Does High Fructose Corn Fuel Cancer?

Does high fructose corn syrup directly feed cancers, boosting their
growth?  The answer is yes according to
an animal study conducted by researchers at Baylor College of Medicine and
Weill Cornell Medicine.

The answer seems to be ‘Yes’ at least in mice according to a study led by
researchers at Baylor College of Medicine and Weill Cornell Medicine.
Their study, published in Science,
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. The team also discovered the mechanism by
which the consumption of sugary drinks can directly feed cancer growth,
suggesting potential novel therapeutic strategies.

“An increasing number of observational studies have raised awareness of the
association between consuming sugary drinks, obesity and the risk of colorectal
cancer,” said 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 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. Therefore, I decided to address this important question when I was
a postdoc in the Dr.
Lewis Cantley
lab at Weill Cornell Medicine.

First, Yun and her colleagues generated a mouse model of early-stage colon
cancer where APC gene is deleted. “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,” Yun said.

Using this mouse model of the disease, 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,”
Yun said. “Further research is needed to translate these 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.”

“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,” said Cantley, co-corresponding author, former mentor of Yun
and professor of cancer biology in medicine and director of the Sandra and
Edward Meyer Cancer Center at Weill Cornell Medicine.

The team then investigated the mechanism by which this sugar promoted tumor
growth. They discovered that the APC-model mice receiving modest high-fructose
corn syrup had high amounts of fructose in their colons. “We 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.

“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 have both glucose and fructose
together in similar amounts,” Yun said. “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.”

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 KHK, which is involved in fructose metabolism, and another group lacked
enzyme FASN, 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,” Cantley said. “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 said. “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.”

While further studies in humans are necessary, Yun and colleagues 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.



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