EAL

DM: FDA-Approved Non-Nutritive Sweeteners (2014)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine what effect aspartame might have on diabetes control.

Inclusion Criteria:

Subjects were 18 to 68 years old and had either insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM).

Exclusion Criteria:

Subjects were older than 18 years old and younger than 65 years old.

Description of Study Protocol:

Study Protocol

Subjects were recruited from clinics of the University of Illinois Hospital and included persons from diverse ethnic, racial and socioeconomic backgrounds. After subject consent, each were randomly assigned to either aspartame or placebo group based on their type of diabetes.

Aspartame was given in capsules, each containing 0.3g aspartame. Three capsules were taken with each meal for a total of nine capsules a day (2.7g aspartame)
Placebo was in identical capsules containing 0.2g corn starch (given in the same manner, for a total of nine capsules a day).

Aspartame and placebo capsules were coded (to ensure blinding) and randomized for assignment to either IDDM or NIDDM subjects to ensure equal numbers in each group. Randomization was further blocked by weight.

Each subject had two baseline visits to assess fasting and two-hour post-prandial glucose and glycohemoglobin. After the second visit, subjects were assigned to aspartame or placebo group and instructed to take three capsules with each meal. Subjects met approximately every three weeks for the 18 weeks of the study. At each visit they returned a log of capsule consumption, were given more capsules and asked about adverse reactions.

In addition, at nine, 17, 18 fasting and two-hour post-prandial glucose and glycohemoglobin were assessed as in baseline.

Statistical Analysis

The statistical power of falsely accepting the null hypothesis in analyzing the glucose results is less than 11%.

Data Collection Summary:

Timing of Measurements

Fasting blood glucose, two-hour post-prandial glucose and glycohemoglobin drawn:

At baseline, two measurements one week apart
Weeks nine, 17 and 18.

Dependent Variables

Glycemic control (venous blood glucose and hemoglobin A1C).

Independent Variables

Aspartame (900mg given three times daily) or placebo.

Description of Actual Data Sample:

Initial N

63 subjects.

Attrition (Final N)

62 subjects
29 aspartame subjects (15 with IDDM and 14 with NIDDM)
33 placebo subjects (16 with IDDM and 17 with NIDDM).

Other Relevant Demographics

Persons from diverse ethnic, racial and socioeconomic backgrounds.

Location

University of Illinois.

Summary of Results:

There were no differences in mean changes in glucose or glycohemoglobin between IDDM and NIDDM subject so data were pooled.

There were no differences in baseline values in placebo and aspartame groups and during 18-week treatment.

Fasting Plasma Glucose (mg per dL±SE)

	Pre-Treatment Week One	Pre-Treatment Week Two	During Treatment Week Nine	During Treatment Week 17	During Treatment Week 18
Placebo	187+15	177±24	175±16	175±13	168±14
Aspartame	168+11	178±14	200±15	195±18	174±14

Two-Hour Post-Prandial Glucose (mg per dL±SE)

	Pre-Treatment Week One	Pre-Treatment Week Two	During Treatment Week Nine	During Treatment Week 17	During Treatment Week 18
Placebo	227+18	223±18	226±23	220±16	245±20
Aspartame	235+20	241±21	268±20	1242±16	244±19

Glycohemoglobin (%±SE)

	Pre-Treatment Week One	Pre-Treatment Week Two	During Treatment Week Nine	During Treatment Week 17	During Treatment Week 18
Placebo	10.7±0.4	10.8±0.5	10.7±0.5	11±0.5	11.4±0.8
Aspartame	12.0±0.6	11.8±0.5	11.5±0.4	11.3±0.4	11.4±0.5

No measures of significance were given.

Adverse Reactions Reported in Aspartame Group

Headache
Constipation (two cases)
Gastroenteritis
Diarrhea
Itch
Sinus congestion.

Adverse Reactions Reported in Placebo Group

Eczema
Dizziness
Eye twitching
Blurred vision
Foot pain
Ketoacidosis
Musculo-skeletal pain
Rash (two cases)
Itching (two cases)
Nausea (three cases)
Loose stool
Less frequent stools
Constipation
Gastroenteritis
Diarrhea
Malaise
Dry skin.

Author Conclusion:

Adverse reactions reported on aspartame were no greater than those reported by subjects taking placebo.

Aspartame is safe for use by persons with diabetes.

Funding Source:

Industry:

G D Searle & Company

Pharmaceutical/Dietary Supplement Company:

University/Hospital:

University of Illinois

Reviewer Comments:

Authors did not give measures of statistical significance.

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)	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?	No
	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")?	Yes
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?	???
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?	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
	7.2.	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?		???
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	No
	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?	No
	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?	No
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	Yes
9.	Are conclusions supported by results with biases and limitations taken into consideration?		N/A
	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