The role of vitamin D in Multiple Sclerosis is still controversially discussed. There is no doubt that vitamin D is a risk factor for susceptibility to MS. However, convincing studies that prove that the supplementation of vitamin D has a relevant therapeutic effect are still lacking.
Especially for the (ultra)high-dose intake of vitamin D (keyword Coimbra protocol) there is no evidence, on the contrary, reports of serious side effects from taking very high doses of vitamin D are increasing.
In practice, most doctors – especially in light of the epidemiological and immunological data on vitamin D – recommend moderate vitamin D supplementation and ensure that a vitamin D deficiency in MS is adequately substituted. Although I generally advise my patients that vitamin D supplementation is an optional measure, I prescribe – if a patient expresses interest in vitamin D supplementation – the (usual) dose of 1000 – 2000 IU daily or the once weekly supplementation with 20,000 IU.
D-lay MS Study Results
At the last ECTRIMS Congress in Copenhagen (September 2024) there were updates on the therapeutic use of vitamin D in Multiple Sclerosis. The French colleagues presented the results of a multicenter study, the so-called “D-lay MS” study, which investigated the use of high-dose vitamin D in patients with clinically isolated syndrome compared to placebo. The fact that the study took a long time to recruit the required number of participants is evident from the fact that since the revision of the McDonald criteria in 2017, the first clinical event (=CIS) in most cases leads to the diagnosis of early MS.
A total of 303 patients with a first clinical event were included in the study. 156 patients received 100,000 IU of vitamin D every two weeks (so a comparatively high dose), 147 patients received placebo. The cohort examined was younger patients with an average age of 34 who were included in the study an average of 60 days after the first event and observed for 24 months.
The primary endpoint of the study was the occurrence of disease activity, either in the form of a renewed clinical relapse or the occurrence of new MRI lesions (both in the form of contrast-enhancing lesions and new T2 lesions). The primary endpoint was reached by 109 patients (74.1 %) in the placebo group whereas only 94 patients (60.3 %) in the vitamin D group reached the endpoint, which represents a statistically significant difference in favor of the vitamin D group. Looking at the results in more detail, it is less the clinical relapses that are prevented, but rather the MRI activity that is reduced by the intake of vitamin D: an observation that has also been made in other therapy studies with vitamin D.
By the way, the authors reevaluated the results also applying the McDonald criteria from 2017. Accordingly, 89 % of the “CIS” patients met the criteria for early MS. Even based on this sample, there was no change in the results. An extensive subgroup analysis was also conducted to find out which patients benefited most from vitamin D supplementation. It was found that primarily patients with manifest vitamin D deficiency benefit.
The authors therefore conclude that vitamin D has a moderate anti-inflammatory effect and should be prescribed to MS patients due to its good safety profile – even with the high doses used in the study. Above all, patients who have a vitamin D deficiency should be treated.
New Aspects in Clinical Care?
The question now is whether this study results in new aspects in the clinical care of MS patients. I rather think not. Substituting vitamin D in MS patients with vitamin D deficiency is recognized practice. The moderate anti-inflammatory effect of vitamin D, which the study again confirms, justifies a supplementation of vitamin D. However, the study also shows that such supplementation alone is not sufficient and additional immunomodulatory MS therapy should not be omitted. For this reason, too many patients in both groups showed renewed inflammatory activity during the observation period. I therefore conclude that the pragmatic approach, which is currently carried out with the supplementation of 1000 – 2000 IU/day or 20,000 IU/week, is supported by the French study and does not need further adjustment. Since this study is very well done qualitatively, I would also doubt that further vitamin D therapy studies will really surprise us.
