EAL

Aspartame

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate the biochemical and clinical effects of aspartame, milk or placebo ingestion in patients with chronic stable alcohol liver disease.

Inclusion Criteria:

Patients with mild to moderate alcoholic liver disease (ALD).

Diagnosis of ALD:

Consistent with a history of greater than 80g per day for a year of ethanol consumption
Criteria recommended by the International Association for the Study of the Liver and Sherlock's Disease of the Liver and Biliary System.

Only stable patients with a minimal risk of mortality (defined as a discriminant function score of less than 60) were allowed to participate.

Exclusion Criteria:

Illicit substance abuse
Clinical evidence of severe liver disease
Other medical diseases or medications that may have confounded the study.

Description of Study Protocol:

Design

Subjects were screened within one week before study with biochemical measure and physical exam
All subject were required to refrain from ingesting alcohol 24 hours before participation and were hospitalized during the entire study period
Subjects were randomized for sequence of administration to aspartame, skim milk or placebo after an overnight fast
Urine was collected for eight hours prior to and after each test dose
Blood was drawn pre-dose and for eight hours throughout each test period
Portal systemic encephalopathy (PSE) index evaluations were performed pre-dose
A two-day washout period separated treatments.

Statistical Analysis

Pharmacokinetic parameters were analyzed by area under the curve for time and concentration, maximum concentration and time to maximum concentration and ANOVA for plasma amino acids, blood methanol and formate and PSE index.

Results were considered to be statistically significant when P<0.05.

Data Collection Summary:

Timing of Measurements

Urine was collected for eight hours prior to and after each test dose
Blood was drawn pre-dose and 0.25, 0.5,0.75. one, 1.5, two, 2.5, three, four, five, six and eight hours after dosing
PSE index evaluations were performed pre-dose
A two-day washout period separated treatments.

Dependent Variables

Biochemical measures (amino acid, formate and methanol levels)
PSE indexes.

Independent Variables

Aspartame (15mg per kg), skim milk or placebo.

Description of Actual Data Sample:

Initial N: 13
Attrition (Final N): 13 for aspartame and milk, 12 for placebo
Age: Mean age 54.6±8.3 years
Ethnicity: Not reported
Other relevant demographics: Mean weight 76.6±18.7kg.

Anthropometrics

Mean levels on admission:

AST 81±48 U per L
ALT 59±43 U per L
Total bilirubin 1.4±1.1mg per dL.

Location

Cincinnati, OH.

Summary of Results:

Mean aspartame dose was 1,154±278mg
Mean volume of skim milk was 385±93ml
Both treatments were estimated to contain approximately 650mg phenylalanine
Following ingestion of aspartame, skim milk or placebo, the change in Phe concentrations from baseline was significantly greater for aspartame than for milk from 0.25 to six hours, for aspartame than for placebo from 0.25 to six hours and for milk than for placebo from 0.5 to 0.75 hour
Aspartame produced a net decrease in the branched-chain amino acid to aromatic amino acid ratio from baseline, which was different from milk and placebo
Blood methanol and formate levels remained unaltered following either treatment and did not differ from placebo
Significant worsening of the PSE indexes occurred only one hour post-ingestion of milk.

Author Conclusion:

Although moderately high aspartame ingestion increases plasma phenylalanine concentrations in patients with ALD, there is no effect on baseline PSE, and a single large dose of aspartame may be used safely by patients with chronic stable liver disease.

Funding Source:

Industry:

NutraSweet Corporation,

Food Company:

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
	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.)	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?	No
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?	???
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?	No
	6.6.	Were extra or unplanned treatments described?	No
	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?	N/A
	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)?	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?	No
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