EAL

Aspartame

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To determine the effects of aspartame when administered for a period of 13 weeks to apparently healthy children and adolescents.

Inclusion Criteria:

Children and adolescents
Ages two to 21 years
Healthy physical condition as determined by physical exam, medical history and fasting blood laboratory assessment, including complete blood count and liver and kidney function tests.

Exclusion Criteria:

Abnormal serum and urine methanol levels
Any abnormal laboratory results completed at screening
Abnormal eye exams
Pregnancy
Married
Immunized within two weeks prior to enrollment.

Description of Study Protocol:

Recruitment

Study subjects were chosen from screening 225 healthy children and adolescents (50% male)
No discussion as to how these children were recruited.

Design

Ages of subjects were divided into five groups
Subjects were randomly assigned to receive foods sweetened with either aspartame or sucrose for 13 consecutive weeks
At the end of 13 weeks, sweetened food products were discontinued. Subjects returned after seven days for final exam.

Blinding Used

The double-blind design would indicate that each subject and research staff involved in data-collection were blinded to which sweetener was randomly assigned to each subject.

Intervention

Subjects received food products sweetened with either aspartame or sucrose. Products were to be consumed in addition to usual food intake. Amount of aspartame given ranged from 0.61g to 2.4g in 24 hours, depending on age group. Range of consumption of aspartame was 27.50mg per kg to 77.19mg per kg a day.
In addition to food products, subjects in the 13-year-old to 21-year-old age group were given a double-blinded capsule to take with each meal (three per day).

Statistical Analysis

T-tests were used to compare the aspartame and the sucrose group's laboratory values from baseline to the end of study.

Data Collection Summary:

Timing of Measurements

Initial screening measures used as baseline measures
Measurements were taken at the end of weeks one, three, five, seven, 11 and 13
Post-study measurements were done one week after end of study.

Dependent Variables

Fasting blood levels of phenylalanine and tyrosine
Body weight
Blood pressure (only age groups 10 to 12 and 13 to 21 years)
Complaints
Fasting blood values for all laboratory parameters conducted at initial screening (at end of week seven and week 13)
Evaluation of facial acne vulgaris lesions done with 13 years to 21 years age group only
Subgroup of 33 subjects were selected at random to determine serum and urine methanol levels during the study.

Independent Variables

Consumption of aspartame or sucrose.

Control Variables

None discussed.

Description of Actual Data Sample:

Initial N

126 randomized (62 male).

Attrition (Final N)

Not discussed other than the number of lab samples analyzed were reported in the tables of data. Only a few results were not reported due to missed patient appointments, inadequate blood sample or sample became lost or spoiled in the lab.

Ages

Two to three years, N=13 (seven male)
Four to six years, N=22 (10 male)
Seven to nine years, N=22 (10 male)
10 to 12 years, N=24 (12 male)
13 to 20 years, N=45 (23 male)

Ethnicity

Not discussed.

Other Relevant Demographics

Not discussed.

Anthropometrics

Authors state it may be assumed the treatment groups were drawn from the same homogeneous populations because of few differences in baseline data.

Location

Not discussed.

Summary of Results:

Findings

There was no evidence of disturbed phenylalanine metabolism as determined by negative results of urinary phenylpyruvic acid testing
Methanol determinations were all negative for the subgroup of subjects tested
There were no significant differences between treatment groups in any age category for phenylalanine levels or tyrosine (P>0.10)
There were no significant changes in physical examination findings, including blood pressure measurements
Eye exams revealed no abnormalities pre-study and post-study
There were no differences between groups in evaluation of facial acne
Most complaints concerned the test preparations themselves and the large quantities subjects were required to consume. Additional complaints were similar in both groups, such as appetite increase, appetite decrease, diarrhea, constipation, etc.

Author Conclusion:

Aspartame appears to be safe for use as a sweetening agent by children of all ages.

Funding Source:

Industry:

G.D. Searle & Co.

Pharmaceutical/Dietary Supplement Company:

Reviewer Comments:

Discrepancies were noted in the article's Table 10. These values are baseline values (not identified in the title) as determined by cross-reference with previous tables in the article. In Table 10, the value for Group D indirect bilirubin for the aspartame group is in error (SD listed not mean). Also, the WBC values for Group E are switched.

Other than Table 1 reporting range of aspartame consumption for study subjects, there was no discussion about how much aspartame was actually consumed, such as mean intake, variation during study, etc. Currently, the FDA has set Acceptable Daily Intake (ADI) of aspartame at 50mg per kg a day. One can of diet soda contains about 180mg of aspartame.

The paper was supported by a grant-in-aid from G. D. Searle & Co. (makers of aspartame).

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)	N/A
	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)	N/A

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?		???
	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?	???
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?		No
	4.1.	Were follow-up methods described and the same for all groups?	No
	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%.)	No
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	???
	4.4.	Were reasons for withdrawals similar across groups?	???
	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.)	???
	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?	???
	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?	???
	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?	No
	7.2.	Were nutrition measures appropriate to question and outcomes of concern?	???
	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?	No
	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?	???
	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)?	???
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	???
	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?	No
9.	Are conclusions supported by results with biases and limitations taken into consideration?		No
	9.1.	Is there a discussion of findings?	No
	9.2.	Are biases and study limitations identified and discussed?	No
10.	Is bias due to study's funding or sponsorship unlikely?		No
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	No