Holmøy et al. 2017

(Secondary analysis of Kampman et al. 2012) 

High dose vitamin D supplementation does not affect biochemical bone markers in MS

UK

RCT

PEDro=10

N_Initial=71, N_Final=68

Population: Vitamin D group (n=35): Mean age=40yr; Gender: males=11, females=24; Disease course: Unspecified; Median EDSS=2.5; Mean disease duration=11yr. Placebo group (n=33): Mean age=41yr; Gender: males=9, females=24; Disease course: Unspecified; Median EDSS=2.0; Mean disease duration=10yr.

Intervention: Participants were randomized to receive vitamin D₃ (20,000IU/wk) or placebo for 96wks. Outcomes were at baseline, 48wks, and 96wks.

Outcomes/Outcome Measures:

1.      Mean C-terminal cross-linking telopeptide of type 1 collagen(CTX1), precollagen type 1 N propeptide (P1NP), parathyroid hormone (PTH) from baseline, at 48 and 96 wks within and between group changes.

2.      Change in 25-hydroxyvitamin-D (25(OH)D) serum level from baseline (vitamin D and placebo group).

3.      Describe proportion bone mass density (BMD) spine, hip and distal radius at baseline (% with low z-score at baseline).

1.       ¼ of patients had low BMD z-scores (below -2) at baseline.

2.       In the vitamin D group, serum concentration of 25(OH)D increased from 55.6 ± 29.0 nmol/L to 123.2 ± 34.2 nmol/L.

3.       In the placebo group, serum concentration of 25(OH)D increased from 57.3 ± 21.8 nmol/L to 61.8 ± 25.2 nmol/L.

4.       Mean CTX1 levels were similar in the vitamin D and placebo groups at baseline (0.22µg/L vs 0.20µg/L, p=0.59), 48wks (0.21µg/L vs 0.22µg/L, p=0.79), and 96wks (0.23µg/L vs 0.23µg/L, p=0.98).

5.       Mean CTX1 reduction in the vitamin D group from baseline to 48wks (-6.68%, p=0.63) and to 96wks (-13.69%, p=0.09) was not significant when compared to placebo.

6.       Mean P1NP levels were similar in the vitamin D and placebo groups at baseline (40.32µg/L vs 43.10µg/L, p=0.57), 48 wks (38.56µg/L vs 43.36µg/L, p=0.43), and 96wks (43.52µg/L vs 42.54µg/L, p=0.22).

7.       Mean P1NP change in the vitamin D₃ group from baseline to 48 wks (-5.10%, p=0.043) and to 96 wks (+10.26%, p=0.12) was not significant when compared to placebo.

8.       Mean PTH levels were similar in the vitamin D and placebo groups at baseline (4.68pmol/L vs 4.75pmol/L, p=0.66), but were significantly lower in the vitamin D group at 48wks (3.13pmol/L vs 3.68pmol/L, p=0.017) and 96wks (3.39pmol/L vs 3.96pmol/L, p=0.046).

9.       Mean PTH reduction in the vitamin D group from baseline to 48wks (-13.69%, p=0.09) and to 96wks (-10.9%, p=0.17) was not significant when compared to placebo.

Steffensen et al. 2013

(Secondary analysis of Steffensen et al. 2011)

What is needed to keep persons with multiple sclerosis vitamin D-sufficient throughout the year?

Norway

RCT

PEDro=8

N_Initial=71, N_Final=68

Population: Vitamin D₃ (n=35): Mean age=40.0yr; Gender: males=11, females=24; Disease course: RRMS; Median EDSS=2.5; Mean disease duration=11.0yr. Placebo (n=33): Mean age=41.0yr; Gender: males=9, females=24; Disease course: RRMS; Median EDSS=2.0; Mean disease duration=10.0yr.

Intervention: Participants were randomized to receive either vitamin D₃ (20,000 IU) or placebo capsules, administered once a wk for 96 wks. All participants received 500mg/d of calcium. Outcomes were assessed at baseline and 96wks.
Outcomes/Outcome Measures:

1.      Change in serum 25-hydroxyvitamin-D (25(OH)D) levels by mass spectroscopy.

2.      Change in dietary vitamin D intake calculated from a food frequency questionnaire.

1.      In the vitamin D₃ supplementation group, 25(OH)D improved significantly from baseline to 96wks (p<0.01), where 91% of participants had high levels >75nmol/L.

2.      In the vitamin D₃ supplemention group, levels of 25(OH)D increased from 56 nmol/L to 123nmol/L (p<0.01), with a mean increase of 2.4nmol/L per 100IU vitamin D₃.

3.      Mean 25(OH)D levels at baseline during winter was 58 nmol/l, and 87 nmol/l during the summer months (p<0.001).

4.      From the food frequency questionnaire, predictors of serum 25(OH)D levels within all participants at baseline are: dietary and supplemental vitamin D, total vitamin D intake, and tanning beds and sun vacation in last 3mo (all p<0.01).

Steffensen et al. 2011

Can vitamin D3 supplementation prevent bone loss in persons with MS? A placebo-controlled trial

Norway

RCT

PEDro=10

N_Initial=71, N_Final=68

Population: Vitamin D₃ (n=35): Mean age=39.7yr; Gender: males=11, females=24; Disease course: RRMS; Median EDSS=2.5; Mean disease duration=10.9yr. Placebo (n=33): Mean age=41.0yr; Gender: males=9, females=24; Disease course: RRMS; Median EDSS=2.0; Mean disease duration=10.0yr.

Intervention: Participants were randomized to receive either vitamin D₃ (20,000 IU) or placebo capsules once a wk, in addition to 500mg calcium daily for 96 wks.
Outcomes/Outcome Measures: Bone mineral density (BMD) at the hip (mean of left and right total hip), spine (anterior-posterior spine L1-L4) and ultradistal radius by DXA using a Lunar Prodigy advanced densitometer; serum 25-hydroxyvitamin-D (25(OH)D) by mass spectroscopy.

1.      After 96wks, there was no significant difference between participants who received vitamin D₃ and placebo in terms of % change in BMD in the hip (p=0.332), lumbar spine (p=0.793) or ultradistal radius (p=0.506).

2.      BMD decreased at the hip by 1.4% in the placebo group (p=0.006) and by 0.7% in the vitamin D₃ group (p=0.118).

3.      In the intervention group, 25(OH)D serum levels increased from 55.6± 29.0 nmol/L to 123.2± 34.2.

4.      32/35 (91%) of participants in the intervention group reached desired vitamin D levels of ≥75 nmol/L.

Hiremath et al. 2009 

Vitamin D status and effect of low-dose cholecalciferol and high-dose ergocalciferol supplementation in multiple sclerosis

UK

Retrospective Cohort

N_Initial=199, N_Final=49

Population: Mean age=42yr; Gender: males=43, female=156; Disease course: RRMS=115, PPMS=10, SPMS=16; Severity: Unspecified; Disease duration: Unspecified. MS participants=141.

Intervention: Participants received low dose cholecalciferol (LDC (vitamin D₃),<800IU/d), high dose ergocalciferol (HDE (vitamin D₂), 50,000IU/d), or no supplement (NS, n=9) for >6mo. The supplemented participants were divided into groups based on those who just started taking LDC (NS-LDC, n=10) and HDE (NS-HDE, n=12), those who continued taking LDC (LDC-LDC, n=8), and those who switched from LDC to HDE (LDC-HDE, n=10). Outcomes were assessed before and after treatment.

Outcomes/Outcome Measures: Change in 25-hydroxyvitamin-D(25(OH)D) serum level from baseline (vitamin D and placebo group).

1.       50 (26%) patients had 25(OH)D levels greater than 100 nmol/L at baseline.

2.       167 (84%) patients had insufficient levels of 25(OH)D and 61 (31%) patients were deficient.

3.       Mean calcifediol increased in the NS group (73nmol/L to 87nmol/L), but the difference was not significant.

4.       Mean serum calcifediol increased in the NS-LDC group (56nmol/L to 84nmol/L) and slightly decreased in the LDC-LDC group (97nmol/L to 92nmol/L), but neither difference was significant.

5.       Mean calcifediol increased from baseline in the LDC-HDE group (64 ± 19 nmol/L to 108 ± 36 nmol/L, p=0.21) and the NS-HDE group (74 ± 26nmol/L to 116 ± 53 nmol/L, p=0.01), but only the latter difference was significant.