COMMENTARY

High-Fructose Corn Syrup Ups CRC Risk, More Data Suggest

David A. Johnson, MD

Disclosures

July 27, 2021

Many fruits and vegetables contain sucrose, a naturally occurring sugar comprising glucose-fructose. Glucose is the most important carbohydrate and the preferred source of energy for the body, where it can be made immediately available or stored as glycogen (particularly in muscle or the liver) for later use. In comparison, fructose is only metabolized by the liver and is more lipogenic than glucose.

High-fructose corn syrup (HFCS) is a derivative of corn starch, processed to convert some of the glucose into fructose. This creates a cheaper and sweeter dietary ingredient than sucrose, but it also appears to come at a steep price to our health.

Regular ingestion of foods and beverages containing HFCS is linked to the obesity epidemic and the related diseases of diabetes and metabolic syndrome. In a recent commentary, I highlighted some of HFCS' reported gastrointestinal adverse effects for extremely common diseases, including — but certainly not limited to — colitis and nonalcoholic fatty liver disease (NAFLD). In fact, the role of regular consumption of added fructose in the increasing cases of NAFLD is substantial enough to have been deemed a public health crisis.

Now, two recent publications — both of which analyzed dietary intake data obtained from women participating in the ongoing Nurses' Health Study II — are raising additional concern about the association of added fructose and colorectal cancer (CRC).

Two Large Studies Highlight Incremental Cancer Risk

Joh and colleagues prospectively analyzed data from 33,106 participants who provided dietary intake during adolescence to determine the effects of high consumption of simple sugar and sugar-sweetened beverages (SSBs), which typically contain HFCS. They noted increased risks for colorectal adenomas, particularly rectal adenomas.

There was a linear incremental risk of 1.17 (95% CI, 1.05-1.31) for all adenomas and 1.30 (95% CI, 1.06-1.60) for high-risk adenomas, per each 5% of calories of total fructose intake. By location, the highest risk was for rectal adenomas, with an associated risk rate of 1.43 (95% CI, 1.10-1.86).

These observations overlap with those of Hur and colleagues, who reported an associated risk between SSBs and early-onset CRC. They analyzed data from 95,464 participants reporting their beverage consumption using validated food frequency questionnaires every 4 years. A subset (41,272) reported their intake between the ages of 13 and 18 years.

Compared with consumption of less than one serving/week of SSB in adulthood, a higher intake was associated with a 2.2 times increased risk. Each serving/day increment of SSB intake in adolescents (13-18 years) was associated with a 32% increased risk of early-onset CRC. Furthermore, replacing each serving/day of SSB with other beverages (eg, coffee, milk, artificially sweetened beverages) in adulthood was associated with a risk reduction for early-onset CRC of 17%-36%.

Disturbing Trends for HFCS Consumption and CRC Risk

These recent reports drawing an association between sweetened beverages in early life and increased risk for colon polyps and CRC are particularly concerning given US food trends.

Beverages are the most common conduit for added sugars among those aged 2 years and older in the United States (47%), and of these, 39% come from SSBs. The use of HFCS in processed foods and sugary beverages is expected to continue its explosive growth globally over the next half-decade.

This is occurring alongside an increasing incidence of CRC among younger adults who would not otherwise meet current screening criteria for this disease. By 2030, the incidence of CRC is projected to increase in those 20-34 years and 35-49 years by 90%-124% and 28%-46%, respectively.

Clearly, our dietary intake influences our health outcomes both directly and indirectly via effects on the inflammatory and immune responses, which are driven by microbiome-related changes. Although we lack interventional prospective studies to address these concerns, the data are provocative enough that healthcare providers should consider having specific discussions about these potential effects with their patients.

When it comes to advice regarding consumption of HFCS, the message may be quite simple: Buyer beware!

David A. Johnson, MD, a regular contributor to Medscape, is professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, Virginia, and a past president of the American College of Gastroenterology. His primary focus is the clinical practice of gastroenterology. He has published extensively in the internal medicine/gastroenterology literature, with principal research interests in esophageal and colon disease, and more recently in sleep and microbiome effects on gastrointestinal health and disease.

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