The controversy regarding high-fructose corn syrup (HFCS) and obesity has been fueled by an array of reports—from food consumption assessments; meta-analyses of ecological, epidemiological, and longitudinal studies; and animal models—that are inconsistent and confusing. The overall strength of the evidence from four ecological studies, six cross-sectional studies, and seven longitudinal studies indicates that the association between the consumption of HFCS and overweight or obesity is limited at best. Yet the HFCS–obesity hypothesis, advanced several years ago (Bray et al., 2004), remains contentious.

Extensive evaluation of the science—the premise of several recent systematic reviews—provides a spectrum of conclusions and recommendations. Some of these reviews examined the fructose and/or HFCS data from a broad, generalist perspective (Vartanian et al., 2007), while others assessed the obesity–lifestyle risk using survey databases (Sun and Empie, 2007). Some examined and expanded these databases further and conducted more-detailed studies to include fundamentals of food science and to address theorized mechanisms (Forshee et al., 2007).

Small studies in rodents investigated specific metabolic effects of fructose over consumption which may perturb energy homeostasis (Havel, 2005), decrease LDL particle size (Aeberli et al., 2007), increase VLDL secretion, impair vascular relaxation (Takagawa et al., 2001), contribute to metabolic syndrome (Nakagawa et al., 2006), and raise the risk of neural tube defects (Shaw et al., 2003). Limited human trials suggested that dietary fructose may or may not induce insulin resistance (Elliott et al., 2002) and modulate circulating insulin, leptin, and ghrelin (Teff et al., 2004).

Food availability data indicate that the per capita availability of total fructose and total glucose generally increased from 1966 to 1999 while experiencing some intermittent periods of decline; it continued to decline after 1999 (USDA, 2007). These data also suggest that the fructose: glucose ratio in the food supply since 1966 when HFCS-42 was introduced has remained in a narrow range (0.71–0.80). None of the randomized clinical trials designed to assess the HFCS–obesity hypothesis incorporated these ratios. Instead, fructose consumption studies, with either human subjects or animal models, had fructose: glucose ratios nearly four times that typically observed in the U.S. food supply. This is clearly a major methodological threat to scientific validity when applying study outcomes to population health and public policy.

Food scientists and nutritionists know that monosaccharides and disaccharides differ in their sweetness and that the relative sweetness of these carbohydrates varies with the food matrix. While a 10% aqueous solution of fructose at room temperature may be slightly sweeter than the equivalent concentration of sucrose, the relative sweetness of HFCS-55 is comparable to that of sucrose at similar concentration at 50°C and 6°C and pH 3–7 (Schiffman et al., 2000). Recentclinical evidence indicated that beverages sweetened with HFCS-42 or HFCS-55 did not affect hunger, satiety, or short-term energy intakes (Monsivais et al., 2007). These data refute the hypothesis that fructose due to HFCS is sweeter than sucrose in solution, and thus counter the notion that this sweetener fosters cravings and subsequent weight gain.

In an effort to prevent childhood obesity, a one-year intervention study to reduce the consumption of sucrose-sweetened carbonated drinks among children in England suggested that despite poor compliance with 3-day dietary records, a reduction in overweight and obese children is possible (James et al., 2004). However, a 2-year followup with this group of children indicated that the prevalence of overweight between the intervention and control groups was the same (James et al., 2007).

Obesity is a multifactorial disease with dietary, genetic, and environmental factors that must be rigorously and critically considered before attributing this disease to any single eating pattern or food ingredient. HFCS consumption, like that of any other sweetener and calorie-dense foods, must be put into the overall context of the total diet and physical activity, genetic context, and sociocultural fabric. It is necessary for individuals to monitor their caloric intake and take appropriate measures to prevent weight gain in order to reap the benefits of a healthy weight and physical activity.

References for the above studies are available from the authors.

by Roger Clemens, Dr.P.H.,
Contributing Editor 
Special Projects Advisor,
ETHorn, La Mirada, Calif.
[email protected]

by Peter Pressman, M.D., Contributing
Editor Attending Staff, Internal
Medicine, Cedars-Sinai Medical
Center, Los Angeles, Calif.
[email protected]