Dietary Fructose Reduction Improves Markers of Cardiovascular Disease Risk in Hispanic-American Adolescents with NAFLD The Effect of Normally Consumed Amounts of Sucrose or High Fructose Corn Syrup on Lipid Profiles, Body Composition and Related Parameters in Overweight/Obese Subjects Effects on uric acid, body mass index and blood pressure in adolescents of consuming beverages sweetened with high-fructose corn syrup No difference in ad libitum energy intake in healthy men and women consuming beverages sweetened with fructose, glucose, or high-fructose corn syrup: a randomized trial. Effect of drinking soda sweetened with aspartame or high-fructose corn syrup on food intake and body weight. High-fructose corn syrup and sucrose have equivalent effects on energy-regulating hormones at normal human consumption levels. Effects of high-fructose corn syrup and sucrose consumption on circulating glucose, insulin, leptin, and ghrelin and on appetite in normal-weight women. The effects of four hypocaloric diets containing different levels of sucrose or high fructose corn syrup on weight loss and related parameters Effects of dietary fructose on plasma lipids in healthy subjects. Effect of short-term carbohydrate overfeeding and long-term weight loss on liver fat in overweight humans. A dose-response study of consuming high-fructose corn syrup-sweetened beverages on lipid/lipoprotein risk factors for cardiovascular disease in young adults. Hepatic steatosis index: a simple screening tool reflecting nonalcoholic fatty liver disease. Effects of Metformin, Pioglitazone, and Silymarin Treatment on Non-Alcoholic Fatty Liver Disease: A Randomized Controlled Pilot Study Sugars and risk of mortality in the NIH-AARP Diet and Health Study. No difference between high-fructose and high-glucose diets on liver triacylglycerol or biochemistry in healthy overweight men. Effect of sugars in solutions on subjective appetite and short-term food intake in 9- to 14-year-old normal weight boys Diet associations with nonalcoholic fatty liver disease in an ethnically diverse population: the Multiethnic Cohort. Regression of Nonalcoholic Fatty Liver Disease with Zinc and Selenium Co-supplementation after Disease Progression in Rats Prevalence of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among a largely middle-aged population utilizing ultrasound and liver biopsy: a prospective study. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study. The fermentable fibre inulin increases postprandial serum short-chain fatty acids and reduces free-fatty acids and ghrelin in healthy subjects. Fructose overconsumption causes dyslipidemia and ectopic lipid deposition in healthy subjects with and without a family history of type 2 diabetes. Atorvastatin and Antioxidants for the Treatment of Nonalcoholic Fatty Liver Disease: The St Francis Heart Study Randomized Clinical Trial
Nonalcoholic fatty liver disease ( NAFLD ) is now thought to be the most common liver disease worldwide . Cardiovascular complications are a leading cause of mortality in NAFLD . Fructose , a common nutrient in the westernized diet , has been reported to be associated with increased cardiovascular risk , but its impact on adolescents with NAFLD is not well understood . We design ed a 4-week r and omized , controlled , double-blinded beverage intervention study . Twenty-four overweight Hispanic-American adolescents who had hepatic fat > 8 % on imaging and who were regular consumers of sweet beverages were enrolled and r and omized to calorie-matched study -provided fructose only or glucose only beverages . After 4 weeks , there was no significant change in hepatic fat or body weight in either group . In the glucose beverage group there was significantly improved adipose insulin sensitivity , high sensitivity C-reactive protein ( hs-CRP ) , and low-density lipoprotein ( LDL ) oxidation . These findings demonstrate that reduction of fructose improves several important factors related to cardiovascular disease despite a lack of measurable improvement in hepatic steatosis . Reducing dietary fructose may be an effective intervention to blunt atherosclerosis progression among NAFLD patients and should be evaluated in longer term clinical trials The American Heart Association ( AHA ) has advocated that women and men not consume more than 100 and 150 kcal/day , respectively , from added sugars . These levels are currently exceeded by over 90 % of the adult population in the United States . Few data exist on longer-term metabolic effects when sucrose and High Fructose Corn Syrup ( HFCS ) , the principal sources of added dietary sugars , are consumed at levels typical of the general population . Sixty five overweight and obese individuals were placed on a eucaloric ( weight stable ) diet for 10-weeks , which incorporated sucrose- or HFCS-sweetened , low-fat milk at 10 % or 20 % of calories in a r and omized , double-blinded study . All groups responded similarly ( interaction p > 0.05 ) . There was no change in body weight in any of the groups over the 10-week study , or in systolic or diastolic blood pressure . Likewise , there were no changes in total cholesterol , triglycerides , low-density lipoprotein ( LDL ) , or apolipoprotein B ( Apo B ) . We conclude that ( 1 ) when consumed as part of a eucaloric diet fructose — when given with glucose ( as normally consumed ) does not promote weight gain or an atherogenic lipid profile even when consumed at two to four times the level recently recommended by the AHA . ( 2 ) There were no differences between HFCS and sucrose on these parameters Objective : The dietary intake of fructose-rich sugar-sweetened beverages ( SSB ) may have a significant role in raising serum uric acid ( SUA ) levels as well as the risk of contracting gout and cardiovascular risk factors . Our objective was to investigate the impact of SSB intake on SUA , body mass index ( BMI ) and systolic blood pressure ( SBP ) among adolescents in Taiwan . Methods : We evaluated data from 2727 representative adolescents who were multistage sample d from 36 Junior High schools in Taiwan . We cross-sectionally collected demographic , physical , dietary and anthropometric variables , and prospect ively measured clinical outcomes . Data were analyzed using multiple regression and logistic models adjusted for covariates . Results : We found that 87.7 % of adolescents were SSB drinkers , with 25.1 % drinking > 500 ml per day of such beverages . Increased SSB intake was associated with increased waist and hip circumferences , body fat , BMI , SBP and SUA . As compared with non-drinkers , SSB drinkers had a 3.2–4.9 elevated risk of obesity . The prevalence of hyperuricemia in heavy SSB  users ( 40.2–49.4 % ) was appreciably greater than that for non-users ( 24.2 % ) . Adolescents who consumed > 500 ml per day of heavy high-fructose corn syrup ( HFCS ) containing beverages had a 0.42 mg dl−1 higher SUA level and a 2.0–2.1 increased risk of developing hyperuricemia than non-drinkers . The consumption of HFCS-rich beverages was also found to interact with obesity in determining higher levels of SUA ( 2.2–2.4 mg dl−1 increases ) . Conclusion : High SSB consumption has a notable effect on increased levels of BMI and SUA . The intake of HFCS-rich beverages and BMI were likely to interactively strengthen SUA levels among obese adolescents BACKGROUND Increased energy intake is consistently observed in individuals consuming sugar-sweetened beverages ( SSBs )  , likely mainly because of an inadequate satiety response to liquid calories . However , SSBs have a high content of fructose , the consumption of which acutely fails to trigger responses in key signals involved in energy homeostasis . It is unclear whether the fructose content of SSBs contributes to the increased energy intake in individuals drinking SSBs . OBJECTIVE We investigated whether the relative amounts of fructose and glucose in SSBs modifies ad libitum energy intake over 8 d in healthy adults without fructose malabsorption . DESIGN We conducted 2 r and omized , controlled , double-blind crossover studies to compare the effects of consuming 4 servings/d of a fructose- , glucose- , or aspartame-sweetened beverage  ( study A ; n = 9 )  or a fructose- , glucose- , or high-fructose corn syrup (HFCS)-sweetened beverage  ( study B ; n = 24 ) for 8 d on overall energy intake . SSBs were provided at 25 % of estimated energy requirement , or an equivalent volume of the aspartame-sweetened beverage , and consumption was m and atory . All solid foods were provided at 125 % of estimated energy requirements and were consumed ad libitum . RESULTS In study A , ad libitum energy intake was 120 % ± 10 % , 117 % ± 12 % , and 102 % ± 15 % of estimated energy requirements when subjects consumed the fructose- , glucose- , and aspartame-sweetened beverages . Energy intake was significantly higher in the fructose and glucose phases than in the aspartame phase ( P < 0.003 for each ) , with no difference between the fructose and glucose phases ( P = 0.462 ) . In study B , total energy intake during the fructose , HFCS , and glucose phases was 116 % ± 14 % , 116 % ± 16 % , and 116 % ± 16 % of the subject 's estimated total energy requirements ( P = 0.880 ) . CONCLUSIONS In healthy adults , total 8-d ad libitum energy intake was increased in individuals consuming SSBs compared with aspartame-sweetened beverages . The energy overconsumption observed in individuals consuming SSBs occurred independently of the relative amounts of fructose and glucose in the beverages . These trials were registered at clinical trials.gov as NCT00475475 and NCT01424306 To examine whether artificial sweeteners aid in the control of long-term food intake and body weight , we gave free-living , normal-weight subjects 1150 g soda sweetened with aspartame ( APM ) or high-fructose corn syrup ( HFCS ) per day . Relative to when no soda was given , drinking APM-sweetened soda for 3 wk significantly reduced calorie intake of both females ( n = 9 ) and males ( n = 21 ) and decreased the body weight of males but not of females . However , drinking HFCS-sweetened soda for 3 wk significantly increased the calorie intake and body weight of both sexes . Ingesting either type of soda reduced intake of sugar from the diet without affecting intake of other nutrients . Drinking large volumes of APM-sweetened soda , in contrast to drinking HFCS-sweetened soda , reduces sugar intake and thus may facilitate the control of calorie intake and body weight 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 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 Background The replacement of sucrose with HFCS in food products has been suggested as playing a role in the development of obesity as a public health issue . The objective of this study was to examine the effects of four equally hypocaloric diets containing different levels of sucrose or high fructose corn syrup ( HFCS ) . Methods This was a r and omized , prospect i ve , double blind trial , with overweight/obese participants measured for body composition and blood chemistry before and after the completion of 12 weeks following a hypocaloric diet .  The average caloric deficit achieved on the hypocaloric diets was 309 kcal . Results Reductions were observed in all measures of adiposity including body mass , BMI , % body fat , waist circumference and fat mass for all four hypocaloric groups , as well as reductions in the exercise only group for body mass , BMI and waist circumference . Conclusions Similar decreases in weight and indices of adiposity are observed when overweight or obese individuals are fed hypocaloric diets containing levels of sucrose or high fructose corn syrup typically consumed by adults in the United States 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 BACKGROUND Cross-sectional studies have identified a high intake of simple sugars as an important dietary factor predicting nonalcoholic fatty liver disease ( NAFLD ) . OBJECTIVE We examined whether overfeeding overweight subjects with simple sugars  increases liver fat and de novo lipogenesis ( DNL ) and whether this is reversible by weight loss . DESIGN Sixteen subjects [ BMI ( kg/m² ) : 30.6 ± 1.2 ] were placed on a hypercaloric diet ( > 1000 kcal simple carbohydrates/d ) for 3 wk and , thereafter , on a hypocaloric diet for 6 mo . The subjects were genotyped for rs739409 in the PNPLA3 gene . Before and after overfeeding and after hypocaloric diet , metabolic variables and liver fat ( measured by proton magnetic resonance spectroscopy ) were measured . The ratio of palmitate ( 16:0 ) to linoleate ( 18:2n-6 ) in serum and VLDL triglycerides was used as an index of DNL . RESULTS Carbohydrate overfeeding increased weight ( ±SEM ) by 2 % ( 1.8 ± 0.3 kg ; P < 0.0001 ) and liver fat by 27 % from 9.2 ± 1.9 % to 11.7 ± 1.9 % ( P = 0.005 ) . DNL increased in proportion to the increase in liver fat and serum triglycerides in subjects with PNPLA3 - 148IIbut not PNPLA3 - 148MM . During the hypocaloric diet , the subjects lost 4 % of their weight ( 3.2 ± 0.6 kg ; P < 0.0001 ) and 25 % of their liver fat content ( from 11.7 ± 1.9 % to 8.8 ± 1.8 % ; P < 0.05 ) . CONCLUSIONS Carbohydrate overfeeding for 3 wk induced a > 10-fold greater relative change in liver fat ( 27 % ) than in body weight ( 2 % ) . The increase in liver fat was proportional to that in DNL . Weight loss restores liver fat to normal . These data indicate that the human fatty liver avidly accumulates fat during carbohydrate overfeeding and support a role for DNL in the pathogenesis of NAFLD . This trial was registered at www.hus.fi as 235780 BACKGROUND National Health and Nutrition Examination Survey data show an increased risk of cardiovascular disease ( CVD ) mortality with an increased intake of added sugar . OBJECTIVE We determined the dose-response effects of consuming beverages sweetened with high-fructose corn syrup ( HFCS ) at zero , low , medium , and high proportions of energy requirements ( Ereq ) on circulating lipid/lipoprotein risk factors for CVD and uric acid in adults [ age : 18 - 40 y ; body mass index ( in kg/m(2 ) ) : 18 - 35 ] . DESIGN We conducted a parallel-arm , nonr and omized , double-blinded intervention study in which adults participated in 3.5 inpatient days of baseline testing at the University of California Davis Clinical and Translational Science Center 's Clinical Research Center . Participants then consumed beverages sweetened with HFCS at 0 % ( aspartame sweetened , n = 23 ) , 10 % ( n = 18 ) , 17.5 % ( n = 16 ) , or 25 % ( n = 28 ) of Ereq during 13 outpatient days and during 3.5 inpatient days of intervention testing at the research center . We conducted 24-h serial blood collection s during the baseline and intervention testing periods . RESULTS Consuming beverages containing 10 % , 17.5 % , or 25 % Ereq from HFCS produced significant linear dose-response increases of lipid/lipoprotein risk factors for CVD and uric acid : postpr and ial triglyceride ( 0 % : 0 ± 4 ; 10 % : 22 ± 8 ; 17.5 % : 25 ± 5 : 25 % : 37 ± 5 mg/dL , mean of Δ ± SE , P < 0.0001 effect of HFCS-dose ) , fasting LDL cholesterol ( 0 % : -1.0 ± 3.1 ; 10 % : 7.4 ± 3.2 ; 17.5 % : 8.2 ± 3.1 ; 25 % : 15.9 ± 3.1 mg/dL , P < 0.0001 ) , and 24-h mean uric acid concentrations ( 0 % : -0.13 ± 0.07 ; 10 % : 0.15 ± 0.06 ; 17.5 % : 0.30 ± 0.07 ; 25 % : 0.59 ± 0.09 mg/dL , P < 0.0001 ) . Compared with beverages containing 0 % HFCS , all 3 doses of HFCS-containing beverages increased concentrations of postpr and ial triglyceride , and the 2 higher doses increased fasting and /or postpr and ial concentrations of non-HDL cholesterol , LDL cholesterol , apolipoprotein B , apolipoprotein CIII , and uric acid . CONCLUSIONS Consuming beverages containing 10 % , 17.5 % , or 25 % Ereq from HFCS produced dose-dependent increases in circulating lipid/lipoprotein risk factors for CVD and uric acid within 2 wk . These results provide mechanistic support for the epidemiologic evidence that the risk of cardiovascular mortality is positively associated with consumption of increasing amounts of added sugars . This trial was registered at clinical trials.gov as NCT01103921 BACKGROUND / AIMS To optimize management of nonalcoholic fatty liver disease ( NAFLD ) , a simple screening tool is necessary . In this study , we aim ed to devise a simple index of NAFLD . STUDY A cross-sectional study with 10,724 health check-up subjects ( 5362 cases with NAFLD versus age- and sex-matched controls ) was conducted . Study subjects were r and omly assigned to a derivation cohort or a validation cohort . RESULTS Multivariate analysis indicated that high serum alanine aminotransferase ( ALT ) to serum aspartate aminotransferase ( AST ) ratio , high body mass index ( BMI ) , and diabetes mellitus were independent risk factors of NAFLD ( all P<0.001 ) . Using these variables , a formula was derived by a logistic regression model : hepatic steatosis index (HSI)= 8 x(ALT/AST ratio)+ BMI ( + 2 , if female ; + 2 , if diabetes mellitus ) . HSI had an area under receiver-operating curve of 0.812 ( 95 % confidence interval , 0.801 - 0.824 ) . At values of < 30.0 or > 36.0 , HSI ruled out NAFLD with a sensitivity of 93.1 % , or detected NAFLD with a specificity of 92.4 % , respectively . Of 2692 subjects with HSI < 30.0 or > 36.0 in the derivation cohort , 2305 ( 85.6 % ) were correctly classified . HSI was vali date d in the subsequent validation cohort . CONCLUSION HSI is a simple , efficient screening tool for NAFLD that may be utilized for selecting individuals for liver ultrasonography and for determining the need for lifestyle modifications Background Nonalcoholic fatty liver disease ( NAFLD ) is one of the most common reasons of enzyme increase in liver . In About 10 percent of patients with NAFLD , the disease progresses toward Non Alcoholic Steatohepatitis ( NASH ) and about one third of them may progress toward cirrhosis , liver dysfunction , and even hepatocellular carcinoma . Objectives According to high prevalence of NAFLD and the fact that there is no consensus on treatment of this disease , the aim of this study was to assess the effects of metformin , pioglitazone , and silymarin on treatment of NAFLD . Patients and Methods Sixty six patients with NAFLD who were presented in the Endocrinology and Metabolism clinic of Boo’ali Hospital , Qazvin , Iran , were assigned r and omly into three groups ( n = 22 ) . First group was treated by pioglitazone 15 mg/d , second group by metformin 500 mg/d , and third group by silymarin 140 mg/d . All patients underwent clinical and biochemical evaluations including weight , fasting blood sugar ( FBS ) , lipid profiles , body mass index ( BMI ) , aspartate aminotransferase ( AST ) , alanine aminotransferase ( ALT ) , and serum insulin levels in pre- and post-intervention after eight-week follow up . Results Before the treatment there was no significant difference between three groups with respect to average age , BMI and gender , FBS , lipid profile , AST , ALT , serum insulin level , and Homeostasis Model Assessment ( HOMA ) index for insulin resistance . After the intervention , a significant reduction was observed in average amount of FBS , lipid profile , ALT , AST , serum insulin level and HOMA index in three groups ( P < 0.01 ) . The most reduction in average FBS , TG , serum insulin level , and HOMA index was observed in pioglitazone group , the most reduction in average amount of cholesterol was seen in metformin group , and the most decrease in average amount of AST and ALT occurred in silymarin group . Conclusions These results suggest that all drugs are beneficial in improving biochemical indices in patients with NAFLD . Changes in AST and ALT in silymarin group were demonstrated more than that in other groups and the average difference between changes was significant between silymarin and metformin groups BACKGROUND Although previous studies have linked intake of sugars with incidence of cancer and other chronic diseases , its association with mortality remains unknown . OBJECTIVE We investigated the association of total sugars , added sugars , total fructose , added fructose , sucrose , and added sucrose with the risk of all-cause , cardiovascular disease , cancer , and other-cause mortality  in the NIH-AARP Diet and Health Study . DESIGN The participants ( n = 353,751 ) , aged 50 - 71 y , were followed for up to 13 y. Intake of individual sugars over the previous 12 mo was assessed at baseline by using a 124-item NIH Diet History Question naire . RESULTS In fully adjusted models ( fifth quartile compared with first quartile ) , all-cause mortality was positively associated with the intake of total sugars [ HR ( 95 % CI ) : 1.13 ( 1.06 , 1.20 ) ; P-trend < 0.0001 ] , total fructose [ 1.10 ( 1.04 , 1.17 ) ; P-trend < 0.0001 ] , and added fructose [ 1.07 ( 1.01 , 1.13 ) ; P-trend = 0.005 ) in women and total fructose [ 1.06 ( 1.01 , 1.10 ) ; P-trend = 0.002 ] in men . In men , a weak inverse association was found between other-cause mortality and dietary added sugars  ( P-trend = 0.04 ) , sucrose ( P-trend = 0.03 ) , and added sucrose ( P-trend = 0.006 ) . Investigation of consumption of sugars by source showed that the positive association with mortality risk was confined only to sugars from beverages , whereas the inverse association was confined to sugars from solid foods . CONCLUSIONS In this large prospect i ve study , total fructose intake was weakly positively associated with  all-cause mortality in both women and men , whereas added sugar , sucrose , and added sucrose intakes were inversely associated with other-cause mortality in men . In our analyses , intake of added sugars was not associated with an increased risk of mortality . The NIH-AARP Diet and Health Study was registered at clinical trials.gov as NCT00340015 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 Background and Objective : The role of sugars in solutions on subjective appetite and food intake ( FI ) has received little investigation in children . Therefore , we examined the effect of isocaloric solutions ( 200 kcal/250 ml ) of sugars including sucrose , high-fructose corn syrup-55 ( HFCS ) or glucose , compared with a non-caloric sucralose control , on subjective appetite and FI in 9- to 14-year-old normal weight ( NW ) boys . Participants and Methods : NW boys ( n=15 ) received each of the test solutions , in r and om order , 60 min before an ad libitum pizza meal .  Subjective appetite was measured at baseline ( 0 min ) , and 15 , 30 , 45 and 60 min . Results : Only glucose ( P=0.003 ) , but neither sucrose nor HFCS , reduced FI compared with the sucralose control . This led to a higher cumulative energy intake , compared with sucralose , after sucrose ( P=0.009 ) and HFCS ( P=0.01 ) , but not after glucose . In all treatment sessions , subjective average appetite increased from baseline to 60 min , but change from baseline average appetite was the highest after sucrose ( P<0.005 ) . Furthermore , sucrose ( r=−0.59 , P=0.02 ) and HFCS ( r=−0.56 , P=0.03 ) , but not glucose , were inversely associated with test meal FI when the treatment dose ( 200 kcal ) was expressed on a body weight ( kg ) basis . Conclusions : Change from baseline subjective average appetite was the highest after sucrose , but only the glucose solution suppressed FI at the test meal 60 min later in NW boys Epidemiological data on dietary risk factors for NAFLD from population -based studies , particularly in an ethnically diverse population , are scarce . We examined  dietary factors  in relation to NAFLD risk in African Americans , Japanese Americans , Latinos , Native Hawaiians , and whites in the Multiethnic Cohort ( MEC ) . A nested case-control analysis was conducted within the MEC , a large prospect i ve study with > 215,000 older-adult participants in Hawaii and California . NAFLD was identified using Medicare cl aims data , and controls were selected among participants without liver disease and individually matched to cases by birth year , sex , ethnicity , and length of Medicare enrollment .  Diet was assessed at baseline via a vali date d quantitative food frequency question naire .  Diet-NAFLD associations were quantified by odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) using multivariable conditional logistic regression . The study consisted of 2,974 NAFLD cases ( 518 with cirrhosis ; 2,456 without cirrhosis ) and 29,474 matched controls .  Red meat ( P trend=0.010 ) , processed red meat ( P trend= 0.004 ) , poultry ( P trend= 0.005 ) and  cholesterol  ( P trend= 0.005 ) intakes were positively associated with NAFLD , while  dietary fiber intake ( P trend=0.003 ) was inversely associated with risk . Stronger associations were observed between red meat and cholesterol and NAFLD with cirrhosis than without cirrhosis ( P heterogeneity ≤0.014 ) . Conclusion Dietary factors are independently associated with NAFLD and NAFLD-related cirrhosis in a multiethnic population . Decreasing the consumption of cholesterol , red and processed meat and poultry and increasing consumption of fiber may reduce the risk for NAFLD and related advanced liver disease Background : Studies have shown that zinc and selenium deficiency is common in nonalcoholic fatty liver disease ( NAFLD ) . However , the effects of zinc and selenium co-supplementation before and /or after disease progression on NAFLD are not clear enough . The aim of this study was to compare the effects of zinc and selenium co-supplementation before and /or after disease progression on NAFLD prognosis . Material s and Methods : Forty male Sprague – Dawley rats ( 197±4 g ) were r and omly assigned to 4 dietary groups : normal-fat diet ( NFD ; receiving 9 % of calories as fat ) , high-fat diet ( HFD ; receiving 82 % of calories as fat ) , supplementation before disease progression ( S+HFD ) , and supplementation after disease progression ( HFD+S ) . The diets were implemented over a 20-week period in all the groups . Biochemical and histologic parameters were compared between the 4 groups , and between-group comparisons were also carried out . Results : There were significant differences in the average food dietary intake ( P<0.001 ) , weight ( P<0.001 ) , fasting blood sugar ( P=0.005 ) , triglyceride ( P<0.001 ) , total cholesterol ( P<0.001 ) , low-density lipoprotein cholesterol ( P=0.002 ) , high-density lipoprotein cholesterol ( P=0.001 ) , alanine aminotransferase ( P<0.001 ) , and aspartate aminotransferase ( P<0.001 ) between the 4 dietary groups . Serum triglyceride and total cholesterol were significantly lower in the HFD+S Group than in the S+HFD Group ( P<0.001 and P=0.003 , respectively ) . Fat accumulation was significantly reduced in the HFD+S Group ( P<0.001 ) . Conclusion : Zinc and selenium co-supplementation after disease progression improved biochemical and histologic parameters in an experimental model of NAFLD BACKGROUND & AIMS Prevalence of nonalcoholic fatty liver disease ( NAFLD ) has not been well established . The purpose of this study was to prospect ively define the prevalence of both NAFLD and nonalcoholic steatohepatitis ( NASH ) . METHODS Out patients 18 to 70 years old were recruited from Brooke Army Medical Center . All patients completed a baseline question naire and ultrasound . If fatty liver was identified , then laboratory data and a liver biopsy were obtained . RESULTS Four hundred patients were enrolled . Three hundred and twenty-eight patients completed the question naire and ultrasound .  Mean age ( range , 28 - 70 years ) was 54.6 years ( 7.35 ) ; 62.5 % Caucasian , 22 % Hispanic , and 11.3 % African American ; 50.9 % female ; mean body mass index ( BMI ) ( calculated as kg/m(2 ) ) was 29.8 ( 5.64 ) ; and diabetes and hypertension prevalence 16.5 % and 49.7 % , respectively . Prevalence of NAFLD was 46 % . NASH was confirmed in 40 patients ( 12.2 % of total cohort , 29.9 % of ultrasound positive patients ) . Hispanics had the highest prevalence of NAFLD ( 58.3 % ) , then Caucasians ( 44.4 % ) and African Americans ( 35.1 % ) . NAFLD patients were more likely to be male ( 58.9 % ) , older ( P = .004 ) , hypertensive ( P < .00005 ) , and diabetic ( P < .00005 ) . They had a higher BMI ( P < .0005 ) , ate fast food more often ( P = .049 ) , and exercised less ( P = 0.02 ) than their non-NAFLD counterparts . Hispanics had a higher prevalence of NASH compared with Caucasians ( 19.4 % vs 9.8 % ; P = .03 ) . Alanine aminotransferase , aspartate aminotransferase , BMI , insulin , Quantitative Insulin-Sensitivity Check Index , and cytokeratin-18 correlated with NASH . Among the 54 diabetic patients , NAFLD was found in 74 % and NASH in 22.2 % . CONCLUSION Prevalence of NAFLD and NASH is higher than estimated previously . Hispanics and patients with diabetes are at greatest risk for both NAFLD and NASH The prevalence of and the risk factors for fatty liver have not undergone a formal evaluation in a representative sample of the general population . We therefore performed a cross-sectional study in the town of Campogalliano ( Modena , Italy ) , within the context of the Dionysos Project . Of 5,780 eligible persons aged 18 to 75 years , 3,345 ( 58 % ) agreed to participate in the study . Subjects with suspected liver disease ( SLD ) , defined on the basis of elevated serum alanine aminotransferase ( ALT ) and gamma-glutamyl-transferase ( GGT ) activity , hepatitis B surface antigen ( HBsAg ) , or hepatitis C virus (HCV)-RNA positivity , were matched with r and omly selected subjects of the same age and sex without SLD . A total of 311 subjects with and 287 without SLD underwent a detailed clinical , laboratory , and anthropometrical evaluation . Fatty liver was diagnosed by ultrasonography , and alcohol intake was assessed by using a 7-day diary . Multinomial logistic regression was used to detect risk factors for normal liver versus nonalcoholic fatty liver disease ( NAFLD ) and for alcoholic fatty liver ( AFLD ) versus NAFLD . The prevalence of NAFLD was similar in subjects with and without SLD ( 25 vs. 20 % , P = .203 ) . At multivariable analysis , normal liver was more likely than NAFLD in older subjects and less likely in the presence of obesity , hyperglycemia , hyperinsulinemia , hypertriglyceridemia , and systolic hypertension ; AFLD was more likely than NAFLD in older subjects , males , and in the presence of elevated GGT and hypertriglyceridemia , and less likely in the presence of obesity and hyperglycemia . In conclusion , NAFLD is highly prevalent in the general population , is not associated with SLD , but is associated with many features of the metabolic syndrome It is thought that diets high in dietary fibre are associated with reduced risk for type 2 diabetes  , at least in part because the short-chain fatty acids ( SCFAs ) produced during the colonic fermentation of fibre beneficially influence circulating concentrations of free-fatty acids ( FFAs ) and gut hormones involved in the regulation of blood glucose and body mass . However , there is a paucity of data showing this sequence of events in humans . Thus , our objective was to determine the effect of the fermentable fibre inulin on postpr and ial glucose , insulin , SCFA , FFA , and gut hormone responses in healthy subjects . Overnight fasted healthy subjects ( n = 12 ) were studied for 6 h after consuming 400 mL drinks , containing 80 g high-fructose corn syrup ( 80HFCS ) , 56 g HFCS ( 56HFCS ) , or 56 g HFCS plus 24 g inulin ( Inulin ) , using a r and omized , single-blind , crossover design . A st and ard lunch was served 4 h after the test drink . Glucose and insulin responses after Inulin did not differ significantly from those after 80HFCS or 56HFCS . Serum acetate , propionate , and butyrate were significantly higher after Inulin than after HFCS drinks from 4 - 6 h. FFAs fell at a similar rate after all 3 test drinks , but were lower after Inulin than after 56HFCS at 4 h ( 0.40 + /- 0.06 vs. 0.51 + /- 0.06 mmol*L-1 ; p < 0.05 ) . Compared with 56HFCS , Inulin significantly increased plasma glucagon-like peptide-1 concentrations at 30 min , and reduced ghrelin at 4.5 h and 6 h. The results are consistent with the hypothesis that dietary fibre increases the production of colonic SCFAs , which may reduce type 2 diabetes risk by reducing postpr and ial FFAs and favorably affecting gut hormones , which regulate food intake 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 OBJECTIVES : Nonalcoholic fatty liver disease ( NAFLD ) is defined as the spectrum of benign fatty liver to necroinflammation and fibrosis . Its prevalence has been found to be as high as 39 % . It is estimated that up to 15 % of those affected will go on to have progressive liver disease . Currently , there is no proven therapy for NAFLD . In this study , we aim to determine whether statin therapy may be an effective treatment for NAFLD and identify independent predictors of NAFLD . METHODS : In all , 1,005 men and women , aged 50–70 years were r and omized to receive either a daily combination of atorvastatin 20 mg , vitamin C 1 g , and vitamin E 1,000 IU vs. matching placebo , as part of the St Francis Heart Study r and omized clinical trial . Liver to spleen ( LS ) ratios were calculated on 455 subjects with available computed tomography scans performed at baseline and follow-up to determine NAFLD prevalence . Baseline and final LS ratios were compared within treatment groups , and results were compared between the treatment and placebo groups using univariate and multivariate analyses . Mean duration of follow-up was 3.6 years . RESULTS : There were 80 patients with NAFLD at baseline . We identified baseline triglyceride levels ( odds ratio (OR)=1.003 , P<0.001 ) and body mass index ( OR=0.10 , P<0.001 ) as independent correlates of NAFLD . Treatment with atorvastatin combined with vitamins E and C significantly reduced the odds of NAFLD at the end of follow-up , 70 vs. 34 % ( OR=0.29 , P<0.001 ) . CONCLUSIONS : In conclusion , atorvastatin 20 mg combined with vitamins C and E is effective in reducing the odds of having hepatic steatosis by 71 % in healthy individuals with NAFLD at baseline after 4 years of active therapy
In addition , there was a low level of evidence that hypercaloric fructose and glucose diets have similar effects on liver fat and liver enzymes in healthy adults .
There was insufficient evidence to draw a conclusion for effects of HFCS or sucrose on NAFLD .
Conclusions : On the basis of indirect comparisons across study findings , the apparent association between indexes of liver health ( ie , liver fat , hepatic de novo lipogenesis , alanine aminotransferase , AST , and γ-glutamyl transpeptase ) and fructose or sucrose intake appear to be confounded by excessive energy intake .
Overall , the available evidence is not sufficiently robust to draw conclusions regarding effects of fructose , HFCS , or sucrose consumption on NAFLD
Background : Concerns have been raised about the concurrent temporal trend between simple sugar intakes , especially of fructose or high-fructose corn syrup ( HFCS ) , and rates of nonalcoholic fatty liver disease ( NAFLD ) in the United States .
Objective : We examined the effect of different amounts and forms of dietary fructose on the incidence or prevalence of NAFLD and indexes of liver health in humans .