title: No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men. The impact of outcome reporting bias in randomised controlled trials on a cohort of systematic reviews Consumption of fructose- but not glucose-sweetened beverages for 10 weeks increases circulating concentrations of uric acid, retinol binding protein-4, and gamma-glutamyl transferase activity in overweight/obese humans Effects of supplementation with essential amino acids on intrahepatic lipid concentrations during fructose overfeeding in humans. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. Magnetic resonance spectroscopy to measure hepatic triglyceride content: prevalence of hepatic steatosis in the general population. Non-alcoholic fatty liver disease and mortality among US adults: prospective cohort study Carbohydrate quality is not associated with liver enzyme activity and plasma TAG and HDL concentrations over 5 years in an older population. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Effects of a short-term overfeeding with fructose or glucose in healthy young males. Thymosin alpha 1 attenuates lipid peroxidation and improves fructose-induced steatohepatitis in rats. A Randomized Controlled Trial of Metformin versus Vitamin E or Prescriptive Diet in Nonalcoholic Fatty Liver Disease The influence of diet upon liver function tests and serum lipids in healthy male volunteers resident in a Phase I unit. Effects of 4-week very-high-fructose/glucose diets on insulin sensitivity, visceral fat and intrahepatic lipids: an exploratory trial. Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes.
abstract: BACKGROUND & AIMS Diets high in fructose have been proposed to contribute to nonalcoholic fatty liver disease . We compared the effects of high-fructose and matched glucose intake on hepatic triacylglycerol ( TAG ) concentration and other liver parameters . DESIGN In a double-blind study , we r and omly assigned 32 healthy but central ly overweight men to groups that received either a high-fructose or high-glucose diet ( 25 % energy ) . These diets were provided during an initial isocaloric period of 2 weeks , followed by a 6-week washout period , and then again during a hypercaloric 2-week period . The primary outcome measure was hepatic level of TAG , with additional assessment s of TAG levels in serum and soleus muscle , hepatic levels of adenosine triphosphate , and systemic and hepatic insulin resistance . RESULTS During the isocaloric period of the study , both groups had stable body weights and concentrations of TAG in liver , serum , and soleus muscle . The high-fructose diet produced an increase of 22 ± 52 μmol/L in the serum level of uric acid , whereas the high-glucose diet led to a reduction of 23 ± 25 μmol/L ( P < .01 ) . The high-fructose diet also produced an increase of 0.8 ± 0.9 in the homeostasis model assessment of insulin resistance , whereas the high-glucose diet produced an increase of only 0.1 ± 0.7 ( P = .03 ) . During the hypercaloric period , participants in the high-fructose and high-glucose groups had similar increases in weight ( 1.0 ± 1.4 vs 0.6 ± 1.0 kg ; P = .29 ) and absolute concentration of TAG in liver ( 1.70 % ± 2.6 % vs 2.05 % ± 2.9 % ; P = .73 ) and serum ( 0.36 ± 0.75 vs 0.33 ± 0.38 mmol/L ; P = .91 ) , and similar results in biochemical assays of liver function . Body weight changes were associated with changes in liver biochemistry and concentration of TAGs . CONCLUSIONS In the isocaloric period , overweight men who were on a high-fructose or a high-glucose diet did not develop any significant changes in hepatic concentration of TAGs or serum levels of liver enzymes . However , in the hypercaloric period , both high-fructose and high-glucose diets produced significant increases in these parameters without any significant difference between the 2 groups . This indicates an energy-mediated , rather than a specific macronutrient-mediated , effect . Clinical trials.gov no : NCT01050140 Objective To examine the prevalence of outcome reporting bias — the selection for publication of a subset of the original recorded outcome variables on the basis of the results — and its impact on Cochrane review s. Design A nine point classification system for missing outcome data in r and omised trials was developed and applied to the trials assessed in a large , unselected cohort of Cochrane systematic review s. Research ers who conducted the trials were contacted and the reason sought for the non-reporting of data . A sensitivity analysis was undertaken to assess the impact of outcome reporting bias on review s that included a single meta- analysis of the review primary outcome . Results More than half ( 157/283 ( 55 % ) ) the review s did not include full data for the review primary outcome of interest from all eligible trials . The median amount of review outcome data missing for any reason was 10 % , whereas 50 % or more of the potential data were missing in 70 ( 25 % ) review s. It was clear from the publications for 155 ( 6 % ) of the 2486 assessable trials that the research ers had measured and analysed the review primary outcome but did not report or only partially reported the results . For reports that did not mention the review primary outcome , our classification regarding the presence of outcome reporting bias was shown to have a sensitivity of 88 % ( 95 % CI 65 % to 100 % ) and specificity of 80 % ( 95 % CI 69 % to 90 % ) on the basis of responses from 62 trialists . A third of Cochrane review s ( 96/283 ( 34 % ) ) contained at least one trial with high suspicion of outcome reporting bias for the review primary outcome . In a sensitivity analysis undertaken for 81 review s with a single meta- analysis of the primary outcome of interest , the treatment effect estimate was reduced by 20 % or more in 19 ( 23 % ) . Of the 42 meta-analyses with a statistically significant result only , eight ( 19 % ) became non-significant after adjustment for outcome reporting bias and 11 ( 26 % ) would have overestimated the treatment effect by 20 % or more . Conclusions Outcome reporting bias is an under-recognised problem that affects the conclusions in a substantial proportion of Cochrane review s. Individuals conducting systematic review s need to address explicitly the issue of missing outcome data for their review to be considered a reliable source of evidence . Extra care is required during data extraction , review ers should identify when a trial reports that an outcome was measured but no results were reported or events observed , and contact with trialists should be encouraged Background Prospect i ve studies in humans examining the effects of fructose consumption on biological markers associated with the development of metabolic syndrome are lacking . Therefore we investigated the relative effects of 10 wks of fructose or glucose consumption on plasma uric acid and RBP-4 concentrations , as well as liver enzyme ( AST , ALT , and GGT ) activities in men and women . Methods As part of a parallel arm study , older ( age 40–72 ) , overweight and obese male and female subjects ( BMI 25–35 kg/m2 ) consumed glucose- or fructose-sweetened beverages providing 25 % of energy requirements for 10 wks . Fasting and 24-h blood collection s were performed at baseline and following 10 wks of intervention and plasma concentrations of uric acid , RBP-4 and liver enzyme activities were measured . Results Consumption of fructose , but not glucose , led to significant increases of 24-h uric acid profiles ( P < 0.0001 ) and RBP-4 concentrations ( P = 0.012 ) , as well as plasma GGT activity ( P = 0.04 ) . Fasting plasma uric acid concentrations increased in both groups ; however , the response was significantly greater in subjects consuming fructose ( P = 0.002 for effect of sugar ) . Within the fructose group male subjects exhibited larger increases of RBP-4 levels than women ( P = 0.024 ) . Conclusions These findings suggest that consumption of fructose at 25 % of energy requirements for 10 wks , compared with isocaloric consumption of glucose , may contribute to the development of components of the metabolic syndrome by increasing circulating uric acid , GGT activity , suggesting alteration of hepatic function , and the production of RBP-4 BACKGROUND A high dietary protein intake has been shown to blunt the deposition of intrahepatic lipids in high-fat- and high-carbohydrate-fed rodents and humans . OBJECTIVE The aim of this study was to evaluate the effect of essential amino acid supplementation on the increase in hepatic fat content induced by a high-fructose diet in healthy subjects . DESIGN Nine healthy male volunteers were studied on 3 occasions in a r and omized , crossover design after 6 d of dietary intervention . Dietary conditions consisted of a weight-maintenance balanced diet ( control ) or the same balanced diet supplemented with 3 g fructose · kg(-1 ) · d(-1 ) and 6.77 g of a mixture of 5 essential amino acids 3 times/d ( leucine , isoleucine , valine , lysine , and threonine ) ( HFrAA ) or with 3 g fructose · kg(-1 ) · d(-1 ) and a maltodextrin placebo 3 times/d ( HFr ) ; there was a washout period of 4 to 10 wk between each condition . For each condition , the intrahepatocellular lipid ( IHCL ) concentration , VLDL-triglyceride concentration , and VLDL-[(13)C]palmitate production were measured after oral loading with [(13)C]fructose . RESULTS HFr increased the IHCL content ( 1.27 ± 0.31 compared with 2.74 ± 0.55 vol % ; P < 0.05 ) and VLDL-triglyceride ( 0.55 ± 0.06 compared with 1.40 ± 0.15 mmol/L ; P < 0.05 ) . HFr also enhanced VLDL-[(13)C]palmitate production . HFrAA significantly decreased IHCL compared with HFr ( to 2.30 ± 0.43 vol% ; P < 0.05 ) but did not change VLDL-triglyceride concentrations or VLDL-[(13)C]palmitate production . CONCLUSIONS Supplementation with essential amino acids blunts the fructose-induced increase in IHCL but not hypertriglyceridemia . This is not because of inhibition of VLDL-[(13)C]palmitate production . This trial was registered at www . clinical trials.gov as NCT01119989 BACKGROUND The consumption of sucrose-sweetened soft drinks ( SSSDs ) has been associated with obesity , the metabolic syndrome , and cardiovascular disorders in observational and short-term intervention studies . Too few long-term intervention studies in humans have examined the effects of soft drinks . OBJECTIVE We compared the effects of SSSDs with those of isocaloric milk and a noncaloric soft drink on changes in total fat mass and ectopic fat deposition ( in liver and muscle tissue ) . DESIGN Overweight subjects ( n = 47 ) were r and omly assigned to 4 different test drinks ( 1 L/d for 6 mo ) : SSSD ( regular cola ) , isocaloric semiskim milk , aspartame-sweetened diet cola , and water . The amount of intrahepatic fat and intramyocellular fat was measured with (1)H-magnetic resonance spectroscopy . Other endpoints were fat mass , fat distribution ( dual-energy X-ray absorptiometry and magnetic resonance imaging ) , and metabolic risk factors . RESULTS The relative changes between baseline and the end of 6-mo intervention were significantly higher in the regular cola group than in the 3 other groups for liver fat ( 132 - 143 % , sex-adjusted mean ; P < 0.01 ) , skeletal muscle fat ( 117 - 221 % ; P < 0.05 ) , visceral fat ( 24 - 31 % ; P < 0.05 ) , blood triglycerides ( 32 % ; P < 0.01 ) , and total cholesterol ( 11 % ; P < 0.01 ) . Total fat mass was not significantly different between the 4 beverage groups . Milk and diet cola reduced systolic blood pressure by 10 - 15 % compared with regular cola ( P < 0.05 ) . Otherwise , diet cola had effects similar to those of water . CONCLUSION Daily intake of SSSDs for 6 mo increases ectopic fat accumulation and lipids compared with milk , diet cola , and water . Thus , daily intake of SSSDs is likely to enhance the risk of cardiovascular and metabolic diseases . This trial is registered at clinical trials.gov as NCT00777647 Despite the increasing prevalence of nonalcoholic fatty liver disease ( NAFLD ) , the criteria used to diagnose the disorder remain poorly defined . Localized proton magnetic resonance spectroscopy ( MRS ) accurately measures hepatic triglyceride content ( HTGC ) but has been used only in small research studies . Here , MRS was used to analyze the distribution of HTGC in 2,349 participants from the Dallas Heart Study ( DHS ) . The reproducibility of the procedure was vali date d by showing that duplicate HTGC measurements were high correlated ( r = 0.99 , P < 0.001 ) and that the coefficient of variation between measurements was low ( 8.5 % ) . Intake of a high-fat meal did not significantly affect the measurements , and values were similar when measurements were made from the right and left hepatic lobes . To determine the " upper limit of normal " for HTGC , the distribution of HTGC was examined in the 345 subjects from the DHS who had no identifiable risk factors for hepatic steatosis ( nonobese , nondiabetic subjects with minimal alcohol consumption , normal liver function tests , and no known liver disease ) . The 95th percentile of HTGC in these subjects was 5.56 % , which corresponds to a hepatic triglyceride level of 55.6 mg/g . With this value as a cutoff , the prevalence of hepatic steatosis in Dallas County was estimated to be 33.6 % . Thus MRS provides a sensitive , quantitative , noninvasive method to measure HTGC and , when applied to a large urban US population , revealed a strikingly high prevalence of hepatic steatosis Objective To evaluate the association between non-alcoholic fatty liver disease and all cause and cause specific mortality in a representative sample of the US general population . Design Prospect i ve cohort study . Setting US Third National Health and Nutrition Examination Survey ( NHANES III : 1988 - 94 ) with follow-up of mortality to 2006 . Participants 11 371 adults aged 20 - 74 participating in the Third National Health and Nutrition Examination Survey , with assessment of hepatic steatosis .  Main outcome measure Mortality from all causes , cardiovascular disease , cancer , and liver disease ( up to 18 years of follow-up ) . Results The prevalence of non-alcoholic fatty liver disease with and without increased levels of liver enzymes in the population was 3.1 % and 16.4 % , respectively . Compared with participants without steatosis , those with non-alcoholic fatty liver disease but normal liver enzyme levels had multivariate adjusted hazard ratios for deaths from all causes of 0.92 ( 95 % confidence interval 0.78 to 1.09 ) , from cardiovascular disease of 0.86 ( 0.67 to 1.12 ) , from cancer of 0.92 ( 0.67 to 1.27 ) , and from liver disease of 0.64 ( 0.12 to 3.59 ) . Compared with participants without steatosis , those with non-alcoholic fatty liver disease and increased liver enzyme levels had adjusted hazard ratios for deaths from all causes of 0.80 ( 0.52 to 1.22 ) , from cardiovascular disease of 0.59 ( 0.29 to 1.20 ) , from cancer of 0.53 ( 0.26 to 1.10 ) , and from liver disease of 1.17 ( 0.15 to 8.93 ) . Conclusions Non-alcoholic fatty liver disease was not associated with an increased risk of death from all causes , cardiovascular disease , cancer , or liver disease Non-alcoholic fatty liver disease ( NAFLD ) is closely associated with insulin resistance and obesity . Hence , carbohydrate quality could be of relevance to the risk of NAFLD , but prospect i ve data are lacking . The aim of the present study was to investigate longitudinal associations between carbohydrate quality ( including dietary glycaemic index  ( GI ) and intakes of sugar , starch and fibre ) and markers of liver function in an older Australian population . The analysis was based on 866 participants ( ≥ 49 years ) of the Blue Mountains Eye Study with fasting blood specimens and dietary intake data at baseline and 5-year follow-up . Multi-level mixed regression analysis was used to relate dietary GI and  sugar , starch and fibre  intake to the liver enzymes alanine aminotransferase ( ALT ) and γ-glutamyltransferase ( GGT ) , as well as fasting TAG and HDL-cholesterol ( HDL-C ) . After adjustment for potential confounding factors , a lower fibre intake was cross-sectionally related to higher GGT ( P= 0.02 ) and fasting TAG ( P= 0.002 ) levels , with fruit fibre being the most relevant fibre source ( P= 0.095 for GGT ; P= 0.003 for TAG ) . A higher dietary GI was associated with lower HDL-C ( P= 0.046 ) . Changes in carbohydrate quality during 5 years were not related to changes in ALT , GGT , TAG or HDL-C ( P≥ 0.08 ) . In conclusion , the absence of longitudinal associations between carbohydrate quality and liver enzymes and serum lipids in this older population does not support a major role of carbohydrate nutrition in liver function among the elderly Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND & AIMS Prevalence of nonalcoholic fatty liver disease ( NAFLD ) has not been well established . The purpose of this study was to prospect ively define the prevalence of both NAFLD and nonalcoholic steatohepatitis ( NASH ) . METHODS Out patients 18 to 70 years old were recruited from Brooke Army Medical Center . All patients completed a baseline question naire and ultrasound . If fatty liver was identified , then laboratory data and a liver biopsy were obtained . RESULTS Four hundred patients were enrolled . Three hundred and twenty-eight patients completed the question naire and ultrasound .  Mean age ( range , 28 - 70 years ) was 54.6 years ( 7.35 ) ; 62.5 % Caucasian , 22 % Hispanic , and 11.3 % African American ; 50.9 % female ; mean body mass index ( BMI ) ( calculated as kg/m(2 ) ) was 29.8 ( 5.64 ) ; and diabetes and hypertension prevalence 16.5 % and 49.7 % , respectively . Prevalence of NAFLD was 46 % . NASH was confirmed in 40 patients ( 12.2 % of total cohort , 29.9 % of ultrasound positive patients ) . Hispanics had the highest prevalence of NAFLD ( 58.3 % ) , then Caucasians ( 44.4 % ) and African Americans ( 35.1 % ) . NAFLD patients were more likely to be male ( 58.9 % ) , older ( P = .004 ) , hypertensive ( P < .00005 ) , and diabetic ( P < .00005 ) . They had a higher BMI ( P < .0005 ) , ate fast food more often ( P = .049 ) , and exercised less ( P = 0.02 ) than their non-NAFLD counterparts . Hispanics had a higher prevalence of NASH compared with Caucasians ( 19.4 % vs 9.8 % ; P = .03 ) . Alanine aminotransferase , aspartate aminotransferase , BMI , insulin , Quantitative Insulin-Sensitivity Check Index , and cytokeratin-18 correlated with NASH . Among the 54 diabetic patients , NAFLD was found in 74 % and NASH in 22.2 % . CONCLUSION Prevalence of NAFLD and NASH is higher than estimated previously . Hispanics and patients with diabetes are at greatest risk for both NAFLD and NASH Consumption of simple carbohydrates has markedly increased over the past decades , and may be involved in the increased prevalence in metabolic diseases . Whether an increased intake of fructose is specifically related to a dysregulation of glucose and lipid metabolism remains controversial . We therefore compared the effects of hypercaloric diets enriched with fructose ( HFrD ) or glucose ( HGlcD ) in healthy men . Eleven subjects were studied in a r and omised order after 7 d of the following diets : ( 1 ) weight maintenance , control diet ; ( 2 ) HFrD ( 3.5 g fructose/kg fat-free mass ( ffm ) per d , + 35 % energy intake ) ; ( 3 ) HGlcD ( 3.5 g glucose/kg ffm per d , + 35 % energy intake ) . Fasting hepatic glucose output ( HGO ) was measured with 6,6 - 2H2-glucose . Intrahepatocellular lipids ( IHCL ) and intramyocellular lipids ( IMCL ) were measured by 1H magnetic resonance spectroscopy . Both fructose and glucose increased fasting VLDL-TAG ( HFrD : + 59 % , P < 0.05 ; HGlcD : + 31 % , P = 0.11 ) and IHCL ( HFrD : + 52 % , P < 0.05 ; HGlcD : + 58 % , P = 0.06 ) . HGO increased after both diets ( HFrD : + 5 % , P < 0.05 ; HGlcD : + 5 % , P = 0.05 ) . No change was observed in fasting glycaemia , insulin and alanine aminotransferase concentrations . IMCL increased significantly only after the HGlcD ( HFrD : + 24 % , NS ; HGlcD : + 59 % , P < 0.05 ) . IHCL and VLDL-TAG were not different between hypercaloric HFrD and HGlcD , but were increased compared to values observed with a weight maintenance diet . However , glucose led to a higher increase in IMCL than fructose OBJECTIVES The aim of this study was to investigate the effects of thymosin alpha(1 ) ( Talpha(1 ) ) in rats having fructose-induced steatosis . Fructose leads to experimental steatosis in the liver by exerting its effect on some components of the oxidant/antioxidant system , and on several cytokines ( interleukin-1beta , -2 , and -6 ) in blood . METHODS Twenty-four rats at r and om were divided into three groups ( each group containing eight animals ) ; the control group ( C ) , which received a purified diet ; the high-fructose-fed group ( F ) ; and the high-fructose-fed and Talpha(1 ) injected group ( F + T ) . After the experimental period of 10 days , liver lipid peroxidation and antioxidant status , and blood IL-1beta , IL-2 , and IL-6 levels were quantified . RESULTS In comparison with the C group , the F group had a higher nitric oxide ( NO ) level , xanthine oxidase ( XO ) activity , and lipid peroxidation , as indicated by concentrations of thiobarbituric acid reactive substances ( TBARS ) , and lower superoxide dismutase ( SOD ) and glutathione peroxidase ( GSH-Px ) activities in the liver . In the F + T group , these markers were near the values of the control group . In addition , increased IL-1beta and IL-6 levels were kept at near to normal levels with treatment of Talpha(1 ) , but not IL-2 levels . In the F group , the most consistent findings in the histologic sections of liver tissues were the macrovesicular and microvesicular steatosis .  Talpha(1 ) treatment protected the majority of the liver cells , while minimal macrovesicular and microvesicular steatosis was observed in the remaining cells . CONCLUSIONS These results show that a high-fructose diet in rats leads to hepatic steatosis and a defect in the free radical defense system , and that treatment of Talpha(1 ) may improve these biochemical and morphologic changes in the fructose-fed rat livers 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 diet upon liver function tests and serum lipids within the restricted environment of a Phase I unit . METHODS An open r and omized three-way crossover study was design ed with subjects consuming three types of diet . The diets comprised , a balanced normal calorie diet , a high-carbohydrate high-calorie diet and a high-fat high-calorie diet . Each diet was consumed in a r and omized sequence over 8 days with a recovery period of 14 days between periods . The blood concentrations of various laboratory parameters were measured at intervals throughout each dietary period and during the recovery periods . RESULTS Blood transaminase activity and triglyceride concentrations increased significantly whilst subjects consumed a high-carbohydrate high-calorie diet but not when fed either a high-fat high-calorie diet or a balanced normal calorie diet . CONCLUSIONS The rises in transaminases and triglycerides were caused by the carbohydrate content of the diet rather than its calorific value . Sucrose rather than starch was the carbohydrate which caused the rise in transaminases and triglycerides . The importance of controlling diet in Phase I studies is stressed An increasing amount of fructose in the diet is suggested to play a causal role in the pathogenesis of the metabolic syndrome , type 2 diabetes and fatty liver . Our aim was to investigate and compare the effects of very high fructose and very high glucose in hyperenergetic diets on glucose and lipid metabolism and on fat depots in healthy humans . We conducted an exploratory , prospect i ve , r and omised , single-blinded , intervention trial . Participants in addition to a balanced weight-maintaining diet received 150 g of fructose or glucose/d for 4 weeks . Insulin sensitivity was estimated from oral glucose tolerance tests . Visceral and subcutaneous abdominal fat was determined with MRI . Liver fat and intramyocellular lipids of the tibialis anterior muscle were measured with (1)H magnetic resonance spectroscopy . A total of twenty healthy subjects ( fructose group n 10 and glucose group n 10 ; twelve males and eight females ) completed the study . They had a mean age of 30·5 ( SEM 2·0 ) years and a mean BMI of 25·9 ( SEM 0·5 ) kg/m(2 ) . Insulin sensitivity appeared to decrease both in the fructose and glucose groups . TAG markedly increased in the fructose group . No strong alterations or treatment effects were found for liver fat , visceral fat , subcutaneous abdominal fat and intramyocellular lipids of the tibialis anterior muscle . In conclusion , the effects of very high fructose and very high glucose in hyperenergetic diets on glucose metabolism and body fat composition were not different in the healthy participants of the present study . However , elevation of plasma TAG seemed to be fructose-specific BACKGROUND Both nutritional and genetic factors are involved in the pathogenesis of nonalcoholic fatty liver disease and insulin resistance . OBJECTIVE The aim was to assess the effects of fructose , a potent stimulator of hepatic de novo lipogenesis , on intrahepatocellular lipids ( IHCLs ) and insulin sensitivity in healthy offspring of patients with type 2 diabetes (OffT2D)--a subgroup of individuals prone to metabolic disorders . DESIGN Sixteen male OffT2D and 8 control subjects were studied in a crossover design after either a 7-d isocaloric diet or a hypercaloric high-fructose diet ( 3.5 g x kg FFM(-1 ) x d(-1 ) , + 35 % energy intake ) . Hepatic and whole-body insulin sensitivity were assessed with a 2-step hyperinsulinemic euglycemic clamp ( 0.3 and 1.0 mU x kg(-1 ) x min(-1 ) ) , together with 6,6-[2H2]glucose . IHCLs and intramyocellular lipids ( IMCLs ) were measured by 1H-magnetic resonance spectroscopy . RESULTS The OffT2D group had significantly ( P < 0.05 ) higher IHCLs ( + 94 % ) , total triacylglycerols ( + 35 % ) , and lower whole-body insulin sensitivity ( -27 % ) than did the control group . The high-fructose diet significantly increased IHCLs ( control : + 76 % ; OffT2D : + 79 % ) , IMCLs ( control : + 47 % ; OffT2D : + 24 % ) , VLDL-triacylglycerols ( control : + 51 % ; OffT2D : + 110 % ) , and fasting hepatic glucose output ( control : + 4 % ; OffT2D : + 5 % ) . Furthermore , the effects of fructose on VLDL-triacylglycerols were higher in the OffT2D group ( group x diet interaction : P < 0.05 ) . CONCLUSIONS A 7-d high-fructose diet increased ectopic lipid deposition in liver and muscle and fasting VLDL-triacylglycerols and decreased hepatic insulin sensitivity . Fructose-induced alterations in VLDL-triacylglycerols appeared to be of greater magnitude in the OffT2D group , which suggests that these individuals may be more prone to developing dyslipidemia when challenged by high fructose intakes . This trial was registered at clinical trials.gov as NCT00523562
target: In addition , there was a low level of evidence that hypercaloric fructose and glucose diets have similar effects on liver fat and liver enzymes in healthy adults .
  There was insufficient evidence to draw a conclusion for effects of HFCS or sucrose on NAFLD .
  Conclusions : On the basis of indirect comparisons across study findings , the apparent association between indexes of liver health ( ie , liver fat , hepatic de novo lipogenesis , alanine aminotransferase , AST , and γ-glutamyl transpeptase ) and fructose or sucrose intake appear to be confounded by excessive energy intake .
  Overall , the available evidence is not sufficiently robust to draw conclusions regarding effects of fructose , HFCS , or sucrose consumption on NAFLD
background: Background : Concerns have been raised about the concurrent temporal trend between simple sugar intakes , especially of fructose or high-fructose corn syrup ( HFCS ) , and rates of nonalcoholic fatty liver disease ( NAFLD ) in the United States .
  Objective : We examined the effect of different amounts and forms of dietary fructose on the incidence or prevalence of NAFLD and indexes of liver health in humans .