Abstract Context The global increase in the intake of ultra-processed food (UPF) parallels rising rates of early-onset colorectal cancer (CRC), raising concern about possible causal links. Although observational studies suggest that UPFs contribute to gastrointestinal inflammation, it remains unclear whether CRC risk is mediated through inflammatory pathways such as inflammatory bowel disease (IBD). Objective In this review we sought to evaluate, using a 2-stage mediation meta-analysis, the association between UPF consumption and CRC risk and to examine whether IBD mediates this relationship. Data Sources We searched PubMed, Embase, Scopus, and Web of Science through September 2025. Data Extraction Two reviewers independently extracted data using a standardized form, including study characteristics, UPF assessment method, exposure categories, follow-up, covariates, and adjusted effect estimates (hazard ratio HR, relative risk RR, odds ratio OR, standardized incidence ratios SIRs). For UPF–CRC and UPF–IBD, the primary contrast was highest vs lowest UPF category, with per-10% increments recorded when reported. For IBD–CRC, adjusted RRs were abstracted similarly. No individual-level data were obtained. Data Analysis Study-specific effect estimates were log transformed and pooled using random-effects models (REMLs). Heterogeneity was assessed via I2 and Cochran’s Q. Associations of UPF–IBD and IBD–CRC were meta-analyzed separately and combined to estimate the indirect UPF–CRC effect via a 2-stage product-of-coefficients method, with SEs derived using the delta method. Conclusions Sixteen cohort studies including over 2 million participants met inclusion criteria. High UPF intake was modestly associated with increased CRC risk (RR 1.13, 95% CI, 1.06-1.20) and incident IBD (RR 1.33, 95% CI, 1.15-1.55), with stronger effects for Crohn disease. The IBD–CRC association was positive but heterogeneous (RR 1.36, 95% CI, 1.14-1.62). A 2-stage mediation model suggested a small indirect UPF to CRC effect via IBD (approximate RR 1.07). Higher UPF consumption is therefore associated with modestly increased risks of IBD and CRC, although the indirect effect through IBD appears limited. Systematic Review Registration PROSPERO registration No. CRD420251035864.
Akkapelli et al. (2025) studied this question.