Australia: Vitamin D Supplementation and Multiple Sclerosis

Vitamin D supplementation is safe and well-tolerated but failed to alter the multiple sclerosis (MS) disease activity and did not lower the risk of developing clinically definite MS in patients with high-risk clinically isolated syndrome, a recent study has shown.

In the double-blinded clinical trial published in Brain, the hazard ratios for conversion to clinically definite multiple sclerosis based on the vitamin D3 dose were 0.87 for 1000 IU, 1.37 for 5000 IU, and 1.28 for 10,000 IU compared with placebo.

Low serum 25-hydroxyvitamin D (25(OH)D) levels and low sunlight exposure are known risk factors for MS development. Therefore, Vitamin D supplementation is routinely recommended for patients with multiple sclerosis. However, no strong evidence exists supporting the role of vitamin D supplementation in reducing the progression rates or relapse rates among patients with MS.

To fill this knowledge gap, Bruce V Taylor, University of Tasmania, Hobart, Tasmania, Australia, and colleagues aimed to test the hypothesis that oral vitamin D3 supplementation in high-risk clinically isolated syndrome (abnormal MRI, at least three T2 brain and/or spinal cord lesions), delays time to conversion to definite multiple sclerosis, that all doses are safe and well tolerated, and that the therapeutic effect is dose-dependent.

For this purpose, they conducted a double-blind trial in New Zealand and Australia. Eligible participants were randomized in a ratio of 1:1:1:1 to placebo, 1000, 5000, or 10,000 IU of oral vitamin D3 daily within each study centre (n=23) and were followed for up to 48 weeks. Two hundred and four participants were enrolled between 2013 and 2021. Brain MRI scans were performed at baseline, 24 and 48 weeks.

The main outcome was conversion to clinically definite multiple sclerosis based on the 2010 McDonald criteria defined as either a clinical relapse or new brain MRI T2 lesion development.

Study Findings

• 199 cases were included in the intention-to-treat analysis based on the assigned dose. Of these, 116 converted to multiple sclerosis by 48 weeks (58%).
• Compared to placebo, the HRs for conversion were:
  • 1000 IU: 0.87
  • 5000 IU: 1.37
  • 10,000 IU: 1.28
• In an adjusted model including sex, age, study centre, latitude, baseline symptom number, clinically isolated syndrome onset site, presence of infratentorial lesions, and steroids use, the HRs (versus placebo) were:
  • 1000 IU: 0.80
  • 5000 IU: 1.36
  • 10,000 IU: 1.07
• Vitamin D3 supplementation was safe and well tolerated.

"We did not demonstrate a reduction in MS disease activity by vitamin D3 supplementation after a high-risk clinically isolated syndrome," the researchers concluded.

Reference

Butzkueven, H., Ponsonby, A., Stein, M. S., Lucas, R. M., Mason, D., Broadley, S., Kilpatrick, T., Barnett, M., Carroll, W., Mitchell, P., Hardy, T. A., Macdonell, R., McCombe, P., Lee, A., Kalincik, T., Lynch, C., Abernethy, D., Willoughby, E., Barkhof, F., . . . Investigators, P. Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome. Brain. https://doi.org/10.1093/brain/awad409