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: 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 : 1 
    Output:
    
agent
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
***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: 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 : 1 
    Output:
    