Effect of high-dose vitamin D3 supplementation on antibody responses against Epstein-Barr virus in relapsing-remitting multiple sclerosis.

BACKGROUND: Elevated antibody levels against Epstein-Barr virus (EBV) and a poor vitamin D status are environmental factors that may interact in relapsing-remitting multiple sclerosis (RRMS) aetiology. OBJECTIVES: To examine effects of high-dose oral vitamin D3 supplementation on antibody levels against EBV nuclear antigen 1 (EBNA1) in RRMS. METHODS: Serum 25-hydroxyvitamin D3 (25(OH)D) and immunoglobulin G antibody levels against EBNA1 (whole protein and amino acid 385-420 fragment), EBV viral capsid antigen (VCA), cytomegalovirus (CMV) and varicella zoster virus (VZV) were measured in 68 RRMS patients enrolled in a 96-week randomised double-blinded placebo-controlled clinical trial of oral vitamin D3 supplementation (20,000 IU/week) (NCT00785473). RESULTS: The mean 25(OH)D level more than doubled in the vitamin D group and was significantly higher than in the placebo group at study conclusion (123.2 versus 61.8 nmol/L, p < 0.001). Compared to the placebo group, both anti-EBNA1 protein and fragment antibody levels decreased in the vitamin D group from baseline to week 48 ( p = 0.038 and p = 0.004, respectively), but not from baseline to week 96. Vitamin D3 supplementation did not affect antibodies against VCA, CMV or VZV. CONCLUSION: The results indicate that high-dose oral vitamin D3 supplementation can affect humoral immune responses against the latent EBV antigen EBNA1 in RRMS.

Vitamin D supplementation and systemic inflammation in relapsing-remitting multiple sclerosis.

Observational studies have suggested that vitamin D may reduce inflammation in relapsing-remitting multiple sclerosis (RRMS), but this has not been clearly confirmed in randomized controlled trials. To further explore the possible anti-inflammatory effects of vitamin D in RRMS, we examined the effect of high-dose oral vitamin D3 on eleven markers of systemic inflammation in 68 RRMS patients enrolled in a double-blinded randomized placebo-controlled trial of vitamin D3 supplementation (20,000 IU/week) (NCT00785473). Serum inflammation markers and 25-hydroxyvitamin D (25(OH)D) were measured at baseline and week 96, and no restrictions were set on additional standard immunomodulatory treatment for RRMS. The mean 25(OH)D level rose from 56 ± 29 to 123 ± 34 nmol/L among patients receiving vitamin D3 supplementation, whereas only a minor increase from 57 ± 22 to 63 ± 24 nmol/L was seen in the placebo group. However, no significant differences appeared between the vitamin D group and the placebo group for any of the inflammation markers. Patients on immunomodulatory therapy had significantly higher levels of interleukin-1 receptor antagonist and chemokine (C-X-C motif) ligand 16 than patients without immunomodulatory treatment, but there were no clear synergistic effects between immunomodulatory therapy and vitamin D3 supplementation on any of the inflammation markers. The rise in 25(OH)D levels after vitamin D3 supplementation was unaffected by immunomodulatory treatment. We conclude that in this study of RRMS patients, high-dose oral vitamin D3 supplementation prominently increased serum 25(OH)D levels without affecting markers of systemic inflammation, while a more anti-inflammatory phenotype was found among patients on immunomodulatory treatment.

What is needed to keep persons with multiple sclerosis vitamin D-sufficient throughout the year?

Vitamin D sufficiency has been associated with lower risk of multiple sclerosis and may also have a favorable effect on the course of the disease. The aim of this work was to identify predictors of serum 25-hydroxy vitamin D (25[OH]D) levels in persons with multiple sclerosis (MS) and to assess the effect of high-dose vitamin D(3) supplementation on vitamin D status. A 96-week randomized controlled trial was performed to assess the effect of supplementation with 20,000 IU of vitamin D(3) weekly on bone mineral density in 68 patients. We collected data on vitamin D intake and UV-exposure and repeatedly measured serum 25(OH)D levels. Half of the participants had sufficient winter vitamin D levels at baseline (≥ 50 nmol/l). Vitamin D status was predicted by sun exposure during the last 3 months and by ingested vitamin D from diet and supplements. In the placebo group, the proportion of the participants with sufficient levels increased from 55 % in winter to 92 % during the summer. In the intervention group, all participants had winter 25(OH)D levels above 50 nmol/l at the end of the study. MS patients who have no sun exposure and low dietary vitamin D intake during the winter months should be recommended to take vitamin D supplements to achieve serum 25(OH)D levels of at least 50 nmol/l.

Effect of vitamin D3 supplementation on relapses, disease progression, and measures of function in persons with multiple sclerosis: exploratory outcomes from a double-blind randomised controlled trial.

BACKGROUND: High vitamin D levels may reduce the risk of relapses and disease progression in multiple sclerosis. METHODS: This 96-week randomised controlled trial was designed to assess the effect of vitamin D(3) supplementation on bone mineral density in persons with multiple sclerosis. Supplementation with 20,000 IU vitamin D(3) weekly raised median serum 25-hydroxy vitamin D (25[OH]D) to 121 nmol/L. The modified intention to treat analysis included 35 persons in the vitamin D(3) group and 33 in the placebo group. Participants were age 21 to 50 years and fully ambulatory (median Expanded Disability Status Scale (EDSS) 2.5). We studied the effect of supplementing vitamin D(3) on the exploratory outcomes annualised relapse rate (ARR), EDSS, multiple sclerosis functional composite (MSFC) components, grip strength, and fatigue. RESULTS: After 96 weeks, there was no significant difference between groups in ARR (absolute difference 0.10, 95% CI -0.07 to 0.27; p = 0.25), EDSS (absolute difference -0.01, 95% CI -0.35 to 0.35; p = 0.97), MSFC components, grip strength, or fatigue. CONCLUSION: Supplementation with 20,000 IU vitamin D(3) weekly did not result in beneficial effects on the measured multiple sclerosis-related outcomes. This study was not powered to address clinical outcomes, but none of the results were suggestive of an effect in this unselected population of fully ambulatory persons with multiple sclerosis.

Can vitamin D supplementation prevent bone loss in persons with MS? A placebo-controlled trial.

Multiple sclerosis (MS) is a possible cause of secondary osteoporosis. In this phase II trial we assessed whether a weekly dose of 20,000 IU vitamin D(3) prevents bone loss in ambulatory persons with MS age 18-50 years. ClinicalTrials.gov ID NCT00785473. All patients managed at the University Hospital of North Norway who fulfilled the main inclusion criteria were invited to participate in this double-blinded trial. Participants were randomised to receive 20,000 IU vitamin D(3) or placebo once a week and 500 mg calcium daily for 96 weeks. The primary outcome was the effect of the intervention on percentage change in bone mineral density (BMD) at the hip, the spine, and the ultradistal radius over the study period. Of 71 participants randomised, 68 completed. Mean serum 25-hydroxyvitamin D [25(OH)D] levels in the intervention group increased from 55 nmol/L at baseline to 123 nmol/L at week 96. After 96 weeks, percentage change in BMD did not differ between groups at any site. BMD decreased at the hip, by 1.4% in the placebo group (95% CI -2.3 to -0.4, SD 2.7, p = 0.006) and by 0.7% in the treatment group (-1.6 to 0.2, 2.7, p = 0.118), difference 0.7% (-1.9 to 0.7, p = 0.332). Findings were not altered by adjustment for sex or serum 25(OH)D. Supplementation with 20,000 IU vitamin D(3) a week did not prevent bone loss in this small population. Larger studies are warranted to assess the effect of vitamin D on bone health in persons with MS.

The role of vitamin D in multiple sclerosis.

Multiple sclerosis (MS) risk is determined by environmental influences acting on the individual genetic background. Recent epidemiologic and experimental evidence supports a role of low environmental supplies of vitamin D in mediating an increased susceptibility to MS. We review available evidence suggesting that vitamin D status may influence MS risk and even modulate clinical disease activity. The level of serum 25-hydroxyvitamin D providing these effects remains to be determined.