NNNS: Effect on Appetite and Food Intake (2011)
Lapierre KA, Greenblatt DJ, Goddard JE, Harmatz JS, Shader RI. The neuropsychiatric effects of aspartame in normal volunteers. J Clin Pharmacol. 1990; 30 (5): 454-460.
Randomized Crossover Trial
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To determine whether normal volunteers, given a dose of aspartame equivalent to to approximately two liters of aspartame-sweetened beverage under double-blind placebo-controlled crossover conditions, would experience any of the effects which have been reported to the FDA.
Individuals with prior or current mental illness, substance abuse, seizure disorder or intolerance to aspartame were excluded.
Description of Study Protocol:
- Recruitment: Recruitment methods not defined.
- Design: Randomized controlled crossover trial.
- Blinding used: Double-blind.
- Intervention: Received a single dose of aspartame or placebo.
- Statistical analysis: Post-dosage scores were expressed as an increment or decrement over the pre-dose baseline. Differences between placebo and aspartame treatment conditions were evaluated by repeated-measures ANOVA and by student's paired T-test.
Data Collection Summary:
Timing of Measurements
- Subjects received a single dose of aspartame or placebo
- Eleven blood samples, collected over 24 hours, were analyzed
- Other variables were measured at one, two, four, eight and 24 hours post-dosage.
- Blood samples were analyzed for plasma glucose and amino acid concentrations
- Changes in mood were measured on visual analog scales
- Cognitive function was determined by digit-symbol substitution test and arithmetic test scores
- Reaction time was measured with a brake-pedal reaction timer
- Memory was tested at two and 24 hours post-dosage, based on recall of 16-item word lists
- Sedation was measured using visual analog scales
- Aspartame (15mg per kg of body weight) or placebo capsules were taken with orange juice after an overnight fast and refraining from drugs, alcohol and aspartame for 72 hours
- One-week washout period.
Description of Actual Data Sample:
- Initial N: 14 were subjects initially recruited. All were screened with standard medical history, laboratory screening profile and urinalysis.
- Attrition (final N): 10 subjects; six men, four women. Dropout rate was 29%. Four subjects failed to complete the study; two due to procedural error, one did not comply with dietary restriction and one due to GI disturbance on both placebo and aspartame trials.
- Age: 21 to 36 years, mean 26.3 years
- Ethnicity: Not mentioned
- Other relevant demographics: Not mentioned.
- Location: Boston.
Summary of Results:
- No significant differences between aspartame and placebo were found in measures of sedation, hunger, headache, mood, reaction time, cognition or memory at any time during the study
- Plasma phenylalanine levels were significantly higher following aspartame (P<0.01) than with placebo between one and six hours post-dosage, reaching a maximum difference of +3.36 micromol/dl at two hours
- Plasma glucose concentrations were not significantly different between aspartame and placebo.
The results of this study suggest that following a single 15mg per kg of body weight dose of aspartame, no detectable differences are observed in healthy volunteers with no history of aspartame intolerance, despite significant increases in plasma phenylalanine concentrations.
|Government:||US Public Health Service|
- Small sample size and large dropout rate
- Recruitment methods not defined.
Quality Criteria Checklist: Primary Research
|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|
|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?||???|
|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?||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?||???|
|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%.)||No|
|4.3.||Were all enrolled subjects/patients (in the original sample) accounted for?||Yes|
|4.4.||Were reasons for withdrawals similar across groups?||No|
|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?||???|
|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|