High-fructose corn syrup fuels tumor growth in animals with cancer, a new study shows

Print Email Share Tweet LinkedIn WhatsApp Reddit Telegram
|

A century ago, an average person consumed just 5 to 10 pounds of fructose per year. Now that number can be as much as 15 times higher. (Photo credit: Andrej Lisakov)

High-fructose corn syrup, a sweetener commonly used in soda and ultra-processed foods, accelerates cancer tumor growth via the liver, according to research published last week [Dec. 4, 2024] in Nature.

High-fructose corn syrup (HFCS) is a sugar derived from corn starch. High fructose intake has been shown to contribute to the development of non-alcoholic fatty liver disease (NAFLD) and obesity, both of which are associated with systemic inflammation and altered lipid metabolism (the way the body processes fats). It has also been linked to diabetes, heart disease, and colorectal cancer.

Cancer occurs when abnormal cells multiply uncontrollably. But cancer cells (as well as healthy cells) can’t readily use fructose directly, even at high levels, to fuel their growth due to the lack of an enzyme that can efficiently process it.

This study, conducted on mice with melanoma, breast cancer, and cervical cancer, highlights one way in which high levels of fructose consumption promote tumor growth. In a process called interorgan lipid transfer (when fats move between organs and tissues in the body), the liver makes fructose more available to cancer cells by turning it into nutrients in the blood they can use.

“When we think about tumors, we tend to focus on what dietary components they consume directly. You put something in your body, and then you imagine that the tumor takes it up,” says Gary Patti, the Michael and Tana Powell Professor of Chemistry in Arts & Sciences and a professor of genetics and of medicine at the Washington University School of Medicine in St. Louis in a news release. “But humans are complex. What you put in your body can be consumed by healthy tissue and then converted into something else that tumors use.”

The study’s first author, Ronald Fowle-Grider, a postdoctoral fellow in Patti’s lab, agrees: “We quickly learned that the tumor cells alone don’t tell the whole story.” 

Liver converts fructose to speed tumor growth 

While the whole body metabolizes glucose, fructose is almost entirely metabolized by the small intestine and liver.

Liver cells, unlike cancer cells, can convert fructose into a type of fat molecule (lipid) called lysophosphatidylcholine (LPC), which enters the bloodstream, the researchers say.

Cancer cells can then take up the available LPCs and use them to make other important molecules called phosphatidylcholines (PCs). These are critical for creating cell membranes, which are needed for cell division and tumor growth. 

To conduct the study, the researchers added high-fructose corn syrup to the diet of the mice with cancer. It significantly increased their LPC blood levels and accelerated tumor growth, without causing weight gain or insulin problems. Similar effects have been found with zebrafish, which also share genetic similarities with humans, the researchers say.

“Over the past few years, it’s become clear that many cancer cells prefer to take up lipids rather than make them,” Patti says. “The complication is that most lipids are insoluble in blood and require rather complex transport mechanisms. LPCs are unique. They might provide the most effective and efficient way to support tumor growth.”

Blocking the enzyme that breaks down fructose in the liver didn’t affect cancer cells directly. However, it reduced LPC levels in the blood and stopped the fructose from boosting tumor growth, the researchers say.

“We looked at numerous different cancers in various tissues throughout the body, and they all followed the same mechanism,” Patti says.

Fructose speeds tumor growth, but not as much as glucose

To confirm that fructose itself was enough to make tumors grow faster, the researchers repeated the experiment with two types of cancer cells (TC-1 and CaSki). Mice were either given regular diets with water containing 10% fructose or had regular food with fructose added.

Mice given a high-fructose diet had higher levels of LPCs. The study also showed that fructose directly contributes to increasing the amount of a specific type of LPC called LPC 18:1, especially in the blood—more than sevenfold in fasting levels in mice given HFCS for several weeks. 

The researchers also found: 

“Our initial expectation was that tumor cells metabolize fructose just like glucose, directly utilizing its atoms to build new cellular components such as DNA. We were surprised that fructose was barely metabolized in the tumor types we tested,” says Fowle-Grider.

Reducing fructose to slow cancer growth

Products that commonly contain high-fructose corn syrup range from candy, soda, packaged sweets like cookies and crackers, and refined carbs (think Wonder Bread) to juice drinks, fast food, ice cream, and breakfast foods like brand name pancake syrups—even applesauce and granola bars. 

The easiest way to avoid high-fructose corn syrup is to carefully read ingredient labels and eat whole unprocessed foods.

The researchers’ findings add to growing evidence that fructose can serve as an alternative fuel for cancer cells when glucose, the main sugar found in blood, is scarce. More research is needed to determine whether other types of tumors might use dietary fructose directly for growth, the authors say. For some tumors, fructose may promote tumor growth and disease progression both directly and indirectly, they suggest.

Future research could also lead to new treatments that target LPCs in cancer cells. In preclinical studies, inhibiting fructose metabolism has shown some promise in slowing tumor growth, they say. 

“It will be exciting to better understand how dietary fructose influences cancer incidence. But one take-home message from this current study is that if you are unfortunate enough to have cancer, then you probably want to think about avoiding fructose,” says Patti. 

Reference

Fowle-Grider R, Rowles JL, Shen I, et al. Dietary fructose enhances tumour growth indirectly via Interorgan Lipid Transfer. Nature. Published online December 4, 2024. doi:10.1038/s41586-024-08258-3