NNNS: High Fructose Corn Syrup (HFCS) (2010)

Study Design:
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Quality Rating:
Research Purpose:

To examine whether there is a difference in response between a high fructose corn syrup sweetened and a sucrose-sweetened isoenergetic, isovolumetric orange-flavored preload and a no-energy control.

Inclusion Criteria:
  • Good health
  • Normotensive
  • Non-smoker
  • Non-restrained eaters
  • Regular breakfast consumers
  • At most, moderate alcohol users
  • Stable body weight (no change greater than 2kg over at least two months)
  • Did not use prescription medications
  • Exercised less than 10 hours per week.
Exclusion Criteria:
  • Poor health
  • Hypertensive
  • Smoker
  • Restrained eater
  • Poor breakfast eater
  • Heavy alcohol user
  • Greater than 2kg weight change in two months
  • Used prescription medication
  • Exercised greater than 10 hours per week.
Description of Study Protocol:


Advertisements in local newspapers and on notice boards at Maastricht University.


Within-subjects design, with each subject returning for four separate test days greater than or equal to one week apart.

Blinding Used

Pre-loads offered blindly and in randomized order.

Statistical Analysis

The changes in concentrations of the hormones from baseline and changes from baseline in visual analogue scales ratings of the appetite profile were compared by analysis of variance, repeated-measures analysis of variance, and analysis of covariance with the baseline values as covariates. Analysis was also carried out by Fisher's protected least-significant difference test.

Data Collection Summary:

Timing of Measurements

  • One pre-load liquid consumed within 10 minutes
  • Immediate visual analogue scale of taste perception and hedonics at first and last sips
  • Blood sampling in study one at 15, 30, 60 and 120 minutes post-consumption
  • Appetite profile at 20, 50, 80, 110 and 140 minutes post-consumption (last time only in study two)
  • Meal in study two served at 50 minutes after pre-load consumption.

Dependent Variables

  • Variable 1: Perception of taste (visual analogue scale of taste perception and hedonics)
  • Variable 2: Determination of the moment in time to serve test meal
  • Variable 3: Serum values of GLP-1, ghrelin, insulin, glucose (venous blood draw)
  • Variable 4:  Appetite profile/subjects' feelings of hunger, satiety, fullness, prospective food and drink consumption and desire to eat and drink (visual analogue scale).

Independent Variables

Consumption of sucrose, high fructose corn syrup, milk, light beverages.

Control Variables

 No consumption of food or beverage after 11:00 P.M. the night prior to the study.

Description of Actual Data Sample:
  • Initial N: 30 subjects (15 men and 15 women), 40 in second study
  • Attrition (final N): 30 subjects (15 men and 15 women), 40 in second study
  • Ethnicity: Dutch
  • Anthropometrics: Measured but not explained
  • Location: Netherlands.
Summary of Results:

Key Findings

  • Perception of taste characteristics:
    • Drinks containing sucrose or high fructose corn syrup did not differ in taste perception or palatability
    • The milk pre-load was perceived as less sweet, sour, refreshing and pleasant (P<0.01) and more rich and creamy than the pre-loads containing sucrose or high fructose corn syrup (P<0.005)
    • Taste perception did not differ between sexes
    • Thirst was significantly more reduced in women than in men (P<0.05)
  • Determination of the moment in time to serve the test meal in study two:
    • This moment was determined to be 50 minutes after pre-load consumption
    • Changes in VAS ratins relative to baseline were a function of changes in concentrations of the hormones GLP-1, ghrelin and insulin relative to baseline values
  • Energy-containing pre-loads compared with the diet pre-load:
    • Meal size and energy intake were significantly lower after consumption of pre-loads containing sucrose or high fructose corn syrup or the milk pre-load than after the diet pre-load. This was supported by higher GLP-1 and insulin concentrations (P<0.001) and the significantly lower ghrelin concentrations (P<0.05) and hunger (P<0.05)
    • Less energy was consumed after consumption of an energy drink than after a drink designed to not deliver energy
    • Men had lower GLP-1 concentrations (P<0.05) and women had lower appetite ratings after drink consumption (P<0.05).



Author Conclusion:

Despite differences in the biochemical properties of pre-loads containing sucrose, high fructose corn syrup, or milk and differences in the mechanisms underlying satiety in relation to GLP-1 release and ghrelin release, no differences in satiety, compensation or over-consumption were observed between pre-loads.

Funding Source:
University/Hospital: Maastricht University, Maastricht, Netherlands
Reviewer Comments:
  • Pre-loads consumed by men provided a lower percentage of total estimated energy needs than identical pre-loads consumed by women
  • Small number of subjects.
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? No
  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? No
  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? No
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? 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? N/A
  4.1. Were follow-up methods described and the same for all groups? N/A
  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%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  4.4. Were reasons for withdrawals similar across groups? N/A
  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? 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.) 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? 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? 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)? 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