title: Management of fatty liver disease with vitamin E and C compared to ursodeoxycholic acid treatment. Vitamin D supplementation for the treatment of non-alcoholic fatty liver disease: A randomized double blind placebo controlled trial. Intakes of magnesium, calcium and risk of fatty liver disease and prediabetes. Does vitamin D improve liver enzymes, oxidative stress, and inflammatory biomarkers in adults with non-alcoholic fatty liver disease? A randomized clinical trial Atorvastatin and Antioxidants for the Treatment of Nonalcoholic Fatty Liver Disease: The St Francis Heart Study Randomized Clinical Trial Efficacy of docosahexaenoic acid-choline-vitamin E in paediatric NASH: a randomized controlled clinical trial. Lifestyle intervention and antioxidant therapy in children with nonalcoholic fatty liver disease: a randomized, controlled trial. A pilot study of vitamin E versus vitamin E and pioglitazone for the treatment of nonalcoholic steatohepatitis. Vitamin E and vitamin C treatment improves fibrosis in patients with nonalcoholic steatohepatitis Effect of vitamin E or metformin for treatment of nonalcoholic fatty liver disease in children and adolescents: the TONIC randomized controlled trial. Antioxidant supplements reduced oxidative stress and stabilized liver function tests but did not reduce inflammation in a randomized controlled trial in obese children and adolescents. A Randomized Controlled Trial of Metformin versus Vitamin E or Prescriptive Diet in Nonalcoholic Fatty Liver Disease Effect of lifestyle intervention on non-alcoholic fatty liver disease in Chinese obese children. Vitamin E Treatment in Pediatric Obesity-Related Liver Disease: A Randomized Study Regression of Nonalcoholic Fatty Liver Disease with Zinc and Selenium Co-supplementation after Disease Progression in Rats Zinc and Selenium Co-supplementation Reduces Some Lipid Peroxidation and Angiogenesis Markers in a Rat Model of NAFLD-Fed High Fat Diet Ursodeoxycholic acid with vitamin E in patients with nonalcoholic steatohepatitis: long-term results. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. Randomized placebo-controlled trial of ursodeoxycholic acid with vitamin e in nonalcoholic steatohepatitis. Plasma transforming growth factor-beta1 level and efficacy of alpha-tocopherol in patients with non-alcoholic steatohepatitis: a pilot study. Vitamin E supplementation, superoxide dismutase status, and outcome of scaling and root planing in patients with chronic periodontitis: a randomized clinical trial.
abstract: BACKGROUND / AIMS Despite a proposed role of oxidative stress in the pathogenesis of nonalcoholic steatohepatitis , antioxidant approaches have not been investigated sufficiently in the therapy of nonalcoholic steatohepatitis . Our aim was to determine whether vitamin E plus C therapy is effective in normalization of liver enzymes compared to ursodeoxycholic acid treatment in patients with fatty liver disease . METHODS This was an open-labeled , prospect i ve , r and omized study enrolling patients with histologically proven fatty liver disease who had chronically elevated alanine aminotransferase , despite a three-month reducing diet . Patients consuming alcohol ( more than 20 g/day ) were excluded . The patients were r and omly prescribed either oral vitamin E ( 600 IU/day ) plus vitamin C ( 500 mg/day ) or ursodeoxycholic acid ( 10 mg/kg/day ) . Patients were r and omized as two groups to receive vitamin E plus vitamin C combination ( 28 patients , 10 F ) or ursodeoxycholic acid treatment ( 29 patients , 13 F ) . RESULTS There was no significant change in body mass index before and after the treatment in both groups . At the end of six months of therapy , serum aspartate aminotransferase and aminotransferase levels significantly decreased in both treatment options . Vitamin E and C combination was more efficacious on serum aminotransferase levels than ursodeoxycholic acid , but the difference was not significant . Alanine aminotransferase decreased to normal levels in 17 of 27 ( 63 % ) and in 16 of 29 patients ( 55 % ) , respectively , in the two groups . Gamma-glutamyl transpeptidase decreased in patients receiving ursodeoxycholic acid , but no change was obtained in the vitamin-treated patients . CONCLUSIONS Vitamin E plus C combination treatment is a safe , inexpensive and effective treatment option in patients with fatty liver disease , with results comparable to those obtained with ursodeoxycholic acid . Since more effective new therapeutic options are lacking , patients with fatty liver disease should be encouraged to take vitamin E and C supplements , which are safe and affordable BACKGROUND Low serum vitamin D has been associated with metabolic syndrome and Non-alcoholic fatty liver disease ( NAFLD ) . This study aim ed to investigate the impact of vitamin D supplementation in treatment of patients with NAFLD . METHODS In a double blind , r and omized ,  placebo  controlled trial patients with NAFLD were r and omized to receive one weekly pearl of placebo , 50,000 U vitamin D3 ( cholecalciferol ) pearl per week and 0.25 mg calcitriol ( 1,25 dihydroxycholecalciferol ) pearl per day for 3 months . RESULTS 106 NAFLD patients were r and omized to receive calcitriol , vitamin D3 and placebo pearls for 12 weeks and data for 91 patients were analyzed . After 12 weeks of treatment , serum alkaline phosphatase levels was significantly decreased from baseline levels in vitamin D and calcitriol treated groups ( P < 0.05 ) . Serum and gamma glutamyl transferase ( GGT ) level was also significantly decreased compared to the baseline levels after 12 weeks of treatment with vitamin D. There was no statistically significant difference between placebo , calcitriol , vitamin D groups in terms of serum aminotransferase , alkaline phosphatase , serum GGT and lipid profile ( P > 0.05 ) . CONCLUSION While significant reduction of serum alkaline phosphatase and GGT were seen with vitamin D and calcitriol supplementation from baseline levels , no beneficial effects was seen when comparing vitamin D , calcitriol and placebo groups at the end of trial OBJECTIVE Obesity and insulin resistance play important roles in the pathogenesis of non-alcoholic fatty liver disease ( NAFLD ) . Mg intake is linked to a reduced risk of metabolic syndrome and insulin resistance ; people with NAFLD or alcoholic liver disease are at high risk of Mg deficiency . The present study aim ed to investigate whether Mg and Ca intakes were associated with risk of fatty liver disease and prediabetes by alcohol drinking status . DESIGN We analysed the association between  Ca or Mg intake and  fatty liver disease , prediabetes or both prediabetes and fatty liver disease in cross-sectional analyses . SETTING Third National Health and Nutrition Examination Survey ( NHANES III ) follow-up cohort of US adults . SUBJECTS Nationally representative sample of US adults in NHANES ( n 13 489 ) . RESULTS After adjusting for potential confounders , Mg intake was associated with approximately 30 % reduced odds of fatty liver disease and prediabetes , comparing the highest intake quartile v. the lowest . Mg intake may only be related to reduced odds of fatty liver disease and prediabetes in those whose Ca intake is less than 1200 mg/d . Mg intake may also only be associated with reduced odds of fatty liver disease among alcohol drinkers . CONCLUSIONS The study suggests that high intake of Mg may be associated with reduced risks of fatty liver disease and prediabetes . Further large studies , particularly prospect i ve cohort studies , are warranted to confirm the findings The aim of this study was to investigate the effects of vitamin D supplementation on serum aminotransferases , insulin resistance , oxidative stress , and inflammatory biomarkers in adult patients with non-alcoholic fatty liver disease ( NAFLD ) . Fifty-three patients with NAFLD were enrolled in a parallel , double-blind , placebo-controlled study . The patients were r and omly allocated to receive either one oral pearl consisting of 50,000 IU vitamin D3 ( n = 27 ) or a placebo ( n = 26 ) , every 14 days for 4 months . Serum aminotransferases , high-sensitive C-reactive protein ( hs-CRP ) , tumor necrosis factor α , malondialdehyde ( MDA ) , total antioxidant capacity , transforming growth factor β1 , as well as grade of hepatic steatosis and homeostasis model assessment of insulin resistance were assessed pre- and post-intervention . In patients who received vitamin D supplement compared to the controls , the median of serum 25(OH)D3 significantly increased ( 16.2 vs. 1.6 ng/ml , P < 0.001 ) . This increase accompanied by significant decrease in serum MDA ( −2.09 vs. −1.23 ng/ml , P = 0.03 ) and near significant changes in serum hs-CRP ( −0.25 vs. 0.22 mg/l , P = 0.06 ) . These between-group differences remained significant even after controlling for baseline covariates . Other variables showed no significant changes . Improved vitamin D status led to amelioration in serum hs-CRP and MDA in patients with NAFLD . This might be considered as an adjunctive therapy to attenuate systemic inflammation and lipid peroxidation alongside other treatments for NAFLD patients OBJECTIVES : Nonalcoholic fatty liver disease ( NAFLD ) is defined as the spectrum of benign fatty liver to necroinflammation and fibrosis . Its prevalence has been found to be as high as 39 % . It is estimated that up to 15 % of those affected will go on to have progressive liver disease . Currently , there is no proven therapy for NAFLD . In this study , we aim to determine whether statin therapy may be an effective treatment for NAFLD and identify independent predictors of NAFLD . METHODS : In all , 1,005 men and women , aged 50–70 years were r and omized to receive either a daily combination of atorvastatin 20 mg , vitamin C 1 g , and vitamin E 1,000 IU vs. matching placebo , as part of the St Francis Heart Study r and omized clinical trial . Liver to spleen ( LS ) ratios were calculated on 455 subjects with available computed tomography scans performed at baseline and follow-up to determine NAFLD prevalence . Baseline and final LS ratios were compared within treatment groups , and results were compared between the treatment and placebo groups using univariate and multivariate analyses . Mean duration of follow-up was 3.6 years . RESULTS : There were 80 patients with NAFLD at baseline . We identified baseline triglyceride levels ( odds ratio (OR)=1.003 , P<0.001 ) and body mass index ( OR=0.10 , P<0.001 ) as independent correlates of NAFLD . Treatment with atorvastatin combined with vitamins E and C significantly reduced the odds of NAFLD at the end of follow-up , 70 vs. 34 % ( OR=0.29 , P<0.001 ) . CONCLUSIONS : In conclusion , atorvastatin 20 mg combined with vitamins C and E is effective in reducing the odds of having hepatic steatosis by 71 % in healthy individuals with NAFLD at baseline after 4 years of active therapy Nonalcoholic steatohepatitis ( NASH ) , a progressive form of nonalcoholic fatty liver disease , is one of the most common hepatic diseases in children . We conducted a r and omized controlled clinical trial on children with biopsy-proven NASH based on a combinatorial nutritional approach compared with placebo . Participants were assigned to lifestyle modification plus placebo or lifestyle modification plus a mix containing docosahexaenoic acid , choline , and vitamin E ( DHA-CHO-VE ) .  Forty children and adolescents participated in the entire trial . The primary outcome was the improvement of liver hyperechogenicity . Secondary outcomes included alterations of alanine aminotransferase ( ALT ) and other metabolic parameters . Furthermore , changes of serum bile acids ( BA ) and plasma fibroblast growth factor 19 ( FGF19 ) levels were evaluated as inverse biomarkers of disease severity . At the end of the study , we observed a significant decrease in severe steatosis in the treatment group ( 50 % to 5 % , p = 0.001 ) . Furthermore , although the anthropometric and biochemical measurements in the placebo and DHA-CHO-VE groups were comparable at baseline , at the end of the study ALT and fasting glucose levels improved only in the treatment group . Finally , we found that BA levels were not influenced whereas FGF19 levels were significantly increased by DHA-CHO-VE . The results suggest that a combination of DHA , VE , and CHO could improve steatosis and reduce ALT and glucose levels in children with NASH . However , further studies are needed to assess the impact of a DHA and VE combination on repair of liver damage in paediatric NASH UNLABELLED No proven treatment exists for nonalcoholic fatty liver disease ( NAFLD ) in children and adolescents . We sought to determine the efficacy of lifestyle intervention with or without antioxidant therapy in pediatric NAFLD . A total of 53 patients ( age 5.7 - 18.8 years , 37 boys ) were included .  Lifestyle intervention consisting of a diet tailored to the patient 's calorie needs , and increased physical activity was prescribed in all . Patients were concomitantly r and omized to alpha-tocopherol 600 IU/day plus ascorbic acid 500 mg/day ( n = 25 ) or placebo ( n = 28 ) , and treated for 24 months . The study was an extension of a previous study aim ed at evaluating the effect of 12-month lifestyle intervention and antioxidant therapy on serum levels of aminotransferases . The primary end point of the present study was change in liver histology on repeated biopsy at 24 months . Secondary end points were changes in body weight , liver enzymes , and insulin sensitivity indices on 2-hour oral glucose tolerance test . The amount of weight lost at 24 months was similar in the placebo and antioxidant groups ( -4.75 [ range , -16 - 4.0 ] versus -5.5 [ range , -12.2 - 0.4 ] kg , respectively , P = 0.9 ) . A significant improvement occurred in the grade of steatosis , lobular inflammation , and hepatocyte ballooning , and in the NAFLD activity score in both groups . Levels of aminotransferases , triglycerides , cholesterol , fasting glucose , and insulin , and insulin sensitivity indices improved significantly as well . The improvement in all these parameters was not significantly different between the two groups . CONCLUSION Lifestyle intervention with diet and increased physical activity induces weight loss and is associated with a significant improvement in liver histology and laboratory abnormalities in pediatric NAFLD . Alpha-tocopherol plus ascorbic acid does not seem to increase the efficacy of lifestyle intervention alone BACKGROUND & AIMS Insulin resistance and oxidative stress contribute to the pathogenesis of nonalcoholic steatohepatitis ( NASH ) . We conducted a pilot study for the following reasons : ( 1 ) to test the hypothesis that a combination of an antioxidant ( vitamin E ) and an insulin sensitizer ( pioglitazone ) would be superior to vitamin E alone for the treatment of NASH , and ( 2 ) to define the effects of these interventions on insulin-sensitive metabolic functions and correlate the effects with changes in liver histology . METHODS A r and omized prospect i ve trial was performed to compare the efficacy and safety of vitamin E alone ( 400 IU/day ) vs. vitamin E ( 400 IU/day ) and pioglitazone ( 30 mg/day ) in nondiabetic , noncirrhotic subjects with NASH . Metabolic functions were assessed by a 2-step , hyperinsulinemic ( 10 and 40 mU/m2/min ) euglycemic clamp . RESULTS A total of 10 patients were r and omized to each arm . Two patients on combination therapy discontinued treatment ; one because of pregnancy and the other because of hepatotoxicity . Treatment with vitamin E only produced a significant decrease in steatosis ( mean grade , 2.2 vs. 1.4 ; P < .02 ) . Compared with baseline , combination therapy produced a significant decrease in steatosis ( mean , 2.3 vs. 1 ; P < .002 ) , cytologic ballooning ( 1.3 vs. 0.2 ; P < .01 ) , Mallory 's hyaline ( 0.7 vs. 0.2 ; P < .04 ) , and pericellular fibrosis ( 1.2 vs. 0.6 ; P < .03 ) . Although vitamin E had no significant effects , combination therapy produced a significant increase in metabolic clearance of glucose and a decrease in fasting free fatty acid ( FFA ) and insulin . The decrease in fasting FFA and insulin independently predicted improvement in hepatic steatosis and cytologic ballooning . CONCLUSIONS A combination of vitamin E and pioglitazone produces a greater improvement in NASH histology . The improvement in steatosis and cytologic ballooning are related to treatment-associated decreases in fasting FFA and insulin levels OBJECTIVE : Nonalcoholic steatohepatitis ( NASH ) is a common cause of liver disease . Although usually indolent , this disease can progress to cirrhosis in some patients . There is currently no proven medical therapy for the treatment of NASH . The aim of our study was to evaluate the efficacy of combination α-tocopherol ( vitamin E ) and vitamin C in reducing histologic inflammation and fibrosis . METHODS : This was a prospect i ve , double-blind , r and omized , placebo-controlled trial with a total enrollment of 49 patients ; 45 patients completed the study . All patients were r and omized to receive either vitamins E and C ( 1000 IU and 1000 mg , respectively ) or placebo daily for 6 months , based on their initial histologic diagnosis of NASH . Additionally , all patients were given st and ard weight-loss counseling and encouraged to follow a low fat diet ( < 30 fat g/day ) . The pre- and posttreatment liver biopsies were review ed by a single pathologist , who was blinded to the patient 's medication . Biopsies were scored based on a modification of the scoring system published by Brunt et al. ( Am J Gastroenterol 1999;94:2467–74 ) . A score of 0–4 was possible for fibrosis , and a score of 0–6 was possible for inflammation and hepatocyte degeneration and necrosis . In addition , body mass index , glycohemoglobin , lipids , and liver enzymes were followed throughout the study . RESULTS : Forty-five patients completed 6 months of therapy without significant side effects  . Vitamin treatment result ed in a statistically significant improvement in fibrosis score ( p = 0.002 ) . No changes were noted in inflammation with treatment . CONCLUSIONS : Vitamin E and vitamin C , in the doses used in this study , were well tolerated and were effective in improving fibrosis scores in NASH patients . No improvement in necroinflammatory activity or ALT was seen with this combination of drug therapy . A larger , multicenter , longer-term trial with vitamin E and vitamin C seems to be warranted CONTEXT Nonalcoholic fatty liver disease ( NAFLD ) is the most common chronic liver disease in US children and adolescents and can present with advanced fibrosis or nonalcoholic steatohepatitis ( NASH ) . No treatment has been established . OBJECTIVE To determine whether children with NAFLD would improve from therapeutic intervention with vitamin E or metformin . DESIGN , SETTING , AND PATIENTS R and omized , double-blind , double-dummy , placebo-controlled clinical trial conducted at 10 university clinical research centers in 173 patients ( aged 8 - 17 years ) with biopsy-confirmed NAFLD conducted between September 2005 and March 2010 . Interventions Daily dosing of 800 IU of vitamin E ( 58 patients ) , 1000 mg of metformin ( 57 patients ) , or placebo ( 58 patients ) for 96 weeks . MAIN OUTCOME MEASURES The primary outcome was sustained reduction in alanine aminotransferase ( ALT ) defined as 50 % or less of the baseline level or 40 U/L or less at visits every 12 weeks from 48 to 96 weeks of treatment . Improvements in histological features of NAFLD and resolution of NASH were secondary outcome measures . RESULTS Sustained reduction in ALT level was similar to placebo ( 10/58 ; 17 % ; 95 % CI , 9 % to 29 % ) in both the vitamin E ( 15/58 ; 26 % ; 95 % CI , 15 % to 39 % ; P = .26 ) and metformin treatment groups ( 9/57 ; 16 % ; 95 % CI , 7 % to 28 % ; P = .83 ) . The mean change in ALT level from baseline to 96 weeks was -35.2 U/L ( 95 % CI , -56.9 to -13.5 ) with placebo vs -48.3 U/L ( 95 % CI , -66.8 to -29.8 ) with vitamin E ( P = .07 ) and -41.7 U/L ( 95 % CI , -62.9 to -20.5 ) with metformin ( P = .40 ) . The mean change at 96 weeks in hepatocellular ballooning scores was 0.1 with placebo ( 95 % CI , -0.2 to 0.3 ) vs -0.5 with vitamin E ( 95 % CI , -0.8 to -0.3 ; P = .006 ) and -0.3 with metformin ( 95 % CI , -0.6 to -0.0 ; P = .04 ) ; and in NAFLD activity score , -0.7 with placebo ( 95 % CI , -1.3 to -0.2 ) vs -1.8 with vitamin E ( 95 % CI , -2.4 to -1.2 ; P = .02 ) and -1.1 with metformin ( 95 % CI , -1.7 to -0.5 ; P = .25 ) . Among children with NASH , the proportion who resolved at 96 weeks was 28 % with placebo ( 95 % CI , 15 % to 45 % ; 11/39 ) vs 58 % with vitamin E ( 95 % CI , 42 % to 73 % ; 25/43 ; P = .006 ) and 41 % with metformin ( 95 % CI , 26 % to 58 % ; 16/39 ; P = .23 ) . Compared with placebo , neither therapy demonstrated significant improvements in other histological features . CONCLUSION Neither vitamin E nor metformin was superior to placebo in attaining the primary outcome of sustained reduction in ALT level in patients with pediatric NAFLD . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00063635 Oxidative stress and low- grade systemic inflammation may contribute to the pathogenesis of obesity-induced comorbidities , including nonalcoholic fatty liver disease . Increasing intake of dietary antioxidants might be beneficial , but there are few data in obese children . To examine the effect of antioxidant supplementation on biomarkers of oxidative stress , inflammation , and liver function , we r and omly assigned overweight or obese children and adolescents ( n = 44 ; mean ± SD age : 12.7 ± 1.5 y ) participating in a lifestyle modification program to a 4-mo intervention with daily antioxidants ( vitamin E , 400 IU ; vitamin C , 500 mg ; selenium , 50 μg ) or placebo . We measured anthropometrics , antioxidant status , oxidative stress ( F(2)-isoprostanes , F(2)-isoprostane metabolites ) , inflammation , liver enzymes , fasting insulin and glucose , and lipid profile at baseline and endpoint . There was a significant treatment effect of antioxidant supplementation on antioxidant status [ α-tocopherol , β = 23.2 ( 95 % CI : 18.0 , 28.4 ) ; ascorbic acid , β = 70.6 ( 95 % CI : 51.7 , 89.4 ) ; selenium , β = 0.07 ( 95 % CI : 0.01 , 0.12 ) ] and oxidative stress [ 8-iso-prostagl and in F2α , β = -0.11 ( 95 % CI : -0.19 , -0.02 ) ] but not on any of the inflammatory markers measured . There was a significant treatment effect on alanine aminotransferase [ β = -0.13 ( 95 % CI : -0.23 , -0.03 ) ] , a trend toward a significant effect on aspartate aminotransferase [ β = -0.04 ( 95 % CI : -0.09 , 0.01 ) ] , and no significant effect on γ-glutamyltransferase [ β = -0.03 ( 95 % CI : -0.11 , 0.06 ) ] . In  summary , antioxidant supplementation for 4 mo improved antioxidant-oxidant balance and modestly improved liver function tests ; however , it did not reduce markers of systemic inflammation despite significant baseline correlations between oxidative stress and inflammation . The study was registered at clinical trials.gov as NCT01316081 OBJECTIVES : Metformin proved useful in the treatment of nonalcoholic fatty liver disease ( NAFLD ) , but its superiority over nutritional treatment and antioxidants has never been demonstrated . We aim ed to compare the usefulness of metformin versus prescriptive diet or vitamin E. METHODS : In an open label , r and omized trial , nondiabetic NAFLD patients were given metformin ( 2 g/day ; n = 55 ) for 12 months . The control cases were given either vitamin E ( 800 IU/day ; n = 28 ) or were treated by a prescriptive , weight-reducing diet ( n = 27 ) . Outcome measures were liver enzymes , insulin resistance ( homeostasis model assessment ) , parameters of the metabolic syndrome , and histology . RESULTS : Aminotransferase levels improved in all groups , in association with weight loss . The effects in the metformin arm were larger ( p < 0.0001 ) , and alanine aminotransferase normalized in 56 % of cases ( odds ratio ( OR ) versus . controls , 3.11 ; 95 % confidence interval ( CI ) , 1.56–6.20 ; p = 0.0013 ) . In multivariate analysis , metformin treatment was associated with higher rates of aminotransferase normalization , after correction for age , gender , basal aminotransferases , and change in body mass index ( OR , 5.98 ; 95 % CI , 2.05–17.45 ) . Differences were maintained when the two control groups were separately analyzed . The distribution of positive criteria for the metabolic syndrome was reduced only in the metformin arm ( p = 0.001 , signed rank test ) . A control biopsy in 17  metformin-treated cases ( 14 nonresponders ) showed a significant decrease in liver fat ( p = 0.0004 ) , necroinflammation , and fibrosis ( p = 0.012 for both ) . No side effects were observed during metformin treatment . CONCLUSIONS : Metformin treatment is better than a prescriptive diet or vitamin E in the therapy of NAFLD patients receiving nutritional counseling . Limited histological data support an association between improved aminotransferases and biopsy findings , which require confirmation in a double-blind trial with appropriate statistical power based on liver histology AIM To investigate the effect of lifestyle intervention on  non-alcoholic fatty liver disease ( NAFLD ) in Chinese obese children . METHODS Seventy-six obese children aged from 10 to 17 years with NAFLD were enrolled for a one-month intervention and divided r and omly into three groups . Group1 , consisting of 38 obese children , was an untreated control group without any intervention . Group 2 , consisting of 19 obese children in summer camp , was strictly controlled only by life style intervention . Group 3 , consisting of 19 obese children , received oral vitamin E therapy at a dose of 100 mg/d . The height , weight , fasting blood glucose ( FBG ) , fasting serum insulin ( FINS ) , plasma alanine aminotransferase ( ALT ) , aspartate aminotransferase ( AST ) , triglyceride ( TG ) , total cholesterol ( TCHO ) and homeostasis model assent-insulin resistance ( HOMA-IR ) were measured at baseline and after one month . All patients were underwent to an ultrasonographic study of the liver performed by one operator who was blinded to the groups . RESULTS The monitor indices of BMI , ALT , AST , TG , TCHO and HOMA-IR were successfully improved except in group 1 . BMI and ALT in group 2 were reduced more significantly than in group 3 ( 2.44 + /- 0.82 vs 1.45 + /- 0.80 , P = 0.001 ; 88.58 + /- 39.99 vs 63.69 + /- 27.05 , P = 0.040 , respectively ) . CONCLUSION Both a short-term lifestyle intervention and vitamin E therapy have an effect on NAFLD in obese children . Compared with vitamin E , lifestyle intervention is more effective . Therefore , lifestyle intervention should represent the first step in the management of children with NAFLD Objective A beneficial role of antioxidants in hepatopathic obese individuals has hitherto been inferred only from uncontrolled pilot studies . The authors compared the effect of vitamin E and weight loss on transaminase values and on ultrasonographic bright liver in a controlled group of children with obesity-related liver dysfunction . Methods Twenty-eight children with obesity-related hypertransaminasemia and bright liver were r and omly allocated to two single-blind groups : group 1 ( n = 14 ) treated with a low-calorie diet associated with oral placebo for 5 months , and group 2 ( n = 14 ) treated with a low-calorie diet associated with oral vitamin E ( 400 mg/d × 2 months , 100 mg/d × 3 months ) . Transaminase values and ultrasonographic liver brightness along with weight loss and vitamin E levels were monitored . Results Variations in transaminase levels and percentage of patients with normalized transaminase values were comparable in the two groups . The disappearance of bright liver was observed only in patients who lost weight and was twice as common in patients from group 1 . Two subgroups of patients with complete normalization of transaminase values emerged as a consequence of controlled adherence to diet alone ( n = 6 ; significant decrease of percent overweight : P = 0.0019 ) and to vitamin E alone ( n = 7 ; unmodified percent overweight and significant increase of vitamin E/cholesterol ratio : P < 0.0001 ) . Changes in treatment-induced alanine aminotransferase levels in these two subgroups were comparable at month 2 , whereas values at month 5 were significantly lower in the subgroup adherent to diet alone ( P = 0.04 ) . In the subgroup adherent to vitamin E alone , after 2 months washout , transaminase remained stable in 5 patients and increased in 2 ; bright liver persisted in all . Conclusions Oral vitamin E warrants consideration in obesity-related liver dysfunction for children unable to adhere to low-calorie diets Background : Studies have shown that zinc and selenium deficiency is common in nonalcoholic fatty liver disease ( NAFLD ) . However , the effects of zinc and selenium co-supplementation before and /or after disease progression on NAFLD are not clear enough . The aim of this study was to compare the effects of zinc and selenium co-supplementation before and /or after disease progression on NAFLD prognosis . Material s and Methods : Forty male Sprague – Dawley rats ( 197±4 g ) were r and omly assigned to 4 dietary groups : normal-fat diet ( NFD ; receiving 9 % of calories as fat ) , high-fat diet ( HFD ; receiving 82 % of calories as fat ) , supplementation before disease progression ( S+HFD ) , and supplementation after disease progression ( HFD+S ) . The diets were implemented over a 20-week period in all the groups . Biochemical and histologic parameters were compared between the 4 groups , and between-group comparisons were also carried out . Results : There were significant differences in the average food dietary intake ( P<0.001 ) , weight ( P<0.001 ) , fasting blood sugar ( P=0.005 ) , triglyceride ( P<0.001 ) , total cholesterol ( P<0.001 ) , low-density lipoprotein cholesterol ( P=0.002 ) , high-density lipoprotein cholesterol ( P=0.001 ) , alanine aminotransferase ( P<0.001 ) , and aspartate aminotransferase ( P<0.001 ) between the 4 dietary groups . Serum triglyceride and total cholesterol were significantly lower in the HFD+S Group than in the S+HFD Group ( P<0.001 and P=0.003 , respectively ) . Fat accumulation was significantly reduced in the HFD+S Group ( P<0.001 ) . Conclusion : Zinc and selenium co-supplementation after disease progression improved biochemical and histologic parameters in an experimental model of NAFLD Studies have shown that non-alcoholic fatty liver disease ( NAFLD ) patients are more prone to cardiovascular disease ( CVD ) . Zinc and selenium deficiency are common in NAFLD . But the effects of zinc and selenium co-supplementation before and /or after disease progression on CVD markers are not clear in NAFLD patients . This study aim ed to compare the effects of zinc and selenium co-supplementation before and /or after disease progression on some of the CVD markers in an experimental model of NAFLD . Forty male Sprague Dawley rats ( 197 ± 4 g ) were r and omly assigned into four dietary groups : control group ( C ; received 9 % of calorie as fat ) , model group ( M ; received 82 % of calorie as fat ) , and supplementation before ( BS ) or after ( AS ) disease progression . Animals were fed diets for 20 weeks in all groups . Fasting plasma glucose ( FPG ) , insulin , HOMA-IR , ALT , AST , lipid profile , malondialdehyde ( MDA ) and vascular endothelial growth factor ( VEGF ) levels were measured as CVD indices . Serum ALT , AST , FPG , insulin , MDA , VEGF and HOMA-IR were significantly higher in the M than C group . Co-supplementation reduced serum ALT and AST levels in the BS and AS groups compared with the M group . FPG , insulin , HOMA-IR , VEGF , MDA , LDL/HDL-c and TC/HDL-c ratio were significantly reduced in the AS compared with the M group . TG/HDL-c ratio was significantly reduced in the BS and AS compared with the M group . Serum MDA , VEGF , Insulin and HOMA-IR were significantly lowered in the AS than BS group ( p < 0.05 ) . Zinc and selenium co-supplementation after NAFLD progression reduced CVD risk indices in an experimental model BACKGROUND The combination of ursodeoxycholic acid ( UDCA ) and vitamin E is a therapeutic option for nonalcoholic steatohepatitis ( NASH ) but r and omized controlled studies have produced inconsistent results . The objective of this study was to report the long-term tolerability and efficacy of this combination in our ten-year single center experience . METHODS The study group included 101 adult patients with persistent elevation of serum aminotransferases ( AST and ALT ) and /or γ glutamyl-transferase ( GGT ) , in whom a histological diagnosis of NASH was made from January 1998 to January 2009 , and who were treated with a combination of UDCA with vitamin E.  RESULTS Median body mass index ( 30 kg/m(2 ) ) remained unchanged during the study . UDCA and vitamin E were well tolerated ( 5 % withdrawal for side effects ) . Mean serum AST , ALT and GGT levels ( expressed as times of Upper Normal Limit ) diminished significantly ( 1.39 ± 0.74 to 0.78 ± 0.34 for AST , 1.72 ± 0.92 to 0.91 ± 0.69 for AST and 3.25 ± 2.85 to 1.30 ± 1.30 for GGT ) . AST , ALT and GGT reached normal range in 80 % , 70 % and 65 % of the patients , respectively . From the ten patients who had a second liver biopsy during follow-up , NAS score improved in seven , and worsened in one . CONCLUSIONS The combination of UDCA with vitamin E significantly improves liver function tests in long-term and is very well tolerated BACKGROUND Nonalcoholic steatohepatitis is a common liver disease that can progress to cirrhosis . Currently , there is no established treatment for this disease . METHODS We r and omly assigned 247 adults with nonalcoholic steatohepatitis and without diabetes to receive pioglitazone at a dose of 30 mg daily ( 80 subjects ) , vitamin E at a dose of 800 IU daily ( 84 subjects ) , or placebo ( 83 subjects ) , for 96 weeks . The primary outcome was an improvement in histologic features of nonalcoholic steatohepatitis , as assessed with the use of a composite of st and ardized scores for steatosis , lobular inflammation , hepatocellular ballooning , and fibrosis . Given the two planned primary comparisons , P values of less than 0.025 were considered to indicate statistical significance . RESULTS Vitamin E therapy , as compared with placebo , was associated with a significantly higher rate of improvement in nonalcoholic steatohepatitis ( 43 % vs. 19 % , P=0.001 ) , but the difference in the rate of improvement with pioglitazone as compared with placebo was not significant ( 34 % and 19 % , respectively ; P=0.04 ) . Serum alanine and aspartate aminotransferase levels were reduced with vitamin E and with pioglitazone , as compared with placebo ( P<0.001 for both comparisons ) , and both agents were associated with reductions in hepatic steatosis ( P=0.005 for vitamin E and P<0.001 for pioglitazone ) and lobular inflammation ( P=0.02 for vitamin E and P=0.004 for pioglitazone ) but not with improvement in fibrosis scores ( P=0.24 for vitamin E and P=0.12 for pioglitazone ) . Subjects who received pioglitazone gained more weight than did those who received vitamin E or placebo ; the rates of other side effects were similar among the three groups . CONCLUSIONS Vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes . There was no benefit of pioglitazone over placebo for the primary outcome ; however , significant benefits of pioglitazone were observed for some of the secondary outcomes . ( Clinical Trials.gov number , NCT00063622 . BACKGROUND & AIMS Nonalcoholic steatohepatitis ( NASH ) is a frequent liver disease that can progress to cirrhosis and for which there is no recognized therapy . UDCA and vitamin E have been considered separately as therapeutic options and have not been shown to be effective . This study tested their combination . METHODS Patients with elevated aminotransferase levels and drinking less than 40 g alcohol/week with biopsy-proven NASH were r and omly assigned to receive UDCA 12 - 15 mg.kg-1.day-1 with vitamin E 400 IU twice a day ( UDCA/Vit E ) , UDCA with placebo ( UDCA/P ) , or placebo/placebo ( P/P ) . After 2 years , they underwent a second liver biopsy . Biopsy specimens were collected , blinded , and scored by a single liver pathologist . RESULTS Forty eight patients were included , 15 in the UDCA/Vit E group , 18 in the UDCA/P group , and 15 in the P/P group ; 8 patients dropped out , none because of side effects .  Baseline parameters were not significantly different between the 3 groups . Body mass index remained unchanged during the study . Serum aspartate aminotransferase ( AST ) and alanine aminotransferase ( ALT ) levels diminished significantly in the UDCA/Vit E group . Neither the AST nor the ALT levels improved in the P/P group and only the ALT levels in the UDCA/P group . Histologically , the activity index was unchanged at the end of the study in the P/P and UDCA/P groups , but it was significantly better in the UDCA/Vit E group , mostly as a result of regression of steatosis . CONCLUSIONS Two years of treatment with UDCA in combination with vitamin E improved laboratory values and hepatic steatosis of patients with NASH . Larger trials are warranted BACKGROUND Non-alcoholic steatohepatitis is a distinct entity , characterized by fatty change , lobular inflammation and fibrosis of the liver . Some cases of non-alcoholic steatohepatitis progress to cirrhosis , but it is not easy to distinguish this disease from non-alcoholic fatty liver by non-invasive examinations . No proven therapy for non-alcoholic steatohepatitis exists . Transforming growth factor-beta1 is implicated in the development of liver fibrosis , and is inhibited by alpha-tocopherol ( vitamin E ) in the liver . Therefore , in this study , the significance of the measurement of the level of plasma transforming growth factor-beta1 and the effect of alpha-tocopherol on the clinical course of non-alcoholic steatohepatitis were investigated . METHODS Twelve patients with non-alcoholic steatohepatitis and 10 patients with non-alcoholic fatty liver , with a diagnosis confirmed by liver biopsy , were studied . None of the patients had a history of alcohol abuse , habitual medicine or malignant or inflammatory diseases . All patients were negative for hepatitis B , C and G virus . Patients were given dietary instruction for 6 months , and then alpha-tocopherol ( 300 mg/day ) was given for 1 year . Blood chemistries , measurement of plasma transforming growth factor-beta1 level and liver biopsies  were undertaken before and after the 1-year alpha-tocopherol treatment . RESULTS The serum alanine transaminase level decreased in non-alcoholic fatty liver patients , but not in non-alcoholic steatohepatitis patients , after 6 months of dietary therapy . Although the serum alanine transaminase level in non-alcoholic steatohepatitis patients was reduced during the 1-year alpha-tocopherol treatment , alpha-tocopherol had no effect on the serum alanine transaminase level in non-alcoholic fatty liver patients . The histological findings , such as steatosis , inflammation and fibrosis , of the non-alcoholic steatohepatitis patients were improved after alpha-tocopherol treatment . The plasma transforming growth factor-beta1 level in non-alcoholic steatohepatitis patients was significantly elevated compared with that in non-alcoholic fatty liver patients and healthy controls , and decreased , accompanied by an improvement in serum alanine transaminase level , with alpha-tocopherol treatment . CONCLUSIONS Our data suggest that the measurement of the level of plasma transforming growth factor-beta1 represents a possible method of distinguishing between non-alcoholic steatohepatitis and non-alcoholic fatty liver . Long-term alpha-tocopherol treatment may be safe and effective for non-alcoholic steatohepatitis . A r and omized , controlled , double-blind trial is needed to confirm the full potential of alpha-tocopherol in the management of non-alcoholic steatohepatitis BACKGROUND This study investigates the levels of superoxide dismutase ( SOD ) activity in serum and saliva of patients with chronic periodontitis ( CP ) . In addition , the outcome of scaling and root planing ( SRP ) with and without vitamin E supplementation is evaluated in terms of changes in periodontal parameters and SOD activity in patients with CP . METHODS Serum and salivary SOD activity in 38 patients with CP were compared with those of 22 systemically and periodontally healthy individuals ( control group ) . At periodontal examination , serum and saliva sample s were obtained . Patients with CP were r and omly divided into treatment groups 1 ( TG-1 ) and 2 ( TG-2 ) . SRP was performed for both groups , and TG-2 also received 200 mg ( 300 IU ) vitamin E every other day . Periodontal parameters and SOD activity were evaluated after 3 months . SOD activity was determined using an SOD assay and enzyme-linked immunosorbent assay reader at 450 nm . RESULTS SOD activity in both serum ( P < 0.05 ) and saliva ( P < 0.001 ) was lower in patients with CP compared with controls . After 3 months of follow-up , SOD activity improved in both treatment groups ; however , the improvement in TG-2 was higher than in TG-1 , along with more improvement in periodontal parameters . Serum SOD levels in TG-2 increased even above the level of the control group . CONCLUSIONS Systemic and local SOD levels are lowered in CP . Adjunctive vitamin E supplementation improves periodontal healing as well as antioxidant defense
target: These studies demonstrated improvement in biochemical profiles , with a decline in or normalization of liver enzymes .
  However , some concerns have been raised regarding the use of vitamin E in patients with NASH due to its adverse effects profile and lack of significant improvement in hepatic fibrosis .
background: There has been a growing interest in the role of vitamin E supplementation in the treatment and /or prevention of nonalcoholic fatty liver ( NAFLD ) .
  Furthermore , histological assessment showed favorable outcomes in lobular inflammation and hepatic steatosis following treatment with vitamin E. Current guidelines regarding the use of vitamin E in the setting of NAFLD recommend that vitamin E-based treatment be restricted to biopsy-proven nondiabetic patients with NASH only .