dietary-fructose-cancer-research

Study Links Dietary Fructose to Accelerated Tumor Growth

The Impact of Fructose on Tumor Growth

Over the past 50 years, fructose intake has risen significantly, primarily due to the prevalent incorporation of high-fructose corn syrup as a sweetener in drinks and processed food products.

Recent research conducted by Washington University in St. Louis that dietary fructose enhances tumor growth in animal models of melanoma, breast cancer, and cervical cancer. Nevertheless, the study, published on December 4 in Nature, indicates that fructose does not directly fuel tumors.

Mechanisms Behind Tumor Growth Acceleration

WashU scientists determined that the liver metabolizes fructose into nutrients accessible to cancer cells, a discovery that may pave the way for innovative cancer care and treatment strategies.

• "The concept of addressing cancer through dietary interventions is fascinating," remarked Gary Patti, Michael and Tana Powell Professor of Chemistry and professor of genetics and medicine at WashU.

"We typically think of tumors, consuming dietary nutrients directly," Patti remarked. "In reality, human metabolism is complex, with healthy tissues processing intake metabolites that tumors can utilize."

• "We initially hypothesized that tumor cells would metabolize fructose in the same manner as glucose, incorporating its atoms into new cellular structures like DNA. To our surprise, fructose was scarcely metabolized in the tumor types we examined," said Ronald Fowle-Grider, the study's lead author and a postdoctoral fellow in Patti's lab.

The Role of the Liver in Fructose Metabolism

It became evident that tumor cells alone do not provide the full picture. The liver plays an equally crucial role by converting fructose into nutrients that tumors can utilize.

Using metabolomics to trace molecular pathways, the study identified increased circulating liquids—driven by high fructose consumption—as a key factor in tumor growth, supplying critical cell membrane components.

• According to Patti, "We analyzed diverse cancers across multiple tissue types, consistently observing the same biological mechanism at play."

The High-Fructose Corn Syrup Era

Fructose's Journey in the American Diet

It has been widely acknowledged by scientists that cancer cells exhibit a high preference for glucose, the body's primary energy-yielding carbohydrate.

Fructose and glucose are chemically alike, yet glucose is metabolized across various tissues, whereas fructose is primarily handled by the liver and small intestine.

Both glucose and fructose are naturally occurring in a range of foods like fruits, vegetables, grains, and dairy. They are also commonly added to processed foods as sweeteners. Fructose, in particular, has become widespread in the American diet over recent decades, thanks to its sweeter taste compared to glucose.

Before the 1960s, the average consumption of fructose was minimal compared to current levels. Around a century ago, an individual typically consumed only 5—10 pounds of fructose annually—equivalent to the weight of about a gallon of milk.

• "Examining the contents of your pantry for items containing high-fructose corn syrup—the most prevalent type of fructose—can be quite surprising," noted Patti, a researcher at the Siteman Cancer Center and the Center for Human Nutrition at WashU Medicine.

"High-fructose corn syrup is present in almost all foods. It's not limited to just sweets like candy and cake; even items like pasta sauce, salad dressing, and ketchup, contain it," he stated. "Unless you make a conscious effort to avoid it, it's likely a part of your diet."

Cancer's Desire for Fructose

How Fructose Accelerates Tumor Growth

With dietary fructose consumption surging in recent decades, researchers at WashU aimed to explore its im pact on tumor growth.

Patti and Fowle-Grider initiated their study by administering a fructose-rich diet to animals with tumors and tracking tumor growth rates. They discovered that fructose intake accelerated tumor growth without im pacting body weight, fasting glucose, or insulin levels.

• "We were astonished by the significant effect it had. In certain instances, the tumor growth rate. doubled or more," said Patti. "Consuming high amounts of fructose clearly accelerated the progression of these tumors."

The Liver's Role in Providing Tumor Nutrients

The next phase of their experiments posed a challenge. When Fowle-Grider tried to replicate this test by introducing fructose to isolated cancer cells in a dish, the cells did not react. "In most instances, their growth was nearly as slow as when no sugar was provided," Patti said.

Patti and Fowle-Grider then returned to examining changes in small molecules within the blood of animals on high-fructose diets. By employing metabolomics, they detected higher levels of various lipid types, including lysophatidylcholines (LPCs). Further tests in culture dishes revealed that liver cells exposed to fructose release LPCs.

Fructose as a Source of Nutrients for Tumors

Patti explained that while cancer cells lack the biochemical machinery to process fructose for nourishment, liver cells are equipped with it. This enables them to convert fructose into LPCs and secrete them to feed tumors.

Cancers is marked by the unregulated growth of malignant cells. For each cell division, replication of its components, including membranes, which demands a significant supply of lipids. Although lipids can be created de novo, cancer cells often find it more efficient to absorb them from their environment.

In recent years, it has become evident that a significant number of cancer cells prefer to absorb lipids rather than synthesize them, according to Patti. "The challenge lies in the fact that most lipids are not soluble in blood and need intricate transport systems. LPCs, however, are distinct in that they could be the most efficient means to support tumor growth," she added.

Opting Out of Fructose

Potential Health Implications and Future Directions

Notably, as human fructose intake has risen over the past decades, the incidence of certain cancers in individuals under 50 has also increased, prompting questions about a potential connection.

With backing from Cancer Grand Challenges, Patti collaborated with Yin Cao at WashU Medicine and other researchers globally, none of whom participated in this particular study, to explore potential links.

• "Understanding the impact of dietary fructose on cancer rates is promising. Nonetheless, a major conclusion from this study is that individuals with cancer should consider reducing their fructose consumption, which, unfortunately, is not simple," Patti remarked.

New Avenues for Cancer Treatment

In addition to dietary changes, the researchers noted that this study could pave the way for developing therapeutic drugs to prevent fructose from stimulating tumor growth.

• "One takeaway from these findings is that treatment options shouldn't be confined to therapies targeting cancerous cells alone," Patti explained. "Instead, we could explore targeting the metabolism of healthy cells as a strategy for cancer treatment. This approach proved effective in our mouse model, and we aim to translate these insights to benefit patients."

The researchers are collaborating with clinical partners at WashU Medicine to investigate a clinical trial focused on the impact of dietary fructose.

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