Background & aims: Some studies have linked low vitamin D status and high risk of diverticular disease, but the causal relationship between vitamin D and diverticular disease remains unclear; clinical trial data are warranted. The objective was to assess the efficacy of vitamin D₃ supplementation on diverticular disease hospitalization.

Methods: Post-hoc analysis of a community-based randomized double-blind placebo-controlled trial (RCT) with 5108 participants randomized to receive monthly 100,000 IU vitamin D (n = 2558) or identical placebo (n = 2550). The outcome was time to first diverticular disease hospitalization from randomization to the end of intervention (July 2015), including a prespecified subgroup analysis in participants with baseline deseasonalized 25-hydroxyvitamin D (25(OH)D) levels < 50 nmol/L.

Results: Over a median of 3.3 years follow-up, 74 participants had diverticular disease hospitalization. There was no difference in the risk of diverticular disease hospitalization between vitamin D supplementation (35/2558 = 1.4%) and placebo (39/2550 = 1.5%) groups (adjusted hazard ratio (HR) = 0.90; p = 0.65), although in participants with deseasonalized 25(OH)D < 50 nmol/L (n = 1272), the risk was significantly lower in the vitamin D group than placebo (HR = 0.08, p = 0.02).

Discussion: Monthly 100,000 IU vitamin D₃ does not reduce the risk of diverticular disease hospitalization in the general population. Further RCTs are required to investigate the effect of vitamin D supplementation on the diverticular disease in participants with low 25(OH)D levels.