title: No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men. Moderate Amounts of Fructose Consumption Impair Insulin Sensitivity in Healthy Young Men Sweetened Beverage Consumption, Incident Coronary Heart Disease, and Biomarkers of Risk in Men Glycemic index and dietary fiber and the risk of type 2 diabetes. Functional magnetic resonance imaging of human hypothalamic responses to sweet taste and calories. Impaired cellular insulin binding and insulin sensitivity induced by high-fructose feeding in normal subjects. Carbohydrates, dietary fiber, and incident type 2 diabetes in older women. Diet and risk of clinical diabetes in women. Dietary sugars stimulate fatty acid synthesis in adults. Sweetened beverage consumption and risk of coronary heart disease in women. Sucrose-sweetened beverages increase fat storage in the liver, muscle, and visceral fat depot: a 6-mo randomized intervention study. No Effect of Added Sugar Consumed at Median American Intake Level on Glucose Tolerance or Insulin Resistance Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. A prospective study of sugar intake and risk of type 2 diabetes in women. Soft drink intake in relation to incident ischemic heart disease, stroke, and stroke subtypes in Japanese men and women: the Japan Public Health Centre-based study cohort I. Effects of high-fructose corn syrup and sucrose consumption on circulating glucose, insulin, leptin, and ghrelin and on appetite in normal-weight women. Effect of allopurinol on blood pressure of adolescents with newly diagnosed essential hypertension: a randomized trial. Fructose ingestion acutely elevates blood pressure in healthy young humans. Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes. Brain functional magnetic resonance imaging response to glucose and fructose infusions in humans. High-fructose corn syrup and sucrose have equivalent effects on energy-regulating hormones at normal human consumption levels.
abstract: 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 OBJECTIVE Adverse effects of hypercaloric , high-fructose diets on insulin sensitivity and lipids in human subjects have been shown repeatedly . The implication s of fructose in amounts close to usual daily consumption , however , have not been well studied . This study assessed the effect of moderate amounts of fructose and sucrose compared with glucose on glucose and lipid metabolism . RESEARCH DESIGN AND METHODS Nine healthy , normal-weight male volunteers ( aged 21–25 years ) were studied in this double-blind , r and omized , cross-over trial . All subjects consumed four different sweetened beverages ( 600 mL/day ) for 3 weeks each : medium fructose ( MF ) at 40 g/day , and high fructose ( HF ) , high glucose ( HG ) , and high sucrose ( HS ) each at 80 g/day . Euglycemic-hyperinsulinemic clamps with [6,6]-2H2 glucose labeling were used to measure endogenous glucose production . Lipid profile , glucose , and insulin were measured in fasting sample s. RESULTS Hepatic suppression of glucose production during the clamp was significantly lower after HF ( 59.4 ± 11.0 % ) than HG ( 70.3 ± 10.5 % , P < 0.05 ) , whereas fasting glucose , insulin , and C-peptide did not differ between the interventions . Compared with HG , LDL cholesterol and total cholesterol were significantly higher after MF , HF , and HS , and free fatty acids were significantly increased after MF , but not after the two other interventions ( P < 0.05 ) . Subjects ’ energy intake during the interventions did not differ significantly from baseline intake . CONCLUSIONS This study clearly shows that moderate amounts of fructose and sucrose significantly alter hepatic insulin sensitivity and lipid metabolism compared with similar amounts of glucose Background — Sugar-sweetened beverage consumption is associated with weight gain and risk of type 2 diabetes mellitus .  Few studies have tested for a relationship with coronary heart disease ( CHD ) or intermediate biomarkers . The role of artificially sweetened beverages is also unclear . Methods and Results — We performed an analysis of the Health Professionals Follow-Up Study , a prospect i ve cohort study including 42 883 men . Associations of cumulatively averaged sugar-sweetened ( eg , sodas ) and artificially sweetened ( eg , diet sodas ) beverage intake with incident fatal and nonfatal CHD ( myocardial infa rct ion ) were examined with proportional hazard models . There were 3683 CHD cases over 22 years of follow-up . Participants in the top quartile of sugar-sweetened beverage intake had a 20 % higher relative risk of CHD than those in the bottom quartile ( relative risk=1.20 ; 95 % confidence interval , 1.09–1.33 ; P for trend < 0.01 ) after adjustment for age , smoking , physical activity , alcohol , multivitamins , family history , diet quality , energy intake , body mass index , pre-enrollment weight change , and dieting . Artificially sweetened beverage consumption was not significantly associated with CHD ( multivariate relative risk=1.02 ; 95 % confidence interval , 0.93–1.12 ; P for trend=0.28 ) . Adjustment for self-reported high cholesterol , high triglycerides , high blood pressure , and diagnosed type 2 diabetes mellitus slightly attenuated these associations . Intake of sugar-sweetened but not artificially sweetened beverages was significantly associated with increased plasma triglycerides , C-reactive protein , interleukin-6 , and tumor necrosis factor receptors 1 and 2 and decreased high-density lipoprotein , lipoprotein(a ) , and leptin ( P<0.02 ) . Conclusions — Consumption of sugar-sweetened beverages was associated with increased risk of CHD and some adverse changes in lipids , inflammatory factors , and leptin . Artificially sweetened beverage intake was not associated with CHD risk or biomarkers OBJECTIVE To examine associations between type 2 diabetes and fiber , glycemic load ( GL ) , dietary glycemic index ( GI ) , and fiber-rich foods . RESEARCH DESIGN AND METHODS This was a prospect i ve study of 36,787 men and women aged 40 - 69 years without diabetes . For all self-reported cases of diabetes at 4-year follow-up , confirmation of diagnosis was sought from medical practitioners . Case subjects were those who reported diabetes at follow-up and for whom there was no evidence that they did not have type 2 diabetes . Data were analyzed with logistic regression , adjusting for country of birth , physical activity , family history of diabetes , alcohol and energy intake , education , 5-year weight change , sex , and age . RESULTS Follow-up was completed by 31,641 ( 86 % ) participants , and 365 cases were identified . The odds ratio ( OR ) for the highest quartile of white bread intake compared with the lowest was 1.37 ( 95 % CI 1.04 - 1.81 ; P for trend = 0.001 ) . Intakes of carbohydrate ( OR per 200 g/day 0.58 , 0.36 - 0.95 ) , sugars ( OR per 100 g/day 0.61 , 0.47 - 0.79 ) , and magnesium ( OR per 500 mg/day 0.62 , 0.43 - 0.90 ) were inversely associated with incidence of diabetes , whereas intake of starch ( OR per 100 g/day 1.47 , 1.06 - 2.05 ) and dietary GI ( OR per 10 units 1.32 , 1.05 - 1.66 ) were positively associated with diabetes . These relationships were attenuated after adjustment for BMI and waist-to-hip ratio . CONCLUSIONS Reducing dietary GI while maintaining a high carbohydrate intake may reduce the risk of type 2 diabetes . One way to achieve this would be to substitute white bread with low-GI breads BACKGROUND Evidence exists that beverages do not trigger appropriate anticipatory physiologic responses , such as cephalic phase insulin release . Therefore , it is of interest to eluci date the food properties necessary for triggering adaptive responses . Previously , we found a prolonged dose-dependent decrease in the hypothalamic functional magnetic resonance imaging signal after ingestion of a glucose solution . OBJECTIVES The aims of the present study were to measure the effects of sweet taste and energy content on the hypothalamic response to glucose ingestion and to measure the concomitant changes in blood glucose and insulin concentrations . DESIGN Five healthy , normal-weight men participated in a r and omized crossover design trial . The subjects were scanned 4 times for 37 min on separate days with functional magnetic resonance imaging . After 7 min , they ingested 1 of the following 4 stimuli ( 300 mL of each ) : water ( control ) , a glucose solution , an aspartame ( sweet taste ) solution , or a maltodextrin ( nonsweet carbohydrate ) solution . RESULTS Glucose ingestion result ed in a prolonged and significant signal decrease in the upper hypothalamus ( P < 0.05 ) . Water , aspartame , and maltodextrin had no such effect . Glucose and maltodextrin ingestions result ed in similar increases in blood glucose and insulin concentrations . However , only glucose triggered an early rise in insulin concentrations . Aspartame did not trigger any insulin response . CONCLUSIONS Our findings suggest that both sweet taste and energy content are required for a hypothalamic response . The combination of sweet taste and energy content could be crucial in triggering adaptive responses to sweetened beverages 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 Dietary carbohydrates may influence the development of  type 2 ( non-insulin-dependent ) diabetes  , for example , through effects on blood glucose and insulin concentrations . OBJECTIVE We examined the relations of baseline intake of carbohydrates , dietary fiber , dietary magnesium , and carbohydrate-rich foods and the glycemic index with incidence of diabetes . DESIGN This was a prospect i ve cohort study of 35988 older Iowa women initially free of diabetes . During 6 y of follow-up , 1141 incident cases of diabetes were reported . RESULTS  Total grain , whole-grain , total dietary fiber , cereal fiber , and dietary magnesium intakes  showed strong inverse associations with incidence of diabetes after adjustment for potential nondietary confounding variables . Multivariate-adjusted relative risks of diabetes were 1.0 , 0.99 , 0.98 , 0.92 , and 0.79 ( P for trend : 0.0089 ) across quintiles of whole-grain intake ; 1.0 , 1.09 , 1.00 , 0.94 , and 0.78 ( P for trend : 0.005 ) across quintiles of total dietary fiber intake ; and 1.0 , 0.81 , 0.82 , 0.81 , and 0.67 ( P for trend : 0.0003 ) across quintiles of dietary magnesium intake . Intakes of total carbohydrates , refined grains , fruit and vegetables , and soluble fiber and the glycemic index were unrelated to diabetes risk . CONCLUSION These data support a protective role for grains ( particularly whole grains ) , cereal fiber , and dietary magnesium in the development of diabetes in older women To determine the relations of diet with risk of clinical noninsulin-dependent diabetes , we analyzed data from a prospect i ve cohort of 84360 US women . During 6 y of follow-up we identified 702 definite incident cases . Because body mass index ( BMI ) is a powerful risk factor for diabetes , we examined the relations of fat ( including type ) , fiber , sucrose , and other components of diet to risk of diabetes , among women with BMI s ( in kg/m2 ) less than 29 kg/m2 . After controlling for body mass index , previous weight change , and alcohol intake , we observed no associations between intakes of energy  , protein , sucrose ,  carbohydrate  ,  or fiber and risk of diabetes . Compared with women in the lowest quintile of energy-adjusted intake , and relative risks ( and tests for trend ) for those in the highest quintile were 0.61 ( P trend = 0.03 ) for vegetable fat , 0.62 ( P trend = 0.008 ) for potassium , 0.70 ( P trend = 0.005 ) for calcium , and 0.68 ( P trend = 0.02 ) for magnesium . These inverse associations were attenuated among obese women ( BMI s greater than or equal to 29 ) The goal of this study was to determine the magnitude by which acute consumption of fructose in a morning bolus would stimulate lipogenesis ( measured by infusion of 13C1-acetate and analysis by GC-MS ) immediately and after a subsequent meal . Six healthy subjects [ 4 men and 2 women ; aged ( mean + /- SD ) 28 + /- 8 y ; BMI , 24.3 + /- 2.8 kg/m(2 ) ; and serum triacylglycerols ( TG ) , 1.03 + /- 0.32 mmol/L ] consumed carbohydrate boluses of sugars  ( 85 g each ) in a r and om and blinded order , followed by a st and ardized lunch 4 h later . Subjects completed a control test of glucose ( 100:0 ) and a mixture of 50:50 glucose : fructose and one of 25:75 ( wt : wt ) . Following the morning boluses , serum glucose and insulin after 100:0 were greater than both other treatments ( P < 0.05 ) and this pattern occurred again after lunch . In the morning , fractional lipogenesis was stimulated when subjects ingested fructose and peaked at 15.9 + /- 5.4 % after the 50:50 treatment and at 16.9 + /- 5.2 % after the 25:75 treatment , values that were greater than after the 100:0 treatment ( 7.8 + /- 5.7 % ; P < 0.02 ) . When fructose was consumed , absolute lipogenesis was 2-fold greater than when it was absent ( 100:0 ) . Postlunch , serum TG were 11 - 29 % greater than 100:0 and TG-rich lipoprotein-TG concentrations were 76 - 200 % greater after 50:50 and 25:75 were consumed ( P < 0.05 ) . The data demonstrate that an early stimulation of lipogenesis after fructose , consumed in a mixture of sugars , augments subsequent postpr and ial lipemia . The postlunch blood TG elevation was only partially due to carry-over from the morning . Acute intake of fructose stimulates lipogenesis and may create a metabolic milieu that enhances subsequent esterification of fatty acids flowing to the liver to elevate TG synthesis postpr and ially BACKGROUND Previous studies have linked full-calorie sugar-sweetened beverages ( SSBs ) with greater weight gain and an increased risk of type 2 diabetes . OBJECTIVE We prospect ively examined the association between consumption of SSBs and the risk of coronary heart disease ( CHD ) in women . DESIGN Women ( n = 88,520 ) from the Nurses ' Health Study aged 34 - 59 y , without previously diagnosed coronary heart disease ( CHD ) , stroke , or diabetes in 1980 , were followed from 1980 to 2004 . Consumption of SSBs was derived from 7 repeated food-frequency question naires administered between 1980 and 2002 . Relative risks ( RRs ) for CHD were calculated by using Cox proportional hazards models and adjusted for known cardiovascular disease risk factors . RESULTS During 24 y of follow-up , we ascertained 3105 incident cases of CHD  ( nonfatal myocardial infa rct ion and fatal CHD ) . After st and ard and dietary risk factors were adjusted for , the RRs ( and 95 % CIs ) of CHD according to categories of cumulative average of SSB consumption ( < 1/mo , 1 - 4/mo , 2 - 6/wk , 1/d , and > or = 2 servings/d ) were 1.0 , 0.96 ( 0.87 , 1.06 ) , 1.04 ( 0.95 , 1.14 ) , 1.23 ( 1.06 , 1.43 ) , and 1.35 ( 1.07 , 1.69 ) ( P for trend < 0.001 ) . Additional adjustment for body mass index , energy intake , and incident diabetes attenuated the associations , but they remained significant . Artificially sweetened beverages were not associated with CHD . CONCLUSION Regular consumption of SSBs is associated with a higher  risk of CHD in women , even after other unhealthful lifestyle or dietary factors are accounted for BACKGROUND The consumption of sucrose-sweetened soft drinks ( SSSDs ) has been associated with obesity , the metabolic syndrome , and cardiovascular disorders in observational and short-term intervention studies . Too few long-term intervention studies in humans have examined the effects of soft drinks . OBJECTIVE We compared the effects of SSSDs with those of isocaloric milk and a noncaloric soft drink on changes in total fat mass and ectopic fat deposition ( in liver and muscle tissue ) . DESIGN Overweight subjects ( n = 47 ) were r and omly assigned to 4 different test drinks ( 1 L/d for 6 mo ) : SSSD ( regular cola ) , isocaloric semiskim milk , aspartame-sweetened diet cola , and water . The amount of intrahepatic fat and intramyocellular fat was measured with (1)H-magnetic resonance spectroscopy . Other endpoints were fat mass , fat distribution ( dual-energy X-ray absorptiometry and magnetic resonance imaging ) , and metabolic risk factors . RESULTS The relative changes between baseline and the end of 6-mo intervention were significantly higher in the regular cola group than in the 3 other groups for liver fat ( 132 - 143 % , sex-adjusted mean ; P < 0.01 ) , skeletal muscle fat ( 117 - 221 % ; P < 0.05 ) , visceral fat ( 24 - 31 % ; P < 0.05 ) , blood triglycerides ( 32 % ; P < 0.01 ) , and total cholesterol ( 11 % ; P < 0.01 ) . Total fat mass was not significantly different between the 4 beverage groups . Milk and diet cola reduced systolic blood pressure by 10 - 15 % compared with regular cola ( P < 0.05 ) . Otherwise , diet cola had effects similar to those of water . CONCLUSION Daily intake of SSSDs for 6 mo increases ectopic fat accumulation and lipids compared with milk , diet cola , and water . Thus , daily intake of SSSDs is likely to enhance the risk of cardiovascular and metabolic diseases . This trial is registered at clinical trials.gov as NCT00777647 Excess sugar consumption may promote adverse changes in  hepatic and total body insulin resistance .  Debate continues over the effects of sugars at more typically consumed levels and whether the identity of the sugar consumed is important . In the present study participants ( 20–60 years old ) were r and omly assigned to one of five groups , three that consumed low fat milk with added fructose containing sugars in amounts equivalent to the 50th percentile of fructose consumption ( US ) , one which consumed low-fat milk sweetened with glucose , and one unsweetened low-fat milk control group . The intervention lasted ten weeks . In the entire study population there was less than 1 kg increase in weight ( 73.6 ± 13.0 vs. 74.5 ± 13.3 kg , p < 0.001 ) , but the change in weight was comparable among groups ( p > 0.05 ) . There were no changes in fasting glucose ( 49 ± 0.4 vs. 5.0 ± 0.5 mmol/L ) , insulin ( 56.9 ± 38.9 vs. 61.8 ± 50.0 pmol/L ) , or insulin resistance , as measured by the Homeostasis Model Assessment method ( 1.8 ± 1.3 vs. 2.0 ± 1.5 , all p > 0.05 ) . These data suggest that added sugar consumed at the median American intake level does not produce changes in measures of insulin sensitivity or glucose tolerance and that no sugar has more deleterious effects than others 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 OBJECTIVE To investigate prospect ively whether intake of total or type of sugar is associated with the risk of developing type 2 diabetes . The contribution of sugar intake to the pathogenesis of type 2 diabetes has not been settled in the context of primary prevention because of limited prospect i ve data . RESEARCH DESIGN AND METHODS The Women 's Health Study is a r and omized controlled trial of aspirin and vitamin E in the prevention of cardiovascular disease and cancer . A vali date d semiquantitative food frequency question naire was completed by 39,345 women aged 45 years and older . The main outcome was the incidence of type 2 diabetes . The predictor was sugar intake , including sucrose , glucose , fructose , and lactose . Using Cox proportional hazard models , multivariate RRs of type 2 diabetes for increasing quintiles of sugar intake compared with the lowest quintile were estimated . RESULTS Compared with the lowest quintile of sugar intake , the RRs and 95 % CIs for the highest quintiles were 0.84 ( 0.67 - 1.04 ) for sucrose , 0.96 ( 0.78 - 1.19 ) for fructose , 1.04 ( 0.85 - 1.28 ) for glucose , and 0.99 ( 0.80 - 1.22 ) for lactose , after adjustment for known risk factors for type 2 diabetes . Similar findings of no association were obtained in subgroup analyses stratified by BMI . CONCLUSIONS Intake of sugars does not appear to play a deleterious role in primary prevention of type 2 diabetes . These prospect i ve data support the recent American Diabetes Association 's guideline that a moderate amount of sugar can be incorporated in a healthy diet BACKGROUND Soft drink intake has been associated with obesity and diabetes , but its relation with risk of cardiovascular disease ( CVD ) is limited . OBJECTIVE We examined the association between soft drink intake and risk of CVD in a Japanese population . DESIGN This was a prospect i ve study in 39,786 Japanese men and women aged 40 - 59 y in which  soft drink intake  was determined by using a self-administered food-frequency question naire . Follow-up was from 1990 to 2008 . HRs and 95 % CIs of incidence were calculated according to categories of soft drink intake . RESULTS During 18 y of follow-up , we ascertained 453 incident cases of ischemic heart disease ( IHD ) and 1922 cases of stroke , including 859 hemorrhagic and 1047 ischemic strokes . Soft drink intake was positively associated with risk of total stroke and more specifically ischemic stroke for women ; the multivariable HR ( 95 % CI ) in the highest soft drink intake ( almost every day ) category compared with the lowest intake ( never or rarely ) category was 1.21 ( 0.88 , 1.68 ; P-trend = 0.02 ) for total stroke and 1.83 ( 1.22 , 2.75 ; P-trend = 0.001 ) for ischemic stroke . That association did not change significantly after the exclusion of early incident cases within 3 - 9 y from baseline . A nonsignificant inverse trend for risks of total and ischemic strokes was shown for men , and it was weakened after the exclusion of early incident cases or after the exclusion of participants with baseline comorbidities . Soft drink intake was not associated with risk of IHD or hemorrhagic stroke for either sex . CONCLUSION Soft drink intake is associated with higher risk of ischemic stroke for women 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 CONTEXT Hyperuricemia is a predictor for the development of hypertension and is commonly present in new-onset essential hypertension . Experimentally increasing uric acid levels using a uricase inhibitor causes systemic hypertension in animal models . OBJECTIVE To determine whether lowering uric acid lowers blood pressure ( BP ) in hyperuricemic adolescents with newly diagnosed hypertension . DESIGN , SETTING , AND PATIENTS R and omized , double-blind , placebo-controlled , crossover trial ( September 2004-March 2007 ) involving 30 adolescents ( aged 11 - 17 years ) who had newly diagnosed , never-treated stage 1 essential hypertension and serum uric acid levels > or = 6 mg/dL. Participants were treated at the Pediatric Hypertension Clinic at Texas Children 's Hospital in Houston . Patients were excluded if they had stage 2 hypertension or known renal , cardiovascular , gastrointestinal tract , hepatic , or endocrine disease . INTERVENTION Allopurinol , 200 mg twice daily for 4 weeks , and placebo , twice daily for 4 weeks , with a 2-week washout period between treatments . The order of the treatments was r and omized . MAIN OUTCOME MEASURES Change in casual and ambulatory blood pressure . RESULTS For casual BP , the mean change in systolic BP for allopurinol was -6.9 mm Hg ( 95 % confidence interval [ CI ] , -4.5 to -9.3 mm Hg ) vs -2.0 mm Hg ( 95 % CI , 0.3 to -4.3 mm Hg ; P = .009 ) for placebo , and the mean change in diastolic BP for allopurinol was -5.1 mm Hg ( 95 % CI , -2.5 to -7.8 mm Hg ) vs -2.4 ( 95 % CI , 0.2 to -4.1 ; P = .05 ) for placebo . Mean change in mean 24-hour ambulatory systolic BP for allopurinol was -6.3 mm Hg ( 95 % CI , -3.8 to -8.9 mm Hg ) vs 0.8 mm Hg ( 95 % CI , 3.4 to -2.9 mm Hg ; P = .001 ) for placebo and mean 24-hour ambulatory diastolic BP for allopurinol was -4.6 mm Hg ( -2.4 to -6.8 mm Hg ) vs -0.3 mm Hg ( 95 % CI , 2.3 to -2.1 mm Hg ; P = .004 ) for placebo . Twenty of the 30 participants achieved normal BP by casual and ambulatory criteria while taking allopurinol vs 1 participant while taking placebo ( P < .001 ) . CONCLUSIONS In this short-term , crossover study of adolescents with newly diagnosed hypertension , treatment with allopurinol result ed in reduction of BP . The results represent a new potential therapeutic approach , although not a fully developed therapeutic strategy due to potential adverse effects . These preliminary findings require confirmation in larger clinical trials . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00288184 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 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 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 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
target: Data from these sources do not support linkages between sugar consumption at normal levels within the human diet and various adverse metabolic and health-related effects
background: Abstract The relationship between sugar consumption and various health-related sequelas is controversial .
  Some investigators have argued that excessive sugar consumption is associated with increased risk of obesity , coronary heart disease , diabetes ( T2D ) , metabolic syndrome , non-alcoholic fatty liver disease , and stimulation of reward pathways in the brain potentially causing excessive caloric consumption .
  These concerns have influenced organizations such as the World Health Organization , the Scientific Advisory Committee on Nutrition in Engl and not to exceed 5 % of total energy and the Dietary Guidelines for Americans Advisory Committee 2015 to recommend upper limits of sugar consumption not to exceed 10 % of calories .
  Data from many r and omized control trials ( RCTs ) do not support linkages between sugar consumption at normal levels within the human diet and various adverse metabolic and health-related effects .
  Fructose and glucose are typically consumed together in roughly equal proportions from high-fructose corn syrup ( also known as isoglucose in Europe ) or sucrose .
  The purpose of this review is to present data from recent RCTs and findings from recent systematic review s and meta-analyses related to sugar consumption and its putative health effects .
  This review evaluates findings from recent r and omized controlled trials , systematic review s and meta-analyses into the relationship of sugar consumption and a range of health-related issues including energy-regulating hormones , obesity , cardiovascular disease , diabetes , and accumulation of liver fat and neurologic responses .