Fructose in Diet Linked to Enhanced Tumor Growth

The corn syrup era

Cancer cells have long been known to have a strong affinity for glucose, a simple sugar that the body uses as its primary carbohydrate-based energy source.

Fructose has a similar molecular structure to glucose. They are both common sugars with the same chemical formula, but they are metabolized differently by the body. Glucose is digested throughout the body, whereas fructose is mostly metabolized by the small intestine and liver.

Both sugars occur naturally in fruits, vegetables, dairy products, and grains. They are also used as a sweetener in many processed goods. Fructose, in particular, has permeated the American diet during the previous few decades. It is popular in the food business because it is sweeter than glucose.

Prior to the 1960s, people consumed significantly less sugar than they do now. A century ago, the average person ingested only 5-10 pounds of fructose per year. That is roughly equivalent to the weight of a gallon of milk. In the twenty-first century, the figure has risen to the equivalent of fifteen gallons of milk.

“If you go through your pantry and look for the items that contain high-fructose corn syrup, which is the most common form of fructose, it is pretty astonishing,” said Patti, who is also a research member of the Siteman Cancer Center at Barnes-Jewish Hospital and the Center for Human Nutrition at WashU Medicine.

“Almost everything has it. It’s not just candy and cake, but also foods such as pasta sauce, salad dressing and ketchup,” he said. “Unless you actively seek to avoid it, it’s probably part of your diet.”

Cancer’s appetite for fructose

Given the dramatic increase in dietary fructose consumption over the last few decades, WashU researchers wanted to learn more about how fructose affects tumor formation.

Patti and Fowle-Grider began their experiment by providing fructose-rich diets to tumor-bearing rats and analyzing how quickly their tumors grew. The researchers discovered that additional fructose increased tumor growth without affecting body weight, fasting glucose, or fasting insulin levels.

“We were surprised to see that it had a rather dramatic impact. In some cases, the growth rate of the tumors accelerated by two-fold or even higher,” Patti said. “Eating a lot of fructose was clearly very bad for the progression of these tumors.”

However, the next phase in their tests initially confused them. When Fowle-Grider sought to replicate this test by feeding fructose to cancer cells isolated in a dish, they did not respond. “In most cases they grew almost as slowly as if we gave them no sugar at all,” Patti told me.

So, Patti and Fowle-Grider returned to studying alterations in small molecules in the blood of animals fed high-fructose diets. Using metabolomics, they discovered higher amounts of a number of lipid species, including lysophosphatidylcholines. Additional dish testing revealed that liver cells fed fructose produce LPCs.

“Interestingly, the cancer cells themselves were unable to use fructose readily as a nutrient because they do not express the right biochemical machinery,” Patti said. “Liver cells do. This allows them to convert fructose into LPCs, which they can secrete to feed tumors.”

Cancer is defined by the uncontrolled expansion of malignant cells. When a cell divides, it must copy its contents, including membranes. This demands a significant amount of lipids. While lipids can be generated from scratch, cancer cells find it far easier to absorb lipids from their environment.

“Over the past few years, it’s become clear that many cancer cells prefer to take up lipids rather than make them,” Patti noted. “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.”