The contribution of dietary advanced glycation end‐products and genetic risk in the development of inflammatory bowel disease: a prospective cohort study

Summary Background Dietary advanced glycation end products (AGEs) may promote oxidative stress and inflammation in the gastrointestinal tract. Aims The aim of this study is to investigate the association between dietary AGE intake and the risk of inflammatory bowel disease (IBD). Methods We included 121,978 participants without IBD at baseline from the UK Biobank. We estimated consumption of three common AGEs (Nε‐(carboxymethyl)‐lysine (CML), Nε‐(1‐carboxyethyl)‐lysine (CEL), and Nδ‐(5‐hydro‐5‐methyl‐4‐imidazolon‐2‐yl)‐ornithine (MG‐H1)) by matching 24‐h dietary questionnaires to a validated dietary AGE database. We used Cox proportional hazards regression models to calculate the hazard ratio (HR) and 95% CI of the association between dietary AGEs and IBD risk. Results During a median follow‐up of 13.72 years, 671 participants developed IBD (192 with Crohn's disease (CD) and 478 with ulcerative colitis (UC)). Among the assessed dietary AGEs, only CEL was associated with an increased risk of IBD (HR = 1.09, 95% CI: 1.01–1.18, p = 0.020) and CD (HR = 1.18, 95% CI: 1.03–1.36, p = 0.014), particularly for participants who were overweight, physically inactive, and non‐smokers. Among participants at a high genetic risk of CD, HRs (95% CI) of CD were 1.26 (1.00–1.57) for CML, 1.41 (1.12–1.77) for CEL, and 1.28 (1.01–1.62) for MG‐H1 ( p < 0.05 for each). However, none of the dietary AGEs was significantly associated with UC risk, irrespective of genetic predisposition. Conclusions Dietary CEL was associated with an increased risk of IBD and CD, but not UC. Further interventional studies are required to support the potential benefit of AGE restriction, especially for individuals at a high genetic risk of CD.