Table 1.

Characterisitcs and main findings of clinical vitamin D treatment-MS trials

Author, year	Design	n	Duration	Intervention	Main Results	Dose tolerability/safety results
Goldberg, 1986	uncontrolled trial	10	up to 24 months	Vitamin D: 5,000 IU/day (fish oil) Calcium: 16 mg/d/kg body weight Magnesium: 10 mg/d/kg body weight	9 relapses observed vs. 22 expected (p<0.01)	No adverse events reported
Mahon, 2003	double blind randomized, controlled trial	39	6 months	Vitamin D: cholecalciferol 1,000 IU/day Calcium: 800 mg/day	↑ TGF-β-1 serum levels; ↓IL-2 mRNA (p=0.07) No change in mRNA: TNF-α, IFN-γ, IL-13;	N/A
Wingerchuk, 2005	uncontrolled trial	15	48 weeks	Vitamin D: Calcitriol 0.5 ug/d increased in 0.5 ug/d increments every 2 weeks to target dose of 2.5 ug/d	observed relapse rate lower than baseline; 33% active lesions at baseline vs. 29% end of trial; 27% increased EDSS 1–2 points	At target dose, 2 cases of asymptomatic and 2 cases symptomatic hypercalcemia (symptomatic cases perhaps due to dietary indescretion)
Kimball, 2007	uncontrolled trial	12	28 weeks	Vitamin D: cholecalciferol 28,000 IU/week incrementally increased to 280,000 IU/week by end of study Calcium: 1,200 mg/day	mean # Gd+ lesions declined (1.75 baseline vs. 0.83, p=0.03); no difference in relapse rates	No hypercalcemia reported and serum calcium levels remained stable over the course of treatment.
Burton, 2010 Kimball, 2011	unblinded randomized, controlled trial	49	52 weeks	Vitamin D: cholecalciferol increased from 4,000 IU/day to 40,000 IU/day over 28 weeks, followed by reduction to 10,000 IU/day for 12 weeks and to 4,000 IU/day for 6 weeks Calcium: 1,200 mg/day	In treated vs. non-treated, non- significant reduction in annualized relapse rate (0.26 vs. 0.45) and proportion of patients experiencing a relapse (0.16 vs. 0.37); T-cell proliferative responses decreased in the treated group (p=0.002), esp. among those with 25(OH)D >100nmol/L Decreased PBMC proliferative responses to MBP and exon-2 seen in treated vs. untreated at 52 weeks. No differences in levels of various cytokines including IL-4, IL-10, IFN-γTNF-α	Serum calcium levels remained normal and stable over course of vitamin D treatment despite 25(OH)D levels reaching a high mean of 413 nmol/L; no adverse events reported
Smolders, 2010 Knippenberg, 2011	uncontrolled trial	15	12 weeks	Vitamin D: cholecalciferol 20,000 IU/day	baseline vs. week 12: no difference in # of circulating total T cells or regulatory T cells(total, memory, or naïve); ↑ IL-10+ CD4+ T cells; ↓ ratio IFN-γ+/IL-4+ CD4+ T cell ratio. No changes in total circulating B cells or B cell subsets. Non statistically significant decrease in B cell Ativating factor	No hypercalcemia reported and serum calcium levels remained stable over the course of treatment.
Mosayebi, 2011	double blind randomized, controlled trial	62	6 months	Vitamin D: cholecalciferol 300,000 IU/month	baseline vs. 6 months: no difference in EDSS or number of Gd-enhancing lesions; in treated vs. untreated, decrease in T cell proliferation in and significant increase in IL-10 and TGF-β levels. No difference in IFN-γ levels.	not reported