Dietary Fructose and Early-Onset Colorectal Cancer: Metabolic, Microbial, and Translational Perspectives.

Early-onset colorectal cancer (eoCRC) is increasing globally, raising interest in modifiable dietary exposures that may contribute to its development. High fructose intake, particularly from sugar-sweetened beverages and high-fructose corn syrup, has been associated with colorectal neoplasia and eoCRC in epidemiologic studies. Experimental evidence suggests that fructose may promote colorectal tumorigenesis through enhanced uptake and metabolism, polyol pathway activation, glycolytic and lipogenic reprogramming, hypoxic adaptation, and interactions with the tumor microenvironment. Excess fructose reaching the colon may also impair intestinal barrier integrity and alter gut microbial composition and metabolite production. Preclinical models support a direct tumor-promoting effect of fructose independent of obesity, whereas human mechanistic and microbiome data remain limited. This review summarizes current evidence linking fructose exposure with eoCRC and discusses emerging metabolic, microbial, and translational implications, while highlighting key gaps that must be addressed to establish causality and clinical relevance.