Table 2.
Characteristics of selected studies.
| Reference | Participant Demographics | Study Design, Duration and Country of Origin | Intervention | Outcome Measures |
|---|---|---|---|---|
| [19] | 68 participants (48f, 20m) with MS; Age mean (range) in vitamin D group 40 (21–50) and placebo 41 (26–50); BMI in vitamin D group 28 and placebo group 26 | Double-blind placebo- controlled RCT; 96 weeks; Norway | 35 participants received supplementation with 20,000 IU vitamin D3 (cholecalciferol)per week; comparator 33 participants received placebo | Serum levels of 25(OH)D; ARR; EDSS; MSFC components; grip strength; FSS |
| [21] | 50 participants (424f, 6m) with RRMS; Age mean (SD) in vitamin D 38.6 (8.4) and placebo 37.9 (7.9); No BMI | Double-blind placebo-controlled RCT; 48 weeks; Iran | 25 participants received 0.25 μg/d of calcitriol for 2 weeks and then 0.5 μg/d; comparator 25 participants received placebo | EDSS; relapse rate |
| [12] | 45 participants (32f, 13m) with RRMS; Age mean in high-dose group 43.1 (21.7–63.7) and in low-dose group 43.6 (26.7–63.9); No BMI | Double-blind placebo-controlled RCT; 48 weeks; Israel | High-dose group, 24 participants received 75,000IU vitamin D3 solution every 3 weeks in addition to 800 IU vitamin D3 per day (total 4370 IU); comparator low dose group, 21 participants received placebo every 3 weeks in addition to 800 IU/d of vitamin D3 | Serum levels of 25(OH)D; FLS; serum calcium, PTH, cytokine levels (IL-17, IL-10, and IFN-γ); EDSS, relapses, adverse events; QoL |
| [14] | 59 participants (37f, 22m) with RRMS; Age mean (range) in vitamin D 38 (22–53) and in placebo 35 (24–53); BMI 24 kg/m2 | Double-blind RCT; 48 weeks; Finland | 30 participants received 20,000 IU of vitamin D3 (cholecalciferol) per week; comparator 29 participants received placebo | Serum levels of 25(OH)D; inflammatory cytokine: Serum concentrations of LAP (TGF-β); IFN-γ, IL-17A, IL-2, IL-10, IL-9, IL-22, IL-6, IL-13, IL-4, IL-5, IL-1β and TNF-α |
| [16] | 89 participants (75f, 14m) with RRMS; Age mean (SD) in vitamin D group 31.50 (7.60) and placebo 34.60 (10.12); No BMI | Double-blind placebo-controlled RCT; 12 weeks; Iran | High-dose vitamin D group, 44 participants received 50,000 IU of vitamin D3 every 5 days; comparator 45 participants received placebo | Serum levels of 25(OH)D; serum calcium; serum interleukin 10 (IL-10) levels |
| [15] | 68 participants (48f, 20m) with RRMS; Age mean (range) in vitamin D group 40 (21–50) and placebo 41 (28–50); BMI vitamin D group 25.9 and placebo 26.5 | Double-blind placebo-controlled RCT; 96 weeks; Norway | 36 participants received 20,000 IU vitamin D3 per week; comparator 32 participants received placebo | Serum 25(OH)D; 11 serum markers of inflammation, bone mineral density, clinical disease activity, disease progression: ALCAMd, CCL21e, CXCL16f, IL-1Rag, MMP-9h, OPGi, OPNj, PTX3k, sFRP3l, sTNF-R1m, TGF-b1n |
| [18] | 89 participants (75f, 14m) with RRMS; Age mean (SD) in vitamin D group 31.50 (7.60) and placebo 34.60 (10.12); No BMI | Double-blind placebo-controlled RCT; 12 weeks; Iran | 44 participants received oral vitamin D3 50,000 IU every 5 days; comparator 45 participants received placebo | Serum levels of 25(OH)D, serum calcium, IL-17 |
| [17] | 53 participants (35f, 18m) with RRMS; Age mean (SD) in vitamin D group 37.7 (7.2) and placebo 37.2 (9.6); BMI ≥ 25 kg/m2 | Double-blind placebo-controlled RCT; 48 weeks; Netherlands | 30 participants received high-dose vitamin D3 supplementation 7000 IU/d for 4 weeks, followed by 14,000 IU/d; comparator 23 participants received placebo | Serum 25(OH)D; serum interleukin 10 (IL-10) levels; cytokine expression of IL4, IFNγ, IL17, IL22, GMCSF and TNFα by CD3+ CD8− T lymphocytes |
| [13] | 40 participants (28f, 12m) with RRMS; Age mean (SD) in high-dose group 41.3 (8.1) and placebo 38.8 (8.8); No BMI | Double-blind RCT; 24 weeks; United States | High-dose group, 19 participants received 10,000 IU/d of cholecalciferol; comparator low-dose group, 21 participants received 400 IU/d of cholecalciferol | Serum 25(OH)D levels; adverse events, relapses, IFN-γ+ IL-17+ CD4+ T cells |
| [20] | 66 participants (41f, 15m) with RRMS; Age median (range) in vitamin D group 39 (22–53) and placebo 35 (24–53); BMI median (range) in vitamin D group 24 (18–40) and placebo 24 (19–38) | Double-blind placebo controlled RCT; 48 weeks; Finland | 34 participants received oral vitamin D3 (cholecalciferol) 20,000 IU once a week; comparator group 32 participants received placebo | Serum levels of 25(OH)D; PTH level, T2 BOD; total number of Gd enhancing T1 lesions; new/enlarging T2 lesions; Gd enhancing lesion volume; MRI activity; ARR, EDSS, T25FW and TTW10 |
ARR, annualised relapse rate; EDSS, Expanded Disability Status Scale; MSFC components, multiple sclerosis functional composite including (25ft timed walk; 9-hole peg test (9-HPT), paced auditory serial addition test (PASAT)); FSS, fatigue severity scale; FLS, flu-like symptoms; QoL, quality of life; T2 BOD, T2 burden of disease; T25FW, timed 25 foot walk; TTW10, timed 10 foot tandem walk; BMI, body mass index; y, years; f, female; m, male; RCT, randomised controlled trial; SD, standard deviation; MS, multiple sclerosis. RRMS, relapsing-remitting multiple sclerosis; 25(OH)D, 25-hydroxy vitamin D.