title: Impaired cellular insulin binding and insulin sensitivity induced by high-fructose feeding in normal subjects. Blood lipid distribution of hyperinsulinemic men consuming three levels of fructose. Effects of dietary fructose on plasma lipids in healthy subjects. Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women Acute fructose administration improves oral glucose tolerance in adults with type 2 diabetes. Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. Effects of a short-term overfeeding with fructose or glucose in healthy young males. Effects of high-fructose corn syrup and sucrose consumption on circulating glucose, insulin, leptin, and ghrelin and on appetite in normal-weight women. Effects of 4-week very-high-fructose/glucose diets on insulin sensitivity, visceral fat and intrahepatic lipids: an exploratory trial. The Effects of Physiologic Amounts of Simple Sugars on Lipoprotein, Glucose, and Insulin Levels in Normal Subjects
abstract: 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 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 Background / Objectives : The results of short-term studies in humans suggest that , compared with glucose , acute consumption of fructose leads to increased postpr and ial energy expenditure and carbohydrate oxidation and decreased postpr and ial fat oxidation . The objective of this study was to determine the potential effects of increased fructose consumption compared with isocaloric glucose consumption on substrate utilization and energy expenditure following sustained consumption and under energy-balanced conditions . Subjects/ Methods : As part of a parallel arm study , overweight/obese male and female subjects , 40–72 years , consumed glucose- or fructose-sweetened beverages providing 25 % of energy requirements for 10 weeks . Energy expenditure and substrate utilization were assessed using indirect calorimetry at baseline and during the 10th week of intervention . Results : Consumption of fructose , but not glucose , led to significant decreases of net postpr and ial fat oxidation and significant increases of net postpr and ial carbohydrate oxidation ( P<0.0001 for both ) . Resting energy expenditure ( REE ) decreased significantly from baseline values in subjects consuming fructose ( P=0.031 ) but not in those consuming glucose . Conclusions : Increased consumption of fructose for 10 weeks leads to marked changes of postpr and ial substrate utilization including a significant reduction of net fat oxidation . In addition , we report that REE is reduced compared with baseline values in subjects consuming fructose-sweetened beverages for 10 weeks OBJECTIVE In normal adults , a small ( catalytic ) dose of fructose administered with glucose decreases the glycemic response to a glucose load , especially in those with the poorest glucose tolerance . We hypothesized that an acute catalytic dose of fructose would also improve glucose tolerance in individuals with type 2 diabetes . RESEARCH DESIGN AND METHODS Five adults with type 2 diabetes underwent an oral glucose tolerance test ( OGTT ) on two separate occasions , at least 1 week apart . Each OGTT consisted of 75 g glucose with or without the addition of 7.5 g fructose ( OGTT + F or OGTT - F ) , in r and om order . Arterialized blood sample s were collected from a heated dorsal h and vein twice before ingestion of the carbohydrate and every 15 min for 3 h afterward . RESULTS The area under the curve ( AUC ) of the plasma glucose response was reduced by fructose administration in all subjects ; the mean AUC during the OGTT + F was 14 % less than that during the OGTT - F ( P < 0.05 ) . The insulin AUC was decreased 21 % with fructose administration ( P = 0.2 ) . Plasma glucagon concentrations declined similarly during OGTT - F and OGTT + F. The incremental AUC of the blood lactate response during the OGTT - F was approximately 50 % of that observed during the OGTT + F ( P < 0.05 ) . Neither nonesterified fatty acid nor triglyceride concentrations differed between the two OGTTs . CONCLUSIONS Low-dose fructose improves the glycemic response to an oral glucose load in adults with type 2 diabetes , and this effect is not a result of stimulation of insulin secretion Previous studies indicate that leptin secretion is regulated by insulin-mediated glucose metabolism . Because fructose , unlike glucose , does not stimulate insulin secretion , we hypothesized that meals high in fructose would result in lower leptin concentrations than meals containing the same amount of glucose . Blood sample s were collected every 30 - 60 min for 24 h from 12 normal-weight women on 2 r and omized days during which the subjects consumed three meals containing 55 , 30 , and 15 % of total kilocalories as carbohydrate , fat , and protein , respectively , with 30 % of kilocalories as either a fructose-sweetened [ high fructose ( HFr ) ] or glucose-sweetened [ high glucose ( HGl ) ] beverage . Meals were isocaloric in the two treatments . Postpr and ial glycemic excursions were reduced by 66 + /- 12 % , and insulin responses were 65 + /- 5 % lower ( both P < 0.001 ) during HFr consumption . The area under the curve for leptin during the first 12 h ( -33 + /- 7 % ; P < 0.005 ) , the entire 24 h ( -21 + /- 8 % ; P < 0.02 ) , and the diurnal amplitude ( peak - nadir ) ( 24 + /- 6 % ; P < 0.0025 ) were reduced on the HFr day compared with the HGl day . In addition , circulating levels of the orexigenic gastroenteric hormone , ghrelin , were suppressed by approximately 30 % 1 - 2 h after ingestion of each HGl meal ( P < 0.01 ) , but postpr and ial suppression of ghrelin was significantly less pronounced after HFr meals ( P < 0.05 vs. HGl ) . Consumption of HFr meals produced a rapid and prolonged elevation of plasma triglycerides compared with the HGl day ( P < 0.005 ) . Because insulin and leptin , and possibly ghrelin , function as key signals to the central nervous system in the long-term regulation of energy balance , decreases of circulating insulin and leptin and increased ghrelin concentrations , as demonstrated in this study , could lead to increased caloric intake and ultimately contribute to weight gain and obesity during chronic consumption of diets high in fructose 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 OBJECTIVE Fructose has been implicated in obesity , partly due to lack of insulin-mediated leptin stimulation and ghrelin suppression . Most work has examined effects of pure fructose , rather than high-fructose corn syrup ( HFCS ) , the most commonly consumed form of fructose . This study examined effects of beverages sweetened with HFCS or sucrose ( Suc ) , when consumed with mixed meals , on blood glucose , insulin , leptin , ghrelin , and appetite . METHODS Thirty lean women were studied on two r and omized 2-d visits during which HFCS- and Suc-sweetened beverages were consumed as 30 % of energy on isocaloric diets during day 1 while blood was sample d. On day 2 , food was eaten ad libitum . Subjects rated appetite at design ated times throughout visits . RESULTS No significant differences between the two sweeteners were seen in fasting plasma glucose , insulin , leptin , and ghrelin ( P > 0.05 ) . The within-day variation in all four items was not different between the two visits ( P > 0.05 ) . Net areas under the curve were similar for glucose , insulin , and leptin ( P > 0.05 ) . There were no differences in energy or macronutrient intake on day 2 . The only appetite variable that differed between sweeteners was desire to eat , which had a higher area under the curve the day after Suc compared with HFCS . CONCLUSION These short-term results suggest that , when fructose is consumed in the form of HFCS , the measured metabolic responses do not differ from Suc in lean women . Further research is required to examine appetite responses and to determine if these findings hold true for obese individuals , males , or longer periods 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 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: The results did not show any evidence of publication bias .
  CONCLUSION Fructose consumption from industrialized foods has significant effects on most components of metabolic syndrome
background: OBJECTIVE The aim of this study was to review the current corpus of human studies to determine the association of various doses and duration s of fructose consumption on metabolic syndrome .