Nutritive and Non-Nutritive Sweeteners

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


Forshee R, Storey M, Allison D, Glinsmann W, Hein G, Lineback D, Miller S, Nicklas T, Weaver G, White J (2007). A Critical Examination of the Evidence Relating High Fructose Corn Syrup and Weight Gain. Critical Reviews in Food Science and Nutrition, 47: (6) 561-582

PubMed ID: 17652981
Study Design:
Meta-analysis or Systematic Review
M - Click here for explanation of classification scheme.
Quality Rating:
Negative NEGATIVE: See Quality Criteria Checklist below.
Research Purpose:

To assess the strength of the evidence for the role of high fructose corn syrup (HCFS) as a unique contributor to an increased risk for overweight and obesity.

Inclusion Criteria:
  • Articles were identified using a thorough literature search in PubMed and a Medical subject heading keyword search for the terms: 
    • High fructose
    • Corn syrup
    • Obesity
    • Sucrose
    • Beverages
  • Widely cited (determined with ISI Web of Science), recent articles were chosen on the basis of professional judgement of the panel
  • Ecological, epidemiological and randomized controlled trials were all included in the review.
Exclusion Criteria:

Exclusion criteria were not defined by the authors

Description of Study Protocol:

Search strategy: PubMed

The reviewers included a panel of members that are not described nor defined. Articles were classified by research type and according to promotion of one of three mechanistic arguments explaining how HFCS contributes to overweight and obesity. The potential arguments included:

  • HFCS is sweeter than sugar and thus leads to higher energy intake and weight gain
  • Humans do not compensate for greater energy  provided by soft drink consumption (labeled a HFCS proxy) which leads to greater energy intake and weight gain
  • Increased levels of HFCS in the diet has altered the fructose: Glucose ratio in the American diet causing metabolic changes which directly or indirectly lead to greater energy intake and weight gain.

Reviewers critiqued the articles by individually analyzing the sampling, data collection methods, and flaws or limitations. There was no description of the criteria used in identifying or examining the articles under review, beyond research design classification and HFCS mechanistic argument. The review summary is provided in table format that includes sample size, data set accessed or data collection methods, results summary and remarks which consistently address the limitations or refute the findings for each study.

Data Collection Summary:

The analysis for each study highlighted limitations of the various study designs and methods and most often included:

  • Failure or inability to control for physical activity or other energy intake as confounders
  • Causal inference being drawn from cross sectional studies
  • Lack of awareness or inaccuracy relative to the composition of various sweeteners
  • Limitations in sample generalizability and inability to use aggregate data to describe relationships between exposure and some other variable.
Description of Actual Data Sample:

The review included:

Four ecological studies

  • Gross et al, 2004: The term "corn syrup" is used inappropriately
  • Harnack et al, 2000: Data are insufficient to determine which trends are associated with rising rates of overweight and obesity
  • Nielson and Popkin 2004: No data are presented supporting an association between obesity and the consumption of soft drinks or fruit drinks
  • Popkin and Nielson 2003: No assessment between the consumption of caloric sweeteners and overweight or obesity.

Eight cross-sectional epidemiological studies

  • Forshee and Storey, 2003: Cannot draw causal inference
  • No controls for sedentary behavior, physical activity and energy intake from other sources Forshee et al, 2004: Cannot draw causal inference; intake and activity were self-reported and subject to measurement error; TV viewing beyond five hours was truncated.
  • French et al, 2003: Cannot draw causal inference; relationship between soft drink consumption and BMI was not examined
  • Giammattei et al, 2003: Cannot draw causal inference; sampling limited to three California schools among 5-6th grade students limits ability to generalize to other populations
  • Grant et al, 2004: Cannot draw causal inference; did not control for physical activity; did not evaluate sucrose (with similar monosaccharide composition to HFCS) and obesity; HFCS is very limited in New Zealand; HFCS beverages are almost exclusively used only in the US
  • Nicklaus et al, 2003: Cannot draw causal inference; models to examine relationships among eating variables did not control for physical activity
  • Rajeshwari et al, 2005: Cannot draw causal inference; regional differences in sweetened beverage consumption patterns; models did not control for physical activity
  • Zizza et al, 2001: Cannot draw causal inference; relationship between snacking and BMI was not examined; model did not control for physical activity.

Seven longitudinal epidemiological studies

  • Berkey et al, 2004: No association found between beverage consumption and BMI after controlling for total energy; data are not nationally representative; limited by self reported data measurement error
  • Field et al, 2004: No association found between snack food (including beverages) and BMI; data are not nationally representative; limited by self reported data measurement error
  • Ludwig et al, 2001: The model predicted an increase in BMI of 0.05kg/m2 with a sweetened beverage consumption increase of 0.22 servings per day; Nielsen and Popkin reported that the increase in BMI based on increased consumption of sweetened beverages from 1997-1996 should be 0.13kg/m2; data not nationally representative
  • Newby et al, 2004: No relationship between soda consumption and BMI values for small children; data not nationally representative, limited by self reported data measurement error
  • Schulze et al, 2004: More than half of the sample subjects (Nurses Health Study) were excluded from analysis; only 2% of sample increased from low to high consumption of sweetened beverages over the study period. Results suggest that small changes in consumption differences did not show significant weight gain.
  • Janke et al, 2003: Neither fructose or glucose or sucrose (similar to HFCS glucose: Fructose ratio) were related to the development of Type 2 diabetes; data were not nationally representative; limited by self reported data measurement error.
  • Mrdjenovic and Levitsky, 2003: Average daily intakes did not exceed RDA for age groups in the study including subjects in the highest and lowest sweetened beverage consumption categories; did not control for changes in weight and height among growing children; small, non-nationally representative sample size (final N=21); model did not control for physical activity.

One randomized controlled trial

James et al, 2004: The sweetened "fizzy" drinks used in the study are most likely sweetened with sucrose since HFCS carbonated beverages are only produced in the US; data are not nationally representative.

No information was provided about the number of articles available for review. 

Summary of Results:
  • None of the current ecological studies reviewed supported or invalidated a hypothesized relationship between HFCS availability and BMI
  • Four out of six cross sectional epidemiological studies could not support a relationship between the consumption of a particular type of beverage or macronutrient and prevalence of overweight and obesity. The two other cross sectional studies examined did not analyze that relationship.
  • Four out of the seven longitudinal epidemiological studies showed no association between BMI and the consumption of soft drinks 
  • There were no randomized clinical trials in the literature revealing the direct relationship between HFCS and overweight and obesity. The RCT in this review erroneously reported on a sweetener that was not HFCS, according to this review. 


Author Conclusion:

The evidence that HFCS consumption uniquely increases the risk of weight gain is very weak. The only evidence directly linking HFCS consumption and weight gain is ecological data, which are insufficient for establishing cause-effect relationships. The expert panel concluded that the current evidence is insufficient to implicate HFCS per se as a causal factor in the overweight and obesity problem in the United States. However, there are significant gaps and weaknesses in the current literature and more research is needed. 

Funding Source:
Tate and Lyle, Inc
Food Company:
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? No
  2. Was the search strategy used to locate relevant studies comprehensive? Were the databases searched and the search termsused described? ???
  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? ???
  6. Was the outcome of interest clearly indicated? Were other potential harms and benefits considered? No
  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? Yes
  9. Are conclusions supported by results with biases and limitations taken into consideration? Are limitations ofthe review identified anddiscussed? ???
  10. Was bias due to the review's funding or sponsorship unlikely? ???