COMMENTARY

Sickeningly Sweet: High-Fructose Corn Syrup's Possible Role in Intestinal Cancer

David A. Johnson, MD

Disclosures

May 14, 2019

This transcript has been edited for clarity.

Hello. I'm Dr David Johnson, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia.

High-fructose corn syrup can be found in almost all of the sweetened, pasteurized, and processed foods we consume. It is cheaper and sweeter than cane sugar, which is why it is a part of so many of these foods. High-fructose corn syrup has also been implicated in the growing epidemic of obesity, diabetes, and metabolic syndrome in the United States. This has led some states to place restrictions on the sale of items containing high-fructose corn syrup, such as the number of large-volume sodas that can be purchased at any one time.

Another emerging health concern in the United States is the dramatic increase in colorectal cancer in relatively younger patients. By 2030, it has been projected that colorectal cancers will increase by 90%-125% in 20- to 34-year-olds and by 28%-46% in 35- to 49-year-olds.[1] This has led the American Cancer Society to change its recommendation to begin screening everybody earlier, by the age of 45.[2]

Rising obesity and diabetes rates are often cited as the reason behind this increase in colorectal cancer. However, a recent study published in Science suggests that high-fructose corn syrup may play a role by enhancing intestinal tumor growth, at least in mice.[3]

Possible Role in Intestinal Cancer

Glucose is transported by intestinal epithelial cells in a very active manner via sodium-coupled glucose transporters. The fructose pathway, however, is mediated by a passive transporter called GLUT5. As little as 5 g of fructose can overwhelm this passive transporter. Rather than being absorbed, the fructose instead gets delivered to the colon.

Researchers behind this latest study used a bioengineered knockout of the adenoma polyposis coli gene, which creates mice predestined to develop colon cancer and colon polyps. They then administered to the mice 20 g of weight-adjusted high-fructose corn syrup, an equivalent of 1 soda a day. Lo and behold, they observed in these mice significant and demonstrable evidence of an increase in polyps that developed very quickly into advanced, high-grade-type dysplastic lesions.

Through carbon labeling, the researchers identified that there was an uptake in fructose within the intestinal tumors themselves. High-fructose corn syrup accelerated the de novo fatty acid–generated synthesis. Intestinal growth generated by fatty acids leads to membrane stabilization, energy storage, and intestinal growth of these lesions. This de novo synthesis of these fatty acids was very apparent as it relates to the high-fructose corn syrup model. It suggests that the tumors rewire the metabolic pathways in favor of fatty acid synthesis after being exposed to high-fructose corn syrup.

A Mouse Study With Actionable Clinical Value?

This study has an incredible potential translational message now. Are we going to wait for randomized controlled trials? We already know that high-fructose corn syrup is at least linked to the epidemic of obesity.

There is also tremendous correlation with high-fructose corn syrup upregulation of inflammasomes, which drives cytokine upregulation. There are a lot of data on this, particularly in inflammatory pathways in nonalcoholic fatty liver disease and steatohepatitis, as well as in cell death in the liver.[4] There is even some similar work relating inflammasome upregulation to cardiovascular disease and the development of things like atherosclerosis, atherosclerotic plaques, plaque rupture, and plaque thrombosis.[5]

Certainly, there needs to be the caveat that these data come from a mouse model, and there is still much to learn. They may one day allow us to identify new treatment horizons. Perhaps fructokinase, which is a pathway that leads to fructose metabolism, particularly in the liver, can be targeted for chemotherapy or chemointervention strategies.

However, I think that even with these limitations, it is appropriate to call "time out" on high-fructose corn syrup. My patients with colon cancer or a colon polyp will often ask me what they can do differently. There are many things that relate to diet that we can counsel our patients about, and high-fructose corn syrup is something that I will add to the very top-of-the-line discussion that I have with them. They'll need to adequately read the labels of the food they eat to keep an eye out for this.

The corn industry itself seems to be clearly aware of the health issues surrounding their product. A couple of years ago, they tried to relabel high-fructose corn syrup as "corn sugar," only for the US Food and Drug Administration to turn them down. This raises questions that maybe there are a lot of things out there that we should be aware of with this product.

Although this is just a mouse model, I think it has a translational message that is actionable now. High-fructose corn syrup is not a good thing. It leads to a lot of inflammatory upregulation. In my own practice, I share this information with my patients with inflammatory bowel disease and nonalcoholic fatty liver disease, and now I also will with those patients with colon neoplasms, colon polyps, and colon cancers.

I recommend that you review and consider these data. I see no reason to wait on randomized controlled trials to show what seems to be intuitively obvious right now. Lots of evidence awaits us, but sometimes we just have to act on instinct and assimilate a translational message. This has changed my practice, and perhaps it will change yours as well.

I'm Dr David Johnson. Thanks again for listening.

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