A new meta-analysis (9 studies, N=867) has concluded that high-dose vitamin D3 supplementation does not have a significant impact on clinical outcomes in patients with MS (Mahler et al. Mult Scler Relat Disord 2024:82:105433).

Study subjects in the randomized controlled trials received >1000 IU/day of cholecalciferol. Overall, there was no significant reduction in EDSS, annualized relapse rate or new T2 lesions at 6-24 months with vitamin D supplementation versus controls.

A separate systematic review published last year also reported that a majority of vitamin D supplementation studies showed no significant effect on relapses or disability (Langlois & Denimal. Nutrients 2023;15:1945).

Vitamin D has been hypothesized to have immunomodulatory and neuroprotective effects in the CNS, reducing neuronal apoptosis and promoting neurogenesis (Menendez & Manucha. Curr Pharm Des 2024; epublished February 1, 2024). However, recent clinical trials have generally reported negative results.

Vitamin D supplementation (1000, 5000 or 10,000 IU/day) did not reduce disease activity in a 48-week double-blind trial of patients with high-risk clinically isolated syndrome (CIS) (Butzkueven et al. Brain 2023; epublished December 12, 2023).

In the phase III Vitamin D to Ameliorate MS (VIDAMS) trial, there was no benefit with high-dose versus low-dose vitamin D (5000 vs. 600 IU/day) in patients receiving glatiramer acetate (Cassard et al. EClinicalMedicine 2023;59:101957). The proportion of patients who relapsed at 96 weeks was 34% with high-dose vitamin D compared to 32% with low-dose vitamin D.

Negative findings were also reported in the SOLAR trial of interferon-β and adjunctive high-dose vitamin D (14,000 IU/day) (Hupperts et al. Neurology 2019;93:e1906-e1916). The proportion of patients achieving no evidence of disease activity (NEDA) at 48 weeks was 36.3% with vitamin D and 35.3% without vitamin D, although MRI outcomes (combined unique active lesions, T2 lesion volume) were improved with add-on therapy.

A subsequent SOLAR subgroup analysis found that higher serum 25(OH)D levels were not associated with lower neurofilament light chain (NfL) levels (Smolders et al. Acta Neurol Scand 2020;141:77-80), suggesting no effect of vitamin D on neurodegenerative processes.