EAL

NNNS: Appetite (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

The purpose of this research was to investigate two hypotheses:
- First, aspartame is often consumed with carbohydrates and it has been hypothesized that this would enhance the impact of phenylalanine on the central nervous system
- Second, young children have a higher energy intake, compared with adults, on body weight basis and have been reported to show clearer evidence of caloric compensation for pre-load consumption. Thus, it can be hypothesized that their regular mechanism would readily recognize energy deficits caused by the consumption of aspartame containing food products and compensate accordingly at subsequent meals.
First experiment: To compare the effects of consuming a high dose of aspartame or of an eqivalent sweetness as sodium cyclamate, with carbohydrate on food intake and subjective measures of appetite in children.
Second experiment: To compare the effects of aspartame with a common nutritive sweetener (sucrose) on food intake and appetite.

Inclusion Criteria:

By parental report, the children had to be in good health
Attending school classes regularly
Not having significant learning, emotional or behavioral problems
Child's weight-for-height had to be between the 10th and 90th percentiles on normal growth charts.

Exclusion Criteria:

Food allergies or restrained eating habits
Family history of phenylketonuria
After parent was interviewed over the phone, if the child didn't meet inclusion criteria, he or she was not asked to come in for a screening session at hospital.

Description of Study Protocol:

Recruitment

By word of mouth and through lists of normal control subjects; by posters placed in area hospitals, a nearby university, boy scout and girl guide meetings, libraries and community recreation centers
One parent of each child completed an informed consent form, which had been approved by Human Subjects Review committees, Hospital for Sick Children and the University of Toronto. At the end of the study, each child received a movie pass in appreciation for his or her participation.

Design

Randomized double-blind crossover
Sessions held on non-consecutive days within one week, in groups of two to four subjects
Children were not allowed to eat after 8:00 p.m. the night before each session
During the two study days, the procedure was as follows
- 8:15 a.m.: Children were brought to the Hospital for Sick Children by parents or taxi. They were trained in the use of the visual analog scales (VAS).
- 8:30 a.m.: A standaridized breakfast was served, which consisted of cereal (28g), 2% milk (188mg) and orange juice(100ml), for a total of 244kcal and a distribution of 72% carbohydrate, 14% fat and 15% protein
- 8:50 to 10:25 a.m.: Children were engaged in card and board games
- 10:30 a.m.: Children were given a drink. Treatment A in one session and Treatment B in the other session.
- 12:00 p.m.: Lunch was provided. Compostion of the lunch was based on foods acceptable to all children, as identified by parents from a list of foods that the children liked. Each subject was served an individual tray containing three kinds of sandwiches [peanut butter (35g), peanut butter (35g) and jam (26g), roast beef (60g)]; each with two slices of white bread (55g per slice), two cartons (250ml) of 2% milk, eight celery sticks (58g), one medium apple (179g), one medium orange (165g) and eight cholcolate chip cookies (88g). Available for addition to the sandwiches were three five-gram packs of butter, three five-gram packs of maragarine and mustard (15g). Regular mayonnaise (38g) was provided as a dip for the celery stick. The food on the tray was weighed before and after serving. Subjects were told they could eat as little or as much as they liked, but were not to exchange food from their trays.
- 12:30 p.m.: Session ended.

Blinding Used

During the screening session, the study was explained to the child and parent as a study of taste of various sweeteners and that it involved the sweetener aspartame. In order to minimize order effects, treatment was randomly assigned with half of the sample receiving the order A-B and the remainder receiving B-A. Both the experimenters and the subjects were blind to treatment order.

Intervention

Experiment One: Treatment consisted of an ice slurry (300ml) of unsweetned strawberry Kool-Aid containing carbohydrate (one gram to 75g per kg polycose) plus either the test dose of aspartame (34mg per kg) or the equivalent sweetness as sodium cyclamate and amino acids as alanine
Experiment Two: The treatment consisted of a drink (300ml) of cold unsweetened strawberry Kool-Aid plus either one gram to 75g per kg sucrose or the equivalent sweetness (nine mg to seven mg per kg) of aspartame.

Statistical Analysis

Food intake and selection: A three-way analysis of variance with repeated measures was done, with sex and treatment order as independent variables and the treatments as the repeated measure. When the effect of sex or treatment order was not significant, the analysis was then collapsed over the variables.
Visual analog scales: Data for each scale were analyzed separately. Ratings were plotted and analyzed as a function of time, in order to determine whether they varied with time and nutritional state. To look at change in perception, a repeated-measures analysis of variance was conducted with sex and treatment order as independent variables. Where sex or treatment was not significant, the analysis was then collapsed over the variable. The repeated measures were the post-treatment ratings obtained after 20 minutes and 85 minutes, expressed as a percentage of the ratings obtained five minutes before consumption of the drinks (baseline) in the two treatment conditions. To be able to compare to previous studies, four comparisons were conducted. These comparisons tested the significance between the post-treatment ratings (after 20 minutes and 85 minutes) after the appropriate baseline rating in the two treatment conditions.

Data Collection Summary:

Dependent Variables

Food intake and selection: Following each session, the total number of calories consumed and percentage of protein, carbohydrate and fat were calculated. The macronutrient composition of all luncheon foods was determined from food composition tables.
Visual analog scales: Six times during each morning, the children were asked to taste a 10-ml sample of 20% sucrose solution (not ingested). Immediately afterwards, they rated their perception of the solution's intensity and pleasantness. Levels of hunger, desire to eat and fullness were rated five minutes before and 20 minutes after breakfast, the mid-morning drink and lunch.

Description of Actual Data Sample:

Initial N: 10 females and 10 males in each study
Attrition (final N): N/A
Age: Nine years to 10 years of age
Location: Hospital for Sick Children, University of Toronto.

Subject Description

	Experiment One	Experiment Two
Age (years)	9-8 (8)¹	10-0 (0-6)
Weight (kg)	32-9 (5-9)	30-4 (5-1)

1: Mean (standard deviation), N=20

Summary of Results:

Experiment One

Food intake and selection: There was no difference, due to the additon of either aspartame or cyclamate, to carbohydrates on food intake and macronutrient selection at lunchtime.
Visual analog scales
- Treatment did not significantly affect ratings of intensity or pleasantness of the 20% sucrose solution nor ratings of hunger, desire to eat or fullness, when changes from baseline VAS (five minutes before treatment) and at 20 minutes or 85 minutes following treatment were analyzed by two-way ANOVA.
- Results of specific post-hoc comparison by paired T-test and aspartame treatment was associated with reduced intensity of the 20% sucrose solution at 20 minutes (P<0.05) and with increased ratings of hunger at 85 minutes (P<0.01). Rated desire to eat increased (P<0.01) and fullness ratings decreased (P<0.01) 85 minutes after the cyclamate treatment.

Experiment Two

Food intake and selection: There were no differences in food intake and macronutrient selection at lunchtime in children who consumed drinks with either sucrose or aspartame.
Visual analog scales
- Meal and time-dependent fluctuations were observed for ratings of stimulus intensity (P<0.01), hunger (P<0.01), desire to eat (P<0.01) and fullness (P<0.01), but not for ratings of hedonic response to sucrose. The effect of treatment was not signifiant for ratings at 20 minutes and 85 minutes of sweetness intensity, pleasantness of the sucrose solution, desire to eat, hunger or fullness. Interactions of treatment and time of ratings were not significant.
- Mean change in VAS at 20 minutes and 85 minutes compared to baseline. After aspartame treatment, the rated intensity of the 20% sucrose solution was decreased at both 20 minutes and 85 minutes (P<0.05), hunger ratings increased (P<0.01) at 85 minutes and the desire to eat incresed (P<0.05) at 85 minutes. After the sucrose treatment, the only significant change in VAS was hunger, which was increased 85 minutes later (P<0.05).

Author Conclusion:

Aspartame, consumed with or without carbohydrate, did not affect hunger or food intake of children, when compared with the sweeteners sodium cyclamate and sucrose.

Limitation and Biases

Time of administration of treatment, to determine sweetness alone another treatment group of vehicle alone should have been added.

Funding Source:

University/Hospital:

University of Toronto, Hospital for Sick Children

Reviewer Comments:

The article was included because cyclamate was used as a control. However, this project excluded cyclamate peer-reviewed articles because it was not approved in the US.

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?		Yes
	3.1.	Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT)	Yes
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	Yes
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	Yes
	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%.)	N/A
	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?	Yes
	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?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	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?	Yes
	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?		N/A
	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?	No
	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