Scopus will be search ed until 1 December 2015 . Screening of potential articles , data abstract ion , and quality appraisal will be completed in duplicate independently . When necessary , corresponding authors will be contacted in order to facilitate the separation of pooled data into age and sex categories . Method ological quality will be determined using the Quality Assessment Framework developed by the Cochrane Collaboration and the Newcastle-Ottawa Quality Assessment Scale as appropriate . Any discrepancies will be resolved by a third author . Findings will be presented in accordance with the preferred reporting items for systematic review s and meta- analysis ( PRISMA ) guidelines . Discussion This systematic review will determine the overall effectiveness  of h and grip exercise training in improving resting blood pressure . A novel , focused assessment will contrast  effectiveness of h and grip training  based on the age ( younger 18–54 years , older > 55 years ) and the sex ( men , women ) of study participants . This information is essential to consoli date before moving forward with the development and implementation of h and grip exercise training programmes which are design ed to best meet the needs of particular cohorts . Systematic review registration PROSPERO 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 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 ABSTRACT Objective “ The obesity epidemic ” has led to an increase in obesity-related conditions including non-alcoholic fatty liver disease ( NAFLD ) , for which effective treatments are in dem and . The polyphenol resveratrol prevents the development of experimental NAFLD through modulation of cellular pathways involved in calorie restriction . We aim ed to test the hypothesis that resveratrol alleviates NAFLD in a r and omised , clinical trial . Material s and methods A total of 28 overweight patients with transaminasemia and histological NAFLD were r and omised 1:1 to placebo or resveratrol 1.5 g daily for 6 months . Twenty-six participants completed the trial and underwent repeated clinical investigation , blood work , MR spectroscopy ; and 19 participants agreed to a repeat liver biopsy . Results Resveratrol treatment was generally not superior to placebo in improving plasma markers of liver injury ( primary outcome : alanine transaminase , p = 0.51 ) . Resveratrol-treated patients showed a 3.8 % decrease in liver lipid content ( p = 0.03 ) , with no difference between the two treatment arms ( p = 0.38 ) and no improvement of histological features .  Resveratrol treatment was not associated with improvements in insulin sensitivity or markers of the metabolic syndrome , except for a transient decrease in systolic BP . Microarray analysis and qRT-PCR revealed no major changes in expression profile . Also , we report a serious adverse event in a patient who developed fever and bicytopenia . Conclusions In this placebo-controlled , high-dose and long-term study , resveratrol treatment had no consistent therapeutic effect in alleviating clinical or histological NAFLD , though there may be a small ameliorating effect on liver function tests and liver fat accumulation 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 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 : 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 Introduction The extraskeletal role of vitamin D is being increasingly recognised . This has important clinical implication s , as vitamin D deficiency has reached epidemic proportions worldwide . Vitamin D has proposed anti-inflammatory properties , yet the role of vitamin D supplementation in reducing inflammation remains largely unknown . The purpose of this review is to investigate the impact of vitamin D supplementation on inflammation , and to identify relevant knowledge gaps in the field . Methods and analysis Medline , CINAHL , EMBASE and All EBM will be systematic ally search ed for r and omised controlled trials ( RCTs ) and systematic review s of RCTs , comparing vitamin D supplementation with placebo , usual care or other pharmacological or non-pharmacological interventions . One review er will assess articles for eligibility according to prespecified selection criteria , after which 2 independent review ers will perform data extraction and quality appraisal . Meta-analyses will be conducted where appropriate . Ethics and dissemination Formal ethical approval is not required as no primary data is collected . This systematic review will identify potential clinical implication s of vitamin D deficiency and supplementation , and will be disseminated through a peer- review ed publication and at conference meetings , to inform future research on the efficacy of vitamin D supplementation for inflammation and inflammatory diseases . PROSPERO registration number CRD42016037104 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 The anti-inflammatory effects of the polyphenol resveratrol in patients with type 2 diabetes mellitus ( T2DM ) are controversial . Its role on pentraxin 3 ( PTX3 ) concentrations , a human acute phase protein , has never been evaluated . Our aim was to determine whether a two-dosage resveratrol supplementation ( 500 and 40 mg/day ) has an impact on PTX3 values in T2DM patients from a double-blind r and omized placebo-controlled trial .  Variations in total antioxidant status ( TAS ) were evaluated too . Methods A total of 192 T2DM patients were r and omized to receive resveratrol 500 mg/day ( Resv 500 arm ) , resveratrol 40 mg/day ( Resv 40 arm ) or placebo for 6 months . At baseline and at the trial end , PTX3 and TAS values were determined . Results A dose-dependent increase in PTX3 concentrations of 4.7 % ( Resv 40 arm ) and 26.3 % ( Resv 500 arm ) , and 8.0 % reduction after placebo were found . Adjusted mean differences of change versus placebo were 0.16 ( 95 % CI 0.01–0.32 ) and 0.25 ( 0.09–0.42 ) in the Resv 40 and Resv 500 arms , respectively . At subgroup analyses , lower diabetes duration , aspirin , alcohol use , younger age , female gender , smoking ( Resv 500 arm ) and female gender and aspirin use ( Resv 40 arm ) were associated with higher PTX3 increments . A dose-dependent increment in TAS values in the resveratrol arms ( 1.4 and 6.4 % for Resv 40 and Resv 500 , respectively ) , and a reduction in placebo arm ( −8.9 % ) were observed . Adjusted mean differences of change were 28.5 ( 95 % CI 10.1–46.8 ) and 44.8 ( 25.4–64.1 ) in the Resv 40 and Resv 500 arms , respectively . Conclusion Resveratrol supplementation  increased PTX3 and TAS levels in a dose-dependent manner in T2DM patients . At present , potential clinical implication s of these results remain unclear . Clinical Trials.gov IdentifierNCT02244879 The purpose of the meta- analysis of r and omized trials was to analyze the significance of ethnicity on the effect of sodium reduction ( SR ) on blood pressure ( BP ) by estimating the effect of SR on BP in Asians , Blacks and Whites under conditions , which were adjusted with respect to baseline BP , baseline sodium intake and quantity of SR . Relevant studies were retrieved from a pool of 167 RCTs published in the period 1973–2010 and identified in a previous Cochrane review . 9 Asian , 9 Black , and 74 White population s st and ardized with respect to the range of baseline blood pressure , the range of baseline sodium , duration of SR ( at least 7 days ) and baseline sodium intake ( at maximum 250 mmol ) intake were included . In the cross-sectional analysis , there was no difference in change in SBP to SR between the ethnic groups , but there was a small difference in SR induced change in DBP between Blacks and Whites ( p = 0.04 ) . The comparison of changes in SBP and DBP to SR in ethnic groups compared in identical studies showed no statistically significant differences between the groups 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 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 Non-alcoholic fatty liver ( NAFL ) disease ( NAFLD ) affects 30 % of overweight adolescents and increases the risk of type 2 diabetes mellitus ( T2D ) . Resveratrol is a naturally occurring compound with potential to reverse NAFL and its associated insulin resistance in adults . The use of resveratrol to reduce risk for T2D through its effect on NAFL has not been examined to date in youth . This paper provides a literature review and protocol for a 30 day proof of principle trial of resveratrol in a population of adolescents at risk for T2D . This r and omized double-blind controlled trial is design ed with the primary objective of evaluating a twice daily supplementation of 75 mg of resveratrol for safety and tolerability in overweight and obese adolescent subjects ( 13 to < 18 years of age ) with NAFL . Secondary objectives are to determine the effect size of the intervention on hepatic steatosis and whole body insulin sensitivity .  Adolescents in the intervention arm ( n = 10 ) will receive oral supplementation of resveratrol 75 mg twice daily ( with breakfast and dinner ) for a total daily dose of 150 mg for the duration of 30 days . The comparison group ( n = 10 ) will receive a placebo twice daily for 30 days . Both cases and controls will receive a st and ardized lifestyle intervention program . Subjects in both groups will be followed for an additional 30 days post intervention for total study duration of approximately 60 days . Primary outcome measures include a primary side effect profile determined by participant interview , a side effect profile determined by serum biochemistry and vital signs . Secondary outcome measures include an oral glucose tolerance test , liver and cardiac fat content measured by magnetic resonance spectroscopy , anthropometric measures of overweight/obesity , inflammatory markers , and cardiac function and morphology measured with ultrasonography . Additional outcome measures include serum concentrations of resveratrol , compliance to protocol , physical activity , and nutritional assessment . This study will determine the safety and tolerability of resveratrol in an overweight adolescent population and inform the design of a larger r and omized controlled trial Objective . The aim of this overview was to summarize the outcome measures of Chinese herbal medicine ( CHM ) for the treatment of hypertension based on available systematic review s ( SRs ) , so as to evaluate the potential benefits and advantages of CHM on hypertension . Methods . Literature search es were conducted in the Cochrane Data base of Systematic Review s , MEDLINE , and 4 data bases in Chinese . SRs of CHM for hypertension were included . Two independent review ers ( J. Wang and X. J. Xiong ) extracted the data . Results . 10 SRs were included . 2 SRs had primary endpoints , while others focused on secondary endpoints to evaluate CHM for hypertension such as blood pressure ( BP ) and Traditional Chinese Medicine ( TCM ) syndrome . 6 SRs have reported the adverse effects , whereas the other 4 SRs have not mentioned it at all . Many CHM appeared to have significant effect on improving BP , TCM syndrome , and so on . However , most SRs failed to make a definite conclusion for the effectiveness of CHM for hypertension due to poor evidence . Conclusion . Primary endpoints have not been widely used currently . The benefits of CHM for hypertension need to be confirmed in the future with r and omized controlled trials ( RCTs ) of more persuasive primary endpoints and high- quality SRs 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 BACKGROUND Sirtuin 1 ( Sirt1 ) plays an important role in vascular biology , and influences aspects of age-dependent atherosclerosis . In animals , the sirtuin system is strongly influenced by resveratrol and caloric restriction , but its expression in humans is controversial . This study investigated the effects of resveratrol and caloric restriction on Sirt1 serum concentrations and vascular biomarkers in a healthy human population . METHODS AND RESULTS Forty-eight healthy participants ( 24 women ) aged 55 - 65years were r and omized to either 30days of resveratrol administration ( 500mg/day ) or caloric restriction ( 1000cal/day ) . Blood was collected at baseline and day 30 . Laboratory data analyzed were triglycerides , total cholesterol , HDL , VLDL , LDL , apolipoprotein A1 , apolipoprotein B , lipoprotein ( a ) , non-esterified fatty acids ( NEFA ) , glucose , insulin , oxidative stress , C-reactive protein , and Sirt1 . Expression of the Sirt1 gene was analyzed using real-time PCR . Caloric restriction diminished the abdominal circumference and improved the lipid profile , but not resveratrol intervention . Resveratrol and caloric restriction increased serum concentrations of Sirt1 , from 1.06±0.71 to 5.75±2.98ng/mL ; p<0.0001 , and from 1.65±1.81 to 5.80±2.23ng/mL ; p<0.0001 , respectively . Sirt1 increased in women and men in both interventions . On the other h and expression of Sirt1 mRNA was not different after caloric restriction and resveratrol treatment . CONCLUSIONS Caloric restriction and resveratrol significantly increased plasma concentrations of Sirt1 . The long-term impact of these interventions on atherosclerosis should be assessed Question In patients with hypertension , do electronic health ( e-health ) interventions improve blood pressure ( BP ) control and other outcomes ? Review scope Included studies compared e-health interventions with usual or st and ard care or attention control in patients with adequately or inadequately controlled hypertension .  E-health interventions had to use portable , Web-based , interactive wireless communication devices and focus on self-care , self-management , self-care behavior change , or education . Studies of interventions that only displayed information ( not interactive ) , were only used for follow-up , or that mostly benefitted health care providers were excluded . Outcomes included physical outcomes ( inadequate BP control , systolic [ SBP ] and diastolic BP [ DBP ] , body mass index [ BMI ] , body weight , and cholesterol levels ) , and self-care behavioral outcomes ( sodium and alcohol intake , smoking , and physical activities ) . Review methods MEDLINE , EMBASE /Excerpta Medica , Cochrane Data base of Systematic Review s , Cochrane Central Register of Controlled Trials , CINAHL Plus , PsycINFO , SCOPUS , Web of Science , Joanna Briggs Institute EBP Data base , INSPEC , China Journal Net , and WanFang Data ( all 2000 to Nov 2017 ) were search ed for English- and Chinese- language r and omized controlled trials ( RCTs ) . 14 RCTs ( n = 3998 , mean age 50 to 68 y ) , ranging in size from 44 to 778 patients , met the selection criteria . Follow-up ranged from 3 to 24 months . Studies were conducted in various setting s , including primary care clinics , community health centers , and hospitals . Intervention strategies included BP monitoring , lifestyle modification techniques , and motivation and maintenance . 9 RCTs had adequate r and omization sequence generation , 6 concealed allocation , 4 blinded outcome assessors , and none adequately reported blinding participants . Main results Results for inadequate BP control , SPB , DBP , BMI , body weight , and sodium intake are in the Table . E-health interventions did not improve total cholesterol levels at 3 to 6 months after the intervention ( 3 RCTs ) ; or alcohol intake , smoking , or physical activity at 6 months after the intervention ( 3 RCTs ) . Conclusion In patients with hypertension , electronic health interventions reduce blood pressure levels and increase likelihood of blood pressure control .  Electronic health interventions vs control in patients with hypertension * Outcomes Assessment times ( after intervention ) Number of trials ( n ) RRR ( 95 % CI ) NNT ( CI ) Inadequate BP control 3 to 12 mo 5 ( 1518 ) 31 % ( 16 to 43 ) 6 ( 4 to 11 ) Mean between-group difference ( CI ) Change in systolic BP ( mm Hg ) 6 mo 12 ( 3171 ) 5.50 ( 9.85 to 1.16 ) 12 mo 3 ( 1272 ) 7.68 ( 9.95 to 5.41 ) 18 mo 2 ( 735 ) 6.26 ( 9.29 to 3.23 ) Change in diastolic BP ( mm Hg ) 6 mo 12 ( 3171 ) 3.40 ( 7.79 to 0.99 ) 12 mo 3 ( 1272 ) 3.36 ( 4.80 to 1.92 ) 18 mo 2 ( 735 ) 2.53 ( 4.72 to 0.34 ) Change in body mass index ( kg/m2 ) 6 mo 5 ( 1486 ) 0.22 ( 0.46 to 0.02 ) 12 mo 3 ( 1272 ) 0.24 ( 0.82 to 0.33 ) 18 mo 2 ( 735 ) 0.07 ( 0.77 to 0.91 ) Change in body weight ( kg ) 3 to 6 mo 3 ( 517 ) 1.08 ( 2.04 to 0.13 ) Change in sodium intake ( SMD ) 6 mo 2 ( 768 ) 0.34 ( 0.49 to 0.20 ) 12 mo 2 ( 753 ) 0.39 ( 0.54 to 0.25 ) 18 mo 2 ( 735 ) 0.30 ( 0.45 to 0.16 ) * BP = blood pressure ; SMD = st and ardized mean difference ; other abbreviations defined in Glossary . Weighted electronic health intervention event rate , RRR , NNT , and CI calculated using control event rate and relative risk in article . Blood pressure 140/90 mm Hg . Weighted event rates 42 % vs 60 % . Commentary The systematic review and meta- analysis by Ma and colleagues showed a small but clinical ly meaningful reduction in SBP and DBP  in patients who received e-health re sources . However , some health outcomes , including BMI and cholesterol levels , were not improved . Despite a risk for selection bias in some of the studies and substantial heterogeneity between studies , the meta- analysis is of high quality . The interventions in the included studies varied greatly and included use of telephone calls , Web sites , and smartphone applications . The comparison treatments were either attention control or usual care , and trials did not directly compare e-health interventions . The outcomes measured also varied among studies . Because clinic BP measurements may overestimate the degree of elevation and ambulatory monitoring is costly and limited to brief periods of measurement , home BP monitoring using newer e-health re sources may provide a cost-effective alternative ( 1 ) . This is an exciting new avenue for improving BP control by allowing for more accurate and streamlined monitoring , leading to more precise and timely interventions . However , based on the heterogeneity of intervention types , the optimum method is unknown . Further studies should directly compare e-health platforms and assess patient-centered outcomes , including usability , satisfaction , affordability , and quality of life as well as BP . Although the evidence indicates that these interventions are not yet ready for routine clinical practice , there is a promising signal that they could be useful for BP management AIMS To analyse the effect on systematic review s in diabetes interventions of including only trials that are indexed in medline , and to assess the impact of adding trials from other data bases and the grey literature . METHODS All systematic review s of diabetes interventions which included a meta- analysis of r and omized controlled trials , and were published since 1996 , were selected . The impact on the meta- analysis of including only those trials indexed in medline , and the effect of then adding trials from other sources , was assessed . Where possible this was measured quantitatively , by redoing the meta- analysis , otherwise a qualitative estimate was made . RESULTS Forty-four systematic review s met our inclusion criteria . There were 120 articles reporting trial data which were not indexed in medline . These came from 52 % of the review s. In 34 % of the review s , basing a meta- analysis on a search of only medline would miss trials that could affect the result . Sources of non- medline data which had the biggest effect on the meta-analyses were journal articles from central and embase ( mainly in Diabetes , Nutrition and Metabolism ) and unpublished data ( mainly from industry ) . The exceptions were journal articles on herbal medicine , mostly indexed in Chinese language data bases . CONCLUSIONS A search of only the medline data base is insufficient for systematic review s of diabetes , because in about 34 % of review s the missed trials could affect the results of the meta- analysis . It is recommended that central ( on the Cochrane Library ) also be search ed . Scanning meeting abstract s , and seeking unpublished data are also recommended if the intervention has only recently been introduced 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 , 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
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 ) .