Effects of meat-based, meat-based with α-tocopherol, and pesco-vegetarian diets on biomarkers associated with colorectal cancer risk: a randomized behavioral intervention trial

Diet may influence early biological processes involved in colorectal carcinogenesis. Red and processed meat intake has been associated to increased colorectal cancer (CRC) risk, potentially through heme-driven oxidative and genotoxic mechanisms. This 12-week behavioral, free-living, randomized, open-label study evaluated how three different diets impact CRC risk markers: a meat-based diet (MBD: high risk), a meat-based diet with α-tocopherol supplementation (MBD-T: medium risk, hypothesized to attenuate heme-induced oxidative stress and lipid peroxidation), and a pesco-vegetarian diet (PVD: low risk). A total of 113 healthy adults (18–50 years) were randomized, and 103 completed the study. The primary outcome was fecal water (FW) genotoxicity at baseline and after 12 weeks; secondary outcomes included FW cytotoxicity, lipoperoxidation, fecal short-chain fatty acids (SCFAs) and bile acids, and blood biomarkers related to iron metabolism and inflammation, also measured pre- and post-intervention. Mixed-effects linear models (time × diet), adjusted for age, sex, and BMI, were applied. FW genotoxicity increased significantly after MBD (+ 15.97%DNA damage; 95% CI 4.61 to 27.32; p = 0.006), with no significant within-group changes in MBD-T or PVD. Between-diet differences in change indicated greater increases in fecal TBARS following MBD (p = 0.010) and MBD-T (p = 0.037) compared with PVD, and a significantly greater increase in 4-HNE after MBD compared with PVD (p = 0.019). The FW Viability Index decreased significantly after MBD (p = 0.021). Differences in change between diets were also significant for circulating ferritin and inflammatory markers, which increased more after MBD compared with PVD (ferritin, IL-6, TNF-α), whereas MBD-T reduced TNF-α and PVD decreased IL-8, TNF-α, and ICAM. No significant between-diet differences in change were observed for fecal SCFAs or bile acids. In summary, over 12 weeks in a free-living setting, a MBD increased several mechanistic biomarkers associated with CRC, while α-tocopherol supplementation attenuated some adverse diet-related effects. In contrast, a PVD was associated with a more favorable biochemical and inflammatory profile. These findings reflect short-term modulation of mechanistic biomarkers rather than CRC outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03416777. Registered 03/05/2018. © The Author(s) 2025.