title: Macronutrient disposal during controlled overfeeding with glucose, fructose, sucrose, or fat in lean and obese women. 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. Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women. Extending the CONSORT statement to randomized trials of nonpharmacologic treatment: explanation and elaboration. Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospective, observational analysis Fructose and insulin sensitivity in patients with type 2 diabetes. Effects of a short-term overfeeding with fructose or glucose in healthy young males. Effects of Decreasing Sugar-Sweetened Beverage Consumption on Body Weight in Adolescents: A Randomized, Controlled Pilot Study 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 Previous short-term studies ( < or = 6 h ) showed differences in energy expenditure ( EE ) and macronutrient oxidation in response to overfeeding with different types of dietary carbohydrate . This finding could have implication s for obesity . OBJECTIVE We used 96-h continuous whole-body calorimetry in 8 lean and 5 obese women to assess metabolic disposal ( energy dissipation and glycogen or fat storage ) of a controlled excess of dietary energy supplied as different carbohydrate sources or as fat . DESIGN Five dietary treatments were applied in r and om order : energy balance ( control ) and overfeeding by 50 % of energy requirements with fat ( O(fat ) ) or predominantly with glucose , fructose , or sucrose ( O(cho ) ) .  Macronutrient oxidation rates were assessed from nonprotein gaseous exchanges . Net macronutrient balances were calculated as cumulative differences between intake and oxidation . RESULTS Increased EE in response to overfeeding dissipated 7.9 % of the energy excess with a variation in EE of < 1.7 % across overfeeding treatments ( NS ) . EE during the O(fat ) treatment significantly exceeded that during the control treatment in the lean but not in the obese women . There were no significant differences between lean and obese women in macronutrient oxidation or balances , so data were pooled . O(cho ) induced glycogen storage on day 1 ( approximately 100 g ) but thereafter progressively stimulated carbohydrate oxidation so that balance was reached on days 3 and 4 . Fat oxidation was proportionately suppressed . Of the excess carbohydrate , 74 % was oxidized ; there were no significant differences between the various O(cho ) treatments . O(fat ) stimulated fat oxidation by 18 % and suppressed carbohydrate oxidation . On average , 12 % of the excess energy was stored as glycogen and 88 % as fat ; there was no significant difference between overfeeding treatments . CONCLUSION There was no significant difference in fat balance during controlled overfeeding with fat , fructose , glucose , or sucrose 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 CONTEXT Sugar-sweetened beverages like soft drinks and fruit punches contain large amounts of readily absorbable sugars and may contribute to weight gain and an increased risk of type 2 diabetes , but these relationships have been minimally addressed in adults . OBJECTIVE To examine the association between consumption of sugar-sweetened beverages and weight change and  risk of type 2 diabetes in women . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort analyses conducted from 1991 to 1999 among women in the Nurses ' Health Study II . The diabetes analysis included 91,249 women free of diabetes and other major chronic diseases at baseline in 1991 . The weight change analysis included 51,603 women for whom complete dietary information and body weight were ascertained in 1991 , 1995 , and 1999 . We identified 741 incident cases of confirmed type 2 diabetes during 716,300 person-years of follow-up . MAIN OUTCOME MEASURES Weight gain and incidence of type 2 diabetes . RESULTS Those with stable consumption patterns had no difference in weight gain , but weight gain over a 4-year period was highest among women who increased their sugar-sweetened soft drink consumption from 1 or fewer drinks per week to 1 or more drinks per day ( multivariate-adjusted means , 4.69 kg for 1991 to 1995 and 4.20 kg for 1995 to 1999 ) and was smallest among women who decreased their intake ( 1.34 and 0.15 kg for the 2 periods , respectively ) after adjusting for lifestyle and dietary confounders . Increased consumption of fruit punch was also associated with greater weight gain compared with decreased consumption . After adjustment for potential confounders , women consuming 1 or more sugar-sweetened soft drinks per day had a relative risk [ RR ] of type 2 diabetes of 1.83 ( 95 % confidence interval [ CI ] , 1.42 - 2.36 ; P<.001 for trend ) compared with those who consumed less than 1 of these beverages per month . Similarly , consumption of fruit punch was associated with increased diabetes risk ( RR for > or = 1 drink per day compared with < 1 drink per month , 2.00 ; 95 % CI , 1.33 - 3.03 ; P = .001 ) . CONCLUSION Higher consumption of sugar-sweetened beverages is associated with a greater magnitude of weight gain and an increased risk for development of  type 2 diabetes in women , possibly by providing excessive calories and large amounts of rapidly absorbable sugars Adequate reporting of r and omized , controlled trials ( RCTs ) is necessary to allow accurate critical appraisal of the validity and applicability of the results . The CONSORT ( Consoli date d St and ards of Reporting Trials ) Statement , a 22-item checklist and flow diagram , is intended to address this problem by improving the reporting of RCTs . However , some specific issues that apply to trials of nonpharmacologic treatments ( for example , surgery , technical interventions , devices , rehabilitation , psychotherapy , and behavioral intervention ) are not specifically addressed in the CONSORT Statement . Furthermore , considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement . Therefore , the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments . A consensus meeting of 33 experts was organized in Paris , France , in February 2006 , to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments . The participants extended 11 items from the CONSORT Statement , added 1 item , and developed a modified flow diagram . To allow adequate underst and ing and implementation of the CONSORT extension , the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting . This extension , in conjunction with the main CONSORT Statement and other CONSORT extensions , should help to improve the reporting of RCTs performed in this field BACKGROUND The rising prevalence of obesity in children has been linked in part to the consumption of sugar-sweetened drinks . Our aim was to examine this relation . METHODS We enrolled 548 ethnically diverse schoolchildren ( age 11.7 years , SD 0.8 ) from public schools in four Massachusetts communities , and studied them prospect ively for 19 months from October , 1995 , to May , 1997 . We examined the association between baseline and change in consumption of sugar-sweetened drinks ( the independent variables ) , and difference in measures of obesity , with linear and logistic regression analyses adjusted for potentially confounding variables and clustering of results within schools . FINDINGS For each additional serving of sugar-sweetened drink consumed , both body mass index ( BMI ) ( mean 0.24 kg/m2 ; 95 % CI 0.10 - 0.39 ; p=0.03 ) and frequency of obesity ( odds ratio 1.60 ; 95 % CI 1.14 - 2.24 ; p=0.02 ) increased after adjustment for anthropometric , demographic , dietary , and lifestyle variables . Baseline consumption of sugar-sweetened drinks was also independently associated with change in BMI ( mean 0.18 kg/m2 for each daily serving ; 95 % CI 0.09 - 0.27 ; p=0.02 ) . INTERPRETATION Consumption of sugar-sweetened drinks is associated with obesity in children 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 OBJECTIVE . The role of sugar-sweetened beverages ( SSBs ) in promoting obesity is controversial . Observational data link SSB consumption with excessive weight gain ; however , r and omized , controlled trials are lacking and necessary to resolve the debate . We conducted a pilot study to examine the effect of decreasing SSB consumption on body weight . METHODS . We r and omly assigned 103 adolescents aged 13 to 18 years who regularly consumed SSBs to intervention and control groups . The intervention , 25 weeks in duration , relied largely on home deliveries of noncaloric beverages to displace SSBs and thereby decrease consumption . Change in  SSB consumption was the main process measure , and change in body mass index ( BMI ) was the primary end point . RESULTS . All of the r and omly assigned subjects completed the study . Consumption of SSBs  decreased by 82 % in the intervention group and did not change in the control group . Change in BMI , adjusted for gender and age , was 0.07 ± 0.14 kg/m2 ( mean ± SE ) for the intervention group and 0.21 ± 0.15 kg/m2 for the control group . The net difference , −0.14 ± 0.21 kg/m2 , was not significant overall . However , baseline BMI was a significant effect modifier . Among the subjects in the upper baseline- BMI tertile , BMI change differed significantly between the intervention ( −0.63 ± 0.23 kg/m2 ) and control ( + 0.12 ± 0.26 kg/m2 ) groups , a net effect of −0.75 ± 0.34 kg/m2 . The interaction between weight change and baseline BMI was not attributable to baseline consumption of SSBs . CONCLUSIONS . A simple environmental intervention almost completely eliminated SSB consumption in a diverse group of adolescents . The beneficial effect on body weight of reducing SSB consumption increased with increasing baseline body weight , offering additional support for American Academy of Pediatrics guidelines to limit SSB consumption 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: The weight-increasing effect of fructose in hypercaloric trials may have been attributable to excess energy rather than fructose itself .
  Fructose does not seem to cause weight gain when it is substituted for other carbohydrates in diets providing similar calories .
  Free fructose at high doses that provided excess calories modestly increased body weight , an effect that may be due to the extra calories rather than the fructose .
background: BACKGROUND The contribution of fructose consumption in Western diets to overweight and obesity in population s remains uncertain .
  PURPOSE To review the effects of fructose on body weight in controlled feeding trials .