Do sugar-sweetened beverages cause adverse health outcomes in children? A systematic review protocol Administration of aspartame in non-insulin-dependent diabetics. Aspartame consumption in relation to childhood brain tumor risk: results from a case-control study. The effects of aspartame versus sucrose on motivational ratings, taste preferences, and energy intakes in obese and lean women. 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. Consumption of Aspartame-Containing Beverages and Incidence of Hematopoietic and Brain Malignancies Consumption of artificial sweetener- and sugar-containing soda and risk of lymphoma and leukemia in men and women. A randomized controlled trial contrasting the effects of 4 low-calorie sweeteners and sucrose on body weight in adults with overweight or obesity. Artificially and sugar-sweetened carbonated beverage consumption is not associated with risk of lymphoid neoplasms in older men and women. Hormonal responses to non-nutritive sweeteners in water and diet soda Cephalic phase responses to sweet taste. Interventions in sports settings to reduce alcohol consumption and alcohol-related harm: a systematic review protocol Lunch eating behavior of preschool children: Effects of age, gender, and type of beverage served Aspartame Consumption for 12 Weeks Does Not Affect Glycemia, Appetite, or Body Weight of Healthy, Lean Adults in a Randomized Controlled Trial. Aspartame Use By Persons with Diabetes Children's food intake following drinks sweetened with sucrose or aspartame: Time course effects Aspartame and sucrose produce a similar increase in the plasma phenylalanine to large neutral amino acid ratio in healthy subjects. Effects of aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages on postprandial glucose, insulin and energy intake The effect of aspartame as part of a multidisciplinary weight-control program on short- and long-term control of body weight. Response to Single Dose of Aspartame or Saccharin by NIDDM Patients Chronic Consumption of Artificial Sweetener in Packets or Tablets and Type 2 Diabetes Risk: Evidence from the E3N-European Prospective Investigation into Cancer and Nutrition Study Consuming aspartame with and without taste: Differential effects on appetite and food intake of young adult males Sources of evidence for systematic reviews of interventions in diabetes.
Background Cardiovascular disease and type 2 diabetes are examples of chronic diseases that impose significant morbidity and mortality in the general population worldwide . Most chronic diseases are associated with underlying preventable risk factors , such as elevated blood pressure , high blood glucose or glucose intolerance , high lipid levels , physical inactivity , excessive sedentary behaviours , and overweight/obesity . The occurrence of intermediate outcomes during childhood increases the risk of disease in adulthood . Sugar-sweetened beverages are known to be significant sources of additional caloric intake , and given recent attention to their contribution in the development of chronic diseases , a systematic review is warranted . We will assess whether the consumption of sugar-sweetened beverages in children is associated with adverse health outcomes and what the potential moderating factors are . Methods / Design Of interest are studies addressing sugar-sweetened beverage consumption , taking a broad perspective . Both direct consumption studies as well as those evaluating interventions that influence consumption ( e.g. school policy , educational ) will be relevant . Non-specific or multi-faceted behavioural , educational , or policy interventions may also be included subject to the level of evidence that exists for the other interventions /exposures . Comparisons of interest and endpoints of interest are pre-specified . We will include r and omized controlled trials , controlled clinical trials , interrupted time series studies , controlled before-after studies , prospect i ve and retrospective comparative cohort studies , case – control studies , and nested case – control design s. The MEDLINE ® , Embase , The Cochrane Library , CINAHL , ERIC , and PsycINFO ® data bases and grey literature sources will be search ed . The processes for selecting studies , abstract ing data , and resolving conflicts are described . We will assess risk of bias using design -specific tools . To determine sets of confounding variables that should be adjusted for , we have developed causal directed acyclic graphs and will use those to inform our risk of bias assessment s. Meta- analysis will be conducted where appropriate ; parameters for exploring statistical heterogeneity and effect modifiers are pre-specified . The Grading of Recommendations Assessment , Development and Evaluation ( GRADE ) approach will be used to determine the quality of evidence for outcomes . Systematic review registration PROSPERO CRD42014009641 A study was design ed to determine the effect of the consumption of the nutritive sweetener aspartame on non-insulin-dependent diabetics . Forty-three adult diabetics between the ages of 21 and 70 completed a 90-day study ; all were diabetics whose conditions were managed by diet and /or hypoglycemic agents . Participants in the blind study were instructed to continue their usual diet and to take two capsules of an assigned preparation three times daily with meals , either the aspartame or the placebo . The 1.8 g of aspartame administered is approximately three times the expected daily consumption of aspartame if used as a sweetener to replace sugar . Throughout the study subjects were examined for ( 1 ) symptoms of intolerance , ( 2 ) fasting plasma phenylalanine levels exceeding 4 mg/100 ml , and ( 3 ) deterioration of diabetic control . At the conclusion of the study subjects exhibited no symptoms that could be traced to the administration of aspartame or the placebo , and diabetic control was unaffected by the chronic administration of these substances . Aspartame seems to be well tolerated by non-insulin-dependent diabetics Brain cancer incidence rates in the United States have been increasing in both adults ( 1 ) and children ( 2 ) . The possibility that aspartame , a widely ingested artificial sweetener , may be a cause of brain cancer in humans was suggested in a recent report by Olney et al. ( 3 ) . From a descriptive analysis of national cancer data , they noted increased brain cancer incidence rates in the United States that coincided with the introduction of aspartame into food stuffs in the early 1980s . As part of a population -based case– control study of environmental and nutritional risk factors for pediatric brain tumor occurrence , we collected data on aspartame consumption before the date of diagnosis for case patients ( or a comparable reference date for control subjects ) from the biologic mothers of study children by in-person interview . The methodology for the study has been published previously ( 4 ) . Briefly , case patients were 19 years of age or older and were diagnosed with a primary brain tumor between 1984 and 1991 in 19 West Coast counties of the United States . Control subjects were recruited using r and om-digit dialing and were frequency-matched by age at diagnosis , year of birth , sex , and study site . We present data on aspartame consumption among the subset of participants from the Los Angeles and San Francisco sites where questions on aspartame consumption were added to the original question naire midway through the interviews . Our analysis of the child ’s exposure was conducted on 56 case patients and 94 control subjects who were born in 1981 or later ( to correspond with the U.S. Food and Drug Administration [ FDA ] approval of aspartame ) . We also evaluated brain tumor risk in relation to mother ’s consumption of aspartame during pregnancy and breast-feeding for 49 case patients and 90 control subjects who were in utero in 1981 or later . We calculated odds ratios ( ORs ) and 95 % confidence intervals and adjusted for the frequency-matched variables with the use of unconditional logistic regression . Additional adjustment for known or suspected risk factors ( maternal vitamin use , cured meat consumption , passive smoke exposure , x-ray exposure , head injury , and family history of brain cancer ) did not change our results . Case children were no more likely than control children to consume foods containing aspartame , either from all sources of aspartame combined ( OR 4 1.1 ) or from diet drinks ( OR 4 0.9 ) ( Table 1 ) . There was no suggestion of a dose – response relation based on age at first consumption , number of years of consumption , or frequency of consumption . We observed no elevated brain tumor risk to the child from maternal consumption of aspartame  during pregnancy nor did we find elevated risks during any trimester of pregnancy or during breast-feeding ( Table 2 ) . Additionally , we found no evidence for an aspartame – brain tumor association when the analysis was stratified by histologic subgroups ( astroglial , primitive neuroectodermal , or all others ) . These findings are not consistent with an aspartame – brain cancer relation , although our study sample was small and the confidence intervals of our risk estimates are relatively wide . Recall bias is unlikely to have affected these results , or we would expect to see elevations in risk ; however , it is conceivable that exposure misclassification that was r and omly distributed between case patients and control subjects could have masked a true effect , if the true effect was weak . We are aware of no other epidemiologic studies that have evaluated brain cancer risk from aspartame consumption . There have been numerous studies ( 5 - 8 ) related to the potential neurotoxic effects of aspartame . However , few experimental or biochemical reports related to the carcinogenicity of aspartame are in the scientific literature . Before approval of aspartame for human consumption , the FDA and an FDA appointed public board of inquiry review ed several studies to determine if aspartame can induce brain neoplasms in mice or rats . The mice studies were negative , but interpretation of two of the three rat studies differed initially between the FDA and its board of inquiry . These differences were resolved , and the FDA commissioner concluded that aspartame did not contribute to brain tumor formation in rats ( 7 - 10 ) . A subsequent rat study also found no association between aspartame and brain tumor occurrence ( 11 ) . Because some dietary constituents can be nitrosated in the stomach to form potentially carcinogenic N-nitroso compounds ( 12 ) , Shephard et al. ( 13 ) evaluated the mutagenic activity of aspartame after nitrosation . They observed only a weak mutagenic effect of nitrosated aspartame at concentrations considerably higher than normal human intake levels . On the basis of the kinetics of nitrosation of mutagenic intermediates , Shephard et al. concluded that the terminal amino group of aspartame , not the amide function , was primarily nitrosated . It would be nitrosation of the amide function , not the terminal amino group , that could produce a potential brain carcinogen , based on the ability of the related nitrosoureas to induce brain tumors in laboratory animals ( 14 ) . Thus , our review revealed little biologic or experimental evidence that aspartame is likely to act as a human brain carcinogen This study examined the effects of four breakfast preloads of different sweetness and energy content on motivational ratings , taste preferences , and energy intakes of 12 obese and 12 lean women . The preloads consisted of creamy white cheese ( fromage blanc ) and were either plain , sweetened with sucrose or aspartame , or sweetened with aspartame and supplemented with maltodextrin . Their energy content was either 300 kcal ( 1,255 kJ ) or 700 kcal ( 2,929 kJ ) . Motivational ratings of hunger and the desire to eat were obtained prior to and at 30 min intervals after breakfast . Taste preferences were measured prior to and 150 min after breakfast . The subjects ate buffet-style lunch , snack , and dinner meals in the laboratory . Obese women consumed significantly more energy at meals ( 2,596 kcal or 10,862 kJ ) than did lean women ( 1,484 kcal or 6,209 kJ ) ; derived a greater proportion of energy from fat ( 39.9 % vs. 35.5 % ) , and had lower dietary carbohydrate-to-fat ratios . Consumption of low-energy as opposed to high-energy breakfast preloads was associated with elevated motivational ratings by noon . However , energy intakes at lunch , snack , or dinner did not vary as a function of preload type , and no compensation was observed for the energy consumed at breakfast . Taste preferences were not affected by preload ingestion or by preload type . The study provided no evidence that aspartame promotes hunger or results in increased energy intakes in obese or in lean women 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 Background : In a few animal experiments , aspartame has been linked to hematopoietic and brain cancers . Most animal studies have found no increase in the risk of these or other cancers . Data on humans are sparse for either cancer . Concern lingers regarding this widely used artificial sweetener . Objective : We investigated prospect ively whether aspartame consumption is associated with the risk of hematopoietic cancers or gliomas ( malignant brain cancer ) . Methods : We examined 285,079 men and 188,905 women ages 50 to 71 years in the NIH-AARP Diet and Health Study cohort . Daily aspartame intake was derived from responses to a baseline self-administered food frequency question naire that queried consumption of four aspartame-containing beverages ( soda , fruit drinks , sweetened iced tea , and aspartame added to hot coffee and tea ) during the past year . Histologically confirmed incident cancers were identified from eight state cancer registries .  Multivariable-adjusted relative risks ( RR ) and 95 % confidence intervals ( CI ) were estimated using Cox proportional hazards regression that adjusted for age , sex , ethnicity , body mass index , and history of diabetes . Results : During over 5 years of follow-up ( 1995 - 2000 ) , 1,888 hematopoietic cancers and 315 malignant gliomas were ascertained . Higher levels of aspartame intake were not associated with the risk of overall hematopoietic cancer ( RR for ≥600 mg/d , 0.98 ; 95 % CI , 0.76 - 1.27 ) , glioma ( RR for ≥400 mg/d , 0.73 ; 95 % CI , 0.46 - 1.15 ; P for inverse linear trend = 0.05 ) , or their subtypes in men and women . Conclusions : Our findings do not support the hypothesis that aspartame  increases hematopoietic or brain cancer risk . ( Cancer Epidemiol Biomarkers Prev 2006;15(9):1654–9 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 Low-calorie sweeteners ( LCSs ) provide sweetness with little or no energy . However , each LCS 's unique chemical structure has potential to elicit different sensory , physiological , and behavioral responses that affect body weight . OBJECTIVE The purpose of this trial was to compare the effects of consumption of 4 LCSs and sucrose on body weight , ingestive behaviors , and glucose tolerance over a 12-wk intervention in adults ( 18 - 60 y old ) with overweight or obesity ( body mass index 25 - 40 kg/m2 ) . METHODS In a parallel-arm design , 154 participants were r and omly assigned to consume 1.25 - 1.75 L of beverage sweetened with sucrose ( n = 39 ) , aspartame ( n = 30 ) , saccharin ( n = 29 ) , sucralose ( n = 28 ) , or rebaudioside A ( rebA ) ( n = 28 ) daily for 12 wk . The beverages contained 400 - 560 kcal/d ( sucrose treatments ) or < 5 kcal/d ( LCS treatments ) . Anthropometric indexes , energy intake , energy expenditure , appetite , and glucose tolerance were measured at baseline . Body weight was measured every 2 wk with energy intake , expenditure , and appetite assessed every 4 wk . Twenty-four-hour urine collection s were completed every 4 wk to determine study compliance via para-aminobenzoic acid excretion . RESULTS Of the participants enrolled in the trial , 123 completed the 12-wk intervention . Sucrose and saccharin consumption led to increased body weight across the 12-wk intervention ( Δweight = + 1.85 ± 0.36 kg and + 1.18 ± 0.36 kg , respectively ; P ≤ 0.02 ) and did not differ from each other . There was no significant change in body weight with consumption of the other LCS treatments compared with baseline , but change in body weight for sucralose was negative and significantly lower compared with all other LCSs at week 12 ( weight difference ≥ 1.37 ± 0.52 kg , P ≤ 0.008 ) . Energy intake decreased with sucralose consumption ( P = 0.02 ) and ingestive frequency was lower for sucralose than for saccharin ( P = 0.045 ) . Glucose tolerance was not significantly affected by any of the sweetener treatments . CONCLUSIONS Sucrose and saccharin consumption significantly increase body weight compared with aspartame , rebA , and sucralose , whereas weight change was directionally negative and lower for sucralose compared with saccharin , aspartame , and rebA consumption . LCSs should be categorized as distinct entities because of their differing effects on body weight . This trial was registered at clinical trials.gov as NCT02928653 BACKGROUND Concern about the carcinogenic potential of aspartame was raised after an increase in lymphomas and leukemia was reported in an animal study at doses similar to human exposure . Two prospect i ve cohort studies published after the report found inconsistent results for estimated aspartame intake , artificially sweetened beverage consumption , and risk of lymphoid neoplasms . OBJECTIVE The objective of this study was to examine associations of artificially and sugar-sweetened carbonated beverage consumption ( for comparison ) and aspartame intake with risk of non-Hodgkin lymphoma ( NHL )  overall and by major histologic subtype in the Cancer Prevention Study -II Nutrition Cohort . METHODS Among 100,442 adult men and women who provided information on diet and lifestyle factors in 1999 , 1196 NHL cases were verified during a 10-y follow-up period . Cox proportional hazards regression was used to estimate multivariable-adjusted RRs and 95 % CIs . RESULTS In women and men combined , there were no associations of consumption of ≥1 ( 355 mL ) servings/d of artificially ( RR : 0.92 ; 95 % CI : 0.73 , 1.17 ; P-trend : 0.14 ) or sugar- ( RR : 1.10 ; 95 % CI : 0.77 , 1.58 ; P-trend : 0.62 ) sweetened carbonated beverages with NHL risk , compared to no consumption ( P-heterogeneity by gender : 0.11 - 1.00 ) . Similarly , aspartame intake was not associated with NHL risk ( RR : 1.02 ; 95 % CI : 0.84 , 1.24 ; P-trend : 0.69 , top vs. bottom quintile ) . Associations with NHL subtype ( multiple myeloma , diffuse large B-cell lymphoma , chronic lymphocytic leukemia/small lymphocytic lymphoma , and follicular and other B-cell lymphoma ) were generally null . CONCLUSION These findings do not support associations of daily consumption of artificially or sugar-sweetened carbonated beverages , or aspartame , with NHL risk Background Non-nutritive sweeteners ( NNS ) , especially in form of diet soda , have been linked to metabolic derangements ( e.g. obesity and diabetes ) in epidemiologic studies . We aim ed to test acute metabolic effects of NNS in isolation ( water or seltzer ) and in diet sodas . Methods We conducted a four-period , cross-over study at the National Institutes of Health Clinical Center ( Bethesda , Maryl and ) . Thirty healthy adults consumed 355 mL water with 0 mg , 68 mg , 170 mg , and 250 mg sucralose , and 31 individuals consumed 355 mL caffeine-free Diet Rite Cola ™ , Diet Mountain Dew ™ ( 18 mg sucralose , 18 mg acesulfame-potassium , 57 mg aspartame ) , and seltzer water with NNS ( 68 mg sucralose and 41 mg acesulfame-potassium , equivalent to Diet Rite Cola ™ ) in r and omized order , prior to oral glucose tolerance tests . Blood sample s were collected serially for 130 min . Measures included GLP-1 , GIP , glucose , insulin , C-peptide , glucose absorption , gastric emptying , and subjective hunger and satiety ratings . Results Diet sodas  augmented active GLP-1 ( Diet Rite Cola ™ vs. seltzer water , AUC , p = 0.039 ; Diet Mountain Dew ™ vs. seltzer water , AUC , p = 0.07 ) , but gastric emptying and satiety were unaffected . Insulin concentrations were nominally higher following all NNS conditions without altering glycemia . Sucralose alone ( at any concentration ) did not affect metabolic outcomes . Conclusions Diet sodas but not NNS in water augmented GLP-1 responses to oral glucose . Whether the trends toward higher insulin concentrations after NNS are of clinical importance remains to be determined . Our findings emphasize the need to test metabolic effects of NNS after chronic consumption . Trial registration The data for this manuscript were gathered from clinical trial # NCT01200940 The sweet taste of nonnutritive sweeteners has been reported to increase hunger and food intake through the mechanism of cephalic-phase insulin release ( CPIR ) . We investigated the effect of oral sensation of sweetness on CPIR and other indexes associated with glucose metabolism using nutritive and nonnutritive sweetened tablets as stimuli . At lunchtime , 12 normal-weight men sucked for 5 min a sucrose , an aspartame-polydextrose , or an unsweetened polydextrose tablet ( 3 g ) with no added flavor . The three stimuli were administered in a counterbalanced order , each on a separate day at 1-wk intervals . Blood was drawn continuously for 45 min before and 25 min after the beginning of sucking and sample s were collected at 1-min intervals . Spontaneous oscillations in glucose , insulin , and glucagon concentrations were assessed as were increments ( slopes ) of fatty acid concentrations during the baseline period . The nature of the baseline ( oscillations : glucose , insulin , and glucagon ; and slopes : fatty acids ) was taken into account in the analyses of postexposure events . No CPIR and no significant effect on plasma glucagon or fatty acid concentrations were observed after the three stimuli . However , there was a significant decrease in plasma glucose and insulin after all three stimuli . Only the consumption of the sucrose tablet was followed by a postabsorptive increase in plasma glucose and insulin concentrations starting 17 and 19 min , respectively , after the beginning of sucking . In conclusion , this study suggested that oral stimulation provided by sweet nonflavored tablets is not sufficient for inducing CPIR Introduction Alcohol consumption is a primary cause of physical , psychological and social harm to both the user and others . At both the professional and non-professional level , sports players and fans report consuming alcohol at greater levels than people not involved in sports . Limited systematic review s have been conducted assessing interventions targeting alcohol consumption behaviour and related harms in the sporting context . Methods and analysis The review aims to determine if interventions implemented in the sport setting decrease alcohol consumption and related harms .  Participants may include all persons regardless of age or other characteristics . Studies will be included which have implemented interventions within the sport setting and have either measured : alcohol consumption , excessive alcohol consumption or intoxication or alcohol-related injury or violence . R and omised controlled trials , staggered enrolment trials , stepped-wedged trials , quasi-r and omised trials , quasi-experimental trials and natural experiments will be included . Studies without a parallel comparison group will be excluded . Data will be source d from a range of electronic data bases and sources of grey literature . Two authors will independently screen all titles and abstract s of papers identified through the search strategy . Two authors will independently examine the full text of all remaining papers to determine eligibility . Two authors will independently extract data from eligible studies and independently assess risk of bias by assessing the adequacy of study characteristics . Where studies are sufficiently homogeneous , trial results will be synthesis ed using a fixed-effects meta- analysis . St and ardised mean differences will be used for continuous outcomes and RRs will be used for binary outcomes . Dissemination The findings of this study will be disseminated widely through mechanisms including peer- review ed publications and conference presentations To examine the eating behavior of preschool children offered chocolate-flavored or plain milk at lunch , food consumption by 135 children , aged 18 - 66 months , was measured . Four different menus were served six times during a 12-week period , each menu being presented twice with each of three test beverages , plain milk ( 18.1 kcal/oz ) , sucrose-sweetened chocolate milk ( 29.4 kcal/oz ) , or aspartame-sweetened chocolate milk ( 18.6 kcal/oz ) . The type of milk beverage served had no significant effect on the consumption of other food items offered at that meal . Subjects did drink significantly more chocolate milk than plain milk during all meals and consequently consumed significantly more energy during those meals in which sucrose-sweetened chocolate milk was served . A macronutrient analysis of lunch-time food intake for each menu revealed significant differences in protein , fat , and carbohydrate content among the four menus . Older children consumed significantly more milk and more energy per lunch-time meal than did younger preschoolers , but no other consistent age-related differences were observed . No significant gender differences were detected in any of the statistical analyses conducted . These findings suggest that young children do not reduce the intake of other food items at a meal to compensate for the increased energy intake that results from excessive sucrose-sweetened milk consumption . Aspartame-sweetened milk increases milk intake in small children without providing them with the additional calories of sucrose-sweetened milk Background Low-calorie sweeteners are often used to moderate energy intake and postpr and ial glycemia , but some evidence indicates that they may exacerbate these aims . Objective The trial 's primary aim was to assess the effect of daily aspartame ingestion for 12 wk on glycemia . Effects on appetite and body weight were secondary aims . Methods One hundred lean [ body mass index ( kg/m2 ) : 18 - 25 ] adults aged 18 - 60 y were r and omly assigned to consume 0 , 350 , or 1050 mg aspartame/d ( ASP groups ) in a beverage for 12 wk in a parallel-arm design . At baseline , body weight and composition were determined , a 240-min oral-glucose-tolerance test ( OGTT ) was administered , and measurements were made of appetite and selected hormones . Participants also collected a 24-h urine sample . During the intervention , the 0-mg/d ASP group consumed capsules containing 680 mg dextrose and 80 mg para-amino benzoic acid . For the 350-mg/d ASP group , the beverage contained 350 mg aspartame and the 1050-mg/d ASP group consumed the same beverage plus capsules containing 680 mg dextrose and 700 mg aspartame .  Body weight , blood pressure , heart rate , and waist circumference were measured weekly . At weeks 4 , 8 , and 12 , participants collected 24-h urine sample s and kept appetite logs . Baseline measurements were repeated at week 12 . Results With the exception of the baseline OGTT glucose concentration at 60 min ( and result ing area under the curve value ) , there were no group differences for glucose , insulin , resting leptin , glucagon-like peptide 1 , or gastric inhibitory peptide at baseline or week 12 . There also were no effects of aspartame ingestion on appetite , body weight , or body composition . Compliance with the beverage intervention was ∼95 % . Conclusions Aspartame ingested at 2 doses for 12 wk had no effect on glycemia , appetite , or body weight among healthy , lean adults . These data do not support the view that aspartame is problematic for the management of glycemia , appetite , or body weight . This trial was registered at www . clinical trials.gov as NCT02999321 Sixty-two subjects having either insulin-dependent or non-insulin-dependent diabetes completed a r and omized , double-blind study comparing effects of aspartame or a placebo on blood glucose control . Twenty-nine subjects consumed 2.7 g aspartame per day for 18 wk , given as aspartame-containing capsules with meals , while 33 subjects took identical appearing placebo capsules . After 18 wk , no changes were seen in fasting or 2-h postpr and ial blood glucose levels or glycohemoglobin levels in either the aspartame- or placebo-treated groups . Adverse reactions were no more common in the group taking aspartame . We conclude that use of aspartame as a low-calorie sweetener does not adversely affect glycemic control of persons with diabetes In two experiments , 2 - 5-year-old children 's responsiveness to caloric density cues was examined . In a preloading protocol , consumption of fixed volumes of drinks ( 205 ml in Experiment 1 ; 150 ml in Experiment 2 ) , sweetened with sucrose , aspartame , aspartame plus low glucose maltodextrin , or a water control , was followed by ad lib consumption from among a variety of foods . Caloric drinks had about 90 kcal in Experiment 1 , 65 kcal in Experiment 2 . The delay interval between the preload and the ad lib consumption was 0 , 30 or 60 minutes . In Experiment 1 , 24 4- and 5-year-old children participated in only one delay interval , while in Experiment 2 , all 20 2- and 3-year-old children were seen in all conditions . Results revealed evidence of caloric compensation , but no evidence of preload x time delay interaction . In both experiments , aspartame also produced a significant suppression of intake relative to water , primarily due to the pattern at 30 min following the preload . Across conditions , the suppression following aspartame was usually significantly less than that produced by the caloric sweet drinks , providing evidence for postingestive effects . In Experiment 1 , suppression of intake was related to the children 's preferences for the foods , not to macronutrient content ; consumption of nonpreferred foods was most suppressed . Consumption of sweetened drinks as long as 1 hour prior to eating suppressed food intake , and this common feeding practice may also reduce dietary variety Aspartame ( L-aspartyl-L-phenylalanine methyl ester ) consumption has been postulated to increase brain phenylalanine levels by increasing the molar ratio of the plasma phenylalanine concentration to the sum of the plasma concentrations of the other large neutral amino acids ( Phe/LNAA ) . Dietary manipulations with carbohydrate or protein can also produce changes in the Phe/LNAA value . To compare the effects of aspartame and carbohydrate on Phe/LNAA , beverages sweetened with aspartame , sucrose , and aspartame plus sucrose , and unsweetened beverage were ingested by 8 healthy , fasted subjects in a r and omized , four-way crossover design . The beverages were sweetened with an amount of aspartame ( 500 mg ) and /or sucrose ( 100 g ) approximately equivalent to that used to sweeten 1 liter of soft drink . The baseline-corrected plasma Phe/LNAA values did not differ significantly following ingestion of aspartame or sucrose . Following aspartame alone , the high mean ratio increased 26 % over baseline 1 h after ingestion . Following sucrose alone , the high mean ratio increased 19 % at 2.5 h. Sucrose increased the Phe/LNAA value due to an insulin-mediated decrease in the plasma LNAA , while aspartame increased the ratio by increasing the plasma Phe concentration . These findings indicate that similar increases in plasma Phe/LNAA occur when healthy , fasting subjects ingest amounts of equivalent sweetness of sucrose or aspartame Background : Substituting sweeteners with non-nutritive sweeteners ( NNS ) may aid in glycaemic control and body weight management . Limited studies have investigated energy compensation , glycaemic and insulinaemic responses to artificial and natural NNS . Objectives : This study compared the effects of consuming NNS ( artificial versus natural ) and sucrose ( 65 g ) on energy intake , blood glucose and insulin responses . Methods : Thirty healthy male subjects took part in this r and omised , crossover study with four treatments : aspartame- , monk fruit- , stevia- and sucrose-sweetened beverages . On each test day , participants were asked to consume a st and ardised breakfast in the morning , and they were provided with test beverage as a preload in mid-morning and ad libitum lunch was provided an hour after test beverage consumption . Blood glucose and insulin concentrations were measured every 15 min within the first hour of preload consumption and every 30 min for the subsequent 2 h. Participants left the study site 3 h after preload consumption and completed a food diary for the rest of the day . Results : Ad libitum lunch intake was significantly higher for the NNS treatments compared with sucrose ( P=0.010 ) . The energy ' saved ' from replacing sucrose with NNS was fully compensated for at subsequent meals ; hence , no difference in total daily energy intake was found between the treatments ( P=0.831 ) . The sucrose-sweetened beverage led to large spikes in blood glucose and insulin responses within the first hour , whereas these responses were higher for all three NNS beverages following the test lunch . Thus , there were no differences in total area under the curve ( AUC ) for glucose ( P=0.960 ) and insulin ( P=0.216 ) over 3 h between the four test beverages . Conclusions : The consumption of calorie-free beverages sweetened with artificial and natural NNS have minimal influences on total daily energy intake , postpr and ial glucose and insulin compared with a sucrose-sweetened beverage This study investigated whether the addition of the high-intensity sweetener aspartame to a multidisciplinary weight-control program would improve weight loss and long-term control of body weight .  One hundred sixty-three obese women were r and omly assigned to consume or to abstain from aspartame-sweetened foods and beverages during 16 wk of a 19-wk weight-reduction program ( active weight loss ) , a 1-y maintenance program , and a 2-y follow-up period . Women in both treatment groups lost approximately 10 % of initial body weight ( 10 kg ) during active weight loss . Among women assigned to the aspartame-treatment group , aspartame intake was positively correlated with percentage weight loss during active weight loss ( r = 0.32 , P < 0.01 ) . During maintenance and follow-up , participants in the aspartame group experienced a 2.6 % ( 2.6 kg ) and 4.6 % ( 4.6 kg ) regain of initial body weight after 71 and 175 wk , respectively , whereas those in the no-aspartame group gained an average of 5.4 % ( 5.4 kg ) and 9.4 % ( 9.4 kg ) , respectively . The aspartame group lost significantly more weight overall ( P = 0.028 ) and regained significantly less weight during maintenance and follow-up ( P = 0.046 ) than did the no-aspartame group . Percentage weight losses at 71 and 175 wk were also positively correlated with exercise ( r = 0.32 , P < 0.001 ; and r = 0.34 , P < 0.01 , respectively ) and self-reported eating control ( r = 0.37 , P < 0.001 ; and r = 0.33 , P < 0.01 , respectively ) . These data suggest that participation in a multidisciplinary weight-control program that includes aspartame may facilitate the long-term maintenance of reduced body weight Twelve normal subjects and 10 subjects with non-insulin-dependent diabetes mellitus were given , in r and om order at intervals of ≥ 1 wk , three drinks of the same beverage : one unsweetened , one sweetened with 400 mg aspartame , and one sweetened with 135 mg saccharin . The amount of sweetener approximated that in 1 L of sugar-free soft drink . Plasma glucose , insulin , and glucagon were measured for 3 h after ingestion of the test beverage . Plasma glucose declined slightly throughout the test period , probably due to fasting , with no differences between the three treatments . Neither sweetener affected peak insulin levels in subjects with or without diabetes . Analysis of area under the curve showed that mean insulin levels were statistically significantly higher after aspartame than after saccharin or unsweetened beverage in normal subjects only , but the magnitude of the difference was small and unlikely to be of physiological importance in the absence of differences in glucose levels . Furthermore , the differences could largely be accounted for by a decrease in insulin values after both unsweetened beverage and saccharin , with no change from baseline after aspartame . Glucagon levels showed time-to-time variation but no overall differences . We conclude that ingestion of aspartame- or saccharin-sweetened beverages by fasting subjects , with or without diabetes , did not affect blood glucose homeostasis Background : The influence of artificial sweeteners on metabolic diseases is controversial . Artificially sweetened beverages have been associated with an increased risk of type 2 diabetes ( T2D ) but biases and reverse causation have been suspected to have influenced the observed association . In addition , it has been suggested that investigation into the relationship between the frequency and duration of the consumption of packet or tablet artificial sweeteners and T2D risk is necessary . Methods : We used data from 61,440 women in the prospect i ve E3N-European Prospect i ve Investigation into Cancer and Nutrition study , conducted between 1993 and 2011 . We estimated hazards ratios ( HRs ) and 95 % CIs of T2D risk associated with both the frequency and the duration of use of artificial sweeteners consumed in packets or tablets . Results : Compared to “ never or rare ” consumers of artificial sweeteners , those using them “ always or almost always ” had an increased risk of T2D ( HR = 1.83 [ 95 % CI 1.66 - 2.02 ] in the multivariate model [ MM ] , HR = 1.33 [ 95 % CI 1.20 - 1.47 ] when further adjusted for body mass index , BMI ) . Women consuming artificial sweeteners in packets or tablets for more than 10 years also had an increased risk of T2D compared to never or rare users ( HR = 2.10 [ 95 % CI 1.83 - 2.40 ] in the MM and HR = 1.15 [ 95 % CI 1.00 - 1.33 ] when adjusted for BMI , respectively ) . Conclusions : Our data suggest that both a higher frequency and a longer consumption of artificial sweeteners in packets or tablets was associated with T2D risk , independently of major T2D risk factors , but partially mediated by adiposity . A pre caution ary principle should be applied to the promotion of these products that are still largely recommended as healthy sugar substitutes Despite some reports that aspartame (APM)-sweetened beverages may increase subjective appetite , previously we demonstrated that drinking 280 ml of an APM-sweetened soft drink ( 170 mg APM ) had no effect on appetite , and 560 ml of the same soft drink ( 340 mg APM ) reduced appetite . The present study examined this appetite reduction to determine its cause . Eighteen normal weight young adult males received five treatments ( beverage preloads ) at 1100 h in a r and omized order , one per week : 280 ml of carbonated mineral water ( CMW ) ( control ) , 560 ml of CMW , 280 ml of CMW with 340 mg of encapsulated APM , 280 ml of CMW sweetened with 340 mg APM , 560 ml of an APM-sweetened soft drink ( 340 mg APM ) . Subjective hunger and food appeal were measured from 0930 a.m. to 1230 h , and food intake from a buffet lunch offered at 1205 h was measured . Treatment had no effect on food intake or macronutrient selection . Both 560 ml of CMW or soft drink suppressed appetite , although 280 ml of APM-sweetened mineral water significantly increased subjective appetite relative to the control . Encapsulated APM had no effect on appetite . Therefore , appetite reduction following consumption of an APM-sweetened drink is likely due to drink volume and not the APM content . In addition , consuming APM-sweetened CMW produces a short-term increase in subjective appetite AIMS To analyse the effect on systematic review s in diabetes interventions of including only trials that are indexed in medline , and to assess the impact of adding trials from other data bases and the grey literature . METHODS All systematic review s of diabetes interventions which included a meta- analysis of r and omized controlled trials , and were published since 1996 , were selected . The impact on the meta- analysis of including only those trials indexed in medline , and the effect of then adding trials from other sources , was assessed . Where possible this was measured quantitatively , by redoing the meta- analysis , otherwise a qualitative estimate was made . RESULTS Forty-four systematic review s met our inclusion criteria . There were 120 articles reporting trial data which were not indexed in medline . These came from 52 % of the review s. In 34 % of the review s , basing a meta- analysis on a search of only medline would miss trials that could affect the result . Sources of non- medline data which had the biggest effect on the meta-analyses were journal articles from central and embase ( mainly in Diabetes , Nutrition and Metabolism ) and unpublished data ( mainly from industry ) . The exceptions were journal articles on herbal medicine , mostly indexed in Chinese language data bases . CONCLUSIONS A search of only the medline data base is insufficient for systematic review s of diabetes , because in about 34 % of review s the missed trials could affect the results of the meta- analysis . It is recommended that central ( on the Cochrane Library ) also be search ed . Scanning meeting abstract s , and seeking unpublished data are also recommended if the intervention has only recently been introduced
Data concerning effects of aspartame on main metabolic variables associated to diabetes and obesity do not support a beneficial related to its consumption
ABSTRACT Data about harms or benefits associated with the consumption of aspartame , a nonnutritive sweetener worldwide consumed , are still controversial .
This systematic review and meta- analysis of r and omized controlled clinical trials aim ed to assess the effect of aspartame consumption on  metabolic parameters related to diabetes and obesity .