Nutritive and Non-Nutritive Sweeteners

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


Stanhope KL, Griffen SC, Bair BR, Swarbrick MM, Keim NL, Havel PJ. 24-hour endocrine and metabolic profiles following consumption of high-fructose corn syrup-, sucrose-, fructose- and glucose-sweetened beverages with meals. Am J Clin Nutr. 2008 May; 87 (5): 1,194-1,203.

PubMed ID: 18469239
Study Design:
Randomized Crossover Trial
A - Click here for explanation of classification scheme.
Quality Rating:
Positive POSITIVE: See Quality Criteria Checklist below.
Research Purpose:
  • To compare the metabolic and endocrine effects of consuming high fructose corn syrup and sucrose sweetened beverages
  • Determine whether responses are affected by sex and adiposity
  • To compare the effects of consuming high fructose corn syrup and sucrose sweetened beverages with the consumption of beverages sweetened with fructose and glucose.
Inclusion Criteria:

No history of the following diseases or conditions:

  • Anemia
  • Hepatic or renal disease
  • Diabetes Mellitus
  • Fasting serum triglyceride level greater than 400mg/dL
  • Hypertension
  • Eating Disorder
  • Surgery for weight loss
  • Smoker
  • Currently taking medication for: Thyroid disease, lipid-lowering, glucose-lowering, anti-hypertensive, antidepressant or weight-loss
  • Pregnant or lactating.
Exclusion Criteria:

History of the following diseases or conditions:

  • Anemia
  • Hepatic or renal disease
  • Diabetes Mellitus
  • Fasting serum triglyceride level greater than 400mg/dL
  • Hypertension
  • Eating Disorder
  • Surgery for weight loss
  • Smoker
  • Currently taking medication for: Thyroid disease, lipid-lowering, glucose-lowering, anti-hypertensive, antidepressant, or weight-loss
  • Pregnant or lactating.
Description of Study Protocol:


Subjects were recruited through newspaper advertisements


  • Two experimental trials conducted in random order one month apart and required an overnight stay
  • Subjects consumed identical meals based on calculated energy requirements that included beverages sweetened with either high fructose corn syrup or sucrose
  • Subjects were required to ingest beverage and meals within 20 minutes
  • A subset of eight subjects completed an extra two days of the study with the identical meals and sweetened beverages.

Blinding used

Subjects and researchers were both blinded to the sweetener contained in the beverages

Statistical Analysis

  • The area under curve was calculated for glucose, insulin, ghrelin, free fatty acid, leptin, and triglyceride
  • General linear model for repeated measures: Sugar x adiposity, group x sex along with age and time (particularly for lipid level changes).
Data Collection Summary:

Timing of Measurements

  • Blood samples drawn every 30 minutes around periods of meal ingestion and during the predicted nocturnal rise of plasma leptin concentrations (five hours after the evening meal) and hourly intervals at other times
  • Baseline blood samples taken at 0:800, 0:830 and 0:900 before ingestion of first meal.

Dependent Variables

Serum values of glucose, insulin, leptin, ghrelin, triglycerides, free fatty acids, cholesterol, LDL, HDL, ApoB: Blood samples taken through intravenous catheter.

Independent Variables

  • Consumption of beverage sweetened with high fructose corn syrup or sucrose
  • Body weight.

Control Variables

  • Food (meals were standardized)
  • Physical activity.
Description of Actual Data Sample:
  • Initial N: 34 (18 men and 16 women)
  • Age: 20-50 years 
  • Location: Campus of University of California, Davis.


Summary of Results:

Baseline Measures

Fasting triglycerides (TG) and apoB concentrations were lower in women and higher in men (P<0.05) on the day of the sucrose feeding compared with the day of the high fructose corn syrup (HFCS) feeding.

Effects of HFCS and Sucrose with 24-hour Profiles and Fasting Lipid Concentrations

  • 24-hour plasma profiles of glucose, leptin, ghrelin, TG and free fatty acids (FFA) concentrations as assessed by area under curver, were not different on the days HFCS-sweetened beverages were consumed with meals compared with when sucrose-sweetened beverages were consumed
  • No difference observed in fasting lipid concentrations between HFCS-sweetened beverages consumed vs. sucrose-sweetened beverages consumed
  • No difference of glucose, insulin, leptin, ghrelin, TG or FFA labs between the lower and higher adiposity groups
  • The 24-hour leptin area under the curve was approximately three times higher in women than men (P<0.01) for both HFCS and sucrose consumption
  • Men had three times higher and seven times higher mean area under curve for sucrose and HFCS, respectively (P<0.01 and P<0.001, respectively.

Effects of HFCS, Sucrose, Fructose and Glucose Sweetened Beverages (seven men who elected to stay an additional two days)

  • Effects of four sugars on 24-hour area under the curve were significantly different for glucose (P=0.010), insulin (P<0.0001) and TG (P=0.007)
  • Consumption of fructose-sweetened beverages resulted in glucose and insulin area under curves that were significantly lower than the area under curve by glucose consumption (P<0.01, P<0.001 respectively)
  • Consumption of all four sugar sweetened beverages with meals also resulted in significant increases in fasting TG concentrations the following morning but no differences among the effects of the four sugars.


Author Conclusion:
  • Based on these results, it appears that sucrose and HFCS do not have substantially different short-term effects on endocrine signals involved in body-weight regulation
  • Consumption of HFCS beverages also did not increase post-prandial TG levels to a greater extent than those observed during consumption of sucrose-sweetened beverages.
Funding Source:
Government: US Department of Agriculture, NIH grants
Food Company:
University/Hospital: UC Davis Clinical and Translational Science Center
Other: American Dietetic Association
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? 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? 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)? 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