Is High Fructose Corn Syrup Unhealthy?

Motivation: Somehow we all know it - high fructose corn syrup makes you gain weight. I cannot remember when I first heard it or when I last read something about it, but this notion is spreading from the health community outwards.  I even had a patient ask me about avoiding foods with high fructose corn syrup.  Not knowing much beyond rumors, I felt that it was time to investigate the merits of different kinds of sugars.  What is the data linking high fructose corn syrup to the epidemic of obesity and diabetes?

As way of background, regular sugar consists of sucrose, which is a disaccharide of fructose and glucose.  High fructose corn syrup (HFCS), in contrast, consists of monosaccharides with varying concentrations of fructose and glucose (from 42% to 90% fructose).

Paper: Forshee, R.A., Storey, M.L., Allison, D.B. et. al. "A Critical Examination of the Evidence Relating High Fructose Corn Syrup and Weight Gain" Crit. Rev. in Food Sci. and Nut. (2007); 47:561-582.

Method: Systematic review conducted by expert panel convened by Center for Food, Nutrition, and Agriculture Policy to examine the evidence linking HFCS and changes in BMI/body weight.

Results:
The strength of evidence from different classes of evidence are summarized below. Given the breadth of evidence, only significant studies are presented:

Ecological Studies: These are large scale studies linking trends between food consumption and health measures.  Between 1909 to 1997, incidence of type 2 diabetes was positively and significantly correlated with corn syrup intake along with intake of fat, total carbohydrate, protein, and total energy.  Using food-consumption data to estimate sweetener consumption from 1962 to 2000, the authors found a 74 kcal/person increase in per capita sweeter availability in this time period.  No causality with disease is implicated in this study.

Cross-Sectional Studies: Four studies were identified examining relationship between soft or sweetened drink consumption (proxy for HFCS) and obesity.  Three out of four studies found that sweetened regular soft drinks were not significantly associated with BMI. One study among European American children showed positive association between overweight and sweetened beverages along with association with consumption of increased total food and beverages.

Longitudinal Studies: Four studies examined growing children and sweetened drink consumption.  Three out of these four studies did not find any association in excess of total calories consumed.  One study showed that over 19 months, BMI increased by 0.24 units for every additional serving of sweetened drink.

Among adults, when 38,480 women health professionals were followed, total caloric sweetener (fructose or glucose) consumption did not correlate to risk of type 2 diabetes.  Another study also examined sweetened beverage consumption among women 24-44 for 15 years and did not find excess weight gain among high consumers of sweetened beverages.  The study did find that women who moved from low consumption to high consumption were at higher risk of weight gain.

Controlled Trial: Only one RCT has been performed to test this question among children 7-11 years of age.  The intervention group received education emphasizing healthy diet and discouraged sweetened and carbonated beverages.  Mean percentage of overweight and obese children decreased in the intervention arm.

Discussion: In summary, the evidence linking high fructose corn syrup and obesity is circumstantial at best.  The overall upward trend in obesity and diabetes can also be explained by increased caloric intake - which has paralleled the weight gain the past few decades.  Of course, the evidence also does not conclusively refute the hypothesis that HFCS is in part responsible for accelerating obesity.  Given the complex interactions between food habits and general health habits, it is hard to see how anything besides a randomized trial can provide more definitive evidence.  For now, though, to avoid obesity and diabetes, limiting caloric intake is likely a better idea than avoiding high fructose corn syrup.