Guess what? A new study has found that the consumption of high-fructose corn syrup (HFCS) indirectly encourages tumor growth through metabolic mechanisms in the liver. Yet, the idea that HFCS causes cancer is nothing new. In 2012, a review in PubMed summarized that there is likely a connection between fructose consumption and a “more aggressive cancer phenotype.” Since then, numerous other studies have stated that a high fructose diet can induce a chronic inflammatory environment and modulate the development of cancer cells. Yet today, the United States has the highest consumption per capita of HFCS, at 55 pounds per year. Yikes! Will this latest study finally be the much-needed wake-up call to halt the widespread use of HFCS in beverages and ultra-processed foods?

Both glucose and fructose naturally occur in fruits, vegetables, dairy products, and grains, but they are also widely used as sweeteners in processed foods. Over recent decades, HFCS—a sugar derived from corn starch (think toxic GMO corn)—has invaded the American diet. The food industry prefers it because it is sweeter than glucose, and undoubtedly, big pharma treasures it because it hooks repeat customers.

Before the 1960s, fructose consumption was relatively low compared to current levels. A century ago, the average person consumed about 5-10 pounds of fructose annually—roughly the weight of a gallon of milk. Today, that figure has risen significantly, increasing to be equal to the weight of as much as 15 gallons of milk per year.

Again, researchers have long understood that cancer cells have a strong attraction to glucose, a simple sugar that acts as the body’s primary energy source derived from carbohydrates. Fructose is another type of sugar that shares a chemical structure similar to glucose, but they are metabolized differently in the body. Glucose is processed throughout the entire body, whereas fructose is almost entirely metabolized in the small intestine and liver.

Fructose metabolism depends on specific enzymes that are generally absent in most cancer cells, indicating that fructose may indirectly influence tumor development. The metabolic interplay between normal organs and tumors, such as the nutrient exchange between the liver and cancer cells, is becoming increasingly recognized as a key aspect of cancer biology. However, the exact processes by which fructose contributes to tumor growth remain uncertain, highlighting the need for further investigation into inter-organ interactions in cancer metabolism.

Cancer develops when abnormal cells grow and multiply uncontrollably. However, as just mentioned, cancer cells—like healthy cells—are unable to directly utilize fructose efficiently for growth, even in high concentrations, because they lack the necessary enzyme to process it effectively. This recent study, conducted on mice with melanoma, breast cancer, and cervical cancer, reveals a mechanism through which excessive fructose consumption can contribute to tumor growth. Through a process known as interorgan lipid transfer—where fats are transported between organs and tissues—the liver converts fructose into blood-borne nutrients that cancer cells can readily utilize.

The study, conducted by researchers from Washington University in St. Louis (WashU), discovered that in some cases, the growth rate of tumors in their animal subjects accelerated two-fold or higher when feeding them a diet high in fructose. Study author 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, remarked in a news release:

“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. 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.”

Ronald Fowle-Grider, first author in the study and a postdoctoral fellow in Patti’s lab, remarked, “We quickly learned that the tumor cells alone don’t tell the whole story.” He explained that the initial expectation was that tumor cells would metabolize fructose in the same way as glucose, directly using its atoms to construct new cellular components like DNA. However, the team was surprised to uncover that fructose was scarcely metabolized in the tumor types they examined. They soon found that tumor cells alone do not provide the whole picture; the liver plays a crucial role by converting fructose into nutrients that tumors can utilize.

So, how does the liver convert fructose to speed tumor growth? According to researchers, liver cells—but not cancer cells—convert fructose into a fat molecule called lysophosphatidylcholine (LPC), which enters the bloodstream. Cancer cells then absorb LPCs and use them to produce phosphatidylcholines (PCs), essential components for building cell membranes, enabling cell division, and supporting tumor growth. In their study, researchers supplemented the diets of cancer-afflicted mice with HFCS, which significantly raised LPC levels in the blood and accelerated tumor growth without causing weight gain or insulin issues. Similar results were observed in zebrafish, which share genetic similarities with humans.

According to Patti, many cancer cells prefer acquiring lipids from their environment rather than producing them internally. LPCs stand out because they are soluble in blood and provide an efficient way to fuel tumor growth. Blocking the liver enzyme that metabolizes fructose didn’t directly affect cancer cells but reduced LPC levels, preventing fructose from enhancing tumor growth. This mechanism was consistent across various cancer types and tissues studied.

The researchers highlighted that fructose accelerates tumor growth but not as much as glucose. To determine if fructose alone could accelerate tumor growth, they conducted experiments using two types of cancer cells (TC-1 and CaSki). Mice were fed either a regular diet supplemented with water containing 10% fructose or regular food with added fructose. The results showed that mice on high-fructose diets displayed elevated lysophosphatidylcholine (LPC) levels, particularly LPC 18:1, with fasting levels increasing more than sevenfold after several weeks of consuming HFCS.

Moreover, as noted by USRTK, the study revealed that higher LPC 18:1 levels promoted faster tumor growth in both laboratory tests and in mice. However, tumor progression slowed significantly by blocking the production of LPC 18:1. Despite this, cancer cells metabolized very little fructose compared to glucose. Even when fructose was abundant, cell growth was slower than when glucose was the sole sugar source, and in some cases, the growth rate resembled that seen in sugar-free environments. Additionally, researchers observed that cancer cells grew significantly faster when cultured alongside liver cells than when grown alone. This growth was inhibited by PF-06835919, an experimental drug initially developed to manage diabetes and obesity. Fowle-Grider explained:

“We initially expected tumor cells to metabolize fructose in the same way as glucose, using its atoms directly to build cellular components like DNA. To our surprise, fructose was barely metabolized in the tumor types we studied.”

The study findings contribute to growing evidence that fructose can act as an alternative energy source for cancer cells when glucose, the primary sugar in the bloodstream, is limited. The researchers emphasize the need for further study to explore whether other types of tumors might directly utilize fructose for growth. They note that for some cancers, fructose may accelerate tumor development and disease progression via both direct and indirect mechanisms. Early preclinical studies have demonstrated that blocking fructose metabolism could be a promising strategy for slowing tumor growth. Patti emphasized the importance of these findings, stating that while understanding how fructose consumption impacts cancer growth is a crucial next step, one clear takeaway from this study is that individuals diagnosed with cancer may want to avoid fructose. Hmmm, perhaps everyone should avoid it.