Vitamin D Deficiency Affects Cognition in Multiple Sclerosis

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Longer studies are needed to further evaluate the effect of vitamin D supplementation on cognition in multiple sclerosis.

Results of a study published in a recent issue of Scientific Reports1 showed significant improvements in cognitive performance among patients with multiple sclerosis (MS) after a short course of vitamin D replacement.

Investigators from the MS Center of the American University of Beirut Medical Center in Lebanon recruited 88 participants (40 men/48 women; average age, 36 ± 12.2 years) with clinically stable relapsing-remitting MS or clinically isolated syndrome, according to MacDonald 2010 criteria, during a 2-year period from 2012 to 2014. The participants were broken up into 2 groups based on vitamin D status: sufficient (25 hydroxyvitamin (OH) D >35 ng/mL) or deficient (<25 ng/mL). Those in the deficient group were given high-dose vitamin D3 supplementation in the form of 10,000 international units daily for 3 months, whereas the sufficient group continued their usual care, which may have included supplementation.

Despite significant improvements in the deficient group scores on the Montreal Cognitive Assessment general memory test (P =.006) and the Brief Visuospatial Memory Test (BVMT)–delayed recall (P =.02), no significant changes occurred in Single Digit Modalities Test scores, which were within normal limits at baseline. At the same time, both the deficient and sufficient groups showed statistically significant improvement in total BVMT learning scores (P =.004 and .003, respectively).

Notably, most of the participants (69.2% of the deficient group and 60% of the sufficient group) were able to maintain attention on the Stroop color-word interference test, and both groups showed moderate improvements in scores, although this was not statistically significant (P =.56). The investigators attributed this, and near normal performance of both groups on the Single Digit Modalities Test, to the short disease duration.

The main finding in multivariate analysis was that, after controlling for other factors (including Expanded Disability Status Scale scores, disease duration, age, sex, education, physical activity, smoking, alcohol consumption, leisure activities, anxiety and depression scores, and total Hopkins score), a level of 25 (OH)D >35 ng/mL at baseline was highly predictive of cognitive performance on the BVMT-DR at baseline and 3 months later.

Deficient 25 (OH)D levels at baseline were associated with reductions of 1.74 (95% CI, −3.01 to 0.47; P =.008) BVMT points at baseline and 1.93 (95% CI, −3.42 to −0.44; P =.01) points at 3 months compared with the sufficient group.

The deficient group had higher Expanded Disability Status Scale scores, which suggested greater impairment of mobility that likely prevented those participants from taking in vitamin D naturally through sunlight exposure. The investigators pointed to previous evidence that suggests that low 25 (OH)D levels correspond to higher disability and increases in relapse rates.2

The results suggest that vitamin D supplementation could improve cognition and quality of life in patients with MS, although the investigators felt that the 3-month time frame of the study was too limiting, and that extending evaluations to 1 year would be valuable to determine whether vitamin D would show a broader effect on cognition over the long term.


  1. Darwish H, Haddad R, Osman O, et al. Effect of vitamin D Replacement of cognition in multiple sclerosis patients. Sci Rep. 2017;7:45926. doi: 10.1038/srep45926
  2. Smolders, J., Muris, A. H. & Damoiseaux, J. Immunomodulation by vitamin D in multiple sclerosis: More than IL-17. J Neuroimmunol. 2016;292:79-80. doi: 10.1016/j.jneuroim.2016.01.017