Vitamin D and Health

6.270 No studies on vitamin D and risk of IBD published after the IOM report could be identified. An RCT in
Denmark assessed the effect of oral vitamin D 3 treatment on clinical relapse in patients (n=94) with
Crohn's disease in remission (Jorgensen et al, 2010). Patients were randomised to receive either
vitamin D 3 (30 µg/1200 IU per day) or placebo for 12 months. The mean serum 25(OH)D
concentration of patients in the vitamin D treatment group increased from 69 to 96 nmol after 3
months (p < 0.001). The relapse rate was lower in the vitamin D 3 treated group compared with the
placebo group (13% compared to 29%; p=0.06).
Multiple Sclerosis
6.271 IOM Report: The IOM report noted that low solar exposure, latitude and polymorphisms in the VDR
gene have been implicated in susceptibility to multiple sclerosis (MS) but observational studies for an
association between MS and vitamin D were inconsistent and no RCTs could be identified. It
concluded that the lack of causal evidence diminished the likelihood for a relationship between
vitamin D and MS.
Evidence considered since IOM report
Cohort studies
6.272 A prospective study in Sweden (Salzer et al., 2012) examined the association between serum 25(OH)D
concentration and risk of MS in blood samples collected prospectively and during gestation. In the
identified cases (n=182) median time from sampling to MS onset was 9 years. Serum 25(OH)D
concentration ≥ 75 nmol/L was associated with a decreased risk of MS (OR=0.39; 95% CI, 0.16-0.98).
No association was found between gestational serum 25(OH)D concentration and MS risk in offspring.
Genetic studies
6.273 Huang & Xie (2012) and Tizaoui et al. (2015) conducted meta-analyses of case-control studies
investigating the association between VDR polymorphisms and risk of MS. Huang & Xie (2012)
reported that the ApaI, BsmI, FokI and TaqI polymorphisms were not associated with MS risk. Tizaoui
et al. (2015) reported a significant association between the ApaI polymorphism and MS pathogenesis
but this was only observed in two of the genetic models (homozygous and codominant); the FokI
polymorphism was significantly associated with MS but only after exclusion of one of the studies
following sensitivity analysis. It was also noted that the FokI polymorphism influences VDR protein
structure but that ApaI does not.
6.274 Ramagopalan et al. (2011) performed whole exome sequencing of individuals (n=43) with MS from
families with 4 or more MS-affected individuals and identified a rare variant of CYP27B1. From
subsequent genotyping in other populations, they concluded that the rare variant was associated with
risk of MS. This variant is rare in the population and by itself cannot account for most cases of MS but
the authors note that CYP27B1 encodes the vitamin D-activating 1-alpha hydroxylase enzyme and that
the identified variant has functional effects on 1,25(OH) 2 D and risk of rickets; because of this, they
interpret their findings as supporting a causative role for vitamin D in MS.
Rheumatoid Arthritis
6.275 IOM Report: The IOM concluded that there were no large prospective studies and no clinical trials to
support a relationship between vitamin D and incidence of rheumatoid arthritis
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