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petite and weight. Vitamin D status has been linked to IBD in association studies of sun exposure and in genetic studies through down-regulation of the Th1-mediated immune response.

Biological plausibility Ecological studies have linked vitamin D, particularly 25OHD levels, to a number of autoimmune diseases. A connection between seasonal vitamin D status and risk for Crohn’s disease was proposed by Peyrin-Biroulet et al. (2009), based largely on ecological evidence for an association between low 25OHD levels in blood and other autoimmune diseases. The effect of seasonal variation on serum 25OHD levels in patients with Crohn’s disease, compared to matched controls found that mean serum 25OHD was lower in Crohn’s patients despite having vitamin D intake from foods and supplements and sunlight exposure similar to those of matched controls (McCarthy et al., 2005). Genetic evidence in humans and in animal models provides some support for a biological association between polymorphisms in the Vdr and susceptibility to IBD and Crohn’s disease. In a human study, a linkage analysis, used to identify the TaqI polymorphism in the Vdr gene, suggested that the variant may be a candidate for conferring susceptibility to IBD (Simmons et al., 2000). Animal model studies in both vitamin D–deficient and Vdr null mice suggested that the risk of developing IBD is increased in several respects: spontaneous occurrences are increased, the disease is more severe, and the disease is more easily provoked in response to agents that induce IBD or bacterial infections transferred from an affected animal (reviewed in Bouillon et al., 2008).

Systematic reviews and meta-analyses The AHRQ-Tufts systematic review found no RCTs for immune function clinical outcomes and no evidence for IBD or Crohn’s disease. Thus, the evidence was insufficient for further analysis in the systematic review. No meta-analyses were identified for this indicator.

Additional evidence from randomized controlled trials No RCTs were identified for this indicator.

Observational studies Two observational studies were identified that evaluated 25OHD levels in patients with Crohn’s disease and/or IBD. A cross–sectional assessment of serum 25OHD levels in children and young adults with IBD living in Boston found that prevalence of low 25OHD status (≤ 38 nmol/L) averaged 34.6 percent overall, with higher prevalence in winter compared with summer (Pappa et al., 2006). A small population-based cohort of patients with Crohn’s disease and ulcerative colitis in Scandinavia found a prevalence of 25OHD levels below 30 nmol/L in 27 percent of those with Crohn’s disease and 15 percent of those with ulcerative colitis. In addition, patients with Crohn’s disease had lower mean serum 25OHD levels compared with those with ulcerative colitis or the reference population (Jahnsen et al., 2002). The study design and poor con-



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