High fructose corn syrup boosts intestinal tumor growth in mice

An increasing number of observational studies have raised awareness of the association between consuming sugary drinks, obesity and the risk of colorectal cancer.  The current thought is that sugar is harmful to our health mainly because consuming too much can lead to obesity. We know that obesity increases the risk of many types of cancer including colorectal cancer; however, we were uncertain whether a direct and causal link existed between sugar consumption and cancer. 

A recent study, published in Science by researchers at Baylor College of Medicine and Weill Cornell Medicine, showed that consuming a daily modest amount of high-fructose corn syrup — the equivalent of people drinking about 12 ounces of a sugar-sweetened beverage daily — accelerates the growth of intestinal tumors in mouse models of the disease, independently of obesity. 

Using a mouse model that is prone to colorectal cancer (named APC-model mice), the team tested the effect of consuming sugar-sweetened water on tumor development. The sweetened water was 25 percent high-fructose corn syrup, which is the main sweetener of sugary drinks people consume. High-fructose corn syrup consists of glucose and fructose at a 45:55 ratio.

When the researchers provided the sugary drink in the water bottle for the APC-model mice to drink at their will, mice rapidly gained weight in a month. To prevent the mice from being obese and mimic humans’ daily consumption of one can of soda, the researchers gave the mice a moderate amount of sugary water orally with a special syringe once a day. After two months, the APC-model mice receiving sugary water did not become obese, but developed tumors that were larger and of higher-grade than those in model mice treated with regular water.

These results suggest that when the animals have early stage of tumors in the intestines — which can occur in many young adult humans by chance and without notice — consuming even modest amounts of high-fructose corn syrup in liquid form can boost tumor growth and progression independently of obesity.   Further research is needed to translate these discoveries to people; however, the findings in animal models suggest that chronic consumption of sugary drinks can shorten the time it takes cancer to develop. In humans, it usually takes 20 to 30 years for colorectal cancer to grow from early stage benign tumors to aggressive cancers.  This observation in animal models might explain why increased consumption of sweet drinks and other foods with high sugar content over the past 30 years is correlating with an increase in colorectal cancers in 25 to 50-year-olds in the United States. 

The team then investigated the mechanism by which high fructose corn syrup promoted tumor growth. They discovered that the APC-model mice receiving modest high-fructose corn syrup had high amounts of fructose in their colons.  It is observed that sugary drinks increased the levels of fructose and glucose in the colon and blood, respectively and that tumors could efficiently take up both fructose and glucose via different routes.

Using cutting-edge technologies to trace the fate of glucose and fructose in tumor tissues, the team showed that fructose was first chemically changed and this process then enabled it to efficiently promote the production of fatty acids, which ultimately contribute to tumor growth.  The findings suggest that the role of fructose in tumors is to enhance glucose’s role of directing fatty acids synthesis. The resulting abundance of fatty acids can be potentially used by cancer cells to form cellular membranes and signaling molecules, to grow or to influence inflammation.

To determine whether fructose metabolism or increased fatty acid production was responsible for sugar-induced tumor growth, the researchers modified APC-model mice to lack genes coding for enzymes involved in either fructose metabolism or fatty acid synthesis. One group of APC-model mice lacked an enzyme involved in fructose metabolism, and another group lacked an enzyme, which participates in fatty acid synthesis. They found that mice lacking either of these genes did not develop larger tumors, unlike APC-model mice, when fed the same modest amounts of high-fructose corn syrup.

This study revealed the surprising result that colorectal cancers utilize high-fructose corn syrup, the major ingredient in most sugary sodas and many other processed foods, as a fuel to increase rates of tumor growth.  Avoiding consuming high fructose corn syrup laced sugary drinks would significantly reduce the availability of sugar in the colon.

While further studies in humans are necessary, Baylor researchers hope this research will help to raise public awareness about the potentially harmful consequences consuming sugary drinks has on human health and contribute to reducing the risk and mortality of colorectal cancer worldwide.

Thanks for reading.

Journal Reference:  Marcus D. Goncalves, Changyuan Lu, Jordan Tutnauer, Travis E. Hartman, Seo-Kyoung Hwang, Charles J Murphy, Chantal Pauli, Roxanne Morris, Sam Taylor, Kaitlyn Bosch, Sukjin Yang, Yumei Wang, Justin Van Riper, H Carl Lekaye, Jatin Roper, Young Kim, Qiuying Chen, Steven S. Gross, Kyu Y. Rhee, Lewis C. Cantley, Jihye Yun. High-fructose corn syrup enhances intestinal tumor growth in mice. Science, 2019; 363 (6433): 1345-1349 DOI: 10.1126/science.aat8515