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<p>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&#xa0;years) were randomized, and 103 completed the study. The primary outcome was fecal water (FW) genotoxicity at baseline and after 12&#xa0;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&#xa0;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.</p><p><b>Trial Registration:</b> ClinicalTrials.gov Identifier: NCT03416777. Registered 03/05/2018.</p>

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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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月8日

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  • Monica Dinu,
  • Sara Ristori,
  • Giuditta Pagliai,
  • Sofia Lotti,
  • Niccolò Meriggi,
  • Alice Nerini,
  • Sylvie Chevolleau,
  • Jildau Bowman,
  • Giovanna Caderni,
  • Barbara Colombini,
  • Philippe Gerard,
  • Lisa Giovannelli,
  • Francoise Gueraud,
  • Rossella Marcucci,
  • Fabrice Pierre,
  • Carlotta De Filippo,
  • Francesco Sofi

摘要

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.