NNNS: Effect on Appetite and Food Intake (2011)

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

To measure plasma glucose and insulin concentration, plasma glucagon and free fatty acid concentrations.

Inclusion Criteria:
Overweight males and females, by Metropolitan Life Insurance Norms.
Exclusion Criteria:
  • Fasting blood sugar above 6.11mmpl per L
  • Blood glucose concentrations below 3.33mmol per L at any point in the study
  • Two glucose values above 11.10mmol per L during the study
  • Glucose at or above 7.77mmol per L at the conclusion of the study
  • Reported medical problems, such as diabetes, heart disease or hypertension and taking medications that might affect carbohydrate metabolism
  • Reported gaining or losing 4.54kg or more in the last three months or if they indicated that they were currently dieting
  • Symptoms of hypoglycemia or undiagnosed diabetes.
Description of Study Protocol:


  • By newspaper advertisement and initially interviews by telephone.


  • Assigned at random with the constraint that at least one overweight and normal weight male and female received the same order. Each subject was tested in four sessions separated by one to three weeks. A 24-hour food record was provided by each subject and was evaluated to establish whether subjects had eaten the recommend amount of carbohydrates. The mean amount was 204g.

  • Blood pressure and pulse were measured and an intravenous line was inserted in the antecubital vein. Subjects rested and two baseline blood samples were drawn 10 minutes apart. Subjects were next asked to drink a pre-load that contained one of four substances:

    • 50g of fructose in 500ml deionized, distilled lemon flavored water
    • 50g of glucose in 500ml deionized, distilled lemon flavored water
    • 0.25g of aspartame in 500ml of deionized, distilled lemon-flavored water
    • 500ml of unflavored unsweetened water.
    Subjects were given 10 minutes to drink the pre-load.
  • After lines were withdrawn, subjects were instucted to rest and were given a pre-weighed buffet lunch and instructed to eat to comfortably full.

Blinding Used

  • Not documented.


  • Overweight and and normal-weight subjects were given a 500ml drink of fructose, glucose or aspartame diluted in lemon-flavored water or plain water at weekly intervals.

Data Collection Summary:

Timing of Measurements

Food intake: Assessed at a buffet lunch that began 38 minutes after the pre-load was completed. The buffet meal was weighed on an electronic balance and nutritional analyses were completed on what the subject had eaten.

Blood samples: Taken at 10, 18, 25, 33, 40 and 48 minutes after the start of the pre-load ingestion. Samples were drawn throughout and assayed for concentrations of glucose, insulin, glucagon and free fatty acid. Analytical methods in further detail in paper.

Description of Actual Data Sample:
  • Initial N: 24 subjects
  • Attrition (final N): 20; four normal-weight subjects (two males and two females) were not willing to return for the last session and their data were dropped for all sessions from the study 
  • Age: 22 to 50
  • Anthropometrics: Six overweight males, six overweight females, four normal-weight males and four normal-weight females
  • Location: Clinical Research Center at Yale-New Haven Hospital.
Summary of Results:

Caloric Intake

  • When subjects were given the glucose pre-load, they ate significantly more calories overall than when they were given any of the other three pre-loads (P<0.05). When subjects drank the fructose load, they tended to consume fewer calories overall (P<0.06) than when they drank the plain water or aspartame-sweetened beverage. Aspatame and water did not differ significantly from one another.
  • When subjects were given fructose, they selected significantly less fat in the subsequent buffet meal than when given water or aspartame (P<0.05) or glucose (P<0.10).

Plasma Concentrations

  • Plasma glucose increased significantly more over time in response to the glucose load, as compared with the other loads (P<0.01)
  • Food intake did not relate significantly to plasma glucose concentrations
  • For non-nutritive pre-loads, food intake after the aspartame and water pre-loads correlated significantly negatively with plasma insulin and glucose concentrations over time (P<0.05)
  • There were no significant relationships with plasma glucagon or FFA for any of the four pre-loads.
Author Conclusion:
Aspartame-sweetened drink does not lead to significantly greater subsequent food intake than does a pre-load of plain water.
Funding Source:
Government: NIH
Xyrofin-Finnsugar (UK)
Food Company:
University/Hospital: Yale University
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.) 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? 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? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? No
  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.) No
  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? 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? 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? 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)? 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? 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? No
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