Sugary Drinks Drive Colorectal Cancer Metastasis via SORD Pathway, Study Finds

For years, sugar-sweetened beverages (SSBs) have been implicated in rising rates of obesity, diabetes, and cancer risk. But a new study in Nature Metabolism adds a sharper edge to the concern: the glucose–fructose blend that sweetens sodas and fruit juices appears to directly fuel the spread of colorectal cancer, offering the first mechanistic link between sugary drinks and metastasis.

A Dangerous Duo: Glucose and Fructose

The research, led by Jihye Yun, Ph.D., at The University of Texas MD Anderson Cancer Center, compared how colorectal cancer (CRC) cells respond to different sugars. While glucose or fructose alone had little effect, the combination—mirroring the high-fructose corn syrup and sucrose used in most beverages—made cancer cells more mobile and invasive. In animal models, this sugar mix accelerated metastasis to the liver, the most common site of CRC spread.

The culprit, the team found, was sorbitol dehydrogenase (SORD), an enzyme that sits in the polyol pathway. When activated by the glucose–fructose mix, SORD catalyzes a reverse reaction that shifts the cellular redox balance, increases glycolytic activity, and fuels the mevalonate pathway—a key driver of cholesterol synthesis. This biochemical shortcut effectively primes cancer cells for migration and metastasis.

Why Metastasis Matters

Colorectal cancer remains one of the leading causes of cancer-related deaths worldwide. While treatments for localized disease have advanced, metastasis continues to account for the majority of mortality. Understanding dietary factors that influence this process is critical.

“Our findings highlight that daily diet matters not only for cancer risk but also for how the disease progresses once it has developed,” Yun said. “While these findings need further investigation, they suggest that reducing sugary drinks, targeting SORD or repurposing statins may benefit patients with colorectal cancer.”

This echoes her laboratory’s earlier work showing that sugary drinks can accelerate tumor growth even in the absence of obesity. The new findings extend that concern from early tumorigenesis to late-stage spread.

Therapeutic Openings: From Diet to Statins

The mechanistic insights are especially provocative because they point to existing therapeutic tools. Statins, widely prescribed cholesterol-lowering drugs, act on the very pathway SORD activates. In preclinical models, blocking SORD reduced metastasis even when the glucose–fructose mix was present. This raises the possibility that repurposing statins—or developing direct SORD inhibitors—could slow progression in patients with advanced CRC.

At the same time, the study underscores the role of dietary intervention. Many patients with cancer are advised to consume calorie-rich supplements or fruit-based drinks to maintain nutrition, but these often contain concentrated glucose and fructose. The findings suggest that such recommendations may need revision, particularly for individuals with colorectal cancer at risk of metastatic progression.

Beyond the Lab: Implications and Next Steps

While the study was conducted in cell lines and mouse models, its conclusions resonate with epidemiological evidence linking high SSB consumption to CRC recurrence and mortality. Future research will need to explore how sugary drinks interact with the tumor microenvironment, including immune cells and gut microbiota, which could amplify or mitigate metastatic potential.

The findings also spotlight the importance of studying sugars in combinations that reflect real-world exposures. Fructose-only experiments, long a staple of metabolic research, do not capture the biochemical interplay triggered by glucose and fructose together. Yun’s team argues that the glucose–fructose condition is the physiologically relevant model, and their data suggest it is uniquely hazardous in the context of cancer.

A Call for Clinical Attention

For clinicians, the takeaway is twofold: counsel patients with CRC to minimize sugary beverage intake, and consider whether targeting metabolic pathways such as SORD could complement existing therapies. For researchers, the study provides a roadmap for dissecting how diet drives not just cancer initiation but its most lethal feature—metastasis.