The effects of four hypocaloric diets containing different levels of sucrose or high fructose corn syrup on weight loss and related parameters The Effect of Normally Consumed Amounts of Sucrose or High Fructose Corn Syrup on Lipid Profiles, Body Composition and Related Parameters in Overweight/Obese Subjects No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men. Effects of Two Energy-Restricted Diets Containing Different Fruit Amounts on Body Weight Loss and Macronutrient Oxidation 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. Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women Acute effects of feeding fructose, glucose and sucrose on blood lipid levels and systemic inflammation Dietary Fructose Reduction Improves Markers of Cardiovascular Disease Risk in Hispanic-American Adolescents with NAFLD Dietary glycemic load, carbohydrate, sugar, and colorectal cancer risk in men and women. Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways.
Background The replacement of sucrose with HFCS in food products has been suggested as playing a role in the development of obesity as a public health issue . The objective of this study was to examine the effects of four equally hypocaloric diets containing different levels of sucrose or high fructose corn syrup ( HFCS ) . Methods This was a r and omized , prospect i ve , double blind trial , with overweight/obese participants measured for body composition and blood chemistry before and after the completion of 12 weeks following a hypocaloric diet .  The average caloric deficit achieved on the hypocaloric diets was 309 kcal . Results Reductions were observed in all measures of adiposity including body mass , BMI , % body fat , waist circumference and fat mass for all four hypocaloric groups , as well as reductions in the exercise only group for body mass , BMI and waist circumference . Conclusions Similar decreases in weight and indices of adiposity are observed when overweight or obese individuals are fed hypocaloric diets containing levels of sucrose or high fructose corn syrup typically consumed by adults in the United States The American Heart Association ( AHA ) has advocated that women and men not consume more than 100 and 150 kcal/day , respectively , from added sugars . These levels are currently exceeded by over 90 % of the adult population in the United States . Few data exist on longer-term metabolic effects when sucrose and High Fructose Corn Syrup ( HFCS ) , the principal sources of added dietary sugars , are consumed at levels typical of the general population . Sixty five overweight and obese individuals were placed on a eucaloric ( weight stable ) diet for 10-weeks , which incorporated sucrose- or HFCS-sweetened , low-fat milk at 10 % or 20 % of calories in a r and omized , double-blinded study . All groups responded similarly ( interaction p > 0.05 ) . There was no change in body weight in any of the groups over the 10-week study , or in systolic or diastolic blood pressure . Likewise , there were no changes in total cholesterol , triglycerides , low-density lipoprotein ( LDL ) , or apolipoprotein B ( Apo B ) . We conclude that ( 1 ) when consumed as part of a eucaloric diet fructose — when given with glucose ( as normally consumed ) does not promote weight gain or an atherogenic lipid profile even when consumed at two to four times the level recently recommended by the AHA . ( 2 ) There were no differences between HFCS and sucrose on these parameters 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 The consumption of specific foods in energy-restricted diets may affect the weight loss process . The purpose of this research was to evaluate whether obese women following two hypocaloric diets with distinct fruit content differ in weight loss and metabolic responses .  Fifteen obese women were included , who were r and omly assigned to follow a low or a high-fruit energy-restricted diet for 8 weeks . The main outcome variables were weight and fat losses . Metabolic measurements concerning macronutrient oxidation were also assessed by using 13C labelled fructose and indirect calorimetry . The induced weight loss was similar for both diets ( 6.9 ± 2 % vs. 6.6 ± 2 % , p = 0.785 ) . Both experimental diets similarly improved the lipid plasma profile in the participants , but the cholesterol fall was higher in obese subjects receiving the diet containing more fruit . No statistical differences in lipids carbohydrates and 13C labelled fructose utilisation were observed , but protein oxidation was differently affected by the experimental diets . The compensatory effects of the associated fibre/fructose intake may explain the lack of a specific effect of the fruit amount on hypocaloric diets design ed to weight loss , although the increased fibre content from enriched fruit diets may be involved in the favourable effects on cholesterol plasma levels 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 / 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 Background Recent studies have demonstrated a relationship between fructose consumption and risk of developing metabolic syndrome . Mechanisms by which dietary fructose mediates metabolic changes are poorly understood . This study compared the effects of fructose , glucose and sucrose consumption on post-postpr and ial lipemia and low grade inflammation measured as hs-CRP . Methods This was a r and omized , single blinded , cross-over trial involving healthy subjects ( n = 14 ) . After an overnight fast , participants were given one of 3 different isocaloric drinks , containing 50 g of either fructose or glucose or sucrose dissolved in water .  Blood sample s were collected at baseline , 30 , 60 and 120 minutes post intervention for the analysis of blood lipids , glucose , insulin and high sensitivity C-reactive protein ( hs-CRP ) . Results Glucose and sucrose supplementation initially result ed in a significant increase in glucose and insulin levels compared to fructose supplementation and returned to near baseline values within 2 hours . Change in plasma cholesterol , LDL and HDL-cholesterol ( measured as area under curve , AUC ) was significantly higher when participants consumed fructose compared with glucose or sucrose ( P < 0.05 ) . AUC for plasma triglyceride levels however remained unchanged regardless of the dietary intervention . Change in AUC for hs-CRP was also significantly higher in subjects consuming fructose compared with those consuming glucose ( P < 0.05 ) , but not sucrose ( P = 0.07 ) . Conclusion This study demonstrates that fructose as a sole source of energy modulates plasma lipids and hsCRP levels in healthy individuals . The significance of increase in HDL-cholesterol with a concurrent increase in LDL-cholesterol and elevated hs-CRP levels remains to be delineated when considering health effects of feeding fructose-rich diets . Registration number for clinical 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 Hyperinsulinemia may explain excess colorectal cancer among individuals who are overweight or inactive . Recent studies have observed elevated colorectal cancer risk among individuals with elevated insulin levels 2 hours after oral glucose challenge or with elevated plasma C-peptide levels . The effect of consuming a high glycemic diet on colorectal risk , however , remains uncertain . Two prospect i ve cohort studies , the Nurses ' Health Study and the Health Professionals Follow-up Study , contributed up to 20 years of follow-up . After exclusions , 1,809 incident colorectal cancers were available for analyses .  Dietary glycemic load ( GL ) was calculated as a function of glycemic index ( postpr and ial blood glucose response as compared with a reference food ) , carbohydrate content , and frequency of intake of individual foods reported on food frequency question naires . Multivariable Cox proportional hazards models were used to adjust for potential confounders . Intakes of dietary carbohydrate , GL , overall glycemic index , sucrose , and fructose were not associated with  colorectal cancer risk in women . A small increase in risk was observed in men with high dietary GL ( multivariate relative risk , 1.32 ; 95 % confidence interval , 0.98 - 1.79 ; highest versus lowest quintile ) , sucrose or fructose ( multivariate relative risk , 1.37 ; 95 % confidence interval , 1.05 - 1.78 ; highest versus lowest quintile of fructose , P = 0.008 ) . Associations were slightly stronger among men with elevated body mass index ( > or = 25 kg/m(2 ) ) . Results among women were similar after stratifying by body mass index or physical activity . High intakes of GL , fructose , and sucrose were related to an elevated  colorectal cancer risk among men . For women , however , these factors did not seem to increase the risk of colorectal cancer IMPORTANCE Increases in fructose consumption have paralleled the increasing prevalence of obesity , and high-fructose diets are thought to promote weight gain and insulin resistance . Fructose ingestion produces smaller increases in circulating satiety hormones compared with glucose ingestion , and central administration of fructose provokes feeding in rodents , whereas central ly administered glucose promotes satiety . OBJECTIVE To study neurophysiological factors that might underlie associations between fructose consumption and weight gain . DESIGN , SETTING , AND PARTICIPANTS Twenty healthy adult volunteers underwent 2 magnetic resonance imaging sessions at Yale University in conjunction with fructose or glucose drink ingestion in a blinded , r and om-order , crossover design . MAIN OUTCOME MEASURES Relative changes in hypothalamic regional cerebral blood flow ( CBF ) after glucose or fructose ingestion . Secondary outcomes included whole-brain analyses to explore regional CBF changes , functional connectivity analysis to investigate correlations between the hypothalamus and other brain region responses , and hormone responses to fructose and glucose ingestion . RESULTS There was a significantly greater reduction in hypothalamic CBF after glucose vs fructose ingestion ( -5.45 vs 2.84 mL/g per minute , respectively ; mean difference , 8.3 mL/g per minute [ 95 % CI of mean difference , 1.87 - 14.70 ] ; P = .01 ) . Glucose ingestion ( compared with baseline ) increased functional connectivity between the hypothalamus and the thalamus and striatum . Fructose  increased connectivity between the hypothalamus and thalamus but not the striatum . Regional CBF within the hypothalamus , thalamus , insula , anterior cingulate , and striatum ( appetite and reward regions ) was reduced after glucose ingestion compared with baseline ( P < .05 significance threshold , family-wise error [ FWE ] whole-brain corrected ) . In contrast , fructose  reduced regional CBF in the thalamus , hippocampus , posterior cingulate cortex , fusiform , and visual cortex ( P < .05 significance threshold , FWE whole-brain corrected ) . In whole-brain voxel-level analyses , there were no significant differences between direct comparisons of fructose vs glucose sessions following correction for multiple comparisons . Fructose vs glucose ingestion result ed in lower peak levels of serum glucose ( mean difference , 41.0 mg/dL [ 95 % CI , 27.7 - 54.5 ] ; P < .001 ) , insulin ( mean difference , 49.6 μU/mL [ 95 % CI , 38.2 - 61.1 ] ; P < .001 ) , and glucagon-like polypeptide 1 ( mean difference , 2.1 pmol/L [ 95 % CI , 0.9 - 3.2 ] ; P = .01 ) . CONCLUSION AND RELEVANCE In a series of exploratory analyses , consumption of fructose compared with glucose result ed in a distinct pattern of regional CBF and a smaller increase in systemic glucose , insulin , and glucagon-like polypeptide 1 levels
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 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 .