title: No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men. Moderate Amounts of Fructose Consumption Impair Insulin Sensitivity in Healthy Young Men 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 Impaired cellular insulin binding and insulin sensitivity induced by high-fructose feeding in normal subjects. Effects of dietary fructose on plasma lipids in healthy subjects. Effects of a short-term overfeeding with fructose or glucose in healthy young males. Effects of 4-week very-high-fructose/glucose diets on insulin sensitivity, visceral fat and intrahepatic lipids: an exploratory trial.
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 Adverse effects of hypercaloric , high-fructose diets on insulin sensitivity and lipids in human subjects have been shown repeatedly . The implication s of fructose in amounts close to usual daily consumption , however , have not been well studied . This study assessed the effect of moderate amounts of fructose and sucrose compared with glucose on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS Nine healthy , normal-weight male volunteers ( aged 21–25 years ) were studied in this double-blind , r and omized , cross-over trial . All subjects consumed four different sweetened beverages ( 600 mL/day ) for 3 weeks each : medium fructose ( MF ) at 40 g/day , and high fructose ( HF ) , high glucose ( HG ) , and high sucrose ( HS ) each at 80 g/day . Euglycemic-hyperinsulinemic clamps with [6,6]-2H2 glucose labeling were used to measure endogenous glucose production . Lipid profile , glucose , and insulin were measured in fasting sample s. RESULTS Hepatic suppression of glucose production during the clamp was significantly lower after HF ( 59.4 ± 11.0 % ) than HG ( 70.3 ± 10.5 % , P < 0.05 ) , whereas fasting glucose , insulin , and C-peptide did not differ between the interventions . Compared with HG , LDL cholesterol and total cholesterol were significantly higher after MF , HF , and HS , and free fatty acids were significantly increased after MF , but not after the two other interventions ( P < 0.05 ) . Subjects ’ energy intake during the interventions did not differ significantly from baseline intake . CONCLUSIONS This study clearly shows that moderate amounts of fructose and sucrose significantly alter hepatic insulin sensitivity and lipid metabolism compared with similar amounts of glucose 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 We have studied whether the sucrose-induced reduction of insulin sensitivity and cellular insulin binding in normal man is related to the fructose or the glucose moiety . Seven young healthy subjects were fed their usual diets plus 1000 kcal extra glucose per day and eight young healthy subjects were fed their usual diets with addition of 1000 kcal extra fructose per day . The dietary regimens continued for 1 week . Before change of diet there were no statistically significant differences between body weight and fasting plasma concentrations of glucose , insulin , and ketone bodies in the two groups studied . High-glucose feeding caused no significant changes in insulin binding or insulin sensitivity whereas high-fructose feeding was accompanied by a significant reduction both of insulin binding ( P less than 0.05 ) and insulin sensitivity ( P less than 0.05 ) . The changes in insulin binding and insulin sensitivity correlated linearly ( r = 0.52 , P less than 0.01 ) . We conclude that fructose seems to be responsible for the impaired insulin binding and insulin sensitivity induced by sucrose BACKGROUND About 9 % of average dietary energy intake in the United States comes from fructose . Such a high consumption raises concern about the metabolic effects of this sugar . OBJECTIVE The objective of this study was to determine the effect of dietary fructose on plasma lipids . DESIGN The study was conducted in the General Clinical Research Center at Fairview-University of Minnesota Medical Center . The participants were 24 healthy adult volunteers ( 12 men and 12 women ; 6 of each sex were aged < 40 y and 6 of each sex were aged > /=40 y ) . All subjects received 2 isoenergetic study diets assigned by using a r and omized , balanced crossover design . One diet provided 17 % of energy as fructose . The other diet was sweetened with glucose and was nearly devoid of fructose . Each diet was fed for 6 wk . Both diets were composed of common foods and contained nearly identical amounts of carbohydrate , protein , fat , fiber , cholesterol , and saturated , monounsaturated , and polyunsaturated fatty acids . All meals were prepared in the metabolic kitchen of the General Clinical Research Center . RESULTS The responses to the study diets differed by sex . In men , the fructose diet produced significantly higher fasting , postpr and ial , and daylong plasma triacylglycerol concentrations than did the glucose diet . The daylong plasma triacylglycerol concentration after 6 wk of the fructose diet was 32 % greater in men than the corresponding concentration during the glucose diet ( P : < 0.001 ) . The fructose diet had no significant effect on fasting or postpr and ial plasma triacylglycerol concentrations in women . The fructose diet also had no persistent effect on fasting plasma cholesterol , HDL cholesterol , or LDL cholesterol in either men or women . CONCLUSIONS Dietary fructose was associated with increased fasting and postpr and ial plasma triacylglycerol concentrations in men . Diets high in added fructose may be undesirable , particularly for men . Glucose may be a suitable replacement sugar 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 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
target: Pooled analyses show that although fructose may increase total cholesterol , uric acid , and postpr and ial triglycerides in isocaloric replacement for glucose , it does not appear to be any worse than glucose in its effects on other aspects of the lipid profile , insulin , or markers of nonalcoholic fatty liver disease .
  It may also have important advantages over glucose for body weight , glycemic control , and blood pressure .
  SUMMARY Depending on the cardiometabolic endpoint in question , fructose has variable effects when replacing glucose .
background: PURPOSE OF REVIEW Fructose is seen as uniquely contributing to the p and emics of obesity and its cardiometabolic complications .
  Much of the evidence for this view derives from the unique biochemical , metabolic , and endocrine responses that differentiate fructose from glucose .
  To underst and whether these proposed mechanisms result in clinical ly meaningful modification of cardiovascular risk in humans , we up date a series of systematic review s and meta-analyses of controlled feeding trials to assess the cardiometabolic effects of fructose in isocaloric replacement for glucose .