Dietary Antioxidant Capacity, Genetic Susceptibility and Polymorphism, and Inflammatory Bowel Disease Risk in a Prospective Cohort

Oxidative stress is an essential factor in the pathogenesis of inflammatory bowel disease (IBD). A previous study found protective potential of some antioxidative nutrients against IBD. However, the association between total antioxidant capacity (TAC) of the diet and incident IBD is unclear. We conducted a prospective cohort study including 186,195 IBD-free participants at baseline from the UK Biobank. We calculated dietary TAC using the oxygen radical absorbance capacity method based on repeated online 24-hour dietary recalls. Crohn's disease (CD) and ulcerative colitis (UC) were identified via inpatient register and primary care data. Genetic susceptibility for IBD was assessed by a polygenic risk score. Cox proportional hazard models were applied to estimate multivariable-adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). During a median follow-up of 11.4 years, we identified 396 CD and 809 UC incident cases. Individuals with the highest quintile of dietary TAC had a lower risk of CD (27.0 vs 17.0 cases/100,000 person-years; aHR, 0.66; 95% CI, 0.49-0.90) but not UC (46.7 vs 35.5 cases/100,000 person-years; aHR, 0.85; 95% CI, 0.69-1.06) compared with the lowest group. We observed interactions between TAC and genetic susceptibility at both multiplicative (P-interaction = .008/0.063 for CD/UC) and additive (both P values > 1) scales. Additionally, a polymorphism of the endogenous antioxidant enzyme gene SOD2 (rs4880) modified the dietary TAC-UC association (P-interaction = .039). This study suggests that a diet with high TAC may help prevent the development of IBD, particularly in individuals at high genetic risk of IBD and in mutation carriers of rs4880 in SOD2.