Chapter 8 - The Way Forward With Vitamin D in Multiple Sclerosis (original) (raw)
Related papers
The case for vitamin D supplementation in multiple sclerosis
Multiple Sclerosis and Related Disorders, 2013
Introduction: Given that vitamin D has a role in immunomodulation, and its levels appear to correlate with the development of Multiple Sclerosis (MS), it is conceivable that vitamin D may also influence disease activity in MS patients. In this regard, we conducted a systematic review investigating the evidence for: (1) the role of vitamin D in disease activity in MS, and (2) the therapeutic supplementation of vitamin D in MS.
An Update on Vitamin D and Disease Activity in Multiple Sclerosis
CNS Drugs, 2019
Vitamin D and its main active metabolite 1,25-dihydroxyvitamin D serve a crucial role in maintenance of a healthy calcium metabolism, yet have additional roles in immune and central nervous system cell homeostasis. Serum levels of 25-hydroxyvitamin D are a biomarker of future disease activity in patients with early relapsing-remitting multiple sclerosis (RRMS), and vitamin D supplementation in patients with low circulating 25-dihydroxyvitamin D levels has been anticipated as a potential efficacious treatment strategy. The results of the first large randomized clinical trials (RCTs), the SOLAR and CHOLINE studies, have now been published. The SOLAR study compared 14,000 IU of vitamin D 3 (cholecalciferol) per day with placebo for 48 weeks in 232 randomized patients, whereas CHOLINE compared vitamin D 3 100,000 IU every other week with placebo for 96 weeks in 129 randomized patients. All patients in both studies also used interferon-β-1a. None of the studies met their primary endpoints, which were no evidence of disease activity (NEDA-3) at 48 weeks in SOLAR and annualized relapse rate at 96 weeks in CHOLINE. Both studies did, however, suggest modest effects on secondary endpoints. Thus, vitamin D reduced the number of new or enlarging lesions and new T2 lesions in SOLAR, and the annualized relapse rate and number of new T1 lesions, volume of hypointense T1 lesions, and disability progression in the 90 patients who completed 96 weeks' follow-up in CHOLINE. We conclude that none of the RCTs on vitamin supplementation in MS have met their primary clinical endpoint in the intention to treat cohorts. This contrasts the observation studies, where each 25 nmol/l increase in 25-hydroxyvitamin D levels were associated with 14-34% reducedrelapse risk and 15-50% reduced risk of new lesions on magnetic resonnance imaging. This discrepancy may have several explanations, including confounding and reverse causality in the observational studies. The power calculations of the RCTs have been based on the observational studies, and the RCTs may have been underpowered to detect less prominent yet important effects of vitamin D supplementation. Although the effect of vitamin D supplementation is uncertain and less pronounced than suggested by observational studies, current evidence still support that people with MS should avoid vitamin D insufficiency, and preferentially aim for vitamin D levels around 100 nmol/L or somewhat higher.
Vitamin D and multiple sclerosis: a critical review and recommendations on treatment
Acta Neurologica Belgica, 2012
Multiple sclerosis (MS) is an immune-mediated and degenerative disease of nervous system, which affects mostly young adults. Vitamin D deficiency is a well-known environmental risk factor for MS and is considerable in terms of immediate clinical implications. In addition to its classical action on regulation of bone homeostasis, vitamin D may have a potent impact on cytokine profiles and neuro-inflammation. Given the immunomodulatory effects of vitamin D and its high rate of deficiency in MS patients, prescribing vitamin D is a remarkable issue in MS. The results from several experimental and clinical studies indicate that vitamin D supplementation may ameliorate the inflammation during the relapse phase and attenuate disease progression. We present the experimental and clinical studies, which assessed the effects of vitamin D on the pathophysiology, prevalence and management of MS. The authors also discuss current recommendations on prescription of this vitamin to MS patients.
Multiple Sclerosis Journal - Experimental, Translational and Clinical, 2020
Background Epidemiological, preclinical, and non-interventional studies link vitamin D (VD) serum levels and disease activity in multiple sclerosis (MS). It is unclear whether high-dose VD supplementation can be used as an intervention to reduce disease activity. Objectives The study aimed to compare the effects of every other day high- (20,400 IU) versus low-dose (400 IU) cholecalciferol supplementation on clinical and imaging markers of disease activity in patients with relapsing–remitting MS or clinically isolated syndrome. Methods The EVIDIMS (efficacy of vitamin D supplementation in multiple sclerosis) trial was a multicentre randomized/stratified actively controlled explorative phase 2a pilot trial with a double-blind intervention period of 18 months, add on to interferon-β1b. Results Fifty-three patients were randomized, and 41 patients completed the study. Cholecalciferol supplementation was well tolerated and safe in both arms. After 18 months, clinical (relapse rates, disa...
THE ROLE OF VITAMIN D IN THE PATHOPHYSIOLOGY OF MULTIPLE SCLEROSIS: SUPPLEMENTATION AND PREVENTIVE AND THERAPEUTIC POTENTIAL (Atena Editora), 2024
Introduction: Multiple sclerosis is a neuroinflammatory disease that can manifest itself in different stages and clinical patterns. There is a growing prevalence worldwide, which is the subject of numerous health studies, and the incidence has been associated with low levels of vitamin D, an important metabolite due to its anti-inflammatory and antioxidant role, which can contribute to the management and prevention of MS. Objective: To analyze the effects of vitamin D on the pathogenesis of multiple sclerosis due to its immunomodulatory potential. Methodology: A bibliographic search was carried out on the PubMed and Virtual Health Library platforms and, using the inclusion and exclusion criteria, 18 articles were selected to support this systematic literature review. Results: This study highlighted the strong association between multiple sclerosis recurrence and decreased serum vitamin D levels, linking the pathophysiology of the disease to the effects of this vitamin on the immune system. These factors suggest that supplementation can be seen as a viable strategy for the prevention and treatment of the disease. Final considerations: The review described associates vitamin D hypovitaminosis with a greater susceptibility to MS, but it concludes that more studies and tests are needed to prove the effectiveness of supplementation
Introduction: Multiple sclerosis is a neuroinflammatory disease that can manifest itself in different stages and clinical patterns. There is a growing prevalence worldwide, which is the subject of numerous health studies, and the incidence has been associated with low levels of vitamin D, an important metabolite due to its anti-inflammatory and antioxidant role, which can contribute to the management and prevention of MS. Objective: To analyze the effects of vitamin D on the pathogenesis of multiple sclerosis due to its immunomodulatory potential. Methodology: A bibliographic search was carried out on the PubMed and Virtual Health Library platforms and, using the inclusion and exclusion criteria, 18 articles were selected to support this systematic literature review. Results: This study highlighted the strong association between multiple sclerosis recurrence and decreased serum vitamin D levels, linking the pathophysiology of the disease to the effects of this vitamin on the immune system. These factors suggest that supplementation can be seen as a viable strategy for the prevention and treatment of the disease. Final considerations: The review described associates vitamin D hypovitaminosis with a greater susceptibility to MS, but it concludes that more studies and tests are needed to prove the effectiveness of supplementation.
Vitamin D and multiple sclerosis: correlation, causality, and controversy
Autoimmune diseases, 2011
The last years, many studies reported associations between correlates of vitamin D exposure and several correlates of multiple sclerosis (MS) disease activity. This review discusses studies on vitamin D status, Expanded Disability Status Scale (EDSS) score, and relapse activity of MS. Furthermore, several considerations for intervention studies on vitamin D supplementation in MS are provided.
Vitamin D and Multiple Sclerosis
Critical Reviews in Food Science and Nutrition, 2012
There has been growing interest in determining environmental risk factors that may play a role in the development or progression of multiple sclerosis (MS). Epidemiological evidence and data from human and animal studies have shown an association between low serum vitamin D levels and an increased incidence of MS and that supplementation with vitamin D may protect against MS development and/or disease relapses. The most appropriate vitamin D dosage for patients with MS is unclear, but investigators have proposed that serum vitamin D concentrations between 75 and 100 nmol/L (30-40 ng/mL) are optimal to achieve favorable clinical outcomes. Vitamin D supplemented in doses up to 3000 International Units (IU) daily may be necessary to achieve these levels in many patients, and doses of 500 to 800 IU daily appear to be necessary to maintain desired serum vitamin D levels. Short-term supplementation with doses up to 40 000 IU daily has been found to be safe. However, larger and longer clinical studies are needed to assess whether a true relationship exists between serum vitamin D concentrations and MS and to determine a safe and effective amount of vitamin D supplementation.
Therapeutic Role of Vitamin D in Multiple Sclerosis: An Essentially Contested Concept
Cureus
Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the nervous system with incredibly intricate etiopathogenesis involving numerous genetic, epigenetic, and environmental risk factors. Major environmental risk factors include ultraviolet (UV) radiation, vitamin D, Epstein-Barr virus (EBV) infection, smoking, and high body mass index (BMI). Vitamin D, in particular, can be viewed as one piece of this puzzle, with various tabs and pockets, occupying a sequential site. In this article, we have briefly discussed the neuroimmunology of MS and the role of vitamin D in regulating immune responses. Various observational studies and clinical trials were reviewed and discussed according to stages of disease activity and course of the disease. The data reviewed in this article implied that serum vitamin D levels greatly influence the risk of developing MS and disease activity. Long-term follow-up studies indicated that low serum vitamin D levels correlate with worse disability outcomes. Since clinical trials did not provide significant evidence, the role of vitamin D in controlling disease activity remains unresolved. Larger clinical trials are needed to support the findings of observational studies and provide significant evidence in favour of vitamin D.
Trials, 2012
Background: Multiple sclerosis is the most common chronic inflammatory disease of the central nervous system in young adults. Despite the fact that numerous lines of evidence link both the risk of disease development and the disease course to the serum level of 25-hydroxyvitamin D it still remains elusive whether multiple sclerosis patients benefit from boosting the serum level of 25-hydroxyvitamin D, mainly because interventional clinical trials that directly address the therapeutic effects of vitamin D in multiple sclerosis are sparse. We here present the protocol of an interventional clinical phase II study to test the hypothesis, that high-dose vitamin D supplementation of multiple sclerosis patients is safe and superior to low-dose supplementation with respect to beneficial therapeutic effects.