A Princeton University research team has demonstrated that all sweeteners are not equal when it comes to weight gain: Rats with access to high-fructose corn syrup gained significantly more weight than those with access to table sugar, even when their overall caloric intake was the same.
In addition to causing significant weight gain in lab animals, long-term consumption of high-fructose corn syrup also led to abnormal increases in body fat, especially in the abdomen, and a rise in circulating blood fats called triglycerides. The researchers say the work sheds light on the factors contributing to obesity trends in the United States.
"Some people have claimed that high-fructose corn syrup is no different than other sweeteners when it comes to weight gain and obesity, but our results make it clear that this just isn't true, at least under the conditions of our tests," said psychology professor Bart Hoebel, who specializes in the neuroscience of appetite, weight and sugar addiction. "When rats are drinking high-fructose corn syrup at levels well below those in soda pop, they're becoming obese -- every single one, across the board. Even when rats are fed a high-fat diet, you don't see this; they don't all gain extra weight."
A Princeton University research team, including (from left) undergraduate Elyse Powell, psychology professor Bart Hoebel, visiting research associate Nicole Avena and graduate student Miriam Bocarsly, has demonstrated that rats with access to high-fructose corn syrup -- a sweetener found in many popular sodas -- gain significantly more weight than those with access to water sweetened with table sugar, even when they consume the same number of calories. The work may have important implications for understanding obesity trends in the United States. (Photo: Denise Applewhite)Photos for news media
In results published online Feb. 26 by the journal Pharmacology, Biochemistry and Behavior, the researchers from the Department of Psychology and the Princeton Neuroscience Institute reported on two experiments investigating the link between the consumption of high-fructose corn syrup and obesity.
The first study showed that male rats given water sweetened with high-fructose corn syrup in addition to a standard diet of rat chow gained much more weight than male rats that received water sweetened with table sugar, or sucrose, in conjunction with the standard diet. The concentration of sugar in the sucrose solution was the same as is found in some commercial soft drinks, while the high-fructose corn syrup solution was half as concentrated as most sodas.
The second experiment -- the first long-term study of the effects of high-fructose corn syrup consumption on obesity in lab animals -- monitored weight gain, body fat and triglyceride levels in rats with access to high-fructose corn syrup over a period of six months. Compared to animals eating only rat chow, rats on a diet rich in high-fructose corn syrup showed characteristic signs of a dangerous condition known in humans as the metabolic syndrome, including abnormal weight gain, significant increases in circulating triglycerides and augmented fat deposition, especially visceral fat around the belly. Male rats in particular ballooned in size: Animals with access to high-fructose corn syrup gained 48 percent more weight than those eating a normal diet.
"These rats aren't just getting fat; they're demonstrating characteristics of obesity, including substantial increases in abdominal fat and circulating triglycerides," said Princeton graduate student Miriam Bocarsly. "In humans, these same characteristics are known risk factors for high blood pressure, coronary artery disease, cancer and diabetes." In addition to Hoebel and Bocarsly, the research team included Princeton undergraduate Elyse Powell and visiting research associate Nicole Avena, who was affiliated with Rockefeller University during the study and is now on the faculty at the University of Florida. The Princeton researchers note that they do not know yet why high-fructose corn syrup fed to rats in their study generated more triglycerides, and more body fat that resulted in obesity.
When male rats were given water sweetened with high-fructose corn syrup in addition to a standard diet of rat chow, the animals gained much more weight than male rats that received water sweetened with table sugar, or sucrose, along with the standard diet. The concentration of sugar in the sucrose solution was the same as is found in some commercial soft drinks, while the high-fructose corn syrup solution was half as concentrated as most sodas, including the orange soft drink shown here. (Photo: Denise Applewhite)
High-fructose corn syrup and sucrose are both compounds that contain the simple sugars fructose and glucose, but there at least two clear differences between them. First, sucrose is composed of equal amounts of the two simple sugars -- it is 50 percent fructose and 50 percent glucose -- but the typical high-fructose corn syrup used in this study features a slightly imbalanced ratio, containing 55 percent fructose and 42 percent glucose. Larger sugar molecules called higher saccharides make up the remaining 3 percent of the sweetener. Second, as a result of the manufacturing process for high-fructose corn syrup, the fructose molecules in the sweetener are free and unbound, ready for absorption and utilization. In contrast, every fructose molecule in sucrose that comes from cane sugar or beet sugar is bound to a corresponding glucose molecule and must go through an extra metabolic step before it can be utilized.
This creates a fascinating puzzle. The rats in the Princeton study became obese by drinking high-fructose corn syrup, but not by drinking sucrose. The critical differences in appetite, metabolism and gene expression that underlie this phenomenon are yet to be discovered, but may relate to the fact that excess fructose is being metabolized to produce fat, while glucose is largely being processed for energy or stored as a carbohydrate, called glycogen, in the liver and muscles.
In the 40 years since the introduction of high-fructose corn syrup as a cost-effective sweetener in the American diet, rates of obesity in the U.S. have skyrocketed, according to the Centers for Disease Control and Prevention. In 1970, around 15 percent of the U.S. population met the definition for obesity; today, roughly one-third of the American adults are considered obese, the CDC reported. High-fructose corn syrup is found in a wide range of foods and beverages, including fruit juice, soda, cereal, bread, yogurt, ketchup and mayonnaise. On average, Americans consume 60 pounds of the sweetener per person every year.
"Our findings lend support to the theory that the excessive consumption of high-fructose corn syrup found in many beverages may be an important factor in the obesity epidemic," Avena said.
The new research complements previous work led by Hoebel and Avena demonstrating that sucrose can be addictive, having effects on the brain similar to some drugs of abuse.
In the future, the team intends to explore how the animals respond to the consumption of high-fructose corn syrup in conjunction with a high-fat diet -- the equivalent of a typical fast-food meal containing a hamburger, fries and soda -- and whether excessive high-fructose corn syrup consumption contributes to the diseases associated with obesity. Another step will be to study how fructose affects brain function in the control of appetite.
The research was supported by the U.S. Public Health Service.
Demand for sugar in the United States grew throughout the 20th century. But it skyrocketed when the food industry began mass producing high-fructose corn syrup (HFCS) in the 1970s. Though HFCS intake has fallen in the new millennium, researchers still struggle to understand how this hotly debated sweetener impacts our health.
Some sugars appear in nature. Table sugar (also known as sucrose, which is half fructose and half glucose) is derived from sugar beets and cane. Fructose is common in fruits and honey.
HFCS, on the other hand, is processed from corn kernels. Producers soak kernels to extract corn starch and then add enzymes, refining the naturally occurring glucose (a.k.a. dextrose) into a syrup that often contains high levels of fructose. (At its peak in 1999, 10 percent of America’s corn crop was being used to make HFCS, according to government figures.)
HFCS is frequently found in soft drinks, breakfast cereals and sauces like ketchup. It is cheaper than sugar (in part because America’s corn crop is government-subsidized) and does not conceal other flavors. Though the level of fructose in most HFCS is advertised as no more than 55 percent, researchers at the University of Southern California have found samples of Pepsi and Coca-Cola containing 65 percent fructose and believe we may be consuming far more fructose than we realize.
Since a landmark paper in 2004, many scientists have linked America’s obesity epidemic to our high HFCS intake. But, as the two sections of research below emphasize, scientists disagree on the role that added sugars play not just in obesity, but in related health concerns as well, such as type 2 diabetes and liver disease. Is the problem that Americans eat too much sugar generally? Or is HFCS more harmful than sugar? Like fructose, HFCS is metabolized in the liver — so is there a connection to liver disease?
Some scientists argue that the data is too limited to vilify HFCS or that many foods containing HFCS simply lack nutritional value. The American Medical Association, in its last public comment on the disagreement in 2008, declared that “there is insufficient evidence” to curb consumption of HFCS or merit placing warning labels on products containing HFCS.
But, affirm many of the papers below, subsequent evidence warrants caution.
In response to these growing concerns, the corn industry has actively championed HFCS. A 2013 commentary in the International Journal of Obesity, for example, condemns research on links between HFCS and health problems. Two of the authors had received funding from the Corn Refiners Association. That industry group, which defends HFCS as “nearly identical to table sugar” often lobbies the Food and Drug Administration (FDA), America’s food regulator, which calls the additive safe. The same group unsuccessfully petitioned the FDA in 2012 to change the name of HFCS to “corn sugar.”
Academic papers that find reasons for concern:
“Fructose Content in Popular Beverages Made with and Without High-Fructose Corn Syrup”
Walker, Ryan W.; Dumke, Kelly A.; Goran, Michael I. Nutrition, 2014. DOI: 10.1016/j.nut.2014.04.003.
Conclusion: “Our results provide evidence of higher than expected amounts of free fructose in some beverages. Popular beverages made with HFCS have a fructose-to-glucose ratio of approximately 60:40, and thus contain 50 percent more fructose than glucose. Some pure fruit juices have twice as much fructose as glucose. These findings suggest that beverages made with HFCS and some juices have a sugar profile very different than sucrose, in which amounts of fructose and glucose are equivalent. Current dietary analyses may underestimate actual fructose consumption.”
“An Assessment of the Relationship Between the High-Fructose Corn Syrup and the Soft Drink Markets in the United States”
Kennedy, P. Lynn; Garcia-Fuentes, Pablo A. Working paper presented at the Southern Agricultural Economics Association annual meeting, 2017.
Abstract: “This study analyzes the market of high fructose corn syrup (HFCS) in the United States and its linkages with soft drink market. […] The results show that soft drinks are the main driver behind the growing demand for HFCS. In addition, negative news on HFCS (the association of HFCS consumption and obesity) has a negative effect on the growth of demand for soft drinks; however, per capita advertising on soft drinks has a positive effect on the growth of demand for soft drinks and more than offsets the effect of negative news.”
“High-Fructose Corn Syrup-55 Consumption Alters Hepatic Lipid Metabolism and Promotes Triglyceride Accumulation”
Mock, Kaitlin; et al. Journal of Nutritional Biochemistry, 2017. DOI: 10.1016/j.jnutbio.2016.09.010.
Abstract: “High-fructose corn syrup-55 (HFCS-55) has been suggested to be more lipogenic than sucrose, which increases the risk for nonalcoholic fatty liver disease (NAFLD) and dyslipidemia. The study objectives were to determine the effects of drinking different sugar-sweetened solutions on hepatic gene expression in relation to liver fatty acid composition and risk of NAFLD. […] Results from gene expression and fatty acid composition analysis showed that, in a hypercaloric state, some types of sugars are more detrimental to the liver. Based on these preclinical study results, excess consumption of caloric sweetened beverage, particularly HFCS-sweetened beverages, should be limited.”
“Sugar Content of Popular Sweetened Beverages Based on Objective Laboratory Analysis: Focus on Fructose Content”
Ventura, Emily E.; Davis, Jaimie N.; Goran, Michael I. Obesity, 2010. DOI: 10.1038/oby.2010.255.
Abstract: “The consumption of fructose, largely in the form of high fructose corn syrup (HFCS), has risen over the past several decades and is thought to contribute negatively to metabolic health. However, the fructose content of foods and beverages produced with HFCS is not disclosed and estimates of fructose content are based on the common assumption that the HFCS used contains 55 percent fructose. The objective of this study was to conduct an objective laboratory analysis of the sugar content and composition in popular sugar-sweetened beverages with a particular focus on fructose content. […] Results showed that the total sugar content of the beverages ranged from 85 to 128 percent of what was listed on the food label. The mean fructose content in the HFCS used was 59 percent (range 47–65 percent) and several major brands appear to be produced with HFCS that is 65 percent fructose. Finally, the sugar profile analyses detected forms of sugar that were inconsistent with what was listed on the food labels. This analysis revealed significant deviations in sugar amount and composition relative to disclosures from producers. In addition, the tendency for use of HFCS that is higher in fructose could be contributing to higher fructose consumption than would otherwise be assumed.”
“High-Fructose Corn Syrup and Diabetes Prevalence: A Global Perspective”
Goran, Michael I.; Ulijaszek, Stanley J.; Ventura, Emily E. Global Public Health, 2012. DOI: 10.1080/17441692.2012.736257.
Abstract: “The overall aim of this study was to evaluate, from a global and ecological perspective, the relationships between availability of high fructose corn syrup (HFCS) and prevalence of type 2 diabetes. […] Diabetes prevalence was 20 percent higher in countries with higher availability of HFCS compared to countries with low availability, and these differences were retained or strengthened after adjusting for country-level estimates of body mass index (BMI), population and gross domestic product (adjusted diabetes prevalence=8.0 vs. 6.7 percent, p=0.03; fasting plasma glucose=5.34 vs. 5.22 mmol/L, p=0.03) despite similarities in obesity and total sugar and calorie availability. These results suggest that countries with higher availability of HFCS have a higher prevalence of type 2 diabetes independent of obesity.”
“Energy and Fructose from Beverages Sweetened with Sugar or High-Fructose Corn Syrup Pose a Health Risk for Some People”
Bray, George A. Advances in Nutrition, 2013. DOI: 10.3945/an.112.002816.
Abstract: “Sugar intake in the United States has increased by >40 fold since the American Revolution. The health concerns that have been raised about the amounts of sugar that are in the current diet, primarily as beverages, are the subject of this review. Just less than 50 percent of the added sugars (sugar and high-fructose corn syrup) are found in soft drinks and fruit drinks. […] Calorically sweetened beverages contribute to obesity through their caloric load, and the intake of beverages does not produce a corresponding reduction in the intake of other food, suggesting that beverage calories are ‘add-on’ calories. The increase in plasma triglyceride concentrations by sugar-sweetened beverages can be attributed to fructose rather than glucose in sugar. Several randomized trials of sugar-containing soft drinks versus low-calorie or calorie-free beverages show that either sugar, 50 percent of which is fructose, or fructose alone increases triglycerides, body weight, visceral adipose tissue, muscle fat, and liver fat. Fructose is metabolized primarily in the liver. […] By worsening blood lipids, contributing to obesity, diabetes, fatty liver, and gout, fructose in the amounts currently consumed is hazardous to the health of some people.”
“Impact of Perinatal Exposure to Sucrose or High-Fructose Corn Syrup (HFCS-55) on Adiposity and Hepatic Lipid Composition in Rat Offspring”
Toop, Carla R.; et al. The Journal of Physiology, 2017. DOI: 10.1113/JP274066.
Abstract: “Perinatal exposure to excess maternal intake of added sugars, including fructose and sucrose, is associated with an increased risk of obesity and type 2 diabetes in adult life. However, it is unknown to what extent the type of sugar and the timing of exposure affect these outcomes. The aim of this study was to determine the impact of exposure to maternal consumption of a 10 percent w/v [weight of solution in the total volume] beverage containing sucrose or high fructose corn syrup-55 (HFCS-55) during the prenatal and/or suckling periods on offspring at 3 and 12 weeks, utilizing a cross-fostering approach in a rodent model. […] This study suggests that the type of sugar and the timing of exposure (prenatal or suckling periods) are both important for determining the impact on metabolic health outcomes in the offspring.”
“Differential Effects of Fructose Versus Glucose on Brain and Appetitive Responses to Food Cues and Decisions for Food Rewards”
Luo, Shan; et al. Proceedings of the National Academy of Sciences, 2015. DOI: 10.1073/pnas.1503358112.
Abstract: “Fructose compared with glucose may be a weaker suppressor of appetite. Here we sought to determine the effects of fructose versus glucose on brain, hormone, and appetitive responses to food cues and food-approach behavior. We show that the ingestion of fructose compared with glucose resulted in smaller increases in plasma insulin levels and greater brain responses to food cues in the visual cortex and left orbital frontal cortex. Ingestion of fructose versus glucose also led to greater hunger and desire for food and a greater willingness to give up long-term monetary rewards to obtain immediate high-calorie foods. These findings suggest that ingestion of fructose relative to glucose activates brain regions involved in attention and reward processing and may promote feeding behavior.”
Academic papers that cast doubt on the alleged dangers:
“Fructose, High-Fructose Corn Syrup, Sucrose, and Nonalcoholic Fatty Liver Disease or Indexes of Liver Health: A Systematic Review and Meta-Analysis”
Chung, Mei; et al. American Journal of Clinical Nutrition, 2014. DOI: 10.3945/ajcn.114.086314.
Conclusions: “On the basis of indirect comparisons across study findings, the apparent association between indexes of liver health […] and fructose or sucrose intake appear to be confounded by excessive energy intake. Overall, the available evidence is not sufficiently robust to draw conclusions regarding effects of fructose, HFCS, or sucrose consumption on [nonalcoholic fatty liver disease].”
“No Differences in Satiety or Energy Intake After High-Fructose Corn Syrup, Sucrose, or Milk Preloads”
Soenen, S.; Westerterp-Plantenga, M.S. American Journal of Clinical Nutrition, 2008.
Conclusions: “Energy balance consequences of HFCS-sweetened soft drinks are not different from those of other isoenergetic drinks, e.g., a sucrose-drink or milk.”
“Twenty-Four-Hour Endocrine and Metabolic Profiles Following Consumption of High-Fructose Corn Syrup-, Sucrose-, Fructose-, and Glucose-Sweetened Beverages with Meals”
Stanhope, K.L.; et al. American Journal of Clinical Nutrition, 2008.
Conclusions: “Sucrose and HFCS do not have substantially different short-term endocrine/metabolic effects. In male subjects, short-term consumption of sucrose and HFCS resulted in postprandial TG responses comparable to those induced by fructose.”
“Effects of High-Fructose Corn Syrup and Sucrose Consumption on Circulating Glucose, Insulin, Leptin, and Ghrelin and on Appetite in Normal-Weight Women”
Melanson, K.J.; et al. Nutrition, 2007. DOI: 10.1016/j.nut.2006.11.001.
Conclusions: “These short-term results suggest that, when fructose is consumed in the form of HFCS, the measured metabolic responses do not differ from [sucrose] in lean women. Further research is required to examine appetite responses and to determine if these findings hold true for obese individuals, males, or longer periods.”
- The Mayo Clinic’s resource pages on two diseases that researchers have associated with HFCS: non-alcoholic fatty liver disease and type 2 diabetes.
- The Environmental Working Group (EWG), a nonpartisan agriculture watchdog based in Washington, calculates the value of U.S. government corn subsidies dating back to 1995.
- The U.S. Department of Agriculture has data on sugar additives like HFCS and a resource page explaining the HFCS refining process.
- The Pew Research Center has explored what Americans eat and how their diet has changed over the last few generations.
- The Corn Refiners Association lists its frequently asked questions.
Last updated: May 11, 2017
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