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 Dietary Fructose Reduction Improves Markers of Cardiovascular Disease Risk in Hispanic-American Adolescents with NAFLD Blood lipid distribution of hyperinsulinemic men consuming three levels of fructose. Effects of dietary fructose on plasma lipids in healthy subjects. Blood lipids, lipoproteins, apoproteins, and uric acid in men fed diets containing fructose or high-amylose cornstarch. Fructose and insulin sensitivity in patients with type 2 diabetes. Effects of a short-term overfeeding with fructose or glucose in healthy young males. Effect of a dietary portfolio of cholesterol-lowering foods given at 2 levels of intensity of dietary advice on serum lipids in hyperlipidemia: a randomized controlled trial. 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. A measure to aid in the interpretation of published clinical trials. The Effects of Physiologic Amounts of Simple Sugars on Lipoprotein, Glucose, and Insulin Levels in Normal Subjects
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 Nonalcoholic fatty liver disease ( NAFLD ) is now thought to be the most common liver disease worldwide . Cardiovascular complications are a leading cause of mortality in NAFLD . Fructose , a common nutrient in the westernized diet , has been reported to be associated with increased cardiovascular risk , but its impact on adolescents with NAFLD is not well understood . We design ed a 4-week r and omized , controlled , double-blinded beverage intervention study . Twenty-four overweight Hispanic-American adolescents who had hepatic fat > 8 % on imaging and who were regular consumers of sweet beverages were enrolled and r and omized to calorie-matched study -provided fructose only or glucose only beverages . After 4 weeks , there was no significant change in hepatic fat or body weight in either group . In the glucose beverage group there was significantly improved adipose insulin sensitivity , high sensitivity C-reactive protein ( hs-CRP ) , and low-density lipoprotein ( LDL ) oxidation . These findings demonstrate that reduction of fructose improves several important factors related to cardiovascular disease despite a lack of measurable improvement in hepatic steatosis . Reducing dietary fructose may be an effective intervention to blunt atherosclerosis progression among NAFLD patients and should be evaluated in longer term clinical trials Twelve carbohydrate-sensitive men selected due to their abnormally high insulin responses to a sucrose load and 12 men with normal insulin responses were fed diets containing 0 , 7.5 , and 15 % fructose for 5 wk each in a cross-over design . The diets contained 43 % total carbohydrate , 42 % fat , and 15 % protein . Initial fasting total cholesterol and low-density lipoprotein cholesterol were higher in the hyperinsulinemic men than in the controls . Diastolic blood pressure was not affected by diet , but systolic blood pressure was slightly higher after the men consumed the 0 % fructose diet . Free fatty acids were not different . Total plasma cholesterol and low-density lipoprotein cholesterol were higher after the men consumed 7.5 and 15 % fructose than when they consumed the 0 % fructose diet . Plasma triglyceride increased significantly as fructose in the diets of the hyperinsulinemics increased , but was not affected in the controls . These changes in blood lipids are associated with heart disease 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 Ten hyperinsulinemic and 11 nonhyperinsulinemic men consumed for 5 wk each in a cross-over design a diet , similar to one currently consumed in the United States , with 20 % of the kilocalories from either fructose or high-amylose cornstarch to determine the effects of the two diets on various blood metabolites considered to be risk factors associated with heart disease . In the hyperinsulinemic men the intake of fructose as compared with cornstarch significantly increased total triglycerides and their lipoprotein distribution ; total and very-low-density lipoprotein cholesterol ; apoproteins B-100 , C-II , C-III ; and uric acid . In the nonhyperinsulinemic men  total triglycerides , total and low-density lipoprotein cholesterol and uric acid were significantly greater after the consumption of fructose than after cornstarch . The results indicate that in a diet high in saturated fatty acids and cholesterol , fructose increases the levels of risk factors associated with heart disease , especially in hyperinsulinemic men The effect of dietary fructose ( 20 % of carbohydrate calories , 45 - 65 g day-1 for 4 weeks ) on glycaemic control , serum lipid , lipoprotein and apoprotein A-I and A-II concentrations and on insulin sensitivity was studied in 10 type 2 diabetic patients . The study was done in a r and omized , double-blind fashion with crystalline fructose or placebo administered evenly during 4 meals or snacks per day . The patients were hospitalized throughout the study periods . The fasting plasma glucose concentration decreased during the fructose ( from 10.7 + /- 1.4 mmol l-1 to 8.0 + /- 0.8 mmol l-1 , P < 0.02 ) and the control diet ( from 10.1 + /- 0.9 mmol l-1 to 8.0 + /- 0.7 mmol l-1 , P < 0.05 ) . The mean diurnal blood glucose concentration also fell both during the fructose ( from 10.8 + /- 0.5 mmol l-1 to 8.4 + /- 0.3 mmol l-1 , P < 0.001 ) and the control diet ( from 10.3 + /- 0.3 mmol l-1 to 8.8 + /- 0.9 mmol l-1 , P < 0.01 ) . The HbA1 concentration improved ( P < 0.02 ) only during the fructose diet . Insulin sensitivity increased by 34 % ( P < 0.05 ) during the fructose diet , but remained unchanged during the control period . Serum insulin , triglyceride , apoprotein A-I and A-II concentrations , body weight , blood pressure and blood lactate remained unchanged during both diets . In conclusion , substitution of moderate amounts of fructose for complex carbohydrates can improve glycaemic control and insulin sensitivity in patients with type 2 diabetes 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 CONTEXT Combining foods with recognized cholesterol-lowering properties ( dietary portfolio ) has proven highly effective in lowering serum cholesterol under metabolically controlled conditions . OBJECTIVE To assess the effect of a dietary portfolio administered at 2 levels of intensity on percentage change in low-density lipoprotein cholesterol ( LDL-C ) among participants following self-selected diets . DESIGN , SETTING , AND PARTICIPANTS A parallel- design study of 351 participants with hyperlipidemia from 4 participating academic centers across Canada ( Quebec City , Toronto , Winnipeg , and Vancouver ) r and omized between June 25 , 2007 , and February 19 , 2009 , to 1 of 3 treatments lasting 6 months . INTERVENTION Participants received dietary advice for 6 months on either a low-saturated fat therapeutic diet ( control ) or a dietary portfolio , for which counseling was delivered at different frequencies , that emphasized dietary incorporation of plant sterols , soy protein , viscous fibers , and nuts . Routine dietary portfolio involved 2 clinic visits over 6 months and intensive dietary portfolio involved 7 clinic visits over 6 months . MAIN OUTCOME MEASURES Percentage change in serum LDL-C. RESULTS In the modified intention-to-treat analysis of 345 participants , the overall attrition rate was not significantly different between treatments ( 18 % for intensive dietary portfolio , 23 % for routine dietary portfolio , and 26 % for control ; Fisher exact test , P = .33 ) . The LDL-C reductions from an overall mean of 171 mg/dL ( 95 % confidence interval [ CI ] , 168 - 174 mg/dL ) were -13.8 % ( 95 % CI , -17.2 % to -10.3 % ; P < .001 ) or -26 mg/dL ( 95 % CI , -31 to -21 mg/dL ; P < .001 ) for the intensive dietary portfolio ; -13.1 % ( 95 % CI , -16.7 % to -9.5 % ; P < .001 ) or -24 mg/dL ( 95 % CI , -30 to -19 mg/dL ; P < .001 ) for the routine dietary portfolio ; and -3.0 % ( 95 % CI , -6.1 % to 0.1 % ; P = .06 ) or -8 mg/dL ( 95 % CI , -13 to -3 mg/dL ; P = .002 ) for the control diet . Percentage LDL-C reductions for each dietary portfolio were significantly more than the control diet ( P < .001 , respectively ) . The 2 dietary portfolio interventions did not differ significantly ( P = .66 ) . Among participants r and omized to one of the dietary portfolio interventions , percentage reduction in LDL-C on the dietary portfolio was associated with dietary adherence ( r = -0.34 , n = 157 , P < .001 ) . CONCLUSION Use of a dietary portfolio compared with the low-saturated fat dietary advice result ed in greater LDL-C lowering during 6 months of follow-up . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00438425 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 The published literature contains numerous reports of clinical studies . A problem in their interpretation is that studies in which the observed efficacy of the treatment is high are much more likely to be reported than those in which the observed efficacy is average or poor . This phenomenon has had the consequence of generally discrediting the reliability of the literature , especially that of non-r and omized studies . In this paper a model is developed which permits estimation of the potential magnitude by which the reported efficacy of a treatment might be inflated . This quantity is termed the publication bias . The magnitude of the bias depends on the sample size of the study and the number of similar studies conducted concurrently . Tabulated values of the bias are presented , permitting easy computation . The new measure may have potential use for physicians in clinical decision making in that it characterizes the reliability of results from a specific published study , especially when there are no definitive r and omized studies . However , correction of publication bias in this manner is not a substitute for a well controlled or a r and omized study . The technique merely assists in the interpretation of available evidence from the literature . Moreover , it must be used with due caution in recognition of the assumptions and approximations involved in the calculation Using a crossover design , eight healthy volunteers r and omly received physiologic amounts ( ⅓ of each subject 's total carbohydrate intake ) of either fructose or sucrose as the primary source of simple sugar , incorporated into isocaloric diets comprised of typical American foods . After 7 and 14 days of consuming either of the two sugars , no change occurred in fasting glucose or insulin levels . In addition , total triglyceride , totalcholesterol , low-density-lipoprotein ( LDL ) cholesterol , and high-density-lipoprotein ( HDL ) cholesterol concentrations were unaltered . Since our study used conventional foods in normal eating patterns rather than contrived formulas or excessive amounts of simple sugar , our data indicate that there is no difference between sucrose or fructose on various lipid components or glucose and fasting insulin levels in the “ real world ” innormal subjects
target: Fructose had no effect on LDL-C , non-HDL-C , apolipoprotein B , triglycerides , or HDL-C in isocaloric trials .
  Conclusions Pooled analyses showed that fructose only had an adverse effect on established lipid targets when added to existing diets so as to provide excess calories ( + 21 % to 35 % energy ) .
  When isocalorically exchanged for other carbohydrates , fructose had no adverse effects on blood lipids .
background: Background Debate over the role of fructose in mediating  cardiovascular  risk remains active .
  To up date the evidence on the effect of fructose on established therapeutic lipid targets for cardiovascular disease ( low-density lipoprotein cholesterol [LDL]-C , apolipoprotein B , non-high-density lipoprotein cholesterol [ HDL-C ] ) , and metabolic syndrome ( triglycerides and HDL-C ) , we conducted a systematic review and meta- analysis of controlled feeding trials .