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

Study Design:
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Quality Rating:
Research Purpose:

To study the effects of glucose-to-fructose ratio consumption in relation to satiety hormones, subjective satiety and food intake at a later meal.

Inclusion Criteria:
  • Male
  • 18 to 35 years old
  • Body mass index of 20 to 26
  • Non-smoker.
Exclusion Criteria:
  • Smoker
  • Female
  • Age less than 18 or greater than 35
  • Body Mass Index less than 20 or greater than 26
  • Diagnosis of diabetes, liver or kidney disease
  • Major medical surgery in past six months
  • Breakfast skippers
  • Medication
  • Score of greater than 11 on an eating habits questionnaire.
Description of Study Protocol:


Subjects were recruited through postings around the Saint George campus of the University of Toronto.


  • Two experiments with randomized repeated-measures at weekly intervals
    • Experiment 1: Subjects received one of six sugar solutions (high fructose corn syrup, sucrose, G20:F80, G80:F20, sucrose solution or water) for 300kcal in 300ml
    • Sweetness was equalized for all solutions with addition of sucralose, and lemon juice was added for palatibility
    • Experiment 2: Subjects received one of six sugar solutions (G20:F80, G35:F65, G50:F50, sucrose, G80:F20 or water) for 300kcal in 300ml
    • Sweetness and palatibility were not equalized in experiment 2
  • After overnight fast, subjects selected a time between 1100 and 1400 to participate
  • Controlled breakfast was provided four hours prior to experiment and subjects were to consume nothing after breakfast
  • Subjects had to complete a questionnaire assessing sleep habits, stress factors, compliance with fasting, and their pattern of activity on the preceding day. If significant deviations were reported, subjects were sent home and rescheduled.
  • Subjects also completed a questionnaire on Visual Analog Scale measuring motivation to eat and physical comfort. Blood sample was also taken.
  • Subjects were then to consume test solution within three minutes and complete questionnaire assessing sweetness and palatability of the treatments
  • Visual Analog Scale tests and blood samples were taken at 15, 30, 45, 60, 75 minutes post-consumption
  • Pizza and water were provided ad libitum 80 minutes after the pre-load solutions. Pizzas were similar in nutrient content. Subjects received three varieties of pizzas and served a different slice every 10 minutes.
  • Trays were weighed with the remaining pizza left until subject declined further pizza
  • Each tray contained two pizzas of subjects' first choice and one pizza of their second or third choice
  • In Experiment 2, to measure thirst prior to eating, subjects were given water at 75 minutes
  • In Experiment 2 subjects had an intravenous catheter inserted in seven subjects for lab draws vs. 12 who received a finger prick.

Statistical Analysis

  • To test for the effect of the treatments on the outcome variables, one-factor repeated-measures analysis of variance (ANOVA) using the general linear model was performed on data for food and water intakes at 80 minutes, perceived sweetness, palatability of treatments and pizza, physical comfort and net areas under the curve for average appetite, blood glucose, uric acid, insulin and ghrelin. ANOVA was also used for the effects of treatment and time and for treatment x time interaction for average appetite. 
  •  In Experiment 2, a two-factor ANOVA was performed to determine the effect of the route of blood sampling and of treatment on blood glucose, average appetite and food intake.
Data Collection Summary:

Timing of Measurements

  • Questionnaires completed prior to test each time
  • Blood samples and Visual Analog Scales were taken at 15, 30, 45, 60, 75 minutes after drink consumption
  • Trays measured every 10 minutes until subject was comfortably full.

Dependent Variables

  • Lab draws (blood glucose, insulin, ghrelin, uric acid): Blood draw through finger prick. In experiment 2, seven subjects had intravenous catheter inserted.
  • Sweetness and palatability of test solutions: Visual Analog Scale
  • Food intake post-test solution consumption: Weight of food consumed.

Independent Variables

Test solutions.

Control Variables

Activity level.

Description of Actual Data Sample:

Initial N

  • Experiment 1: N=12
  • Experiment 2: N=19.


  • Experiment 1: 29±1.33
  • Experiment 2: 23.6±1.05.


  • Experiment 1: BMI 22.8±0.52
  • Experiment 2: BMI 24.0±0.37.


St. George campus, University of Toronto.


Summary of Results:

Key Findings

Food Intake (FI)

  • All sugar solutions except G20:F80 suppressed FI at the test meal significantly (P=0.0001) more than the water control
  • Only G80:F20 and sucrose solution suppressed FI significantly (P=0.0001) more than did the sweet control
  • No differences in FI among high fructose corn syrup (HFCS) and other sugar solutions.

Cumulative Energy Intake, Calorie Compensation, Water Intake, Average Appetite Score

  • Experiment 1:
    • G20:F80 led to the highest cumulative energy intake
    • HFCS and sucrose solutions did not differ significantly from each other or the water control but did result in higher cumulative energy intakes than the sucralose control (P=0.0001)
    • Caloric compensation of 92% and 89% for the G80:F20 and sucrose solutions was significantly (P<0.05) greater than that of 45% for G20:F80. At 63%, HFCS did not differ from any other sugar solution.
    • Subjects had the highest and lowest water intakes at the test meals after HFCS and sucralose respectively. No significant differences observed between all solutions.
    • All sugar solutions except G20:F80 and HFCS lowered subjective average appetite (AA) area under curve significantly (P<0.01) more than water control
  • Experiment 2:
    • G20:F80 and G35:F65 solutions resulted in significantly (P=0.0001) higher cumulative energy intakes than did sucrose and G80:F20 solutions but not different from water control or G50:F50
    • G80:F20 resulted in a caloric compensation (155%) that was significantly (P=0.001) greater than that of 46%, 41% and 56% seen for G20:F80, G35:F65, and G50:F50 respectively
    • No significant differences between solutions observed with regards to water intake
    • All sugar solutions lowered except G50:F50 lowered subjective AA area under curve more than water control.

Average Appetite Score

The AA score was significantly (P<0.05) affected by treatment, time and treatment x time interaction. The interaction is explained by the significantly (P<0.05) greater and earlier increase in AA score with time after the controls than after the sugar solutions.

Blood Glucose

Both experiments:

  • All sugar solutions resulted in significant (P<0.0001) higher blood glucose area under curve than controls
  • Blood glucose was significantly (P<0.0001) affected by treatment, time, and treatment x time interaction.

Uric Acid

  • Except for G80:F20 solution, all sugar solutions increased the uric acid area under curve significantly (P<0.0001) more than water control
  • G80:F20 and G20:F80 had the lowest and highest uric acid area under curve respectively
  • Uric acid concentrations were significantly (P<0.05) affected by treatment, time and treatment x time interaction.


  • G80:F20 solution had the highest and G20:F80 and G35:F65 solutions had the lowest insulin area under curves
  • Insulin concentrations were significantly (P<0.05) affected by treatment, time and treatment x time interaction
  • All sugar solutions increased insulin concentrations at 15, 30, 45 minutes significantly (P<0.05) more than the water control.


  • All sugar solutions resulted in significantly (P<0.05) lower ghrelin concentrations than did the water control
  • Ghrelin concentrations were significantly (P<0.05) affected by treatment, time and treatment x time interaction. Greater and earlier suppression of ghrelin seen by sucrose and G50:F50.

Relations Among Dependent Measures

  • FI were positively correlated with AA scores at 75 minutes (P<0.001, P<0.005 for Experiments 1 and 2 respectively)
  • FI inversely correlated with blood glucose and insulin (P<0.01, P<0.05 respectively).



Author Conclusion:
  • The results indicate that the replacement of sucrose with high fructose corn syrup as a caloric sweetener does not contribute to overeating and obesity because of the differences in their short-term physiologic affects
  • Solutions of high fructose corn syrup, F50:G50, and sucrose were similar in their effects on subjective measures and physiologic signals of satiety, plasma uric acid concentrations and food intakes in young men
  • However, high G:F in isocaloric sugar solutions resulted in higher blood glucose and insulin concentrations and lower uric acid concentrations and food intake than did low G:F.
Funding Source:
Other: International Life Sciences Institute North America, the Bristol Myers Squibb/Mead Johnson Freedom to Discover Award, Scholarship from Natural Sciences and Engineering Research Council of Canada
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%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  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? 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? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  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? 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? No