The effects of resveratrol supplementation on cardiovascular risk factors in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study. Resveratrol supplementation improves inflammatory biomarkers in patients with nonalcoholic fatty liver disease. Resveratrol Supplementation in Schizophrenia Patients: A Randomized Clinical Trial Evaluating Serum Glucose and Cardiovascular Risk Factors Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease The Effect of Chlorella vulgaris Supplementation on Liver En-zymes, Serum Glucose and Lipid Profile in Patients with Non-Alcoholic Fatty Liver Disease. Resveratrol does not benefit patients with nonalcoholic fatty liver disease. 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. Lipoic acid prevents high-fat diet-induced dyslipidemia and oxidative stress: a microarray analysis. l-Carnitine Supplementation to Diet: A New Tool in Treatment of Nonalcoholic Steatohepatitis—A Randomized and Controlled Clinical Trial Six months of resveratrol supplementation has no measurable effect in type 2 diabetic patients. A randomized, double blind, placebo-controlled trial. Effect of resveratrol supplementation on lipid profile in subjects with dyslipidemia: A randomized double-blind, placebo-controlled trial. The Effect of Vitamin A Supplementation on Biochemical Parameters in Multiple Sclerosis Patients Regression of Non-Alcoholic Fatty Liver by Vitamin D Supplement: A Double-Blind Randomized Controlled Clinical Trial. Effects of resveratrol supplementation on liver fat content in overweight and insulin‐resistant subjects: A randomized, double‐blind, placebo‐controlled clinical trial Serum concentrations and gene expression of sirtuin 1 in healthy and slightly overweight subjects after caloric restriction or resveratrol supplementation: A randomized trial. Resveratrol as Add-on Therapy in Subjects With Well-Controlled Type 2 Diabetes: A Randomized Controlled Trial Anti-inflammatory and antioxidant effects of resveratrol in healthy smokers a randomized, double-blind, placebo-controlled, cross-over trial. Oral resveratrol and calcium fructoborate supplementation in subjects with stable angina pectoris: effects on lipid profiles, inflammation markers, and quality of life. Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial. Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus. Effects of Resveratrol on Polycystic Ovary Syndrome: A Double-blind, Randomized, Placebo-controlled Trial. The effects of 30 days resveratrol supplementation on adipose tissue morphology and gene expression patterns in obese men
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 Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in the world . Resveratrol is a polyphenolic compound with antioxidant capacity that shows beneficial effects on down-regulation of inflammatory mediators and metabolic disorders . We hypothesized that supplementation with resveratrol can further improve the efficacy of lifestyle modifications in the management of NAFLD . In this r and omized , double-blinded , controlled clinical trial , 50 NAFLD patients were supplemented with either a 500-mg resveratrol capsule or a placebo capsule for 12 weeks . Both groups were advised to follow an energy-balanced diet and received physical activity recommendations  . Serum liver enzymes , inflammatory markers , hepatic steatosis and fibrosis , dietary intake , anthropometric measurements , and physical activity were assessed at both baseline and the end of the study . In both groups , anthropometric measurements ( weight , body mass index , waist circumference ) , liver enzymes , and steatosis grade improved ( P < 005 ) . Resveratrol supplementation was associated with a significant reduction in liver enzyme alanine aminotransferase , inflammatory cytokines , nuclear factor κB activity , serum cytokeratin-18 , and hepatic steatosis grade , as compared with placebo supplementation ( P < .05 ) . For the treatment of NAFLD , our results showed that 12 weeks of supplementation of 500 mg resveratrol , along with lifestyle modification , is superior to lifestyle modification alone . This is at least partially due to the attenuation of inflammatory markers and hepatocellular apoptosis . More studies are needed to confirm and increase the clinical application of the present results 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 ABSTRACT Objective “ The obesity epidemic ” has led to an increase in obesity-related conditions including non-alcoholic fatty liver disease ( NAFLD ) , for which effective treatments are in dem and . The polyphenol resveratrol prevents the development of experimental NAFLD through modulation of cellular pathways involved in calorie restriction . We aim ed to test the hypothesis that resveratrol alleviates NAFLD in a r and omised , clinical trial . Material s and methods A total of 28 overweight patients with transaminasemia and histological NAFLD were r and omised 1:1 to placebo or resveratrol 1.5 g daily for 6 months . Twenty-six participants completed the trial and underwent repeated clinical investigation , blood work , MR spectroscopy ; and 19 participants agreed to a repeat liver biopsy . Results Resveratrol treatment was generally not superior to placebo in improving plasma markers of liver injury ( primary outcome : alanine transaminase , p = 0.51 ) . Resveratrol-treated patients showed a 3.8 % decrease in liver lipid content ( p = 0.03 ) , with no difference between the two treatment arms ( p = 0.38 ) and no improvement of histological features .  Resveratrol treatment was not associated with improvements in insulin sensitivity or markers of the metabolic syndrome , except for a transient decrease in systolic BP . Microarray analysis and qRT-PCR revealed no major changes in expression profile . Also , we report a serious adverse event in a patient who developed fever and bicytopenia . Conclusions In this placebo-controlled , high-dose and long-term study , resveratrol treatment had no consistent therapeutic effect in alleviating clinical or histological NAFLD , though there may be a small ameliorating effect on liver function tests and liver fat accumulation BACKGROUND Non-alcoholic fatty liver disease ( NAFLD ) is becoming a public health problem worldwide and using microalgae is a new approach on its treatment . The aim of this study was to investigate the effect of Chlorella vulgaris supplementation on liver enzymes , serum glucose and lipid profile in patients with NAFLD . METHODS This double-blind r and omized placebo-controlled clinical trial was conducted on 60 NAFLD patients from specialized clinics of Tabriz University of Medical Sciences from December 2011 to July 2012 . The subjects were r and omly allocated into 2 groups : 1 ) " intervention " ( n=30 ) received 400 mg/day vitamin E plus four 300 mg tablets of Chlorella vulgaris and , 2 ) " placebo " ( n=30 ) received 400 mg/day vitamin E and four placebo tablets per day for 8 weeks . Weight , liver enzymes and metabolic factors were assessed in fasting serum and dietary data was collected at baseline and end of the study . RESULTS Weight , liver enzymes , fasting blood sugar ( FBS ) and lipid profile decreased significantly in both groups ( P<0.05 ) . The differences in weight , ALP and FBS between the two groups were statistically significant ( P=0.01 , P=0.04 and P=0.02 , respectively ) . CONCLUSION C. vulgaris seems to improve FBS and lipid profile and therefore could be considered as an effective complementary treatment in NAFLD BACKGROUND & AIMS Nonalcoholic fatty liver disease ( NAFLD ) , characterized by accumulation of hepatic triglycerides ( steatosis ) , is associated with abdominal obesity , insulin resistance , and inflammation . Although weight loss via calorie restriction reduces features of NAFLD , there is no pharmacologic therapy . Resveratrol is a polyphenol that prevents high-energy diet-induced steatosis and insulin resistance in animals by up-regulating pathways that regulate energy metabolism . We performed a placebo-controlled trial to assess the effects of resveratrol in patients with NAFLD . METHODS Overweight or obese men diagnosed with NAFLD were recruited from hepatology outpatient clinics in Brisbane , Australia from 2011 through 2012 . They were r and omly assigned to groups given 3000 mg resveratrol ( n = 10 ) or placebo ( n = 10 ) daily for 8 weeks . Outcomes included insulin resistance ( assessed by the euglycemic-hyperinsulinemic clamp ) , hepatic steatosis , and abdominal fat distribution ( assessed by magnetic resonance spectroscopy and imaging ) . Plasma markers of inflammation , as well as metabolic , hepatic , and antioxidant function , were measured ; transcription of target genes was measured in peripheral blood mononuclear cells .  Resveratrol pharmacokinetics and safety were assessed . RESULTS Eight-week administration of resveratrol did not reduce insulin resistance , steatosis , or abdominal fat distribution when compared with baseline . No change was observed in plasma lipids or antioxidant activity . Levels of alanine and aspartate aminotransferases increased significantly among patients in the resveratrol group until week 6 when compared with the placebo group . Resveratrol did not significantly alter transcription of NQO1 , PTP1B , IL6 , or HO1 in peripheral blood mononuclear cells . Resveratrol was well-tolerated . CONCLUSIONS Eight weeks administration of resveratrol did not significantly improve any features of NAFLD , compared with placebo , but it increased hepatic stress , based on observed increases in levels of liver enzymes . Further studies are needed to determine whether agents that are purported to mimic calorie restriction , such as resveratrol , are safe and effective for complications of obesity . Clinical trials registration no : ACTRN12612001135808 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 We previously found that lipoic acid ( LA ) improved high-fat diet (HFD)-induced dyslipidemia in rats . To eluci date the molecular mechanisms of that effect , we carried out experiments aim ed at analyzing biochemical parameters and gene expression profiles . METHODS C57BL/6 mice were r and omly assigned to one of three groups ( n = 8) . The control group consumed an ordinary diet ( 4.89 % fat , w/w ) . The other two experimental groups were fed with an HFD ( 21.45 % fat , w/w ) or an HFD plus 0.1 % LA . After 6 wk , plasma lipid level and antioxidant status were examined . To investigate the molecular mechanisms underlying the effects of LA on lipid metabolism and oxidative stress , we examined gene expression profiles in liver using the GeneChip microarray system . The differential expression of genes of interest identified by microarray technique was vali date d by real-time reverse transcription-polymerase chain reaction . RESULTS HFD result ed in significant alterations in lipid profiles and a depressed antioxidant defense system .  LA supplementation induced decreases in lipid peroxidation , plasma cholesterol , triacylglycerols , and low-density lipoprotein cholesterol and an increase in high-density lipoprotein in HFD-fed mice . DNA microarray analysis of the liver showed that LA ingestion upregulated the expression of genes related to beta-oxidation and free radical scavenger enzymes , whereas those involved in cholesterol synthesis were downregulated . CONCLUSION LA can prevent HFD-induced dyslipidemia by modulating lipid metabolism , especially by increasing beta-oxidation and decreasing cholesterol synthesis , and oxidative stress by increasing those of free radical scavenger enzyme gene expression OBJECTIVES : Nonalcoholic steatohepatitis ( NASH ) is a known metabolic disorder of the liver . No treatment has been conclusively shown to improve NASH or prevent disease progression . The function of L-carnitine to modulate lipid profile , glucose metabolism , oxidative stress , and inflammatory responses has been shown . The aim of this study was to evaluate the effects of L-carnitine 's supplementation on regression of NASH . METHODS : In patients with NASH and control subjects , we r and omly dispensed one 1-g L-carnitine tablet after breakfast plus diet and one 1 g tablet after dinner plus diet for 24 weeks or diet alone at the same dosage and regimen . We evaluated liver enzymes , lipid profile , fasting plasma glucose , C-reactive protein ( CRP ) , tumor necrosis factor (TNF)-α , homeostasis model assessment (HOMA)-IR , body mass index , and histological scores . RESULTS : At the end of the study , L-carnitine-treated patients showed significant improvements in the following parameters : aspartate aminotransferase ( P=0.000 ) , alanine aminotransferase ( ALT ) ( P=0.000 ) , γ-glutamyl-transpeptidase ( γ-GT ) ( P=0.000 ) , total cholesterol ( P=0.000 ) , low-density lipoprotein ( LDL ) ( P=0.000 ) , high-density lipoprotein ( HDL ) ( P=0.000 ) , triglycerides ( P=0.000 ) , glucose ( P=0.000 ) , HOMA-IR ( P=0.000 ) , CRP ( P=0.000 ) , TNF-α ( P=0.000 ) , and histological scores ( P=0.000 ) . CONCLUSIONS : L-carnitine supplementation to diet is useful for reducing TNF-α and CRP , and for improving liver function , glucose plasma level , lipid profile , HOMA-IR , and histological manifestations of NASH 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 OBJECTIVES The aim of this study was to explore the effect of resveratrol supplementation on lipid profile in individuals with dyslipidemia . METHODS Apparently healthy men and non-pregnant women 20 to 65 y of age with new diagnosis of dyslipidemia were enrolled in a r and omized double-blind , placebo-controlled trial and r and omly allocated to receive either resveratrol 100 mg/d or placebo ( sucrose 0.5 g/d ) for 2 mo . Smoking , alcohol intake , diabetes , acute or chronic renal or hepatic diseases , malignancy , cardiovascular disease , serum triacylglycerol levels ≥400 mg/dL , low-density lipoprotein cholesterol levels ≥190 mg/dL , and consumption of lipid-lowering drugs or supplements containing resveratrol were exclusion criteria . RESULTS Seventy-one individuals with new diagnosis of dyslipidemia were enrolled and r and omly allocated to the resveratrol ( n = 35 ) or placebo groups ( n = 36 ) . At baseline , there were no significant differences between the study groups . After intervention period , individuals in the resveratrol group showed a significant decrease in total cholesterol ( 201.4 ± 34.4 versus 220.6 ± 37.4 , P = 0.04 ) and triacylglycerol ( 133.4 ± 55.3 versus 166.7 ± 68.5 , P = 0.04 ) concentrations compared with the placebo group , without significant statistical differences for high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels . CONCLUSION The results suggest that resveratrol supplementation significantly reduces total cholesterol and triacylglycerol concentrations in individuals with dyslipidemia Background Vitamin A has different functions in the body and after being converted to acid form ; it can play many roles in immune system regulation . Therefore , this vitamin can be used as a supplement in the treatment of diseases , such as cancer and autoimmune diseases . Vitamin A is a fat-soluble compound and its long-term consumption in high doses can have some adverse effects . Objective The current study aim ed to investigate the possible complications and find solutions to minimize the adverse effects . Patients and Methods This study was a double blind r and omized clinical trial . In the main study , vitamin A ( as retinyl palmitate ) was given to 35 multiple sclerosis ( MS ) patients in order to regulate their immune system with a dose of 25000 IU/day for a period of six months . To investigate the possible biochemical complications , lipid profiles , fasting blood sugar ( FBS ) , liver enzymes , and C-reactive protein ( CRP ) were tested . Results Vitamin A did not have a significant difference in lipid profiles , FBS and liver enzymes between the two groups receiving vitamin A and the placebo , but CRP increased in patients who were taking vitamin A , 1.65±0.43 ( mg/L ) and 2.88±0.67 , ( Mean±SEM ) , before and after the intervention respectively ( P=0.029 ) , and statistical analysis showed significant differences with the group receiving placebo ( P=0.011 ) and CRP level  in vitamin A group was 1.3 mg/L more than those of the placebo group after intervention ( P=0.011 ) . Conclusions Considering that no significant difference was found in the proven vitamin A side effects , due to the increase in CRP , frequent clinical and biochemical controls are required along with vitamin A supplementation OBJECTIVE Evidence indicates that NAFLD patients are vitamin D deficient . Vitamin D has new roles in lipid and glucose metabolism . The aim of this study was to examine the effects of calcitriol supplementation on the NAFLD progression based on liver lipid accumulation , serum lipid profile and insulin resistance . METHODS We r and omly assigned 73 patients with NAFLD-confirmed by ultra-sonography to 12 weeks of treatment with hypocaloric diet ( reduction of 500 kcal per day ) plus 25 µg of calcitriol supplement or a hypocaloric diet plus placebo . Before and after treatment , we assessed anthropometric parameters , grade of fatty liver , serum lipoproteins , liver enzymes and insulin level . RESULT Baseline variables were not significantly different between groups . A statistically significant reduction in anthropometric measures was observed over the 12 weeks in both groups . However , no significant differences were seen between groups after intervention . Compared with the placebo , reductions in triglyceride and an increase in HDL cholesterol were seen over the 12 weeks of intervention in the calcitriol group ( P = 0.002 and P = 0.004 ) . AST level was decreased in the calcitriol group ( -4.2 ± 4.3 µmol/L , P < 0.001 ) , but increased in the placebo group ( 12.6 ± 6.1 µmol/L , P = 0.02 ) after 12 weeks . Reductions in mean difference of ALT , insulin and HOMA were significantly higher in the calcitriol than placebo group ( P = 0.01 , P = 0.007 and 0.01 ) . CONCLUSIONS Calcitriol supplementation combined with weight loss diet showed no significant effects on anthropometric measures in NAFLD patients . However , it may have positive effects on lipid profile , liver enzyme tests and insulin sensitivity during a weight-loss program We performed the largest r and omized , placebo‐controlled clinical trial to date ( N = 112 , 12‐week intervention ) to investigate the effects and safety of resveratrol supplementation on liver fat content and cardiometabolic risk parameters in overweight and obese and insulin‐resistant subjects . At baseline the variability in liver fat content was very large , ranging from 0.09 % to 37.55 % ( median , 7.12 % ; interquartile range , 3.85%‐12.94 % ) . Mean ( SD ) liver fat content was 9.22 ( 6.85 ) % in the placebo group and 9.91 ( 7.76 ) % in the resveratrol group . During the study liver fat content decreased in the placebo group ( −0.7 % ) but not in the resveratrol group ( −0.03 % ) ( differences between groups : P = .018 for the intention‐to‐treat [ ITT ] population ; N = 54 , resveratrol , N = 54 , placebo and P = .0077 for the per protocol [ PP ] population ) . No effects  of resveratrol supplementation on cardiometabolic risk parameters were observed . Resveratrol supplementation was well tolerated and safe 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 OBJECTIVE To determine whether resveratrol supplementation can improve insulin sensitivity and promote overall metabolic health on top of st and ard diabetes care . RESEARCH DESIGN AND METHODS Seventeen subjects with well-controlled type 2 diabetes ( T2D ) were treated with placebo and 150 mg/day resveratrol ( resVida ) in a r and omized double-blind crossover study for 30 days . The main outcome measure was insulin sensitivity by the hyperinsulinemic-euglycemic clamp technique . RESULTS Hepatic and peripheral insulin sensitivity were not affected by resveratrol treatment . Intrahepatic lipid content also remained unaffected by resveratrol ; however , the change in intrahepatic lipid content correlated negatively with plasma resveratrol levels ( R = −0.68 , P = 0.03 ) . Intramyocellular lipid content increased in type 2 muscle fibers ( P = 0.03 ) , and systolic blood pressure tended to decrease ( P = 0.09 ) upon resveratrol treatment . In addition , resveratrol significantly improved ex vivo mitochondrial function ( state 3 and state U respiration upon malate with octanoyl-carnitine , P < 0.005 ) . Intriguingly , a correlation was found between plasma levels of a metabolite of resveratrol  ( dihydroresveratrol ) and the metformin dose used by the patients ( R = 0.66 , P = 0.005 ) , suggesting an interaction between metformin and resveratrol . It could be speculated that the lack of a  resveratrol-induced insulin-sensitizing effect is caused by this interaction . CONCLUSIONS Resveratrol supplementation does not improve hepatic or peripheral insulin sensitivity . Our results question the generalized value of resveratrol as an add-on therapy in the treatment of T2D and emphasize the need to perform studies in drug-naive patients with T2D or subjects with prediabetes OBJECTIVE Smokers are characterized by a low- grade systemic inflammatory state and an oxidant-antioxidant imbalance . Few human studies were conducted on the effects of resveratrol , a natural compound with anti-inflammatory and antioxidant properties , and no trial on smokers has been performed to date . We evaluated whether resveratrol has beneficial effects on markers of inflammation and oxidative stress in smokers . METHODS AND RESULTS A r and omized , double- blind , cross-over trial was performed in 50 healthy adult smokers : 25 were r and omly allocated to " resveratrol-first " ( 30-days : 500 mg resveratrol/day , 30-days wash-out , 30-days placebo ) and 25 to " placebo-first " ( 30-days placebo , 30-days wash-out , 30-days 500 mg resveratrol/day ) . Resveratrol significantly reduced C-reactive protein ( CRP ) and triglyceride concentrations , and increased Total Antioxidant Status ( TAS ) values . After analyzing data with general linear models to assess period and carry-over effects , the ratios of the values after resveratrol to those after placebo were respectively : 0.47 ( 95%CI 0.38 - 0.59 ) -CRP- and 0.71 ( 95%CI 0.65 - 0.78 ) -triglycerides- , while TAS increased by 74.2 μmol/L ( 95%CI 60.8 - 87.6 ) . Uric acid , glucose , insulin , cholesterol , liver enzyme concentrations , and weight , waist circumference , and blood pressure values did not significantly change after resveratrol supplementation . CONCLUSIONS Because resveratrol has anti-inflammatory , anti-oxidant , and hypotriglyceridemic effects , its supplementation may beneficially affect the increased cardiovascular risk of healthy smokers 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 BACKGROUND The obese insulin-resistant state is characterized by impairments in lipid metabolism . We previously showed that 3-d supplementation of combined epigallocatechin-3-gallate and resveratrol ( EGCG+RES ) increased energy expenditure and improved the capacity to switch from fat toward carbohydrate oxidation with a high-fat mixed meal ( HFMM ) test in men . OBJECTIVE The present study aim ed to investigate the longer-term effect of EGCG+RES supplementation on metabolic profile , mitochondrial capacity , fat oxidation , lipolysis , and tissue-specific insulin sensitivity . DESIGN In this r and omized double-blind study , 38 overweight and obese subjects [ 18 men ; aged 38 ± 2 y ; body mass index ( kg/m(2 ) ) : 29.7 ± 0.5 ] received either EGCG+RES ( 282 and 80 mg/d , respectively ) or placebo for 12 wk . Before and after the intervention , oxidative capacity and gene expression were assessed in skeletal muscle . Fasting and postpr and ial ( HFMM ) lipid metabolism was assessed by using indirect calorimetry , blood sampling , and microdialysis . Tissue-specific insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp with [6,6-(2)H2]-glucose infusion . RESULTS EGCG+RES supplementation did not affect the fasting plasma metabolic profile . Although whole-body fat mass was not affected , visceral adipose tissue mass tended to decrease after the intervention compared with placebo ( P-time × treatment = 0.09 ) . EGCG+RES supplementation significantly increased oxidative capacity in permeabilized muscle fibers ( P-time × treatment < 0.05 , P-EGCG+RES < 0.05 ) . Moreover , EGCG+RES  reduced fasting ( P-time × treatment = 0.03 ) and postpr and ial respiratory quotient ( P-time × treatment = 0.01 ) compared with placebo . Fasting and postpr and ial fat oxidation was not significantly affected by EGCG+RES ( P-EGCG+RES = 0.46 and 0.38 , respectively ) but declined after placebo ( P-placebo = 0.05 and 0.03 , respectively ) . Energy expenditure was not altered ( P-time × treatment = 0.96 ) . Furthermore , EGCG+RES supplementation attenuated the increase in plasma triacylglycerol concentrations during the HFMM test that was observed after placebo ( P-time × treatment = 0.04 , P-placebo = 0.01 ) . Finally , EGCG+RES had no effect on insulin-stimulated glucose disposal , suppression of endogenous glucose production , or lipolysis . CONCLUSION Twelve weeks of EGCG+RES supplementation increased mitochondrial capacity and stimulated fat oxidation compared with placebo , but this did not translate into increased tissue-specific insulin sensitivity in overweight and obese subjects . This trial was registered at clinical trials.gov as NCT02381145 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 CONTEXT Polycystic ovary syndrome ( PCOS ) is the most common endocrinopathy affecting women of reproductive age . Hyper and rogenism is the central feature of PCOS . Studies on isolated ovarian theca-interstitial cells suggest that resveratrol , a natural polyphenol , reduces and rogen production . OBJECTIVE This study was design ed to evaluate endocrine and metabolic effects of resveratrol on PCOS . DESIGN AND SETTING This was a r and omized ( 1:1 ) double-blind , placebo-controlled trial that evaluated the effects of resveratrol over a period of 3 months in an academic hospital . PATIENTS AND OTHER PARTICIPANTS Subjects with PCOS were identified according to the Rotterdam criteria . Thirty-four subjects were enrolled and 30 subjects completed the trial . Evaluations were performed at baseline and repeated after 3 months of treatment . INTERVENTION Resveratrol ( 1,500 mg p.o . ) or placebo were administered daily . MAIN OUTCOME MEASURE Primary outcome was the change in the serum total T. RESULTS Resveratrol treatment led to a significant decrease of total T by 23.1 % ( P = .01 ) . In parallel , resveratrol induced a 22.2 % decrease of dehydroepi and rosterone sulfate ( P = .01 ) , a decrease of fasting insulin level by 31.8 % ( P = .007 ) and an increase of the Insulin Sensitivity Index ( Matsuda and DeFronzo ) by 66.3 % ( P = .04 ) . Levels of gonadotropins , the lipid profile as well as markers of inflammation and endothelial function were not significantly altered . CONCLUSIONS Resveratrol significantly reduced ovarian and adrenal and rogens . This effect may be , at least in part , related to an improvement of insulin sensitivity and a decline of insulin level Polyphenolic compounds , such as resveratrol , have recently received widespread interest because of their ability to mimic effects of calorie restriction . The objective of the present study was to gain more insight into the effects of 30 days resveratrol supplementation on adipose tissue morphology and underlying processes . Eleven healthy obese men were supplemented with placebo and resveratrol for 30 days ( 150 mg per day ) , separated by a 4-week washout period in a double-blind r and omized crossover design . A postpr and ial abdominal subcutaneous adipose tissue biopsy was collected to assess adipose tissue morphology and gene expression using microarray analysis . Resveratrol significantly decreased adipocyte size , with a shift toward a reduction in the proportion of large and very-large adipocytes and an increase in small adipocytes . Microarray analysis revealed downregulation of Wnt and Notch signaling pathways and upregulation of pathways involved in cell cycle regulation after resveratrol supplementation , suggesting enhanced adipogenesis . Furthermore , lysosomal/phagosomal pathway and transcription factor EB were upregulated reflecting an alternative pathway of lipid breakdown by autophagy . Further research is necessary to investigate whether resveratrol improves adipose tissue function
This meta- analysis demonstrated that resveratrol supplementation among patients with MetS and related disorders  significantly reduced total cholesterol and increased GGT concentrations , but did not affect triglycerides , LDL- , HDL-cholesterol , ALT , and AST concentrations .
This data suggests that resveratrol may have a potential cardio-protective effect in patients with MetS and related disorders
There are current trials investigating the effect of resveratrol supplementation on lipid profiles and liver enzymes among patients with metabolic syndrome ( MetS ) and related disorders ; however , their findings are controversial .
This systematic review and meta- analysis were aim ed to determine the effects of resveratrol supplementation on lipid profiles and liver enzymes among patients with MetS and related disorders .