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 Acute effects of feeding fructose, glucose and sucrose on blood lipid levels and systemic inflammation No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men. Effects of fructose vs glucose on regional cerebral blood flow in brain regions involved with appetite and reward pathways. Effects of high-fructose corn syrup and sucrose consumption on circulating glucose, insulin, leptin, and ghrelin and on appetite in normal-weight women. Differential effects of fructose versus glucose on brain and appetitive responses to food cues and decisions for food rewards Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans. Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. Consumption of fructose-sweetened beverages for 10 weeks reduces net fat oxidation and energy expenditure in overweight/obese men and women Appetite hormones and energy intake in obese men after consumption of fructose, glucose and whey protein beverages Dissociable Behavioral, Physiological and Neural Effects of Acute Glucose and Fructose Ingestion: A Pilot Study Fructose ingestion acutely elevates blood pressure in healthy young humans. Carbohydrate-induced thermogenesis in liver cirrhosis: glucose vs. fructose. High-fructose corn syrup and sucrose have equivalent effects on energy-regulating hormones at normal human consumption levels. Effects of 4-week very-high-fructose/glucose diets on insulin sensitivity, visceral fat and intrahepatic lipids: an exploratory trial. Mechanisms for the acute effect of fructose on postprandial lipemia. Day-long glucose, insulin, and fructose responses of hyperinsulinemic and nonhyperinsulinemic men adapted to diets containing either fructose or high-amylose cornstarch. Acute effects of fructose and glucose ingestion with and without caffeine in young and old humans. Effects of oral fructose and glucose on plasma GLP-1 and appetite in normal subjects Differential Effects of FODMAPs (Fermentable Oligo-, Di-, Mono-Saccharides and Polyols) on Small and Large Intestinal Contents in Healthy Subjects Shown by MRI Effects of dietary fructose on plasma lipids in healthy subjects. Blunted suppression of acyl-ghrelin in response to fructose ingestion in obese adolescents: the role of insulin resistance. An isocaloric glucose-fructose beverage's effect on simulated 100-km cycling performance compared with a glucose-only beverage.
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 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 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 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 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 Significance Fructose compared with glucose may be a weaker suppressor of appetite . Here we sought to determine the effects of fructose versus glucose on brain , hormone , and appetitive responses to food cues and food-approach behavior . We show that the ingestion of fructose compared with glucose result ed in smaller increases in plasma insulin levels and greater brain responses to food cues in the visual cortex and left orbital frontal cortex . Ingestion of fructose versus glucose also led to greater hunger and desire for food and a greater willingness to give up long-term monetary rewards to obtain immediate high-calorie foods . These findings suggest that ingestion of fructose relative to glucose activates brain regions involved in attention and reward processing and may promote feeding behavior . Prior studies suggest that fructose compared with glucose may be a weaker suppressor of appetite , and neuroimaging research shows that food cues trigger greater brain reward responses in a fasted relative to a fed state . We sought to determine the effects of ingesting fructose versus glucose on brain , hormone , and appetitive responses to food cues and food-approach behavior . Twenty-four healthy volunteers underwent two functional magnetic resonance imaging ( fMRI ) sessions with ingestion of either fructose or glucose in a double-blinded , r and om-order cross-over design . fMRI was performed while participants viewed images of high-calorie foods and nonfood items using a block design . After each block , participants rated hunger and desire for food . Participants also performed a decision task in which they chose between immediate food rewards and delayed monetary bonuses . Hormones were measured at baseline and 30 and 60 min after drink ingestion . Ingestion of fructose relative to glucose result ed in smaller increases in plasma insulin levels and greater brain reactivity to food cues in the visual cortex ( in whole-brain analysis ) and left orbital frontal cortex ( in region-of-interest analysis ) . Parallel to the neuroimaging findings , fructose versus glucose led to greater hunger and desire for food and a greater willingness to give up long-term monetary rewards to obtain immediate high-calorie foods . These findings suggest that ingestion of fructose relative to glucose results in greater activation of brain regions involved in attention and reward processing and may promote feeding behavior AIMS In animals , intracerebroventricular glucose and fructose have opposing effects on appetite and weight regulation . In humans , functional brain magnetic resonance imaging ( fMRI ) studies during glucose ingestion or infusion have demonstrated suppression of hypothalamic signalling , but no studies have compared the effects of glucose and fructose . We therefore sought to determine if the brain response differed to glucose vs. fructose in humans independently of the ingestive process . METHODS Nine healthy , normal weight subjects underwent blood oxygenation level dependent ( BOLD ) fMRI measurements during either intravenous ( IV ) glucose ( 0.3 mg/kg ) , fructose ( 0.3 mg/kg ) or saline , administered over 2 min in a r and omized , double-blind , crossover study . Blood was sample d every 5 min during a baseline period and following infusion for 60 min in total for glucose , fructose , lactate and insulin levels . RESULTS No significant brain BOLD signal changes were detected in response to IV saline .  BOLD signal in the cortical control areas increased during glucose infusion ( p = 0.002 ) , corresponding with increased plasma glucose and insulin levels . In contrast , BOLD signal decreased in the cortical control areas during fructose infusion ( p = 0.006 ) , corresponding with increases of plasma fructose and lactate . Neither glucose nor fructose infusions significantly altered BOLD signal in the hypothalamus . CONCLUSION In normal weight humans , cortical responses as assessed by BOLD fMRI to infused glucose are opposite to those of fructose . Differential brain responses to these sugars and their metabolites may provide insight into the neurologic basis for dysregulation of food intake during high dietary fructose intake 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 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 : To investigate appetite responses over 4 h to fructose beverages in obese men , relative to glucose and whey protein . Second , to investigate the effect of combining whey and fructose on postpr and ial appetite hormones . Design : R and omized , double-blind crossover study of four beverages ( 1.1 MJ ) containing 50 g of whey , fructose , glucose or 25 g whey+25 g fructose . Blood sample s and appetite ratings were collected for 4 h then a buffet meal was offered . Subjects : Twenty-eight obese men ( age : 57.0±1.6 years , body mass index : 32.5±0.6 kg/m2 )  Measurements : Plasma ghrelin ( total ) , glucagon-like peptide-1 ( GLP-1 7–36 ) , cholecystokinin-8 , glucose , insulin and appetite ratings were assessed at baseline and 30 , 45 , 60 , 90 , 120 , 180 , 240 min after beverages , followed by measurement of ad libitum energy intake . Results : Fructose  produced lower glycaemia and insulinaemia compared to the glucose treatment ( P<0.0001 ) ; whereas postpr and ial ghrelin , GLP-1 and cholecystokinin responses were similar after both treatments . Whey protein produced a prolonged ( 2–4 h ) suppression of ghrelin ( P=0.001 ) and elevation of GLP-1 ( P=0.002 ) and cholecystokinin ( P=0.003 ) that were reduced when combined with fructose , while glucose and insulin responses were similar . Energy intake after 4 h was independent of beverage type ( glucose 4.7±0.2 MJ ; fructose 4.9±0.3 MJ ; whey 4.6±0.3 MJ ; whey/fructose 4.8±0.3 MJ ; P>0.05 ) . Conclusion : In obese men  , fructose- and glucose-based beverages had similar effects on appetite and associated regulatory hormones , independent of the differing glycaemic and insulinaemic responses . The contrasting profile of plasma ghrelin , GLP-1 and cholecystokinin after whey protein consumption did not impact on ad libitum intake 4 h later and was attenuated when 50 % of whey was replaced with fructose Previous research has revealed that glucose and fructose ingestion differentially modulate release of satiation hormones . Recent studies have begun to eluci date brain-gut interactions with neuroimaging approaches such as magnetic resonance imaging ( MRI ) , but the neural mechanism underlying different behavioral and physiological effects of glucose and fructose are unclear . In this paper , we have used resting state functional MRI to explore whether acute glucose and fructose ingestion also induced dissociable effects in the neural system . Using a cross-over , double-blind , placebo-controlled design , we compared resting state functional connectivity ( rsFC ) strengths within the basal ganglia/limbic network in 12 healthy lean males . Each subject was administered fructose , glucose and placebo on three separate occasions . Subsequent correlation analysis was used to examine relations between rsFC findings and plasma concentrations of satiation hormones and subjective feelings of appetite . Glucose ingestion induced significantly greater elevations in plasma glucose , insulin , GLP-1 and GIP , while feelings of fullness increased and prospect i ve food consumption decreased relative to fructose . Furthermore , glucose increased rsFC of the left caudatus and putamen , precuneus and lingual gyrus more than fructose , whereas within the basal ganglia/limbic network , fructose increased rsFC of the left amygdala , left hippocampus , right parahippocampus , orbitofrontal cortex and pre central gyrus more than glucose . Moreover , compared to fructose , the increased rsFC after glucose positively correlated with the glucose-induced increase in insulin . Our findings suggest that glucose and fructose induce dissociable effects on rsFC within the basal ganglia/limbic network , which are probably mediated by different insulin levels . A larger study would be recommended in order to confirm these findings Overconsumption of fructose , particularly in the form of soft drinks , is increasingly recognized as a public health concern . The acute cardiovascular responses to ingesting fructose have not , however , been well-studied in humans . In this r and omized crossover study , we compared cardiovascular autonomic regulation after ingesting water and drinks containing either glucose or fructose in 15 healthy volunteers ( aged 21 - 33 yr ) . The total volume of each drink was 500 ml , and the sugar content 60 g. For 30 min before and 2 h after each drink , we recorded beat-to-beat heart rate , arterial blood pressure , and cardiac output . Energy expenditure was determined on a minute-by-minute basis . Ingesting the fructose drink significantly increased blood pressure , heart rate , and cardiac output but not total peripheral resistance . Glucose ingestion result ed in a significantly greater increase in cardiac output than fructose but no change in blood pressure and a concomitant decrease in total peripheral resistance . Ingesting glucose and fructose , but not water , significantly increased blood pressure variability and decreased cardiovagal baroreflex sensitivity . Energy expenditure increased by a similar amount after glucose and fructose ingestion , but fructose elicited a significantly greater increase in respiratory quotient . These results show that ingestion of glucose and fructose drinks is characterized by specific hemodynamic responses . In particular , fructose ingestion elicits an increase in blood pressure that is probably mediated by an increase in cardiac output without compensatory peripheral vasodilatation Reduced thermic response after a glucose load has been reported in liver cirrhosis . To determine the mechanism and the site of this phenomenon , the effects of glucose and fructose on energy expenditure ( EE ) were measured in seven well-nourished cirrhotic patients and in six healthy control subjects .  EE and fuel utilization were measured via indirect calorimetry for 3 h after oral glucose or fructose administration ( 1 g/kg body wt ) . After a glucose load , plasma glucose and insulin concentrations were higher in cirrhotic patients than in control subjects ( p < 0.05 ) . During the glucose trial , the cumulative incremental changes in EE over the 3-h measurement period were lower ( p < 0.01 ) in patients than in the control subjects ( 0.98 + /- 0.13 vs. 1.70 + /- 0.23 kJ.kg-1.3 h-1 ) . After fructose ingestion , the cumulative changes in the EE of control subjects ( 1.76 + /- 0.24 kJ.kg-1.3 h-1 ) and cirrhotic patients ( 1.59 + /- 0.15 kJ.kg-1.3 h-1 ) were similar . In cirrhotic patients , the EE increase after fructose was higher than after glucose ( p < 0.05 ) . After glucose and fructose ingestion , no difference was observed between the carbohydrate oxidation in cirrhotic patients and that in control subjects , and lipid oxidation was suppressed to the same extent in both groups . We conclude that glucose-induced thermogenesis is impaired in liver cirrhosis , whereas fructose can normalize the thermic response . Because fructose is chiefly metabolized in the liver , these findings suggest that extrahepatic tissues are the site of defective thermogenesis in liver cirrhosis Intake of high-fructose corn syrup ( HFCS ) has been suggested to contribute to the increased prevalence of obesity , whereas a number of studies and organizations have reported metabolic equivalence between HFCS and sucrose . We hypothesized that HFCS and sucrose would have similar effects on energy-regulating hormones and metabolic substrates at normal levels of human consumption and that these values would not change over a 10-week , free-living period at these consumption levels . This was a r and omized , prospect i ve , double-blind , parallel group study in which 138 adult men and women consumed 10 weeks of low-fat milk sweetened with either HFCS or sucrose at levels of the 25th , 50th , and 90th percentile population consumption of fructose ( the equivalent of 40 , 90 , or 150 g of sugar per day in a 2000-kcal diet ) . Before and after the 10-week intervention , 24-hour blood sample s were collected . The area under the curve ( AUC ) for glucose , insulin , leptin , active ghrelin , triglyceride , and uric acid was measured . There were no group differences at baseline or posttesting for all outcomes ( interaction , P > .05 ) . The AUC response of glucose , active ghrelin , and uric acid did not change between baseline and posttesting ( P > .05 ) , whereas the AUC response of insulin ( P < .05 ) , leptin ( P < .001 ) , and triglyceride ( P < .01 ) increased over the course of the intervention when the 6 groups were averaged . We conclude that there are no differences in the metabolic effects of HFCS and sucrose when compared at low , medium , and high levels of 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 A high fructose intake can lead to postpr and ial hypertriacylglycerolemia . The underlying mechanism is unclear . OBJECTIVE The objective of the study was to investigate the mechanisms involved in fructose-induced hypertriacylglycerolemia and the contribution of de novo lipogenesis in an acute setting . DESIGN In a r and omized , crossover study , 14 subjects were given a fructose or glucose test meal after an overnight fast . [(2)H2]Palmitate and [U(13)C]d-fructose or [U(13)C]d-glucose were added to trace the h and ling of dietary fats and the fate of dietary sugars in the body . Blood sample s were taken before and after the meal . Respiratory exchange ratio was measured by using indirect calorimetry , and breath sample s were collected . RESULTS Plasma triacylglycerol and VLDL-triacylglycerol concentrations were significantly higher ( P = 0.001 for both ) , whereas the concentrations of insulin and [(2)H2]palmitate in nonesterified fatty acids were significantly lower after fructose than after glucose ( P = 0.002 and 0.03 , respectively ) . The respiratory exchange ratio was higher after fructose ( P = 0.04 ) ; significantly ( P = 0.003 ) more carbon from sugars was recovered in breath carbon dioxide over 6 h after fructose ( 30.5 % ) than after glucose ( 24.5 % ) . At 240 min , newly synthesized fatty acids from fructose made up approximately 0.4 % of circulating VLDL-triacylglycerol , whereas newly synthesized triacylglycerol-glycerol made up 38 % . Newly synthesized fatty acids and triacylglycerol-glycerol from glucose contributed almost none of VLDL-triacylglycerol ( P = 0.002 and 0.007 for glucose and fructose , respectively ) . CONCLUSIONS The lower insulin excursion after fructose may result in less activation of adipose tissue lipoprotein lipase , which led to impaired triacylglycerol clearance . The contribution of de novo lipogenesis to fructose-induced hypertriacylglycerolemia is small , but its effect on altering the partitioning of fatty acids toward esterification may be considerable Ten hyperinsulinemic and 11 nonhyperinsulinemic men consumed a typical American diet containing 20 % of calories either as fructose or as high-amylose cornstarch for 5 wk in a crossover design to determine their effects on indices of glucose tolerance . Blood glucose , insulin , and fructose  were determined before and 30 , 60 , 90 , 120 and 180 min after breakfast , lunch , and dinner . Glucose responses were significantly lower 60 and 120 min and the insulin response lower 60 min after the meals containing fructose .  Hyperinsulinemic men showed a tendency toward decreased insulin sensitivity after consuming fructose on the basis of an increased insulin-to-glucose ratio and decreased insulin binding to erythrocytes . These results generally show a beneficial effect of fructose on glucose tolerance ; however , recommendations for including large amounts of fructose in the diet should also be based on a complete evaluation of the effect on other metabolic risk factors Aging is associated with a decline in energy expenditure ( EE ) , glucose intolerance , and a reduction in body nitrogen content . In addition , a reduction in the thermic response to glucose but not to fructose or protein has been reported in the elderly . The present study was conducted to further examine nutrient-induced thermogenesis and the effects of specific sugars on amino acid metabolism in relation to age . After 3 days on a weight-maintaining , 250-g carbohydrate diet , 16 healthy non-obese men and women in two age groups ( 18 to 29 and 66 to 80 years ) consumed on 4 different days 500 mL of either a 75-g fructose or 75-g glucose solution , with or without 300 mg caffeine or vitamin C as a placebo .  Blood substrate and hormone levels and EE , using indirect calorimetry , were measured at timed intervals for 3 hours after consumption of the drinks . There was no difference in the carbohydrate-induced increase in EE in either young or old even after adjustments for body weight and fat-free mass ( FFM ) . An approximately 20-fold increase in serum caffeine levels increased EE in both groups ( P < .003 ) , but had minimal effects on substrate and hormone responses . In contrast to glucose , fructose induced a marked elevation in plasma alanine from combined basal levels of 301 + /- 24 to approximately 500 + /- 18 mumol/L ( mean + /- SEM ) in both groups ( P < .001 ) . However , both fructose and glucose ingestion result ed in a similar decline in branched-chain and aromatic amino acids . ( ABSTRACT TRUNCATED AT 250 WORDS Oral glucose is a potent stimulant of glucagon-like peptide-1 ( GLP-1 ) secretion . The effect of oral fructose on GLP-1 secretion in humans is unknown . The aims of this study were to determine ( i ) whether oral fructose stimulates GLP-1 secretion and ( ii ) the comparative effects of oral glucose and fructose on appetite . On 3 separate days , 8 fasting healthy males received , in single-blind r and omized order ( i ) 75 g glucose , ( ii ) 75 fructose , or ( iii ) 75 g glucose followed by 75 g fructose I h later . Venous glucose , insulin and GLP-1 were measured . Appetite was assessed by visual analog question naires and intake of a buffet meal . Whereas glucose and fructose both increased plasma glucose , insulin and GLP-1 ( P < 0.000 ) ] for all ) , the response to glucose was much greater ( P < 0.005 for all ) . There was no increase in plasma GLP-1 when fructose was given after glucose . There was no difference in food intake after oral glucose or fructose . We conclude that oral fructose ( 75 g ) stimulates GLP-1 ( and insulin ) secretion , but the response is less than that to 75 g glucose . These observations suggest that neither GLP-1 nor insulin play a major role in the regulation of satiation OBJECTIVES : The objective of this study was to investigate whether ingestion of fructose and fructans ( such as inulin ) can exacerbate  irritable bowel syndrome ( IBS ) symptoms .  The aim was to better underst and the origin of these symptoms by magnetic resonance imaging ( MRI ) of the gut . METHODS : A total of 16 healthy volunteers participated in a four-way , r and omized , single-blind , crossover study in which they consumed 500 ml of water containing 40 g of either glucose , fructose , inulin , or a 1:1 mixture of 40 g glucose and 40 g fructose . MRI scans were performed hourly for 5 h , assessing the volume of gastric contents , small bowel water content ( SBWC ) , and colonic gas . Breath hydrogen ( H2 ) was measured and symptoms recorded after each scan . RESULTS : Data are reported as mean ( s.d . ) ( 95 % CI ) when normally distributed and median ( range ) when not . Fructose increased area under the curve ( AUC ) from 0–5 h of SBWC to 71 ( 23 ) l/min , significantly greater than for glucose at 36 ( 11–132 ) l/min ( P<0.001 ) , whereas AUC SBWC after inulin , 33 ( 17–106 ) l/min , was no different from that after glucose . Adding glucose to fructose  decreased AUC SBWC to 55 ( 28 ) l/min ( P=0.08 ) vs. fructose . Inulin substantially increased AUC colonic gas to 33 ( 20 ) l/min , significantly greater than glucose and glucose+fructose ( both P<0.05 ) . Breath H2 rose more with inulin than with fructose . Glucose when combined with fructose significantly reduced breath H2 by 7,700 ( 3,121–12,300 ) p.p.m./min relative to fructose alone ( P<0.01 , n=13 ) . CONCLUSIONS : Fructose but not inulin distends the small bowel with water . Adding glucose to fructose reduces the effect of fructose on SBWC and breath hydrogen .  Inulin distends the colon with gas more than fructose , but causes few symptoms in healthy volunteers 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 OBJECTIVE Fructose consumption has risen alongside obesity and diabetes . Gut hormones involved in hunger and satiety ( ghrelin and PYY ) may respond differently to fructose compared with glucose ingestion . This study evaluated the effects of glucose and fructose ingestion on ghrelin and PYY in lean and obese adolescents with differing insulin sensitivity . METHODS Adolescents were divided into lean ( n = 14 ) , obese insulin sensitive ( n = 12 ) ( OIS ) , and obese insulin resistant ( n = 15 ) ( OIR ) . In a double-blind , cross-over design , subjects drank 75 g of glucose or fructose in r and om order , serum was obtained every 10 minutes for 60 minutes . RESULTS Baseline acyl-ghrelin was highest in lean and lowest in OIR ( P = 0.02 ) . After glucose ingestion , acyl-ghrelin decreased similarly in lean and OIS but was lower in OIR ( vs. lean , P = 0.03 ) . Suppression differences were more pronounced after fructose ( lean vs. OIS , P = 0.008 , lean vs. OIR , P < 0.001 ) . OIS became significantly hungrier after fructose ( P = 0.015 ) . PYY was not significantly different at baseline , varied minimally after glucose , and rose after fructose . CONCLUSIONS Compared with lean , OIS adolescents have impaired acyl-ghrelin responses to fructose but not glucose , whereas OIR adolescents have blunted responses to both . Diminished suppression of acyl-ghrelin in childhood obesity , particularly if accompanied by insulin resistance , may promote hunger and overeating A number of recent research studies have demonstrated that providing glucose and fructose together in a beverage consumed during exercise results in significantly higher oxidation rates of exogenous carbohydrate ( CHO ) than consuming glucose alone . However , there is insufficient evidence to determine whether the increased exogenous CHO oxidation improves endurance performance . The purpose of this study was to determine whether consuming a beverage containing glucose and fructose ( GF ) would result in improved cycling performance compared with an isocaloric glucose-only beverage ( G ) .  Nine male competitive cyclists ( 32.6 + /- 5.8 years , peak oxygen uptake 61.5 + /- 7.9 ml x kg(-1 ) x min(-1 ) ) completed a familiarization trial and then 2 simulated 100-km cycling time trials on an electronically braked Lode cycle ergometer separated by 5 - 7 d. During the r and omly ordered experimental trials , participants received 36 g of CHO of either G or GF in 250 ml of water every 15 min . All 9 participants completed the 100-km time trial significantly faster when they received the GF beverage than with G ( 204.0 + /- 23.7 vs. 220.6 + /- 36.6 min ; p = .023 ) . There was no difference at any time point between trials for blood glucose or for blood lactate . Total CHO oxidation increased significantly from rest during exercise but was not statistically significant between the GF and G trials , although there was a trend for CHO oxidation to be higher with GF in the latter stages of the time trial . Consumption of a CHO beverage containing glucose and fructose results in improved 100-km cycling performance compared with an isocaloric glucose-only beverage
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 .
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 .