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.
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
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 .