A recent randomized controlled trial published in the Multiple Sclerosis Journal found that high-dose vitamin D3 supplementation temporarily reduced elevated antibody levels against Epstein Barr virus antigen I (EBNAI), a characteristic sign of multiple sclerosis.
Multiple sclerosis (MS) is characterized by an abnormal response of the body’s immune system against the central nervous system, which is comprised of the brain, spinal cord and optic nerves. Within the central nervous system, the immune system attacks myelin, the insulating fibers that surround nerves. The damage to the myelin sheath causes nerve impulses traveling to and from the brain and spinal cord to become distorted or interrupted. This can lead to various symptoms, including fatigue, trouble walking, bladder problems, dizziness and body pain.
The pathogenesis of MS remains largely unknown; though, Epstein-Barr virus (EBV) has consistently been associated with the disease. EBV, also known as human herpes virus 4, is one of the most common human viruses. Most people get infected by EBV at some point in their lives. However, in patients with MS, it’s not merely the presence of EBV that is distinctive of the disease, it’s the elevation of antibody levels against EBV nuclear antigen I (EBNAI) that acts as a better distinguished marker of MS. Furthermore, this elevation in EBNAI levels are commonly reported years before the development of MS symptoms. These antibody levels remain elevated throughout the course of MS compared to healthy EBV carriers.
Research continues to accumulate scientific evidence in support of vitamin D’s role in MS. A clinical trial suggested that high dose vitamin D supplementation reduces immune system hyperactivity in patients with MS. Another study discovered that a protein activated by vitamin D may repair damage to the myelin sheath. Yet, no studies have been conducted on the relationship between vitamin D and EBV.
In a recent randomized controlled trial, researchers sought to determine the effects of vitamin D supplementation on antibody levels against EBNAI in patients with relapsing-remitting MS (RRMS). A total of 68 RRMS patients were enrolled into the 96-week trial. Half of the patients received 20,000 IU of vitamin D3 weekly; whereas, the other half received a matching placebo. Here is what the researchers found:
- The average vitamin D status increased significantly from 22.2 ng/ml at baseline to 49.3 ng/ml after 96 weeks in the vitamin D group (p < 0.001).
- The average vitamin D status at week 96 in the vitamin D group was significantly higher than in the placebo group (49.3 ng/ml vs. 24.7 ng/ml, respectively, p < 0.001).
- The average anti-EBNAI levels decreased significantly in the vitamin D group (p = 0.038) after 48 weeks of supplementation.
- Anti-EBNAI levels increased somewhat from 48 weeks to 96 among patients who received vitamin D.
The researchers concluded,
“We found that vitamin D3 supplementation selectively reduced IgG levels against EBNA1 protein…from baseline to week 48 when compared to placebo, but a significant effect was not evident from baseline to week 96 despite profoundly increased 25(OH)D levels.”
They went on to state,
“This suggests that vitamin D may have a transient immunomodulatory effect.”
The explanation for these curious findings is currently unexplainable and will be until further research investigates. Though, the researchers hypothesized a reason for these findings. The enzyme responsible for the destruction of active vitamin D, 24-hydroxylase, is up-regulated (its expression increases) by sustained high active vitamin D levels. Therefore, high dose vitamin D supplementation may only lead to a transient increase in the amount of active vitamin D available in immune cells before active vitamin D is destructed at an increased rate due to the higher prevalence of 24-hydroxylase.
While the study design allowed the researchers to prove causation, there were still a few limitations to note. Whether EBNAI levels are a reliable marker of MS disease activity or not remains unclear. Additionally, the study’s population size was relatively small, limiting the generalizability of the study. Lastly, weekly doses of vitamin D were used opposed to daily, and daily supplementation may be more effective.
Tovey, A. & Cannell, JJ. New study finds vitamin D supplementation temporarily reduces Epstein-Barr virus antibody levels among patients with MS. The Vitamin D Council Blog & Newsletter, 2016.