human
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CONTEXT Caffeine acutely increases blood pressure , but the association between habitual consumption of caffeinated beverages and incident hypertension is uncertain . OBJECTIVE To examine the association between caffeine intake and incident hypertension in women . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study conducted in the Nurses ' Health Studies ( NHSs ) I and II of 155,594 US women free from physician-diagnosed hypertension followed up over 12 years ( 1990 - 1991 to 2002 - 2003 question naires ) .  Caffeine intake and possible confounders were ascertained from regularly administered question naires . We also tested the associations with types of caffeinated beverages . MAIN OUTCOME MEASURE Incident physician-diagnosed hypertension . RESULTS During follow-up , 19,541 incident cases of physician-diagnosed hypertension were reported in NHS I and 13,536 in NHS II . In both cohorts , no linear association between  caffeine  consumption and risk of incident hypertension was observed after multivariate adjustment ( NHS I , P for trend = .29 ; NHS II , P for trend = .53 ) . Using categorical analysis , an inverse U-shaped association between caffeine consumption and incident hypertension was found . Compared with participants in the lowest quintile of caffeine consumption , those in the third quintile had a 13 % and 12 % increased risk of hypertension , respectively ( 95 % confidence interval in NHS I , 8%-18 % ; in NHS II , 6%-18 % ) . When study ing individual classes of caffeinated beverages , habitual coffee consumption was not associated with increased risk of hypertension . By contrast , consumption of cola beverages was associated with an increased risk of hypertension , independent of whether it was sugared or diet cola ( P for trend < .001 ) . CONCLUSION No linear association between caffeine consumption and incident hypertension was found . Even though habitual coffee consumption was not associated with an increased risk of hypertension , consumption of sugared or diet cola was associated with it . Further research to eluci date the role of cola beverages in hypertension is warranted BACKGROUND Despite safety reports of the artificial sweetener aspartame , health-related concerns remain . OBJECTIVE We prospect ively evaluated whether the consumption of aspartame- and sugar-containing soda is associated with  risk of hematopoetic cancers .  DESIGN We repeatedly assessed diet in the Nurses ' Health Study ( NHS ) and Health Professionals Follow-Up Study ( HPFS ) . Over 22 y , we identified 1324 non-Hodgkin lymphomas ( NHLs ) , 285 multiple myelomas , and 339 leukemias . We calculated incidence RRs and 95 % CIs by using Cox proportional hazards models . RESULTS When the 2 cohorts were combined , there was no significant association between soda intake and risks of NHL and multiple myeloma . However , in men , ≥1 daily serving of diet soda  increased risks of NHL ( RR : 1.31 ; 95 % CI : 1.01 , 1.72 ) and multiple myeloma ( RR : 2.02 ; 95 % CI : 1.20 , 3.40 ) in comparison with men who did not consume diet soda . We observed no increased risks of NHL and multiple myeloma in women . We also observed an unexpected elevated risk of NHL ( RR : 1.66 ; 95 % CI : 1.10 , 2.51 ) with a higher consumption of regular , sugar-sweetened soda in men but not in women . In contrast , when sexes were analyzed separately with limited power , neither regular nor diet soda  increased risk of leukemia but were associated with increased leukemia risk when data for men and women were combined ( RR for consumption of ≥1 serving of diet soda/d when the 2 cohorts were pooled : 1.42 ; 95 % CI : 1.00 , 2.02 ) . CONCLUSION Although our findings preserve the possibility of a detrimental effect of a constituent of diet soda , such as aspartame , on select cancers , the inconsistent sex effects and occurrence of an apparent cancer risk in individuals who consume regular soda do not permit the ruling out of chance as an explanation BACKGROUND It has been extensively shown , mainly in US population s , that sugar-sweetened beverages ( SSBs ) are associated with increased risk of type 2 diabetes ( T2D ) , but less is known about the effects of artificially sweetened beverages ( ASBs ) . OBJECTIVE We evaluated the association between self-reported SSB , ASB , and 100 % fruit juice consumption and T2D risk over 14 y of follow-up in the French prospect i ve Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale-European Prospect i ve Investigation into Cancer and Nutrition cohort . DESIGN A total of 66,118 women were followed from 1993 , and 1369 incident cases of T2D were diagnosed during the follow-up . Cox regression models were used to estimate HRs and 95 % CIs for T2D risk . RESULTS The average consumption of sweetened beverages in consumers was 328 and 568 mL/wk for SSBs and ASBs , respectively . Compared with nonconsumers , women in the highest quartiles of SSB and ASB consumers were at increased risk of T2D with HRs ( 95 % CIs ) of 1.34 ( 1.05 , 1.71 ) and 2.21 ( 1.56 , 3.14 ) for women who consumed > 359 and > 603 mL/wk of SSBs and ASBs , respectively . Strong positive trends in T2D risk were also observed across quartiles of consumption for both types of beverage ( P = 0.0088 and P < 0.0001 , respectively ) . In sensitivity analyses , associations were partly mediated by BMI , although there was still a strong significant independent effect . No association was observed for 100 % fruit juice consumption . CONCLUSIONS Both SSB consumption and ASB consumption were associated with increased T2D risk . We can not rule out that factors other than ASB consumption that we did not control for are responsible for the association with diabetes , and r and omized trials are required to prove a causal link between ASB consumption and T2D Safety of long-term administration of 75 mg/kg of aspartame per day was evaluated with the use of a r and omized , double-blind , placebo-controlled , parallel-group design in 108 male and female volunteers aged 18 to 62 years . Subjects received either aspartame or placebo in capsule form three times daily for 24 weeks . No persistent changes over time were noted in either group in vital signs ; body weight ; results of st and ard laboratory tests ; fasting blood levels of aspartame 's constituent amino acids ( aspartic acid and phenylalanine ) , other amino acids , and methanol ; or blood formate levels and 24-hour urinary excretion of formate . There also were no statistically significant differences between groups in the number of subjects experiencing symptoms or in the number of symptoms per subject . These results further document the safety of the long-term consumption of aspartame at doses equivalent to the amount of aspartame in approximately 10 L of beverage per day The long-term physiological effects of refined carbohydrates on appetite and mood remain unclear . Reported effects when subjects are not blind may be due to expectations and have rarely been studied for more than 24 h. The present study compared the effects of supplementary soft drinks added to the diet over 4 weeks on dietary intake , mood and BMI in normal-weight women ( n 133 ) . Subjects were categorised as ' watchers ' or ' non-watchers ' of what they ate then received sucrose or artificially sweetened drinks ( 4 x 250 ml per d ) . Expectancies were varied by labelling drinks ' sugar ' or ' diet ' in a counter-balanced design . Sucrose supplements provided 1800 kJ per d and sweetener supplements provided 67 kJ per d. Food intake was measured with a 7 d diary and mood with ten single Likert scales . By 4 weeks , sucrose supplements significantly reduced total carbohydrate intake ( F(1,129 ) = 53.81 ; P<0.001 ) , fat ( F(2,250 ) = 33.33 ; P<0.001 ) and protein intake ( F(2,250 ) = 28.04 ; P<0 - 001 ) compared with sweetener supplements .  Mean daily energy intake increased by just under 1000 kJ compared with baseline ( t ( 67 df ) = 3.82 ; P < 0.001 ) and was associated with a non-significant trend for those receiving sucrose to gain weight . There were no effects on appetite or mood . Neither dietary restraint status as measured by the Dutch Eating Behaviour Question naire nor the expectancy procedure had effects . Expectancies influenced mood only during baseline week . It is concluded that sucrose satiates , rather than stimulates , appetite or negative mood in normal-weight subjects BACKGROUND The consumption of beverages that contain sugar is associated with overweight , possibly because liquid sugars do not lead to a sense of satiety , so the consumption of other foods is not reduced . However , data are lacking to show that the replacement of sugar-containing beverages with noncaloric beverages diminishes weight gain . METHODS We conducted an 18-month trial involving 641 primarily normal-weight children from 4 years 10 months to 11 years 11 months of age . Participants were r and omly assigned to receive 250 ml ( 8 oz ) per day of a sugar-free , artificially sweetened beverage ( sugar-free group ) or a similar sugar-containing beverage that provided 104 kcal ( sugar group ) . Beverages were distributed through schools . At 18 months , 26 % of the children had stopped consuming the beverages ; the data from children who did not complete the study were imputed . RESULTS The z score for the body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) increased on average by 0.02 SD units in the sugar-free group and by 0.15 SD units in the sugar group ; the 95 % confidence interval ( CI ) of the difference was -0.21 to -0.05 . Weight increased by 6.35 kg in the sugar-free group as compared with 7.37 kg in the sugar group ( 95 % CI for the difference , -1.54 to -0.48 ) . The skinfold-thickness measurements , waist-to-height ratio , and fat mass also increased significantly less in the sugar-free group . Adverse events were minor . When we combined measurements at 18 months in 136 children who had discontinued the study with those in 477 children who completed the study , the BMI z score increased by 0.06 SD units in the sugar-free group and by 0.12 SD units in the sugar group ( P=0.06 ) . CONCLUSIONS Masked replacement of sugar-containing beverages with noncaloric beverages reduced weight gain and fat accumulation in normal-weight children . ( Funded by the Netherl and s Organization for Health Research and Development and others ; DRINK Clinical Trials.gov number , NCT00893529 . ) We conducted a population -based case-control study of patients with bladder cancer and of controls drawn r and omly from the general population of Metropolitan Nagoya and interviewed both groups . The incidence rates of bladder cancer were 2.42 and 7.05/100,000 for females and males , respectively . The analysis , based on 293 patients and 589 controls who were frequency matched for age , sex , and residence , provided the following major findings . Age-adjusted relative risks of 1.89 ( 1.15 - 3.10 ) and 3.53 ( 1.71 - 7.27 ) were found in male and female cigarette smokers , respectively . Significant relative risk was also found in males who drank cocoa . Elevated risk with a dose-response relationship was observed among women who used hair dye and who smoke , but this risk was insignificant , with the disappearance of a dose-response relationship , when it was adjusted for smoking . Age- and smoking-adjusted relative risk of coffee drinking was insignificant with no dose-response relationship . Relative risk of artificial sweetener use was below 1 with adjustment for age and smoking . Intake of alcoholic beverages and cola  was insignificantly associated . Reduced risk of significance was suggested for the intake of black tea and matcha ( powdered green tea ) in females and of fruit juice in males BACKGROUND Increased intake of sugar-sweetened beverages and fruit juice has been associated with overweight in children . OBJECTIVE This study prospect ively assessed beverage consumption patterns and their relationship with weight status in a cohort of children born at different risk for obesity . METHODS AND PROCEDURES Participants were children born at low risk ( n = 27 ) or high risk ( n = 22 ) for obesity based on maternal prepregnancy BMI ( kg/m(2 ) ) . Daily beverage consumption was generated from 3-day food records from children aged 3 - 6 years and coded into seven beverage categories ( milk , fruit juice , fruit drinks , caloric and non-caloric 
    Output:
    
agent
In healthy subjects , appetite and short term food intake , risk of cancer , risk of diabetes , risk of dental caries , weight gain and risk of obesity are the most investigated health outcomes .
Overall there is no conclusive evidence for beneficial and harmful effects on those outcomes .
In subjects with diabetes and hypertension , the evidence regarding health outcomes of NNS use is also inconsistent .
***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: CONTEXT Caffeine acutely increases blood pressure , but the association between habitual consumption of caffeinated beverages and incident hypertension is uncertain . OBJECTIVE To examine the association between caffeine intake and incident hypertension in women . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study conducted in the Nurses ' Health Studies ( NHSs ) I and II of 155,594 US women free from physician-diagnosed hypertension followed up over 12 years ( 1990 - 1991 to 2002 - 2003 question naires ) .  Caffeine intake and possible confounders were ascertained from regularly administered question naires . We also tested the associations with types of caffeinated beverages . MAIN OUTCOME MEASURE Incident physician-diagnosed hypertension . RESULTS During follow-up , 19,541 incident cases of physician-diagnosed hypertension were reported in NHS I and 13,536 in NHS II . In both cohorts , no linear association between  caffeine  consumption and risk of incident hypertension was observed after multivariate adjustment ( NHS I , P for trend = .29 ; NHS II , P for trend = .53 ) . Using categorical analysis , an inverse U-shaped association between caffeine consumption and incident hypertension was found . Compared with participants in the lowest quintile of caffeine consumption , those in the third quintile had a 13 % and 12 % increased risk of hypertension , respectively ( 95 % confidence interval in NHS I , 8%-18 % ; in NHS II , 6%-18 % ) . When study ing individual classes of caffeinated beverages , habitual coffee consumption was not associated with increased risk of hypertension . By contrast , consumption of cola beverages was associated with an increased risk of hypertension , independent of whether it was sugared or diet cola ( P for trend < .001 ) . CONCLUSION No linear association between caffeine consumption and incident hypertension was found . Even though habitual coffee consumption was not associated with an increased risk of hypertension , consumption of sugared or diet cola was associated with it . Further research to eluci date the role of cola beverages in hypertension is warranted BACKGROUND Despite safety reports of the artificial sweetener aspartame , health-related concerns remain . OBJECTIVE We prospect ively evaluated whether the consumption of aspartame- and sugar-containing soda is associated with  risk of hematopoetic cancers .  DESIGN We repeatedly assessed diet in the Nurses ' Health Study ( NHS ) and Health Professionals Follow-Up Study ( HPFS ) . Over 22 y , we identified 1324 non-Hodgkin lymphomas ( NHLs ) , 285 multiple myelomas , and 339 leukemias . We calculated incidence RRs and 95 % CIs by using Cox proportional hazards models . RESULTS When the 2 cohorts were combined , there was no significant association between soda intake and risks of NHL and multiple myeloma . However , in men , ≥1 daily serving of diet soda  increased risks of NHL ( RR : 1.31 ; 95 % CI : 1.01 , 1.72 ) and multiple myeloma ( RR : 2.02 ; 95 % CI : 1.20 , 3.40 ) in comparison with men who did not consume diet soda . We observed no increased risks of NHL and multiple myeloma in women . We also observed an unexpected elevated risk of NHL ( RR : 1.66 ; 95 % CI : 1.10 , 2.51 ) with a higher consumption of regular , sugar-sweetened soda in men but not in women . In contrast , when sexes were analyzed separately with limited power , neither regular nor diet soda  increased risk of leukemia but were associated with increased leukemia risk when data for men and women were combined ( RR for consumption of ≥1 serving of diet soda/d when the 2 cohorts were pooled : 1.42 ; 95 % CI : 1.00 , 2.02 ) . CONCLUSION Although our findings preserve the possibility of a detrimental effect of a constituent of diet soda , such as aspartame , on select cancers , the inconsistent sex effects and occurrence of an apparent cancer risk in individuals who consume regular soda do not permit the ruling out of chance as an explanation BACKGROUND It has been extensively shown , mainly in US population s , that sugar-sweetened beverages ( SSBs ) are associated with increased risk of type 2 diabetes ( T2D ) , but less is known about the effects of artificially sweetened beverages ( ASBs ) . OBJECTIVE We evaluated the association between self-reported SSB , ASB , and 100 % fruit juice consumption and T2D risk over 14 y of follow-up in the French prospect i ve Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l'Education Nationale-European Prospect i ve Investigation into Cancer and Nutrition cohort . DESIGN A total of 66,118 women were followed from 1993 , and 1369 incident cases of T2D were diagnosed during the follow-up . Cox regression models were used to estimate HRs and 95 % CIs for T2D risk . RESULTS The average consumption of sweetened beverages in consumers was 328 and 568 mL/wk for SSBs and ASBs , respectively . Compared with nonconsumers , women in the highest quartiles of SSB and ASB consumers were at increased risk of T2D with HRs ( 95 % CIs ) of 1.34 ( 1.05 , 1.71 ) and 2.21 ( 1.56 , 3.14 ) for women who consumed > 359 and > 603 mL/wk of SSBs and ASBs , respectively . Strong positive trends in T2D risk were also observed across quartiles of consumption for both types of beverage ( P = 0.0088 and P < 0.0001 , respectively ) . In sensitivity analyses , associations were partly mediated by BMI , although there was still a strong significant independent effect . No association was observed for 100 % fruit juice consumption . CONCLUSIONS Both SSB consumption and ASB consumption were associated with increased T2D risk . We can not rule out that factors other than ASB consumption that we did not control for are responsible for the association with diabetes , and r and omized trials are required to prove a causal link between ASB consumption and T2D Safety of long-term administration of 75 mg/kg of aspartame per day was evaluated with the use of a r and omized , double-blind , placebo-controlled , parallel-group design in 108 male and female volunteers aged 18 to 62 years . Subjects received either aspartame or placebo in capsule form three times daily for 24 weeks . No persistent changes over time were noted in either group in vital signs ; body weight ; results of st and ard laboratory tests ; fasting blood levels of aspartame 's constituent amino acids ( aspartic acid and phenylalanine ) , other amino acids , and methanol ; or blood formate levels and 24-hour urinary excretion of formate . There also were no statistically significant differences between groups in the number of subjects experiencing symptoms or in the number of symptoms per subject . These results further document the safety of the long-term consumption of aspartame at doses equivalent to the amount of aspartame in approximately 10 L of beverage per day The long-term physiological effects of refined carbohydrates on appetite and mood remain unclear . Reported effects when subjects are not blind may be due to expectations and have rarely been studied for more than 24 h. The present study compared the effects of supplementary soft drinks added to the diet over 4 weeks on dietary intake , mood and BMI in normal-weight women ( n 133 ) . Subjects were categorised as ' watchers ' or ' non-watchers ' of what they ate then received sucrose or artificially sweetened drinks ( 4 x 250 ml per d ) . Expectancies were varied by labelling drinks ' sugar ' or ' diet ' in a counter-balanced design . Sucrose supplements provided 1800 kJ per d and sweetener supplements provided 67 kJ per d. Food intake was measured with a 7 d diary and mood with ten single Likert scales . By 4 weeks , sucrose supplements significantly reduced total carbohydrate intake ( F(1,129 ) = 53.81 ; P<0.001 ) , fat ( F(2,250 ) = 33.33 ; P<0.001 ) and protein intake ( F(2,250 ) = 28.04 ; P<0 - 001 ) compared with sweetener supplements .  Mean daily energy intake increased by just under 1000 kJ compared with baseline ( t ( 67 df ) = 3.82 ; P < 0.001 ) and was associated with a non-significant trend for those receiving sucrose to gain weight . There were no effects on appetite or mood . Neither dietary restraint status as measured by the Dutch Eating Behaviour Question naire nor the expectancy procedure had effects . Expectancies influenced mood only during baseline week . It is concluded that sucrose satiates , rather than stimulates , appetite or negative mood in normal-weight subjects BACKGROUND The consumption of beverages that contain sugar is associated with overweight , possibly because liquid sugars do not lead to a sense of satiety , so the consumption of other foods is not reduced . However , data are lacking to show that the replacement of sugar-containing beverages with noncaloric beverages diminishes weight gain . METHODS We conducted an 18-month trial involving 641 primarily normal-weight children from 4 years 10 months to 11 years 11 months of age . Participants were r and omly assigned to receive 250 ml ( 8 oz ) per day of a sugar-free , artificially sweetened beverage ( sugar-free group ) or a similar sugar-containing beverage that provided 104 kcal ( sugar group ) . Beverages were distributed through schools . At 18 months , 26 % of the children had stopped consuming the beverages ; the data from children who did not complete the study were imputed . RESULTS The z score for the body-mass index ( BMI , the weight in kilograms divided by the square of the height in meters ) increased on average by 0.02 SD units in the sugar-free group and by 0.15 SD units in the sugar group ; the 95 % confidence interval ( CI ) of the difference was -0.21 to -0.05 . Weight increased by 6.35 kg in the sugar-free group as compared with 7.37 kg in the sugar group ( 95 % CI for the difference , -1.54 to -0.48 ) . The skinfold-thickness measurements , waist-to-height ratio , and fat mass also increased significantly less in the sugar-free group . Adverse events were minor . When we combined measurements at 18 months in 136 children who had discontinued the study with those in 477 children who completed the study , the BMI z score increased by 0.06 SD units in the sugar-free group and by 0.12 SD units in the sugar group ( P=0.06 ) . CONCLUSIONS Masked replacement of sugar-containing beverages with noncaloric beverages reduced weight gain and fat accumulation in normal-weight children . ( Funded by the Netherl and s Organization for Health Research and Development and others ; DRINK Clinical Trials.gov number , NCT00893529 . ) We conducted a population -based case-control study of patients with bladder cancer and of controls drawn r and omly from the general population of Metropolitan Nagoya and interviewed both groups . The incidence rates of bladder cancer were 2.42 and 7.05/100,000 for females and males , respectively . The analysis , based on 293 patients and 589 controls who were frequency matched for age , sex , and residence , provided the following major findings . Age-adjusted relative risks of 1.89 ( 1.15 - 3.10 ) and 3.53 ( 1.71 - 7.27 ) were found in male and female cigarette smokers , respectively . Significant relative risk was also found in males who drank cocoa . Elevated risk with a dose-response relationship was observed among women who used hair dye and who smoke , but this risk was insignificant , with the disappearance of a dose-response relationship , when it was adjusted for smoking . Age- and smoking-adjusted relative risk of coffee drinking was insignificant with no dose-response relationship . Relative risk of artificial sweetener use was below 1 with adjustment for age and smoking . Intake of alcoholic beverages and cola  was insignificantly associated . Reduced risk of significance was suggested for the intake of black tea and matcha ( powdered green tea ) in females and of fruit juice in males BACKGROUND Increased intake of sugar-sweetened beverages and fruit juice has been associated with overweight in children . OBJECTIVE This study prospect ively assessed beverage consumption patterns and their relationship with weight status in a cohort of children born at different risk for obesity . METHODS AND PROCEDURES Participants were children born at low risk ( n = 27 ) or high risk ( n = 22 ) for obesity based on maternal prepregnancy BMI ( kg/m(2 ) ) . Daily beverage consumption was generated from 3-day food records from children aged 3 - 6 years and coded into seven beverage categories ( milk , fruit juice , fruit drinks , caloric and non-caloric 
    Output:
    