human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Our aim was to test , through a crossover , double-blind , placebo-controlled r and omized clinical trial , if a short-term treatment with 10 mg monacolins combined with antioxidants could improve lipid pattern , high-sensitivity C-reactive protein ( hs-CRP ) , and endothelial function in a small cohort of moderately hypercholesterolemic subjects . Thus , 25 healthy , moderately hypercholesterolemic subjects were consecutively enrolled and , after 4 weeks of stabilization diet , were r and omized to the sequence placebo followed by a washout , monacolins or monacolins followed by a washout , placebo , with each period being 4 weeks long . At each study step , a complete lipid pattern , safety parameters , hs-CRP , and endothelial function have been measured . When compared to the placebo phase , during monacolin treatment , patients experienced a more favorable percentage change in total cholesterol ( TC ) ( TC after monacolin treatment , −18.35 % ; TC after placebo treatment , −5.39 % ) , low-density lipoprotein cholesterol ( LDL-C ) ( LDL after monacolin treatment , −22.36 % ; LDL after placebo treatment , −1.38 % ) , non-high-density lipoprotein cholesterol ( HDL-C ) ( non-HDL after monacolin treatment , −22.83 % ; non-HDL after placebo treatment : −7.15 % ) , hs-CRP ( hs-CRP after monacolin treatment : −2.33 % ; hs-CRP after placebo treatment , 2.11 % ) , and endothelial function ( pulse volume displacement after monacolin treatment , 18.59 % ; pulse volume displacement after placebo treatment , −6.69 % ) . No significant difference was observed with regard to triglycerides , HDL-cholesterol , and safety parameters . On the basis of our data , we could demonstrate that a 10 mg monacolin nutraceutical treatment appears to safely reduce cholesterolemia , hs-CRP , and markers of vascular remodeling in moderately hypercholesterolemic subjects . These results need to be confirmed in larger patient sample s and in studies with longer duration 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 Abstract Background and Aims Nonalcoholic fatty liver disease is epidemiologically associated with hepatic and metabolic disorders . The aim of this study was to examine whether hepatic fat accumulation has a causal role in determining liver damage and insulin resistance . Methods We performed a Mendelian r and omization analysis using risk alleles in PNPLA3 , TM6SF2 , GCKR and MBOAT7 , and a polygenic risk score for hepatic fat , as instruments . We evaluated complementary cohorts of at‐risk individuals and individuals from the general population : 1515 from the liver biopsy cohort ( LBC ) , 3329 from the Swedish Obese Subjects Study ( SOS ) and 4570 from the population ‐based Dallas Heart Study ( DHS ) . Results Hepatic fat was epidemiologically associated with liver damage , insulin resistance , dyslipidemia and hypertension . The impact of genetic variants on liver damage was proportional to their effect on hepatic fat accumulation . Genetically determined hepatic fat was associated with aminotransferases , and with inflammation , ballooning and fibrosis in the LBC . Furthermore , in the LBC , the causal association between hepatic fat and fibrosis was independent of disease activity , suggesting that a causal effect of long‐term liver fat accumulation on liver disease is independent of inflammation . Genetically determined hepatic steatosis was associated with insulin resistance in the LBC and SOS . However , this association was dependent on liver damage severity . Genetically determined hepatic steatosis was associated with liver fibrosis/cirrhosis and with a small increase in risk of type 2 diabetes in publicly available data bases . Conclusion These data suggest that long‐term hepatic fat accumulation plays a causal role in the development of chronic liver disease 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 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 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 BACKGROUND Case-control studies have reported that patients with ischemic heart disease ( IHD ) have a higher proportion of small , dense LDL particles than do healthy control subjects . The extent to which the risk attributed to small LDL particles may be independent of concomitant variations in plasma lipoprotein-lipid concentrations remains to be clearly determined , however , particularly through prospect i ve studies . METHODS AND RESULTS Baseline characteristics were obtained in 2103 men initially free of IHD , among whom 114 developed IHD during a 5-year follow-up period . These 114 case patients were matched with healthy control subjects for age , body mass index , smoking habits , and alcohol intake . LDL peak particle diameter ( PPD ) was measured a posteriori in 103 case-control 
    Output:
    
agent
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
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: 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 Our aim was to test , through a crossover , double-blind , placebo-controlled r and omized clinical trial , if a short-term treatment with 10 mg monacolins combined with antioxidants could improve lipid pattern , high-sensitivity C-reactive protein ( hs-CRP ) , and endothelial function in a small cohort of moderately hypercholesterolemic subjects . Thus , 25 healthy , moderately hypercholesterolemic subjects were consecutively enrolled and , after 4 weeks of stabilization diet , were r and omized to the sequence placebo followed by a washout , monacolins or monacolins followed by a washout , placebo , with each period being 4 weeks long . At each study step , a complete lipid pattern , safety parameters , hs-CRP , and endothelial function have been measured . When compared to the placebo phase , during monacolin treatment , patients experienced a more favorable percentage change in total cholesterol ( TC ) ( TC after monacolin treatment , −18.35 % ; TC after placebo treatment , −5.39 % ) , low-density lipoprotein cholesterol ( LDL-C ) ( LDL after monacolin treatment , −22.36 % ; LDL after placebo treatment , −1.38 % ) , non-high-density lipoprotein cholesterol ( HDL-C ) ( non-HDL after monacolin treatment , −22.83 % ; non-HDL after placebo treatment : −7.15 % ) , hs-CRP ( hs-CRP after monacolin treatment : −2.33 % ; hs-CRP after placebo treatment , 2.11 % ) , and endothelial function ( pulse volume displacement after monacolin treatment , 18.59 % ; pulse volume displacement after placebo treatment , −6.69 % ) . No significant difference was observed with regard to triglycerides , HDL-cholesterol , and safety parameters . On the basis of our data , we could demonstrate that a 10 mg monacolin nutraceutical treatment appears to safely reduce cholesterolemia , hs-CRP , and markers of vascular remodeling in moderately hypercholesterolemic subjects . These results need to be confirmed in larger patient sample s and in studies with longer duration 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 Abstract Background and Aims Nonalcoholic fatty liver disease is epidemiologically associated with hepatic and metabolic disorders . The aim of this study was to examine whether hepatic fat accumulation has a causal role in determining liver damage and insulin resistance . Methods We performed a Mendelian r and omization analysis using risk alleles in PNPLA3 , TM6SF2 , GCKR and MBOAT7 , and a polygenic risk score for hepatic fat , as instruments . We evaluated complementary cohorts of at‐risk individuals and individuals from the general population : 1515 from the liver biopsy cohort ( LBC ) , 3329 from the Swedish Obese Subjects Study ( SOS ) and 4570 from the population ‐based Dallas Heart Study ( DHS ) . Results Hepatic fat was epidemiologically associated with liver damage , insulin resistance , dyslipidemia and hypertension . The impact of genetic variants on liver damage was proportional to their effect on hepatic fat accumulation . Genetically determined hepatic fat was associated with aminotransferases , and with inflammation , ballooning and fibrosis in the LBC . Furthermore , in the LBC , the causal association between hepatic fat and fibrosis was independent of disease activity , suggesting that a causal effect of long‐term liver fat accumulation on liver disease is independent of inflammation . Genetically determined hepatic steatosis was associated with insulin resistance in the LBC and SOS . However , this association was dependent on liver damage severity . Genetically determined hepatic steatosis was associated with liver fibrosis/cirrhosis and with a small increase in risk of type 2 diabetes in publicly available data bases . Conclusion These data suggest that long‐term hepatic fat accumulation plays a causal role in the development of chronic liver disease 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 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 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 BACKGROUND Case-control studies have reported that patients with ischemic heart disease ( IHD ) have a higher proportion of small , dense LDL particles than do healthy control subjects . The extent to which the risk attributed to small LDL particles may be independent of concomitant variations in plasma lipoprotein-lipid concentrations remains to be clearly determined , however , particularly through prospect i ve studies . METHODS AND RESULTS Baseline characteristics were obtained in 2103 men initially free of IHD , among whom 114 developed IHD during a 5-year follow-up period . These 114 case patients were matched with healthy control subjects for age , body mass index , smoking habits , and alcohol intake . LDL peak particle diameter ( PPD ) was measured a posteriori in 103 case-control 
    Output:
    