- In good health
- Attending a regular school class
- No appreciable learning, emotional or behavioral problems according to parental report.
- Food allergies or other restrained eating habits
- Family history of phenylketonuria.
- Recruited by word of mouth, lists of normal control subjects, posters placed at area hospitals, a nearby university, Boy Scout and Girl Guide meetings, libraries and recreational settings.
- Randomized controlled trial, crossover design
- Treatments received in random balanced order
- Tests administered in random order
- Method of randomization not described.
Intervention (if applicable)
- Experiment One: Ice slurry containing carbohydrate plus aspartame or sodium cyclamate
- Experiment Two: Cold drink containing sucrose or aspartame.
- Given sample size of 20 and a power of 80% for each measure, the difference between treatments was calculated to observe statistically significant differences. Data were entered into ANOVA for a two-period crossover design. With one exception, neither the main effect of occasion not the treatment by occasion interaction were significant for any variable and were not reported.
Timing of Measurements
- Each child participated in two morning sessions on non-consecutive days within one week
- After overnight fast and standard breakfast, children were given randomized treatments at 10:30 a.m.
- Learning tasks, mood scales and an arithmetic test were administered between 10:55 a.m. and 11:55 a.m.
- Lunch was served at 12 noon.
- Conditional associative learning task: Learning associations between randomly-chosen spatial locations on an Apple IIe computer screen and specific response keys on a response box
- Arithmetic calculation: Two forms of the Canadian Tests of Basic Skills, the Arithmetic Calculation subtest
- Behavior (activity level and social interaction): Measured through actometers and videotaping
- Mood scales: Children's Depression Inventory and State Scale of State-Trait Anxiety Inventory for Children
- Measures of food intake, appetite and hedonic response were reported elsewhere.
- Research kitchen prepared all study food
- Experiment One: Ice slurry (300ml) of unsweetened strawberry Kool-Aid containing 1.75g per kg of polycose plus either aspartame (34mg per kg) or the equivalent sweetness as sodium cyclamate and amino acids as alanine
- Experiment Two: Cold drink (300ml) of unsweetened strawberry Kool-Aid containing either 1.75g per kg of sucrose or 9.7mg per kg of aspartame.
- Initial N: 20 children (10 girls, 10 boys). Different samples used in both experiments.
- Attrition (final N): 20 children in each experiment
- Age: Experiment One, mean age=9.8±0.8 years; Experiment Two, mean age=10.0±0.6 years
- Ethnicity: Not mentioned
- Other relevant demographics: Experiment One, estimated IQ=122.2±14.6; Experiment Two, estimated IQ=115.5±11.7.
- Location: Canada.
Experiment One: Aspartame
|Experiment One: Cyclamate||F-Value||Experiment Two: Aspartame||Experiment Two: Sugar||F-Value|
|Learning Task Reaction Time (ms)||2,959±247||2,982±297||0.0||2,931±203||2,775±184||0.45|
|Arithmetic Problems Attempted||31.2±2.0||32.1±1.6||0.38||32.1±1.6||32.5±1.7||0.21|
|Arithmetic % Correct||82.5±2.2||80.4±2.9||0.63||78.7±2.5||83.0±2.0||2.49|
|Mood Scales - CDI||6.8±1.6||6.8±1.3||0.0||5.1±1.2||5.7±1.5||0.38|
Mood Scales - STAIC
Positive Social Interaction
|Negative Social Interaction||0.6±0.3||0.5±0.2||-0.43||0.1±0.1||0.2±0.1||1.00|
|Minor Motor||6.8±1.3||8.1±1.5||1.43||14.7±2.2||9.8±1.8||-3.19, P < 0.01|
|Gross Motor||0.7±0.3||1.4±0.5||1.08||2.2±0.6||1.0±0.3||-2.42, P < 0.05|
- Experiment One: Measures of associative learning, arithmetic calculation, activity level, social interaction and mood were unaffected by treatment. Regarding behavior, there was a significant main effect of period [F(6,114)=5.62, P<0.01], but not of treatment or of interaction between treatment and period.
- Experiment Two: Measures of associative learning, arithmetic calculation, activity level, social interaction and mood were unaffected by treatment. Regarding behavior, there was a significant main effect of period [F(6,114)=4.35, P<0.01], but not of treatment or of interaction between treatment and period. A significant treatment effect was on frequency of minor and gross motor behaviors, which were less frequent after the consumption of sucrose than after aspartame.
|University/Hospital:||University of Toronto, Hospital for Sick Children (Canada)|
|In-Kind support reported by Industry:||Yes|
- Method of randomization was not described
- Some measures were valid and reliable
- All food was prepared in a research kitchen
- 34mg per kg of aspartame is estimated to represent the 99th percentile of consumption if aspartame replaced all added nutritive sweetener in the diet
- 1.75g per kg of glucose is known to elicit a strong insulin response
- Authors note that studies such as these should have a water baseline control as well as the possibility that the measures used lacked sensitivity for phenylalanine-induced neurochemical effects.
Quality Criteria Checklist: Primary Research
|1.||Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies)||Yes|
|2.||Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about?||Yes|
|3.||Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice?||Yes|
|4.||Is the intervention or procedure feasible? (NA for some epidemiological studies)||Yes|
|1.||Was the research question clearly stated?||Yes|
|1.1.||Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?||Yes|
|1.2.||Was (were) the outcome(s) [dependent variable(s)] clearly indicated?||Yes|
|1.3.||Were the target population and setting specified?||Yes|
|2.||Was the selection of study subjects/patients free from bias?||Yes|
|2.1.||Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study?||Yes|
|2.2.||Were criteria applied equally to all study groups?||Yes|
|2.3.||Were health, demographics, and other characteristics of subjects described?||Yes|
|2.4.||Were the subjects/patients a representative sample of the relevant population?||Yes|
|3.||Were study groups comparable?||N/A|
|3.1.||Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)||N/A|
|3.2.||Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?||N/A|
|3.3.||Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)||N/A|
|3.4.||If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis?||N/A|
|3.5.||If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.)||N/A|
|3.6.||If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?||N/A|
|4.||Was method of handling withdrawals described?||Yes|
|4.1.||Were follow-up methods described and the same for all groups?||Yes|
|4.2.||Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.)||Yes|
|4.3.||Were all enrolled subjects/patients (in the original sample) accounted for?||Yes|
|4.4.||Were reasons for withdrawals similar across groups?||N/A|
|4.5.||If diagnostic test, was decision to perform reference test not dependent on results of test under study?||N/A|
|5.||Was blinding used to prevent introduction of bias?||Yes|
|5.1.||In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?||Yes|
|5.2.||Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.)||Yes|
|5.3.||In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?||N/A|
|5.4.||In case control study, was case definition explicit and case ascertainment not influenced by exposure status?||N/A|
|5.5.||In diagnostic study, were test results blinded to patient history and other test results?||N/A|
|6.||Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?||Yes|
|6.1.||In RCT or other intervention trial, were protocols described for all regimens studied?||Yes|
|6.2.||In observational study, were interventions, study settings, and clinicians/provider described?||N/A|
|6.3.||Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?||???|
|6.4.||Was the amount of exposure and, if relevant, subject/patient compliance measured?||Yes|
|6.5.||Were co-interventions (e.g., ancillary treatments, other therapies) described?||Yes|
|6.6.||Were extra or unplanned treatments described?||Yes|
|6.7.||Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups?||Yes|
|6.8.||In diagnostic study, were details of test administration and replication sufficient?||N/A|
|7.||Were outcomes clearly defined and the measurements valid and reliable?||Yes|
|7.1.||Were primary and secondary endpoints described and relevant to the question?||Yes|
|7.2.||Were nutrition measures appropriate to question and outcomes of concern?||Yes|
|7.3.||Was the period of follow-up long enough for important outcome(s) to occur?||???|
|7.4.||Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?||Yes|
|7.5.||Was the measurement of effect at an appropriate level of precision?||Yes|
|7.6.||Were other factors accounted for (measured) that could affect outcomes?||Yes|
|7.7.||Were the measurements conducted consistently across groups?||Yes|
|8.||Was the statistical analysis appropriate for the study design and type of outcome indicators?||Yes|
|8.1.||Were statistical analyses adequately described and the results reported appropriately?||Yes|
|8.2.||Were correct statistical tests used and assumptions of test not violated?||Yes|
|8.3.||Were statistics reported with levels of significance and/or confidence intervals?||Yes|
|8.4.||Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)?||N/A|
|8.5.||Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?||Yes|
|8.6.||Was clinical significance as well as statistical significance reported?||Yes|
|8.7.||If negative findings, was a power calculation reported to address type 2 error?||N/A|
|9.||Are conclusions supported by results with biases and limitations taken into consideration?||Yes|
|9.1.||Is there a discussion of findings?||Yes|
|9.2.||Are biases and study limitations identified and discussed?||Yes|
|10.||Is bias due to study's funding or sponsorship unlikely?||Yes|
|10.1.||Were sources of funding and investigators' affiliations described?||Yes|
|10.2.||Was the study free from apparent conflict of interest?||Yes|