High-fructose corn syrup promotes tumor growth, mouse study finds

28 Mar 2019 --- Consuming a modest amount of high-fructose corn syrup – the equivalent of a can of soda for humans – every day promotes the growth of intestinal tumors in mice models of the disease. This is according to a study from Baylor College of Medicine and Weill Cornell Medicine published in Science. The researchers found the mechanism by which high-fructose syrup feed tumor growth and suggest potential treatments to block this side effect. Further research is needed in human models, however, the findings could explain why the increased consumption of high sugar foods and drinks has correlated with a rise in colorectal cancers in the US, note the researchers.

“An increasing number of observational studies have raised awareness of the association between consuming sugary drinks, obesity and the risk of colorectal cancer,” notes co-corresponding author Dr. Jihye Yun, Assistant Professor of Molecular and Human Genetics at Baylor. 

“The current thought is that sugar is harmful to our health mainly because consuming too much may 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. Therefore, I decided to address this important question,” Professor Yun says.

Deleting an obesity gene to determine pathologyYun and her colleagues generated a mouse model of early-stage colon cancer and deleted a gene protein called APC. “APC is a gatekeeper in colorectal cancer. Deleting this protein is like removing the breaks of a car. Without it, normal intestinal cells neither stop growing nor die, forming early-stage tumors called polyps. More than 90 percent of colorectal cancer patients have this type of APC mutation,” Professor Yun says.

The researchers then tested the effects of sugar-sweetened water on tumor development, using this mouse model. The solution was 25 percent high-fructose corn syrup which is the main ingredient of most sugary soft beverages and consists of glucose and fructose at a 45:55 ratio.

The mice provided with the sugary drink in the water bottle rapidly gained weight. 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. 

Two months later, the APC-model mice receiving sugary water did not become obese, however, they developed tumors that were larger in size and of a higher grade than the mice treated with regular water.

“These results suggest that when the animals have early-stage 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,” Yun warns. 

“Further research is needed to translate this discovery to people; however, our 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.”

According to Dr. Lewis Cantley of Weill Cornell Medicine, 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 US. 

Identifying the mechanism
By employing cutting-edge technology to trace glucose and fructose in tumor tissues, the researchers also found 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. Essentially, this means 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.

“Most previous studies used either glucose or fructose alone to study the effect of sugar in animals or cell lines. We thought that this approach did not reflect how people actually consume sugary drinks because neither drinks nor foods have only glucose or fructose. They (can) have both glucose and fructose together in similar amounts,” Professor Yun says. 

“Our 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.”

The next step was to determine if fructose metabolism or increased fatty acid production was responsible for sugar-induced tumor growth. 

The researchers modified the 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 called KHK, which is involved in fructose metabolism, and another group lacked enzyme FASN, which participates in the synthesis of fatty acids. 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,” Cantley says. “While many studies have correlated increased rates of colorectal cancer with diet, this study shows a direct molecular mechanism for the correlation between consumption of sugar and colorectal cancer.”

“Our findings also open new possibilities for treatment,” Yun says. “Unlike glucose, fructose is not essential for the survival and growth of normal cells, which suggests that therapies targeting fructose metabolism are worth exploring. Alternatively, avoiding consuming sugary drinks as much as possible instead of relying on drugs would significantly reduce the availability of sugar in the colon.”

The researchers note that further studies are necessary to reveal more about the correlation. However, they hope that their research will bring attention to the potential harmful effects of sugary beverages on human health.

Earlier this month, a Harvard study found that high consumption of sugary beverages is linked with increased risk of mortality, particularly from cardiovascular disease (CVD) and to a lesser extent cancer. The study, however, was slammed by the British Soft Drinks Association (BSDA) who insisted that the research “failed to acknowledge key facts” and reiterated that soft drinks are safe to consume, as part of a balanced diet.

https://www.nutritioninsight.com/news/soft-drinks-industry-hits-back-after-harvard-study-links-higher-consumption-of-sugary-drinks-to-early-death.html

Sugar is nonetheless increasingly brought to the fore as the key culprit for many non communicable diseases, which has spurred several preventative measures to be taken around the globe. The Californian city of Berkley, for example, saw a 52 percent drop in the consumption of sugary drinks after it levied the first soda tax on sugar-sweetened beverages in the US, effective since November 2014.

The UK also enforced a sugar tax on sugary soft drinks in April 2018, which followed the government’s food and beverage sugar-reduction plan from 2016. The moves are part of Britain’s non-communicablee negative effects of increased sugar consumption. The latter challenged all sectors of the food industry – including retailers, manufacturers, restaurants, cafés and pub chains – to reduce by 20 percent the level of sugar in food formulations by 2020. Industry was also challenged to achieve a 5 percent reduction in the first year of the program which was not successful.