Fructose and Glucose from Sugary Drinks Enhance Colorectal Cancer Metastasis via SORD

Fructose and Glucose from Sugary Drinks Enhance Colorectal Cancer Metastasis via SORD

Nature Metabolism

October 2025; Vol. 7; No. 10; pp. 2018-2032

Tianshi Feng, Qin Luo, Yanlin Liu, and 16 more; authors are from:

• The University of Texas MD Anderson Cancer Center, Houston.
• Baylor College of Medicine, Houston.
• Harvard Medical School, Boston.

This study cites 52 references.

These authors investigated whether sugar-sweetened beverage consumption promotes progression and metastasis of advanced colorectal cancer and explored the underlying mechanisms.

The sugar experiments used 3 formulas:

• Glu + Fru = 10 mM glucose + 10 mM fructose
• Glu only = 20 mM glucose
• Fru only = 20 mM fructose

BACKGROUND FROM DAN MURPHY:

Sucrose (white table sugar) is a disaccharide: 50% glucose + 50% fructose.

High Fructose Corn Syrup is roughly 55% fructose and 45% glucose.

Sorbitol dehydrogenase (SORD) is a key enzyme that catalyzes the NAD (nicotinamide adenine dinucleotide) to fructose.

KEY POINTS FROM THIS ARTICLE:

1) “Diet is widely recognized as one of the most significant environmental factors contributing to the development of CRC [colorectal cancer].”

• “Diet is a key environmental factor in CRC [colorectal cancer] development.”
• “Among the dietary factors that have gained increasing attention is the consumption of SSBs [sugar-sweetened beverages].” [Important]
• SSBs are any liquids sweetened with added sugars, including sucrose and high-fructose corn syrup.

2) “The consumption of sugar-sweetened beverages (SSBs), which contain high levels of fructose and glucose, has been causally and mechanistically linked to an increased risk of colorectal cancer (CRC).” [Key Point]

3) “[These authors] show that exposure of CRC cells to a glucose and fructose formulation—reflecting the composition of both high-fructose corn syrup and sucrose found in SSBs—enhances cellular motility and metastatic potential compared to glucose alone.” [Important]

4) “Since the 1980s, SSB consumption has risen globally.”

5) “In the USA, over half of adults and nearly two-thirds of youth consume SSBs daily.” [Very Important]

• “This surge parallels alarming increases in young-onset CRC incidence and mortality.” [Key Point]

6) Prior research showed that SSBs can directly promote CRC tumorigenesis independent of obesity.

7) A large epidemiological study has confirmed that SSB intake doubled the risk of young-onset CRC. [Important]

8) “Many patients with CRC are diagnosed at advanced stages, and some continue to consume SSBs even after diagnosis.” [Crazy]

• “Oncologists and nutritionists often recommend energy drinks and concentrated juices, which are essentially SSBs owing to their high glucose and fructose content.” [Crazier]

9) Mechanisms:

• “Cancer cells rely on aerobic glycolysis [to fuel themselves], known as the Warburg effect.” [see Ravenous book below on Otto Warburg]
• The combination of glucose + fructose promotes cytosolic aerobic glycolysis. [Glycolysis is the mechanism by which cancer cells fuel themselves.]

10) Sorbitol:

• Sorbitol is the only consistently endogenously produced metabolite following Glu + Fru ingestion.
• Sorbitol is a sugar alcohol that converts glucose into fructose:

• “SORD expression is elevated in human colorectal tumours.” [Important]

11) Findings:

• “Glucose and fructose together promote CRC metastasis more than glucose alone [or fructose alone].”
• “Glucose and fructose together enhance CRC motility and metastasis.”

12) Conclusions:

• “Glucose and fructose together enhance the migration, invasion and metastatic potential of CRC cells in vitro and in vivo.” [Key Point]
• “SORD mediates glucose–fructose-driven CRC motility and metastasis.”

13) “Despite advances in CRC treatment, metastasis remains the primary cause of CRC-related mortality.” [Important]

• “Human epidemiological studies demonstrate a positive correlation between SSB intake and increased CRC recurrence and mortality.” [Key Point]
• “[In this] study, CRC cells were exposed to a combination of glucose and fructose, closely mimicking the physiological environment resulting from the consumption of SSBs.” [Important]

14) Future:

• “Our preclinical data highlight the potential of SSB consumption to accelerate CRC metastasis, underscoring the urgent need for dietary guidance focused on reducing SSB intake to lower CRC mortality.” [Key Point]
• “Our findings highlight the detrimental impact of SSBs on CRC progression and suggest potential dietary and therapeutic strategies to mitigate metastasis in patients with CRC.”
• This study demonstrated the direct effects of SSBs on cancer migration and metastasis. However, “further investigation is warranted to elucidate how SSBs influence other components of the tumour microenvironment—such as immune cells and the microbiota—and their collective roles in promoting metastasis.”

COMMENTS FROM DAN MURPHY:

The cover article (February 24, 2025) from the political magazine TIME, highlighted CRC is young Americans. The article title is More Young Adults are Getting Cancer; Researchers are Racing to Understand Why. The statistics are disturbing. This present study attributes much of the increased incidence of CRC to the consumption of SSB; the TIME article also suggests increased risk attributed to ultraprocessed foods, micro and nanoplastics, and antibiotics that decimate the normal flora of the microbiome; see Article Reviews:

20-24: Rapid Single-particle Chemical Imaging of Nanoplastics

36-25: Bioaccumulation of Microplastics in Decedent Human Brains

38-24: Implications of Ultraprocessed Food Addiction

13-25: Ultraprocessed Food Intake and Psoriasis

11-26: The Addicted Brain: How Processed Foods Hijack Reward Pathways

A Troubling Increase for Colon and Breast Cancer in Younger Adults:

Aishwarya Thakur, MD, is a resident physician in pediatrics at Columbia University and a member of the ABC News Medical Unit.

January 17, 2024; ABC News

More people are being diagnosed with cancer than ever before, and at an earlier age, according to a major new report from the American Cancer Society.

Especially concerning is the rising number of deaths of young people from colon cancer – same illness that killed Marvel actor Chadwick Boseman at the age of 43.

“Colon cancer is now the number one cause of death among men younger than 50, and the number two cause of death in women of the same age group.”

“Colon and breast cancer now exceed lung cancer as leading causes of cancer death for those under the age of 50.”

“It’s something that wasn’t represented in statistics yet – that there has been a creep toward younger age of onset of certain common cancers. Colorectal and breast are the dominant ones,” said Dr. Larry Norton, oncologist and researcher at Memorial Sloan Kettering, and doctors and researchers have been noticing this in their practice and research.

“For colon cancer, oncologists say that the trends in the U.S. are matched by other high-income countries and say it’s possible the increase could be due to new lifestyles or environmental exposures for younger generations.”

“Environmental factors, such as exposure to chemicals in foods and in the air, and other currently unidentified factors, such as the recent legalization of cannabis and increased cannabis use, can’t be ruled out as risk factors.”

“There are studies that even show that risk factors like whether or not you were breastfed, whether or not you had antibiotics at a high rate as a child — that these factors might be predicting your chances of getting cancer when you’re an adult.”

SSB drive (feed) cytosol glycolysis which feed cancer cells, allowing them to grow bigger, stronger, divide, and metastasize. For those that are interested, read the book Ravenous by Sam Apple, which is a book about the cancer researcher Otto Warburg who discovered the cytosolic fermentation (glycolysis) of sugar to feed cancer cells: