Nutritive and Non-Nutritive Sweeteners

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


Melanson K, Angelopoulos T, Nguyen V, Zukley L, Lowndes J, Rippe J. High-fructose corn syrup, energy intake, and appetite regulation. Am J Clin Nutr. 2008 Dec; 88(6): 1,738S-1,744S.

PubMed ID: 19064539
Study Design:
Narrative Review
R - Click here for explanation of classification scheme.
Quality Rating:
Negative NEGATIVE: See Quality Criteria Checklist below.
Research Purpose:

To examine current scientific evidence on HFCS and energy intake regulation in humans to discern whether there may be something inherent about this sweetener that would warrant moderation beyond that of other sweeteners to curb obesity.

Inclusion Criteria:

Not described.

Exclusion Criteria:

Not described.

Description of Study Protocol:

Clinical trial studies examined were those designed to measure energy intake regulation when subjects were served either fructose in the presence of other carbohydrates or HFCS.

Data Collection Summary:

The role of HFCS upon the regulation of energy intake needs to be explored to determine if consumption of HFCS has a greater impact upon the incidence of obesity beyond that of other sweeteners. The data collection was designed to examine the evidence of how fructose impacts endocrine and hormonal regulation of appetite and energy intake when used as it is commonly occurs, as in mixed carbohydrate foods or with glucose as in HFCS. Studies comparing sweeteners that include HFCS or fructose in combination with glucose or other carbohydrates and meals were examined.

Description of Actual Data Sample:

Ten short-term clinical trials were reviewed that examined appetite rating (visual analog scale), energy intake or metabolic response to a test and comparative sweetener.

Summary of Results:
Reference   Subjects  Test Sweetener  Comparative Sweetener

Metabolic Response* 

Holt et al, 2000  11 lean males Sugared cola Sugar-free cola Not measured
Anderson et al, 2002 14 healthy weight males 80% fructose; 20% glucose (f per g) Glucose, sucrose, polycose Blood glucose significantly lower after f per g than glucose or sucrose
Almiron-Roig and Drewnowski, 2003 32 normal weight adults HFCS Orange juice; 1% milk Not measured
Teff et al, 2004 12 normal weight females Fructose beverage with meal Glucose beverage with meal Lower blood glucose, insulin and leptin and less ghrelin suppression after fructose
Wei and Melanson, 2006 12 obese males Fructose milk shakes  glucose milk shakes Lower blood glucose after fructose; higher EE and RQ
Perrigue et al, 2006 37 young adults  HFCS-55; HFCS-42

sucrose; 1% milk

Not measured
Melanson et al, 2007  30 normal weight females  HFCS beverage with meals sucrose beverage with meals No significant differences in blood glucose, insulin, leptin or ghrelin suppression
Zuckley et al, 2007 29 obese females HFCS with meals  sucrose beverage with meals No significant difference in blood glucose, insulin, leptin or ghrelin suppression 
Akhavan and Anderson, 2007 31 healthy males HFCS sucrose, varied fructose:glucose No significant difference in blood glucose, uric acid, insulin or ghrelin
Soenen and Westerterp-Plantenga, 2007 70 healthy males and females HFCS sucrose (and milk) No significant difference in blood glucose, GLP-1, insulin or ghrelin

EE=Energy Expenditure; RQ=Respiratory Quotient.

*No significant differences in the appetite ratings or energy intake between the test and comparative sweeteners.

Author Conclusion:

Evidence suggests that high consumption of pure fructose may be problematic to energy intake regulation, but HFCS is more similar to sucrose than fructose in terms of its content, appetite and metabolic response. Most studies have compared HFCS beverages with non-caloric beverages and are more relevant to the increase in caloric intake from sweeteners than to the effects of specific sweeteners on energy regulation. Insufficient evidence exists to indicate that HFCS disrupts short-term energy balance signals or energy regulation more than other tested sweeteners. A connection has not been established between hormonal and physiologic responses to HFCS and longer-term impacts upon appetite, metabolism and body weight regulation. More research is needed, exploring both mechanistic and outcome oriented foci on energy intake and body weight regulation in response to consumption of HFCS, to determine if any sweetener needs to be limited more than others.

Funding Source:
Food Company:
Other: One author has received grants from PepsiCo
Reviewer Comments:
Quality Criteria Checklist: Review Articles
Relevance Questions
  1. Will the answer if true, have a direct bearing on the health of patients? Yes
  2. Is the outcome or topic something that patients/clients/population groups would care about? Yes
  3. Is the problem addressed in the review one that is relevant to dietetics practice? Yes
  4. Will the information, if true, require a change in practice? Yes
Validity Questions
  1. Was the question for the review clearly focused and appropriate? ???
  2. Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described? No
  3. Were explicit methods used to select studies to include in the review? Were inclusion/exclusion criteria specified andappropriate? Wereselectionmethods unbiased? No
  4. Was there an appraisal of the quality and validity of studies included in the review? Were appraisal methodsspecified,appropriate, andreproducible? No
  5. Were specific treatments/interventions/exposures described? Were treatments similar enough to be combined? Yes
  6. Was the outcome of interest clearly indicated? Were other potential harms and benefits considered? ???
  7. Were processes for data abstraction, synthesis, and analysis described? Were they applied consistently acrossstudies and groups? Was thereappropriate use of qualitative and/or quantitative synthesis? Was variation in findings among studies analyzed? Were heterogeneity issued considered? If data from studies were aggregated for meta-analysis, was the procedure described? No
  8. Are the results clearly presented in narrative and/or quantitative terms? If summary statistics are used, are levels ofsignificance and/or confidence intervals included? No
  9. Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed? No
  10. Was bias due to the review's funding or sponsorship unlikely? ???