EAL

NNNS: Behavior Changes, Cognitive Function and Moods (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine if sucrose or aspartame, compared to saccharin (placebo), affects behavior and cognitive performance in children.

Inclusion Criteria:

Primary school-aged children (six to 10 years), reported by their parents to respond adversely to sugar
Pre-school-aged children (three to five years), considered to be "normal."

Exclusion Criteria:

None stated.

Description of Study Protocol:

Recruitment

Recruited through advertisements in popular media
Presentations at pre-school programs.

Design

Randomized controlled trial, Latin square design

Blinding Used

Double-blind
Children, families and research staff were kept unaware of the sequence of the diets
Blinding was reinforced by visible changes made weekly in the diets, but the sweetener was changed only every third week.

Intervention

Subjects and families were placed on a different diet for each of the three consecutive three-week periods
One diet was high in sucrose (no non-nutritive sweetner)
The second diet was low in sucrose but contained aspartame
The third diet was low in sucrose but contained saccharin (placebo).

Statistical Analysis

Separate repeated-measures analyses of variance conducted for each dependent variable
Used Tukey post-hoc analysis to assess treatment difference
Dietary intake data was compared to cognitive and behavioral assessments using an analysis of variance
Adverse effects to sugar or aspartame were ranked and examined to determine whether the poorest scores were clustered during a particular dietary period.

Data Collection Summary:

Timing of Measurements

Children and their families consumed three different diets for three weeks each
Sweetener contained in the foods changed every three weeks, but visible changes were made to the diets every week
Food diaries were kept daily by parents and reviewed weekly by an RD
Urine samples were collected weekly to assess compliance
- One mg ascorbic acid per mg of aspartame was added to foods sweetened with aspartame
- One mg riboflavin per five mg sucrose added to foods sweetened with sucrose.
Baseline measurements
- Battery of tests to assess attention, behavior, mood, motor activity
- Biochemical indices to assess sucrose tolerance and fasting plasma amino acid concentrations.
Weekly assessments
- Battery of tests to assess attention, behavior, mood and motor activity.
Weeks Three, Six and Nine
- Biochemical tests to assess post-prandial plasma glucose and amino acid concentrations
  - Two to three hours post-meal, plasma glucose and amino acid concentrations were assessed
  - 30 minutes following the consumption of the 250ml beverage, plasma glucose and amino acid concentrations were assessed
    - The beverage contained 170mg aspartame, 30g sucrose or 40mg saccharin.

Dependent Variables: Cognitive and Behavioral Measures

Pediatric Behavior Scale, completed by the parent
- Assesses attention, impulsivity, hyperactivity, aggression, mood and cognition.
ADDH Comprehensive Teacher's Rating scale, completed by the teacher
- Assesses attention, hyperactivity and aggressive behavior.
Behavior Symptom Checklist, completed by an examiner
- Assesses attention, impulsivity, hyperactivity, aggression and mood.
Pediatric Assessment of Mood, completed by the child
Paired Associate Learning, completed by an examiner
- Assesses memory and learning.
Wisconsin Card Sorting Test, completed by an examiner
- Assesses conceptual grouping and mental flexibility.
Continuous performance tests, completed by an examiner
- Assesses attention and impulsivity.
Grooved Pegboard Test
- Assesses fine-motor speed and coordination.
Static steadiness test, completed by an examiner
- Asseses hand tremor and motor control.
Timed reading and mathematics test, completed by an examiner
- Asseses academic performance.
Motor-activity test, completed by an examiner
- Asseses motor activity.
Structured behavioral observations, completed by an examiner
- Asseses attention to task and activity level.

Dependent Variables: Biochemical Measures

Oral glucose tolerance test to assess sucrose tolerance
- Glucose concentrations assessed by glucose-6-phosphate dehydrogenase method.
Plasma amino acid concentrations
- Fasting and post-prandial response
- Assessed via automated amino acid analyzer
- Calculations included molar ratio of plasma phenylalanine concentration to other large neutral amino acids sharing its transport to the brain.

Independent Variables

One diet was high in sucrose (no non-nutritive sweetner)
The second diet was low in sucrose but contained aspartame
The third diet was low in sucrose but contained saccharin (placebo)
All food provided, parents kept food records of children's intake
To determine dietary compliance, ascorbic acid was added to foods sweetened with aspartame and riboflavin was added to foods sweetened with sucrose. Urine samples were tested weekly.

Control Variables

Saccharin
Other foods shown to influence behavior were kept to a minimum in the diets which included artificial colors, artificial flavors, additives, monosodium glutamate, chocolate and caffeine.

Description of Actual Data Sample:

Initial N

58 subjects were recruited.

Attrition (Final N)

Withdrawals
- First three subjects were used to refine the protocol and were eliminated from the final analysis
- Three subjects were eliminated due to poor compliance, as assessed via urine analysis
- Three withdrew before completing the study
- The youngest individual could not complete the cognitive and behavioral tests.
Final N=48
- 25 normal pre-school children
- 23 school-aged children thought to be sensitive to sugar.

Age

Pre-school group (three to five years): 4.7 years
School-age group (six to 10 years): 8.1 years

Ethnicity

Not mentioned.

Other relevant demographics

Not mentioned.

Anthropometrics

Not mentioned.

Location

Iowa.

Summary of Results:

Other Findings

The pre-school children ingested 5,600±2,100mg sucrose per kg of body weight while on the sucrose diet, 38±13mg aspartame per kg of body weight while on the aspartame diet and 12.0±4.5mg saccharin per kg of body weight while on the saccharin diet
The school-age children considered to be "sugar sensitive" ingested 4,500±1,200mg of sucrose per kg of body weight, 32±8.9mg of aspartame per kg of body weight and 9.9±3.9mg of saccharin per kg of body weight
For the children described as "sugar sensitive," there were no significant differences among the three diets in any of 39 behavioral and cognitive variables
For the pre-school children, only four of the 31 measures differed significantly among the three diets and there was no consistent pattern in the differences that were observed. Parents' ratings on the cognition subscale of the Pediatric Behavior Scale were significantly better during the sucrose diet than during the aspartame and saccharin diets (P<0.008).

Author Conclusion:

We conclude from this carefully controlled nine-week study that neither sucrose nor aspartame produces discernible cognitive or behavioral effects in normal pre-school children or in school-age children believed to be sensitive to sugar.

Funding Source:

Government:

NICHD, NIH

Not-for-profit

Foundation associated with industry:

Reviewer Comments:

Sugar sensitivity was identified by parental report
The sample of children not well defined
All foods were provided for families and compliance was measured through urinalysis
No washout period between the three-week dietary interventions.

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?		No
	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?	No
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
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?	Yes
	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?	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?	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?		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)?	N/A
	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