Aspartame Use By Persons with Diabetes Administration of aspartame in non-insulin-dependent diabetics. Response to Single Dose of Aspartame or Saccharin by NIDDM Patients An evaluation of the effect of aspartame on weight loss Use of aspartame by apparently healthy children and adolescents. Aspartame Consumption for 12 Weeks Does Not Affect Glycemia, Appetite, or Body Weight of Healthy, Lean Adults in a Randomized Controlled Trial. Blood glucose and meal patterns in time-blinded males, after aspartame, carbohydrate, and fat consumption, in relation to sweetness perception. The effect of aspartame as part of a multidisciplinary weight-control program on short- and long-term control of body weight. Effects of aspartame in young persons during weight reduction. Consumption of Aspartame-Containing Beverages and Incidence of Hematopoietic and Brain Malignancies Effects of aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages on postprandial glucose, insulin and energy intake The effects of aspartame versus sucrose on motivational ratings, taste preferences, and energy intakes in obese and lean women. Effects on obese women of the sugar sucrose added to the diet over 28 d: a quasi-randomised, single-blind, controlled trial Do sugar-sweetened beverages cause adverse health outcomes in children? A systematic review protocol Adverse reactions to aspartame: Double-blind challenge in patients from a vulnerable population Comparative effects of fructose, aspartame, glucose, and water preloads on calorie and macronutrient intake. Consumption of artificially and sugar-sweetened beverages and incident type 2 diabetes in the Etude Epidemiologique aupres des femmes de la Mutuelle Generale de l'Education Nationale-European Prospective Investigation into Cancer and Nutrition cohort.
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 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 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 This study explores whether the addition of aspartame-sweetened foods and beverages to a low fat , hypocaloric diet enhances compliance and result ing weight loss .  Fifty-nine obese ( 130 - 225 % of ideal body weight ) , free living men and women were r and omly assigned to either a Balanced Deficit Diet ( BDD ) or a BDD supplemented with aspartame . Over a 12-week weight loss period , volunteers attended weekly support group meetings including behavior modification training and exercise instruction . Males achieved a clinical ly significant weight loss ( greater than 23 lb ) in both study groups , while females lost an average of 12.8 lb in the control group vs. 16.5 lb in the experimental group . In both treatment groups , sleep , general energy level , level of physical activity , and feeling of well-being showed clinical ly meaningful improvement . This study suggests possible advantages to supplementing a BDD with aspartame-sweetened foods as part of a multidisciplinary weight loss program . The small sample size prohibits definitive conclusions but does provide the protocol for a larger , outpatient clinical trial This study was conducted to determine the effects and the differences , if any , result ing from the ingestion of aspartame ( sweetener ) versus sucrose . A 13-wk , double-blind study was conducted using 126 apparently healthy children and adolescents as panelists . Individuals were r and omly assigned in a double-blind design to aspartame or sucrose in each of five age groups ; dosage levels were assigned according to age and weight groups . Physical examinations and special eye examinations were performed at the beginning and end of the study . Other parameters determined including laboratory tests of liver and renal function , hematologic status , and plasma levels of phenylalanine and tyrosine . Clinical ly significant differences in laboratory parameters measured could not be demonstrated ; all mean values were within normal limits . No unusual findings were observed in phenylalanine or tyrosine levels . All phenylpyruvic acid and methanol determinations were negative . No important physical changes occurred , and no product-related side effects were reported 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 In a study of the impact of aspartame , fat , and carbohydrate on appetite , we monitored blood glucose continuously for 431 ( SE 16 ) min . Ten healthy males ( 19 - 31 years ) participated in three time-blinded visits . As blood glucose was monitored , appetite ratings were scored at r and omized times . On the first meal initiation , volunteers consumed one of three isovolumetric drinks ( aspartame , 1 MJ simple carbohydrate , and 1 MJ high-fat ; r and omized order ) . High-fat and high-carbohydrate foods were available ad libitum subsequently . Blood glucose patterns following the carbohydrate drink ( + 1.78 ( SE 0.28 ) mmol/l in 38 ( SE 3 ) min ) and high-fat drink ( + 0.83 ( SE 0.28 ) mmol/l in 49 ( SE 6 ) min ) were predictive of the next intermeal interval ( R 0.64 and R 0.97 respectively ) . Aspartame ingestion was followed by blood glucose declines ( 40 % of subjects ) , increases ( 20 % ) , or stability ( 40 % ) . These patterns were related to the volunteers ' perception of sweetness of the drink ( R 0.81 , P = 0.014 ) , and were predictive of subsequent intakes ( R -0.71 , P = 0.048 ) . For all drinks combined , declines in blood glucose and meal initiation were significantly associated ( chi 2 16.8 , P < 0.001 ) , the duration of blood glucose responses and intermeal intervals correlated significantly ( R 0.715 , P = 0.0001 ) , and sweetness perception correlated negatively with hunger suppression ( R -0.471 , P = 0.015 ) . Effects of fat , carbohydrate , and aspartame on meal initiation , meal size , and intermeal interval relate to blood glucose patterns . Varied blood glucose responses after aspartame support the controversy over its effects , and may relate to sweetness perception 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 Given the potential use of a low-calorie sweetener during weight reduction , a toxicity study of chronic aspartame ingestion was conducted . Particular attention was given to possible long-term effects of aspartame on the fuel hormonal alterations characteristically caused by weight reduction . As a group mean age was 19.3 yr , body weight was 164.6 lb , and mean height was 65.4 in . Subjects were an average of 33 % in excess of ideal body weight . The aspartame dose was 2.7 g/day and was compared on a double-blind r and omized basis with a lactose placebo . Both material s were given in gelatin capsules . An average of 6.9 + /- 1.5 lb was lost by the aspartame group during the 13-wk study on a calculated 1,000-calorie diet . The placebo group lost 4.5 + /- 1.2 lb ( no significant difference between the two groups ) . After an overnight fast , reductions in glucose and immunoreactive insulin were seen in both groups , while rising trends in immunoreactive glucagon were observed . These changes are all characteristic of calorie restriction . In no instance was there a detectable effect of the ingested aspartame . No meaningful effect of weight reduction or aspartame was seen on plasma triglyceride and cholesterol , nor on any other parameter of hematologic , hepatic , or renal function that was measured . Similarly , side effects were equally distributed between asparatame and placebo 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 : 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 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 To investigate whether obese women can compensate for sucrose added to the diet when it is given blind , rather than gaining weight or exhibiting dysfunctional regulation of intake , in the present study , forty-one healthy obese ( BMI 30–35 kg/m2 ) women ( age 20–50 years ) , not currently dieting , were r and omly assigned to consume sucrose ( n 20 ) or aspartame ( n 21 ) drinks over 4 weeks in a parallel single-blind design . Over the 4 weeks , one group consumed 4 × 250 ml sucrose drinks ( total 1800 kJ/d ) and the other group consumed 4 × 250 ml aspartame drinks . During the baseline week and experimental weeks , body weight and other biometric data were measured and steps per day , food intake using 7 d unweighed food diaries , and mood using ten- or seven-point Likert scales four times a day were recorded . At the end of the experiment , the participants weighed 1·72 ( se 0·47 ) kg less than the value predicted by the National Institute of Diabetes and Digestive and Kidney Diseases ( NIDDK ) model ; the predicted body weight accounted for 94·3 % of the variance in the observed body weight and experimental group accounted for a further 1·1 % of the variance in the observed body weight , showing that women consuming sucrose drinks gained significantly less weight than predicted . The reported daily energy intake did not increase significantly , and sucrose supplements significantly reduced the reported voluntary sugar , starch and fat intake  compared with aspartame . There were no effects on appetite or mood . Over 4 weeks , as part of everyday eating , sucrose given blind in soft drinks was partially compensated for by obese women , as in previous experiments with healthy and overweight participants 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 This study was design ed to ascertain whether individuals with mood disorders are particularly vulnerable to adverse effects of aspartame . Although the protocol required the recruitment of 40 patients with unipolar depression and a similar number of individuals without a psychiatric history , the project was halted by the Institutional Review Board after a total of 13 individuals had completed the study because of the severity of reactions within the group of patients with a history of depression . In a crossover design , subjects received aspartame 30 mg/kg/day or placebo for 7 days . Despite the small n , there was a significant difference between aspartame and placebo in number and severity of symptoms for patients with a history of depression , whereas for individuals without such a history there was not . We conclude that individuals with mood disorders are particularly sensitive to this artificial sweetener and its use in this population should be discouraged Using a within-subjects design , we gave over-weight and normal-weight subjects a 500-mL drink of fructose , glucose , or aspartame diluted in lemon-flavored water or plain water in a r and omized fashion at about weekly intervals . Food intake was assessed at a buffet lunch that began 38 min after the preload was completed . Blood was drawn throughout and assayed for concentrations of glucose , insulin , glucagon , and free fatty acid . When subjects drank the fructose preload , they subsequently ate fewer overall calories and fewer grams of fat than when they drank any of the other preloads . The aspartame load did not stimulate intake beyond the plain-water control . The effects of the oxidation of fructose as a possible mechanism for the reduction in food intake is discussed . The effects of insulin in stimulating intake are also discussed 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
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 .