Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation

Abstract

Background: Vitamin D could play a protective role in multiple sclerosis.

Methods: In an observational, uncontrolled study, vitamin D3 supplementation (3010 IU/day on average) was given to 156 consecutive patients with relapsing-remitting multiple sclerosis, under first-line immunomodulatory therapy and with initial 25-OH-D serum level lower than 100 nmol/l (40 ng/ml). Relapses were determined for 29.1 ± 8.4 months during vitamin D and 29.8 ± 10.1 months before supplementation. The 25-OH-D level was measured before supplementation and several times during supplementation. The incidence rate of relapses before and during supplementation was estimated using negative binomial regression models with follow-up durations as offset terms. The incidence rate and incidence rate ratio of relapses at various 25-OH-D levels were also calculated using negative binomial regression models.

Results: In 76 patients, immunomodulatory therapy preceded vitamin D supplementation (by 4.2 ± 2.7 years) and in 80 patients both treatments were started simultaneously. Under supplementation, the 25-OH-D level increased from 49 ± 22 nmol/l to 110 ± 26 nmol/l on average. Pooling data collected before and during supplementation, we found a significant strong inverse relationship between the relapse incidence rate and the 25-OH-D level (p < 0.0001), suggesting that vitamin D did indeed influence the relapse rate. Results of univariate, bivariate and multivariate analyses were analogous: in the multivariate model adjusted for age, disease duration and previous use of immunomodulatory therapy, every 10 nmol increase in 25-OH-D level was associated with a reduction in the relapse incidence rate of 13.7%. Dividing iteratively the population made up of pooled periods into two subgroups according to the 25-OH-D levels, the relapse incidence rate ratio decreased as the 25-OH-D level increased up to 110 nmol/l, but a plateau effect was observed beyond this limit.

Conclusion: Further studies are warranted for accurate quantification of the vitamin D effect.

Keywords: multiple sclerosis; relapse rate; vitamin D; vitamin D supplementation.

Figure 1.

Effect of vitamin D supplementation on 25-OH-D serum level in all patients. In yellow, before vitamin D supplementation; in blue, during vitamin D supplementation (averaged serum level); X-axis: 25-OH-D serum level; Y-axis: number of patients.

Figure 2.

Relapse incidence rate according to 25-OH-D serum level. X-axis: quintile of 25-OH-D serum levels; Y-axis: incidence rate. Q1 to q5 are quintiles of 25-OH-D serum levels, numbers are relapse incidence rate: q1 : ≤ 55.5 nmol/l; q2: > 55.5 to ≤ 78.5 nmol/l; q3: > 78.5 to ≤ 97.25 nmol/l; q4: > 97.25 to ≤ 121.5 nmol/l; q5: >121.5 nmol/l. In black, whole population; in blue, Group 1 (IMT started prior to vitamin D supplementation); in red, Group 2 (IMT started concomitantly with vitamin D supplementation).

Figure 3.

Evolution of relapse incidence rate ratio according to 25-OH-D serum level. X-axis: 25-OH-D serum level (nmol/l); Y-axis: relapse incidence rate ratio. In black, whole population; in blue, Group 1 (IMT started prior to vitamin D supplementation); in red, Group 2 (IMT started concomitantly with vitamin D supplementation).