NNNS: Effect on Energy Balance (Weight) (2010)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To test toxicity of chronic aspartame ingestion in overweight children.

Inclusion Criteria:
  • Greater than ideal body weight (IBW)
  • Between 10 and 21 years of age.
Exclusion Criteria:
  • Ideal body weight
  • Less than ideal body weight
  • Those younger than 10 years old or older than 21 years old.
Description of Study Protocol:

Recruitment

  • Area nursing schools
  • Pediatric referrals for obesity.

Design

Randomized controlled trial: Subjects randomized to either placebo or aspartame group

Blinding used

Double-blinded study

Intervention

  • Subjects gave medical history and had physical examination, including estimation of facial acne, laboratory testing and ophthalmologic examination before administration of aspartame or placebo
  • Subjects were given three 300mg aspartame capsules three times per day for a total of 2.7 grams per day of aspartame for 13 weeks or subjects were given three lactose placebo pills three times per day for 13 weeks
  • Substances were given in a randomized double-blind fashion in gelatin capsules
  • At the initial visit a dietary history was obtained and instruction was given in an individualized calorie restricted diet of 1,000 calories per day.

Statistical Analysis

  • Mean values ± standard error of the mean (SEM) for blood pressure, total bilirubin, direct bilirubin, indirect bilirubin, total T4, SGOT, Uric acid, tyrosine and phenylalanine were reported
  • Stated side effects of aspartame and placebo were reported.
Data Collection Summary:

Timing of Measurements

  • Subjects returned every 14 days for a review of symptoms, blood sampling for plasma phenylalanine and tyrosine levels and further discussion with the dietitian
  • At the seventh week and at the termination of the study repeat hematologic and chemical screening was conducted
  • Final eye examination was given on week 13
  • All blood samples were drawn in the morning after an overnight fast and before that days medication was taken.

Dependent Variables

  • Weight loss
  • Blood pressure
  • Total bilirubin
  • Direct bilirubin
  • Indirect bilirubin
  • Total T4
  • SGOT (serum glutamic oxaloacetic transaminase)
  • Uric acid
  • Immunoreactive insulin
  • Immunoreactive glucagon
  • Plasma tyrosine
  • Plasma phenylalanine
  • Urinary methanol.

Independent Variables

  • Aspartame: Three 300mg aspartame capsules administered three times per day for a total of 2.7 grams of aspartame per day for 13 weeks; 2.7 grams approximately four times the anticipated daily intake of ordinary use during weight loss
  • Placebo: Three capsules of lactose placebo administered three times per day for 13 weeks.

 

 

Description of Actual Data Sample:

Initial N

59 enrolled (93% female)

Attrition (final N)

55 completed

Age

10-21 years old; mean age 19.3 years.

Ethnicity

Not discussed

Anthropometrics

  • Mean body weight: 164.6 pounds
  • Mean height: 65.4 inches
  • Subjects were an average of 33% in excess of ideal body weight.

Location

 Boston, Massachusetts area

Summary of Results:

 Table: Characteristics of Aspartame and Placebo Groups and the Effect of Weight Reduction

Variables

Aspartame (n=24)

Placebo (n=33)

 

Statistical Significance of Group Difference (t)

Age (years)

19.8±0.2 (mean ± SEM) 18.7±0.4 2.6 (P<0.02)
Height (inches)

65.5±0.6

65.3±0.4

0.3

Weight (pounds)

167±6

162±5

0.8

Calculated intake (kcal) 1,023±24 1,034±13 0.4
Weight loss (pounds) 6.88±1.47 4.49±1.22 0.8

 Other Findings

  • Physical findings
    • Opthalmologic slit lamp examination disclosed no lens or anterior/posterior chamber abnormalities developing in either aspartame or placebo groups
  • Side effects
    • Most commonly reported complaints associated with drug taking were bowel change, menstrual change and febrile illnesses; their frequency are seen to be closely parallel in aspartame and placebo groups
  • Blood tests
    • In no instance does there appear to be any basis for suspecting a toxicity of aspartame after assessing hematologic, clotting and chemical parameters
  • Urinalysis
    • Urinalysis done initially and at weeks seven and 13 show no important differences between aspartame and placebo
  • Urinary methanol
    • Because of the methyl ester present in the aspartame molecule, urinary methanol was measured on eight occasions during aspartame administration and in 17 instances during placebo ingestion. No detectable methanol was found in any instance.
  • Plasma amino acids
    • Phenylalanine was measured and compared with its metabolic product, tyrosine to determine if aspartame administration led to a plasma elevation in any of the amino acids comprising aspartame
    • Plasma tyrosine levels were generally slightly higher during aspartame administration but the difference was never significant
    • Similar tendency toward higher phenulalanine level was seen in five of seven occasions during aspartame ingestion
    • Significant elevation was seen statistically at week 11
    • No certainty that any of these findings represents the prior ingestion of aspartame inasmuch as the last dose would have been taken approximately 12 hours previously
  • Glucoregulatory hormones
    • Immunoreactive insulin (IRI) and glucagon (IRG) were measured and compared
    • Results illustrate that the weight reduction in these subjects caused a detectable metabolic shift, while simultaneous aspartame administration resulted in no discernible effect
  • Lipids
    • No meaningful effect of weight reduction or aspartame was seen on plasma triglyceride and cholesterol.

 

Author Conclusion:

Aspartame is without detectable effect in this setting.

No meaningful effect of weight reduction or aspartame was seen on plasma triglyceride and cholesterol, nor on any other parameter of hematologic, hepatic or renal function that was measured. Similarly, side effects were equally distributed between aspartame and placebo.

Funding Source:
Reviewer Comments:
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
  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
  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
  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
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
  1. Was the research question clearly stated? 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
  1.1. 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
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
  1.3. Were the target population and setting specified? Yes
  2. Was the selection of study subjects/patients free from bias? 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? ???
  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? ???
  2.2. Were criteria applied equally to all study groups? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
  3. Were study groups comparable? 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
  3.1. 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
  3.2. 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
  3.3. 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
  3.4. 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
  3.5. 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")? Yes
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? Yes
  4. Was method of handling withdrawals described? No
4. Was method of handling withdrawals described? No
  4.1. Were follow-up methods described and the same for all groups? 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
  4.2. 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? ???
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? ???
  4.4. Were reasons for withdrawals similar across groups? ???
  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? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? Yes
  5. Was blinding used to prevent introduction of bias? Yes
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
  5.1. 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
  5.2. 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
  5.3. 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
  5.4. 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? Yes
  5.5. In diagnostic study, were test results blinded to patient history and other test results? Yes
  6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
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
  6.1. 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
  6.2. 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
  6.3. 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
  6.4. 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
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments 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
  6.7. 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? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? Yes
  7. Were outcomes clearly defined and the measurements valid and reliable? Yes
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
  7.1. 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
  7.2. 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
  7.3. 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
  7.4. 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
  7.5. 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
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? 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. 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
  8.1. 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
  8.2. 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
  8.3. 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)? 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)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? ???
  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
  8.6. 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
  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. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? 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. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes
  10.2. Was the study free from apparent conflict of interest? Yes