The indirect way fructose fuels tumor growth

Fructose has steadily been on the rise in Western diets as high-fructose corn syrup, an inexpensive sweetnener, has become popular. A downside of this fructose boom is that fructose is known to fuel tumor growth, and now scientists think they have solved the mystery of how the sugar makes cancer cells proliferate.

Glucose—a structural isomer of fructose—can boost cancer cell growth directly. Feed glucose to cancer cells in a test tube, and they’ll grow and divide. But that’s not the case with fructose. Cancer cells in fructose solutions don’t grow any faster than cancer cells in nonsugar solutions.

“That was initially quite confusing because when animals had tumors and we put them on high-fructose diets, the tumors grew faster,” says Gary Patti, who studies metabolic systems at Washington University in St. Louis.

Patti led a team that used isotope labeling and mass spectrometry to track fructose metabolism in mice and found that the sugar gets converted by enzymes in the liver to lipids known as lysophosphatidylcholines. Cancer cells then scavenge these lipids to make membranes for new cancer cells (Nature 2024, DOI: 10.1038/s41586-024-08258-3).

Kayvan R. Keshari, who studies cancer metabolism at Memorial Sloan Kettering Cancer Center and was not involved in the work, says the finding is a nice demonstration of how isotope tracing methods can determine the role nutrients play in living organisms. However, he says in an email, “fructose metabolism remains a key area of controversy with many studies arguing it enhances growth for various reasons across many different tissues of origin.” While the study is important for the nutritional metabolism field, Keshari says, more work is needed to see how relevant the finding is to human cancers.

Ralph DeBerardinis, an expert in metabolic disorders at the University of Texas Southwestern Medical Center and was also not involved in the research, says in an email that “there’s evidence that part of the problem with high fructose diets is that they promote obesity, and obesity increases the risk of some kinds of cancer.” The recent study suggests that consuming fructose “may also stimulate growth of existing tumors through its effects on lipid metabolism in the liver,” he says.

Patti points out that the researchers didn’t find that fructose causes cancer but rather that it makes existing cancer cells proliferate. “What this really underscores is that when we think about cancer metabolism, you can’t just think about the malignant cells themselves,” he says. “You have to recognize that all of the healthy tissues in the body also are contributing to what happens.”