Study review finds inconsistent evidence for vitamin D in MS care

Vitamin D supplementation did not consistently reduce relapse rates in adults with multiple sclerosis (MS), although it may reduce the number of MS lesions seen on MRI scans, according to a systematic review of published studies.

Several trials found reductions in new or active lesions even when vitamin D did not significantly reduce relapse frequency. This suggests that potential benefits of supplementation may be easier to detect on MRI than through clinical symptoms, although the results were still variable.

“The evidence reviewed here would not support vitamin D supplementation as a standalone treatment or replacement of disease-modifying therapy in MS,” the researchers wrote. “High-dose supplementation for disease modification is not supported by current data, and the evidence here does not provide a basis for expanding its clinical role.”

The study, “Vitamin D Supplementation and its Effect on Relapse Frequency and MRI Activity in Adults With Multiple Sclerosis: A Systematic Review,” was published in Brain and Behavior.

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Taking high-dose vitamin D daily over the long term helps reduce MS relapses

Regulating the immune system

In MS, the immune system mistakenly attacks myelin, a protective layer around nerve fibers in the brain and spinal cord. Many patients experience MS relapses, characterized by periods of worsening symptoms interspersed with periods of relative recovery.

Vitamin D has attracted interest as a potential factor influencing the course of MS because of its role in regulating the immune system. Low vitamin D levels have been associated with an increased risk of developing MS and a more severe disease course. Some studies have also suggested that higher vitamin D levels may be linked to lower disease activity.

However, clinical trials testing vitamin D supplementation in people with MS have yielded inconsistent results, and the potential benefits remain uncertain.

To learn more, researchers conducted a systematic review of 11 prior clinical studies with 14 associated publications evaluating the use of vitamin D supplements in adults with MS.

Eight were randomized controlled trials (RCTs), in which participants were randomly assigned to treatment groups. Most of these trials involved people with relapsing-remitting MS (RRMS). Vitamin D was administered on top of an MS disease-modifying therapy in five.

Multiple forms of vitamin D were tested at various doses. These included alfacalcidol, a partially active, lab-made form of vitamin D, and cholecalciferol, a naturally occurring, inactive form that requires additional processing in the body. Study follow-up. times ranged from six months to four years.

Across the studies, vitamin D supplementation did not consistently reduce relapse rates. Five of the six RCTs reporting relapse outcomes found no statistically significant benefit, regardless of whether vitamin D was administered alone or alongside an existing DMT.

In the one trial that did show a benefit, the proportion of patients experiencing relapses while receiving 1 microgram per day of alfacalcidol was significantly lower than in a group of people receiving a placebo (10% vs. 32%) — corresponding to an 80% lower relapse risk.

While the collective findings don’t show a clear role for vitamin D supplementation in reducing relapses, differences in vitamin D formulations, doses, and treatment durations make it hard to interpret the results, the authors noted. For example, the one study that saw a benefit tested alfacalcidol, while most of the others tested cholecalciferol.

The scientists also pointed out that participants’ initial vitamin D levels varied across trials, and whether people with vitamin D deficiency respond differently remains unclear and warrants further investigation.

Some studies reported that vitamin D supplementation led to significant reductions in inflammatory brain lesions on MRI scans despite no clear effect on relapses. For example, in the SOLAR trial (NCT01285401), which tested cholecalciferol as an add-on to Rebif (interferon beta-1a), supplementation significantly reduced the number of active lesions and overall lesion burden.

In a secondary analysis of the FREEDOMS trials (NCT00289978 and NCT00355134), which evaluated Gilenya (fingolimod) against a placebo, participants who received daily vitamin D supplementation were more likely to remain free of new or enlarging lesions than those who did not receive supplementation.

Not every trial showed these benefits. The VIDAMS trial (NCT01490502) showed no significant change in the overall lesion burden with vitamin D supplementation, while the CHOLINE trial (NCT01198132) showed mixed results on lesion-related outcome measures.

The researchers said the findings show that “if vitamin D supplementation has any effect in MS, it may be more detectable at the radiographic [MRI] level than at the level of clinical relapses.”

However, it is not clear whether the findings are clinically meaningful because the analyses involve relatively small numbers of patients, the trials were designed differently, and results varied.

“Future research should prioritize larger multicenter RCTs … to help clarify the potential of vitamin D supplementation beyond use as a correction of a deficiency in MS,” the team concluded.