High-Fructose Corn Syrup Causes More, Faster Weight Gain Than Table Sugar

Reading time: 6 – 9 minutes

High-fructose corn syrup, common in processed foods, is more likely than table sugar to increase the rate and amount of weight gain, according to a study in Pharmacology, Biochemistry and Behavior [1]. Specifically, consuming high-fructose corn syrup (HFCS) increases the likelihood of gaining abdominal fat, which is particularly dangerous with regard to risk of heart disease.

High-Fructose Corn Syrup Causes More, Faster Weight Gain Than Table Sugar

Researchers at Princeton University examined the effect of HFCS and other sweeteners on the eating habits and weight gain of Sprague-Dawley rats, which are commonly used in nutrition studies because of their metabolic similarity to humans. In the first phase of the study, some male rats were given plain water to drink, while others consumed either water sweetened with HFCS or water sweetened with table sugar (sucrose). In all instances, rats had free access to rat chow. The rats were examined for weight gain and body changes after eight weeks. The scientists found that HFCS-consuming rats gained more total weight than sucrose-consuming rats. This was despite the fact that the two groups of rats consumed approximately equal total daily calories, and that the HFCS rats consumed fewer calories from HFCS than the sucrose rats consumed from sucrose. A little HFCS, it appears, goes a long way toward influencing weight gain.

In the second phase of the study, the researchers examined the effect of HFCS-sweetened water on the body weight and general constitution of male rats over the course of 6 months. Rats with free access to rat chow and plain water gained less weight, while rats with free access to rat chow and HFCS-sweetened water gained more. The fat pads on the HFCS-fed rats were much heavier than those of the rats who had access to only food and water, and specifically, the fat pads in the abdomen were much larger.

Fat Pad: The area of accumulated body fat. Fat pad analysis is important in this study because it helps to rule out the possibility that the HFCS-fed rats gained more weight due to increased growth and proliferation of lean tissue. Larger fat pads indicate that the weight gain represents fat gain.

The investigators found similar long-term results in female rats, and additionally noted that among the females, access to long-term HFCS-sweetened water had a greater impact on total body weight gain and fat gain than access to long-term sucrose-sweetened water, echoing the results of the first phase of the study.

HFCS is a common additive to processed foods, and occurs in everything from packaged desserts to fast food meals to condiments like ketchup. Many nutrition researchers have speculated in recent years that it’s no coincidence that the American obesity rate has increased tremendously since the advent of HFCS in the American diet. However, there has been debate among scientists as to whether the increased obesity rate was due to increased caloric intake or was specific to HFCS.

On the surface, HFCS appears quite similar to sucrose. Sucrose is a disaccharide, made up of the smaller sugars glucose and fructose, chemically bonded together.

Disaccharide: a carbohydrate made up of two smaller sugar units, or monosaccharides. Common monosaccharides include glucose, fructose (fruit sugar), and galactose (a component of lactose, which is milk sugar).
Carbohydrate: a chemical compound made up of the elements carbon, hydrogen, and oxygen on a 1:2:1 ratio. Important energy-providing carbohydrates in the human diet include sugars and starch. Sugars consist of one or two monosaccharide units, while starch consists of many. Fiber is also a carbohydrate, but humans lack the enzyme to digest it, so it can’t provide energy to the human body.

Because of its chemical makeup, sucrose contains 50% glucose and 50% fructose. Digestive enzymes in the intestine break sucrose into glucose and fructose, which are absorbed separately into the bloodstream. There are several types of HFCS, but the most prevalent in processed food is HFCS-55, which consists of 55% fructose and 42% glucose [2]. The chemical difference between HFCS and sucrose is significant because glucose stimulates the release of insulin and has been linked to higher circulating levels of leptin [3], and there’s a significantly higher proportion of glucose in sucrose than in HFCS-55.

Insulin: a hormone released from the endocrine portion of the pancreas in response to glucose in the bloodstream. Cells require insulin to take up glucose for energy.
Leptin: a hormone that regulates appetite and metabolism; appropriate circulating leptin levels help to keep appetite proportional to energy needs.

Consuming a meal high in fructose (one sweetened with HFCS, for instance) results in lower circulating insulin and leptin, which can cause a reduced sense of satisfaction and stimulate overeating. Moreover, high fructose diets can induce leptin resistance, accelerating high-fat induced obesity [4].

A recent study demonstrated this by offering different groups of rats either plain water or water sweetened with a variety of compounds, including both sucrose and HFCS [5]. The rats that drank sweetened water, regardless of sweetener type, consumed more total calories than those that drank plain water. This result suggests that consumption of sweetened beverages may increase the risk of obesity, as appetite doesn’t completely accommodate for calories consumed in the form of liquid. Further, however, rats consuming HFCS-sweetened water had the greatest final weight and fat mass, despite the fact that all the rats drinking sweetened water took in approximately the same number of total calories. This suggests once again that HFCS influences fat accumulation to a disproportionately large extent per calorie consumed, compared to other sweeteners.

While researchers haven’t completely elucidated the mechanism through which HFCS promotes rapid fat gain — particularly in the abdominal region — accumulating evidence suggests that avoiding HFCS in the diet might help reduce the risk of obesity and obesity-related disease.


  1. Bocarsly et al. High-fructose corn syrup causes characteristics of obesity in rats: increased body weight, body fat and triglyceride levels. Pharmacol Biochem Behav. 2010 Nov;97(1):101-6. Epub 2010 Feb 26.
    View abstract
  2. White JS. Straight talk about high-fructose corn syrup: what it is and what it ain’t. Am J Clin Nutr. 2008 Dec;88(6):1716S-1721S.
    View abstract
  3. Teff et al. Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J Clin Endocrinol Metab. 2004 Jun;89(6):2963-72.
    View abstract
  4. Shapiro et al. Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding. Am J Physiol Regul Integr Comp Physiol. 2008 Nov;295(5):R1370-5. Epub 2008 Aug 13.
    View abstract
  5. Light et al. The type of caloric sweetener added to water influences weight gain, fat mass, and reproduction in growing Sprague-Dawley female rats. Exp Biol Med (Maywood). 2009 Jun;234(6):651-61. Epub 2009 Apr 9.
    View abstract
About the Author

Kirstin Hendrickson, Ph.D., is a science journalist and faculty in the Department of Chemistry and Biochemistry at Arizona State University. She has a PhD in Chemistry, and studied mechanisms of damage to DNA during her graduate career. Kirstin also holds degrees in Zoology and Psychology. Currently, both in her teaching and in her writing, she’s interested in methods of communicating about science, and in the reciprocal relationship between science and society. She has written a textbook called Chemistry In The World, which focuses on the ways in which chemistry affects everyday life, and the ways in which humans affect each other and the environment through chemistry.