Nonlinear Association between Serum 25-Hydroxyvitamin D and All-Cause Mortality in Adults with Inflammatory Bowel Disease in a Prospective Cohort Study

Background Nonlinear association between serum 25-hydroxyvitamin D [25(OH)D] concentration and all-cause mortality has been widely reported for the general population, but this association has not been quantified for individuals with inflammatory bowel disease (IBD). Objectives The aim was to explore the association between serum 25(OH)D and all-cause mortality in individuals with IBD. Methods We identified 2690 females and 2532 males aged 40-69 y with diagnosed IBD at baseline in the UK Biobank. Serum 25(OH)D concentration was measured by direct competitive chemiluminescent immunoassay. The outcome was all-cause mortality, ascertained via the death registry. Cox proportional hazard regression was used to evaluate associations between serum 25(OH)D in quintiles and all-cause mortality among individuals with IBD [Crohn disease (CD; n = 1760) and ulcerative colitis (UC; n = 3462)]. Restricted cubic splines were used to investigate potential nonlinearity. Results During the mean follow-up period of 11.9 y, 529 deaths (198 in CD and 331 in UC) were documented among 5222 individuals with IBD. Compared with the lowest quintile of serum 25(OH)D, HRs for the second to the highest quintiles were 0.82 (95% CI: 0.63, 1.06), 0.63 (95% CI: 0.47, 0.83), 0.64 (95% CI: 0.48, 0.85), and 0.74 (95% CI: 0.55, 0.99), respectively. Nonlinearity was detected in the dose-response association between serum 25(OH)D concentration and all-cause mortality (P-nonlinearity < 0.001), and 25(OH)D concentrations of 44-78 nmol/L were associated with a 50% lower risk of all-cause mortality (than 10 nmol/L). Subgroup analyses showed that the nonlinear association mostly applied to females (P-nonlinearity < 0.001 compared with 0.080 in males). Conclusions We observed a nonlinear association, mostly applicable to females, between serum 25(OH)D concentrations and all-cause mortality among individuals with IBD. A 25(OH)D concentration range of 44-78 nmol/L can serve as a starting point for future research to confirm recommended 25(OH)D concentrations for individuals with IBD.