Pre-DMT Vitamin D Levels Influence MS Disease Activity and Onset, study finds

"Having a genetic predisposition to higher vitamin D levels is linked to a reduced risk of disease activity and is associated with a delayed onset of multiple sclerosis," Antonino Giordano, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy, and colleagues wrote in Journal of Neurology, Neurosurgery, and Psychiatry.

Multiple sclerosis is characterized by the immune system attacking the protective sheath (myelin) covering nerve fibers, disrupting communication between the brain and the rest of the body. Disease activity in MS can manifest in various forms, including relapses, progression of disability, and overall worsening of symptoms.

The role of Vitamin D (VitD) in multiple sclerosis (MS) risk is well-established, yet its specific influence on disease activity remains a topic of debate. Considering this, Dr. Giordano and colleagues aimed to evaluate whether VitD is associated with the No-Evidence of Disease Activity-3 (NEDA-3) status two years from the DMT start. They also assessed whether this association is causal or the result of confounding factors, and explored if a genetic predisposition to higher VitD levels impacts the risk of disease activity.

For this purpose, the researchers tested the association between seasonally adjusted VitD and disease activity in 230 untreated relapsing-remitting MS patients who also underwent serum 25-OH-vitamin-D measurement.

Using a polygenic risk score derived from a genome-wide association study involving approximately 400,000 individuals, the researchers investigated how genetic predisposition to higher Vitamin D levels impacts NEDA-3 status in a cohort of 1,408 independent patients with MS. We employed two-sample Mendelian randomization (MR) to evaluate causality.

The study led to the following findings:

• Lower baseline VitD was associated with a decreased probability of NEDA-3 at two years.
• VitD levels <20 ng/mL conferred an over twofold risk of disease activity (OR 2.36).
• Genetic predisposition to higher VitD levels was associated with delayed age at MS onset and a higher probability of NEDA-3 status.
• MR confirmed causality between VitD and the risk of disease activity.

Vitamin D levels before starting treatment were tied to subsequent multiple sclerosis disease activity. Genetic predisposition to higher vitamin D levels confers a lower disease activity risk and is tied to delayed MS onset," the researchers wrote.

"Our research underscores the need for future prospective studies on Vitamin D supplementation and lifestyle interventions aimed at mitigating disease activity in MS," they concluded.

Reference:

Giordano A, Clarelli F, Pignolet B, et al. Vitamin D affects the risk of disease activity in multiple sclerosis. Journal of Neurology, Neurosurgery & Psychiatry Published Online First: 14 July 2024. doi: 10.1136/jnnp-2024-334062