Effects of resveratrol and methylprednisolone on biochemical, neurobehavioral and histopathological recovery after experimental spinal cord injury Placebo-controlled, randomised clinical trial: high-dose resveratrol treatment for non-alcoholic fatty liver disease Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Effects of 6 months of resveratrol versus placebo on pentraxin 3 in patients with type 2 diabetes mellitus: a double-blind randomized controlled trial 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. Alterations of antioxidant status in asymptomatic hypercholesterolemic individuals after resveratrol intake Trans-Resveratrol Alters Mammary Promoter Hypermethylation in Women at Increased Risk for Breast Cancer The effects of 30 days resveratrol supplementation on adipose tissue morphology and gene expression patterns in obese men
Abstract Aim : To investigate the neuroprotective effect of resveratrol in an experimental spinal cord injury ( SCI ) model in rats . Methods : Male Wistar albino rats weighing 200–250 g were r and omized into six groups . Weight-drop trauma was performed for SCI . Group 1 underwent laminectomy alone . Group 2 underwent laminectomy followed by SCI . Groups 3 , 4 , 5 , and 6 underwent laminectomy followed by SCI and received resveratrol ( 100 mg/kg ) , methylprednisolone ( MP ) ( 30 mg/kg ) , resveratrol ( 100 mg/kg ) plus MP ( 30 mg/kg ) , and ethanol ( 2 % ) , respectively . The rats were divided into two subgroups for biochemical analysis ( killed at 24 h after surgery ) and for neurobehavioral and histopathological evaluation ( killed at 6 weeks after surgery ) . Posttraumatic neurological recovery after surgery was recorded weekly . Results : Groups 3 and 5 revealed significantly lower malondialdehyde , nitric oxide , xanthine oxidase , and higher glutathione levels than group 4 ( P<0.05 ) . Neurological recovery rates were significantly better in groups 3 and 5 than group 4 ( P<0.05 ) . When spinal trauma size ratios were compared , there was no significant difference between treatment groups . Conclusion : Resveratrol treatment revealed better biochemical recovery in the acute stage of trauma than MP treatment . Although resveratrol and combined treatment revealed better neurobehavioral recovery than MP treatment ; resveratrol , MP , and combined treatment modalities improved histopathological recovery at the same level in the final stage of the experiment . Future studies involving different doses of resveratrol and different doses combinations with MP could promise better results as each drug has a different anti-oxidative mechanism of action 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 Although resveratrol has widely been studied for its potential health benefits , little is known about its metabolic effects in humans . Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action . After an initial general examination ( including blood chemistry ) , nineteen patients enrolled in the 4-week-long double-blind study were r and omly assigned into two groups : a resveratrol group receiving oral 2 × 5 mg resveratrol and a control group receiving placebo . Before and after the second and fourth weeks of the trial , insulin resistance/sensitivity , creatinine-normalised ortho-tyrosine level in urine sample s ( as a measure of oxidative stress ) , incretin levels and phosphorylated protein kinase B (pAkt):protein kinase B ( Akt ) ratio in platelets were assessed and statistically analysed . After the fourth week , resveratrol  significantly decreased insulin resistance ( homeostasis model of assessment for insulin resistance ) and urinary ortho-tyrosine excretion , while it increased the pAkt : Akt ratio in platelets . On the other h and , it had no effect on parameters that relate to β-cell function ( i.e. homeostasis model of assessment of β-cell function ) . The present study shows for the first time that resveratrol  improves insulin sensitivity in humans , which might be due to a resveratrol-induced  decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway 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 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 Abstract High cholesterol is one of the risk factors for atherogenesis , leading to oxidative stress and cardiovascular disease ( CVD ) . The focus of this study was to evaluate the role and the pathways of action of a natural antioxidant , resveratrol , in asymptomatic hypercholesterolemic ( AHC ) individuals . Forty healthy AHCs and normocholesterolemics ( NCs ) participated in the study . They received r and om-order resveratrol and placebo capsules for four weeks . Total antioxidant capacity ( TAC ) , vitamin E and total cholesterol ( TC ) were measured at baseline and at the end of each intervention . Resveratrol provided a direct antioxidant effect in healthy NC individuals , but in AHC individuals , with a higher dem and for antioxidant activity due to higher cholesterol levels , it acted by facilitating an increase in vitamin E. Our findings suggest that resveratrol acts synergistically with other antioxidants against oxidative stress and highlights the importance of hypercholesterolemic individuals consuming natural antioxidants instead of medications to reduce the risk of CVD , while the situation is still reversible Trans-resveratrol , present in high concentration in the skin of red grapes and red wine , has a dose-dependent antiproliferative effect in vitro , prevents the formation of mammary tumors , and has been touted as a chemopreventive agent . Based upon in vitro studies demonstrating that trans-resveratrol downregulates the expression of 1 ) DNA methyltransferases and 2 ) the cancer promoting prostagl and in (PG)E2 , we determined if trans-resveratrol had a dose-related effect on DNA methylation and prostagl and in expression in humans . Thirty-nine adult women at increased breast cancer risk were r and omized in double-blind fashion to placebo , 5 or 50 mg trans-resveratrol twice daily for 12 wk . Methylation assessment of 4 cancer-related genes ( p16 , RASSF-1α , APC , CCND2 ) was performed on mammary ductoscopy specimens . The predominant resveratrol species in serum was the glucuronide metabolite . Total trans-resveratrol and glucuronide metabolite serum levels increased after consuming both trans-resveratrol doses ( P < .001 for both ) . RASSF-1α methylation decreased with increasing levels of serum trans-resveratrol ( P = .047 ) . The change in RASSF-1α methylation was directly related to the change in PGE2 ( P = .045 ) . This work provides novel insights into the effects of trans-resveratrol on the breast of women at increased breast cancer risk , including a decrease in methylation of the tumor suppressor gene RASSF-1α . Because of the limited sample size , our findings should be vali date d in a larger study 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
Resveratrol  significantly improves adiponectin but does not affect leptin concentrations .
Abstract The results of human clinical trials have revealed that the effects of resveratrol on adipokines are inconsistent .