trols characteristic of these observational studies diminish the reliability of their findings. Another confounding problem is that vitamin D is absorbed with fat in the terminal ileum, and this is the area that is most inflamed in Crohn’s disease (and can become inflamed in ulcerative colitis). Consequently, low 25OHD levels can be expected to occur as a consequence of the inflammatory condition. The question not answered by these studies is whether low 25OHD levels can predispose individuals to the conditions.
Multiple sclerosis MS is a chronic disease of the central nervous system that manifests as numbness in the limbs or, in more severe cases, paralysis or loss of vision. The progress, severity, and specific symptoms of MS are unpredictable and vary among individuals. The disease is an autoimmune response directed against myelin. Damaged myelin forms scar tissue (sclerosis), which impairs nerve impulse conduction, producing the variety of symptoms associated with the disease.
Biological plausibility Similar to findings with other autoimmune-related diseases, low solar exposure, latitude, and polymorphisms in the Vdr gene have been implicated in susceptibility to MS (Partridge et al., 2004; Dwyer et al., 2008; Sloka et al., 2008; Dickinson et al., 2009). However, whether a lack of sun exposure is causally related to MS cannot be shown. Findings from animal models are not consistent. In a mouse model, vitamin D deficiency accelerated development of autoimmune encephalomyelitis (the murine model of MS in humans), whereas treatment with calcitriol reduced it (Cantorna et al., 1996). In contrast, a subsequent study, using a mouse model null for the Vdr gene, found that the Vdr null mice were protected from development of the disease compared with wild-type mice (Meehan and DeLuca, 2002). A recent genetic study in humans evaluating associations between specific Vdr gene polymorphisms (Apal and Taq1) and serum 25OHD levels in healthy adults compared with those with MS, found no relationship between mutations in Apal and Taq1 and incidence of MS (Smolders et al., 2009). Taken together, neither ecological studies nor genetic studies in animal models and humans show consistency in finding a significant relationship between serum 25OHD level and presence of MS.
Systematic reviews and meta-analyses The AHRQ-Tufts systematic review found no RCTs for immune function clinical outcomes and no evidence for MS related to vitamin D. In a recent review paper of observational studies on the effects of vitamin D on incidence and severity of MS, Smolders et al. (2008) concluded that there was no strong direct evidence supporting the ability of vitamin D to modulate MS or influence risk for the disease. Their review included observational evidence in humans linking low serum 25OHD levels with incidence of MS in white American adolescents; associations between lower circulating levels of 25OHD after onset of MS;