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Research papers – Vitamin D and multiple sclerosis

Learn about the research studies that demonstrate the impact of vitamin D on multiple sclerosis.

Published research illustrating the impact of diet found in Jan 2024 in a project with student G H Alzanbaqi and Dr Jonathan White.

Vitamin D and multiple sclerosis

Paper: Vitamin D3 as an add-on treatment for multiple sclerosis: a systematic review and meta-analysis of randomized controlled trials

Journal: Multiple Sclerosis and Related Disorders, 2024

Key findings: On average, there is an estimated reduction of approximately 35.38% in new T2 lesions associated with vitamin D supplementation compared to the control group means.

Conclusions: A systematic review and meta-analysis of nine studies involving 867 participants were conducted to assess the impact of high-dose vitamin D3 supplementation on clinical and radiological outcomes in patients with multiple sclerosis (MS). The results indicate that while vitamin D3 did not significantly reduce disability scores (EDSS), annual relapse rate (ARR), or new T2 lesions at 6-24 months, the non-significant reduction in new T2 lesions suggests a potential for long-term clinical benefits, warranting validation in further studies.

Paper: Effect of Vitamin D Supplementation on Fatigue in Multiple Sclerosis: A Systematic Review and Meta-Analysis

Journal: Nutrients, 2023,15(13)

Key findings: In a meta-analysis of five studies involving 345 participants with multiple sclerosis (MS), researchers assessed the impact of vitamin D supplementation on fatigue. The analysis revealed a significant reduction in fatigue with vitamin D compared to a control group (effect size: −0.18; 95% CI: −0.36 to −0.01; I2 = 0%). The findings suggest a potential therapeutic use of vitamin D for managing fatigue in MS individuals. However, due to the lack of consensus on the recommended dosage, medical supervision is advised for its use.

Paper: Clinical and Imaging Outcomes after Vitamin D Supplementation in Patients with Multiple Sclerosis: A Systematic Review

Journal: Nutrients, 2023, 15(8),

Key findings: Supplementation with vitamin D3 has a beneficial effect against new lesions. However, there is no significant evidence that it is effective for preventing relapses or the progression of MS.

Description: A systematic review of literature aimed to evaluate the impact of vitamin D supplementation on clinical and imaging outcomes in patients with MS. The review included 19 independent clinical studies, analysing the risk of bias in RCTs. Fifteen trials investigated relapse events, and most reported no significant effect of vitamin D supplementation. Eight of 13 RCTs found no effect on disability compared to controls. However, recent RCTs reported a significant reduction in new MRI lesions in the central nervous system of MS patients during vitamin D3 supplementation

Paper: High-dose vitamin D3 supplementation in relapsing-remitting multiple sclerosis: a randomised clinical trial.

Journal: eClinical Medicine, ,2023, 59.

Key findings: Both groups taking vitamin D achieved similar results. At 96 weeks, there was no significant difference in the number of people having confirmed relapses between the two groups: 32% for the low-dose vitamin D (LDVD) and 34% for the high-dose vitamin D (HDVD).

Description: This U.S. study, which included 172 participants, found no advantages of high-dose (5,000 IU/day) vitamin D over low-dose (600 IU/day). However, the low-dose group did show a trend towards lower relapse rates and reduced severity of relapse.

Paper: Low serum 25‑hydroxy-vitamin D levels are associated with cognitive impairment in multiple sclerosis

Journal: Multiple Sclerosis and Related Disorders, 2023; 79

Key findings: Higher vitamin D levels are linked to better cognitive scores. (SDMT (Symbol Digit Modalities Test) scores increased by 0.9 ng/mL for each unit rise.) CVLT-II (California Verbal Learning Test-II) scores rose by 0.7 ng/mL per unit increase. BVMT-R (Brief Visuospatial Memory Test-Revised) scores increased by 0.6 ng/mL for each unit boost. Impaired BICAMS (Brief International Cognitive Assessment for MS) test linked to -9.63 ng/mL decrease. EDSS (Expanded Disability Status Scale) scores associated with -2.2 ng/mL decrease per unit increase.)

Description: In this cross-sectional study conducted at the MS Unit of the Policlinico Federico II University Hospital of Naples, Italy, from January to April 2022, they investigated associations between vitamin D levels and cognitive status in 181 consecutively recruited multiple sclerosis (MS) patients. Serum 25‑hydroxy vitamin D was measured, and cognitive assessment was performed using the Brief International Cognitive Assessment for MS (BICAMS). Univariable linear regression models revealed that higher serum 25-OH-vitamin D levels were associated with better adjusted scores in Symbol Digit Modalities Test (SDMT), California Verbal Learning Test-II (CVLT-II), and Brief Visuospatial Memory Test-Revised (BVMT-R), while lower levels were linked to impaired BICAMS tests and increased Expanded Disability Status Scale (EDSS). Multivariable models confirmed associations between 25-OH-vitamin D and EDSS, SDMT, and CVLT-II. The findings suggest that lower serum 25-OH-vitamin D is associated with worse cognitive function in MS, emphasising the need for future studies to explore longitudinal variations in cognitive function relative to vitamin D supplementation.

Paper: Vitamin D and marine omega 3 fatty acid supplementation and incident autoimmune disease: VITAL randomized controlled trial.

Journal: BMJ, 2022,376.

Key findings: Daily supplementation with 2000 international units (IU) of vitamin D3 for a median of 5.3 years decreased the incidence of autoimmune diseases by 22%. Combining vitamin D and omega-3 fatty acids led to a substantial 31% reduction in risk of autoimmune diseases

Description: A study with 25,000 participants over 5.3 years found that vitamin D supplementation was associated with a significant 22% lower risk of autoimmune diseases. Omega-3 fatty acids alone did not show a significant impact. However, combining vitamin D and omega-3 fatty acids led to a substantial 31% reduction in risk, surpassing the effects of individual supplements. The study suggests that vitamin D supplementation may be beneficial in lowering the risk of autoimmune diseases.

Paper: High-dose vitamin D supplementation in multiple sclerosis – results from the randomized EVIDIMS (efficacy of vitamin D supplementation in multiple sclerosis) trial

Journal: Multiple Sclerosis Journal – Experimental, Translational and Clinical, 2020,6(1),

Key findings: Both groups taking vitamin D achieved similar results. There were no differences in the number of new T2-weighted hyperintense lesions, T2 lesion volume, the number of contrast-enhancing lesions, and brain atrophy between both treatment groups.

Description: This study investigated whether high-dose vitamin D (VD) supplementation could reduce disease activity in multiple sclerosis (MS). The EVIDIMS trial involved 53 patients receiving either high (20,400 IU) or low-dose (400 IU) cholecalciferol supplementation over 18 months. The results showed no significant differences in clinical or imaging markers of disease activity between the two groups. The study concluded that while the results don’t confirm or refute the therapeutic benefits of high-dose VD supplementation, they offer valuable insights for designing future studies with more appropriate sample sizes.

Paper: Randomized trial of daily high-dose vitamin D3 in patients with RRMS receiving subcutaneous interferon β-1a.

Journal: Neurology, 2019

Key findings: Those taking high-dose vitamin D3 had better MRI results, with a lower incidence of unique active lesions and a decrease in the total volume of T2 lesions compared to the placebo group.

After 48 weeks, 36.3% of patients taking a high dose of vitamin D3 didn’t show evidence of disease activity (NEDA-3), but this wasn’t significantly different from the placebo group (35.3%).

Description: SOLAR Phase 2 clinical trial was one of the biggest studies looking into how vitamin D supplementation affected MS disease activity. More than 200 patients with relapsing-remitting multiple sclerosis (RRMS) from Europe were enrolled in it. They were then randomly assigned to receive either high-dose vitamin D3 (14,007 international units per day, or IU/day) or the widely-approved MS therapy Rebif (interferon beta-1a), in combination with a placebo. The patients in this group developed fewer lesions than those on a placebo, but the rate of relapses and the progression of the disability over almost a year was not decreased by vitamin D3 supplementation, according to the results.

Paper: An Update on Vitamin D and Disease Activity in Multiple Sclerosis.

Journal: CNS Drugs, 2019, 33(12), 1187–1199

Key findings: Each 25 nmol/l increase in 25-hydroxyvitamin D levels were associated with 14–34% reduced relapse risk and 15–50% reduced risk of new lesions on MRI.

Description: Vitamin D and its active form, 1,25-dihydroxyvitamin D, play a crucial role in maintaining healthy calcium metabolism and have additional functions in immune and central nervous system cell balance. Serum levels of 25-hydroxyvitamin D serve as a biomarker for future disease activity in early relapsing–remitting multiple sclerosis (RRMS) patients. Large randomized clinical trials (SOLAR and CHOLINE) comparing vitamin D supplementation to a placebo in RRMS patients did not meet their primary endpoints, but showed modest effects on secondary endpoints. Despite discrepancies between trial results and observational studies, evidence suggests that individuals with MS should avoid vitamin D insufficiency and strive for levels around 100 nmol/L or higher.

Paper: Efficacy of high-dose vitamin D3 supplementation in vitamin D deficient pregnant women with multiple sclerosis: Preliminary findings of a randomized-controlled trial.

Journal: Iranian Journal of Neurology, 2015,14(2), 67–73.

Key findings: Relapse during Pregnancy: 55.6% reduction in relapse risk with Vitamin D3. Relapse up to 6 Months After Delivery: 44.4% reduction in relapse risk with Vitamin D3.

Description: The systematic review assessed the impact of vitamin D supplementation on clinical and imaging outcomes in multiple sclerosis (MS) patients. Nineteen independent clinical studies were included, covering relapse events, disability progression (measured by Expanded Disability Status Scale scores), and magnetic resonance imaging (MRI) lesions. While most trials found no significant effect on relapse events or disability, recent randomized controlled trials reported a notable reduction in new MRI lesions in the central nervous system during vitamin D3 supplementation, highlighting a potential positive impact on specific imaging outcomes.

Regarding Vitamin D dosage:

  • Vitamin D is crucial, especially in autumn and winter when sunlight exposure is limited.
  • It’s challenging to get enough vitamin D from food alone, so a daily supplement of 10 micrograms (400 IU) is recommended for adults and children over 4, including pregnant and breastfeeding women (NHS, 2017).
  • Adults with risk factors should take a daily 400 IU vitamin D supplement throughout the year; others should consider it, especially in autumn and winter (NICE, 2022).
  • Recommended daily vitamin D intake varies between 600-800 IU for adults, or 1500-4000 IU for those at risk of deficiency (ESPEN Guidelines, 2022).
  • Vitamin D deficiency, defined as a plasma concentration <50 nmol/L, affects about 40% of Europeans, with severe deficiency (<30 nmol/L) present in 13% (ESPEN Guidelines, 2022).
  • The general upper daily limit for vitamin D intake is 4000 IU, but the Endocrine Society recommends up to 10,000 IU for those at risk of deficiency (ESPEN Guidelines, 2022).

Note: The recommended intake (RNI) of vitamin D, which is based on the quantity needed to maintain bone health, is 10 micrograms, or 400 IU.

There are also many references in the main book by Professor George Jelinek. The Diet section is covered on pages 71-147 of the book and includes a total of 150 scientific evidence-based research articles.