EAL

Aspartame

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

First, the effect on neurobehavioral response in children of a large dose of aspartame was compared with the effect of sodium cyclamate, when both were consumed with carbohydrates. Second, the effect of aspartame on behavior was compared with the effect of a nutritive sweetener (sucrose).

Inclusion Criteria:

In good health
Attending a regular school class
No appreciable learning, emotional or behavioral problems according to parental report.

Exclusion Criteria:

Food allergies or other restrained eating habits
Family history of phenylketonuria.

Description of Study Protocol:

Recruitment

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.

Design

Randomized controlled trial, crossover design
Treatments received in random balanced order
Tests administered in random order
Method of randomization not described.

Blinding Used

Double-blind.

Intervention (if applicable)

Experiment One: Ice slurry containing carbohydrate plus aspartame or sodium cyclamate
Experiment Two: Cold drink containing sucrose or aspartame.

Statistical Analysis

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.

Data Collection Summary:

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.

Dependent Variables

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.

Independent Variables

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.

Description of Actual Data Sample:

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.

Summary of Results:

	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	26.0±1.0	26.5±1.4	0.35	26.6±1.1	25.5±1.4	0.95
Positive Social Interaction	13.9±1.7	14.5±1.5	0.55	15.5±1.4	13.7±1.8	-1.06
Negative Social Interaction	0.6±0.3	0.5±0.2	-0.43	0.1±0.1	0.2±0.1	1.00
Self-Stimulation	16.1±2.4	15.9±3.3	-0.08	15.0±2.9	14.3±3.5	-0.45
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

Other Findings

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.

Author Conclusion:

In summary, the results of this investigation suggest that the consumption of aspartame by normal, nine- to 10-year-old children does not have detrimental effects on learning, behavior or mood. Rather, the findings offer only the slightest suggestion that activity levels following aspartame consumption are not reduced, as they are after the consumption of nutritive sweeteners. Thus, the effect of aspartame on the short-term behavior appears to be related to the absence of metabolic consequences of aspartame, rather than to its amino acid composition and putative neurochemical impact.

Funding Source:

Industry:

Novopharm Ltd (Ontario)

Pharmaceutical/Dietary Supplement Company:

University/Hospital:

University of Toronto, Hospital for Sick Children (Canada)

Not-for-profit

Foundation associated with industry:

In-Kind support reported by Industry:

Yes

Reviewer Comments:

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
Relevance Questions
	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

Validity Questions
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