Table 1.
Overview of relevant vitamin D supplementation studies.
| Study | Vitamin D supplementation vitamin D serum levels (baseline-> treatment) | Hypercalcemia | Immunological outcomes | Clinical outcomes |
|---|---|---|---|---|
| Burton et al. (41) | Escalation trial up to 40,000 IU/day Peak at 413 nmol/L |
1,200 mg Calcium/day Not observed |
Not measured | Trend toward reduced relapse rate |
| Camu et al. (43) (CHOLINE) | 100,000 IU/2 weeks 49.19 to 156.92 nmol/L |
Exclusion criterion: Hypercalcemia | Not measured | Primary endpoint was not met, however reduction in ARR, lesion formation/volume and lower EDSS progression |
| Fragoso et al. (46) | 21 cases Up to 150,000 IU/day (average 87,000 IU) Typically 375 nmol/L |
Five patients with severe hypercalcemia | Not measured | Worsening of neurological condition, new relapses and MRI lesions, EDSS deterioration |
| Golan et al. (40) | Low: 800 IU/day 48 to 68 nmol/L High: 4,370 IU/day 48.2 to 122.6 nmol/L |
Not observed | Increased IL-17 levels in the low dose group | No significant differences in relapse rate, EDSS, QoL, serum IL-10, and IFNγ |
| Hupperts et al. (42) (SOLAR) | 14,000 IU/day | Not observed | Not measured | Reduction of new MRI lesions NEDA-3 was not reached |
| Jorde et al. (47) | 20,000 IU/week 60 to 122 nmol/L |
Exclusion criterion: serum calcium >2.55 mmol/l | N.A. | N.A. (type 2 diabetes mellitus) |
| Kampman et al. (37) | 20,000 IU/week 55.6 to 123.1 nmol/L |
500 mg Calcium/day Not observed, as described in a previous publication (48) |
Not measured | No effect on relapse rate, functional outcomes or fatigue |
| Lehouck et al. (49) | 100,000 IU/4 weeks | Exclusion when history of hypercalcemia, small and transient risk of hypercalcemia | N.A. | N.A. (chronic obstructive pulmonary disease) |
| Mahon et al. (38) | 1,000 IU/day 42.5 to 70 nmol/L |
Not measured | Increased serum TGF-h1 | Not mentioned |
| Marcus et al. (50) | Single case 5,500 IU/day 257 nmol/L |
2,020 mg Calcium/day Severe hypercalcemia |
Not measured | Acute-onset tremors and confusion |
| McLaughlin et al. (45) | Meta-analysis of 12 studies | Rare (1.5%) | N.A. | Significant increase in ARR and trends of increased EDSS and Gd+-lesions for the higher-dose arms |
| Rolf et al. (51) | 4,000 IU/day Not measured |
Not measured | No effect of 16-weeks vitamin D3 supplements except for a decreased TNF-α concentration in culture supernatant | Not measured |
| Smolders et al. (52) | 20,000 IU/day 50 to 380 nmol/L |
Not observed | Shift toward anti-inflammatory cytokine profile | Not measured |
| Soilu-Hanninen et al. (39) | 20,000 IU/week 54 to 110 nmol/L |
Exclusion criterion: serum calcium >2.6 mmol/l | Not measured | Reduced disability accumulation Improved time tandem walk Reduced lesion formation |
| Stein et al. (44) | Low: 1,000 IU/once daily 59 to 69 nmol/L High: 6,000 IU/twice daily 59 to 120 nmol/L |
Not observed | Not measured | Increased adjusted EDSS and more relapses in high vitamin D group |
| Zittermann et al. (53) | 4,000 IU/day <40 to 100 nmol/L |
Higher incidence of hypercalcemia (6.2 vs. 3.1% in placebo) | N.A. | N.A. (cardiovascular disease) |
IU, international unit; TGF, transforming growth factor; IL, interleukin; EDSS, expanded disability status scale; QoL, quality of life; IFN, interferon; MRI, magnet resonance imaging; NEDA, no evidence of disease activity; ARR, annual relapse rate; Gd, gadolinium; N.A., not applicable.