Cholecalciferol Plus Calcium Suppresses Abnormal PBMC Reactivity in Patients with Multiple Sclerosis

Kimball, Samantha; Vieth, Reinhold; Dosch, Hans‐Michael; Bar‐Or, Amit; Cheung, Roy K.; Gagné, Donald; O’Connor, Paul; D'Souza, Cheryl; Ursell, Melanie R.; Burton, Jodie M.

doi:10.1210/jc.2011-0325

Cited by 73 publications

(50 citation statements)

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“…30,31 Vitamin D and MS disease activity or progression Vitamin D deficiency has also been associated with increased disease activity or progression in subjects with already established disease. The findings of a few small therapeutic trials using vitamin D in MS patients have been inconsistent, [32][33][34][35][36][37] and none of these studies was powered sufficiently to observe a treatment effect. Large randomised interventional clinical trials in the United States, Europe and Australasia are currently evaluating vitamin D supplementation to decrease the risk of relapses (Table 1).…”

Section: Vitamin D and Ms Riskmentioning

confidence: 99%

Environmental modifiable risk factors for multiple sclerosis: Report from the 2016 ECTRIMS focused workshop

et al. 2017

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Multiple sclerosis (MS) is an inflammatory and neurodegenerative demyelinating disease of the central nervous system (CNS), most likely autoimmune in origin, usually beginning in early adulthood. The aetiology of the disease is not well understood; it is viewed currently as a multifactorial disease which results from complex interactions between genetic predisposition and environmental factors, of which a few are potentially modifiable. Improving our understanding of these factors can lead to new and more effective approaches to patient counselling and, possibly, prevention and management of the disease. The 2016 focused workshop of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) addressed the topic of environmental, modifiable risk factors for MS, gathering experts from around the world, to collate experimental and clinical research into environmental factors that have been associated with the disease onset and, in a few cases, disease activity and progression. A number of factors, including infections, vitamin D deficiency, diet and lifestyle factors, stress and comorbidities, were discussed. The meeting provided a forum to analyse available evidence, to identify inconsistencies and gaps in current knowledge and to suggest avenues for future research.

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Section: Vitamin D and Ms Riskmentioning

confidence: 99%

Environmental modifiable risk factors for multiple sclerosis: Report from the 2016 ECTRIMS focused workshop

et al. 2017

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“…[10][11][12] The immunologic effects of high-dose compared to lowdose vitamin D in patients with MS remain unclear. We also sought to confirm that cholecalciferol at 10,000 IU daily is well-tolerated in patients with MS.…”

Section: -9mentioning

confidence: 99%

Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis

et al. 2016

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Objective: To study the safety profile and characterize the immunologic effects of high-vs low-dose cholecalciferol supplementation in patients with multiple sclerosis (MS).Methods: In this double-blind, single-center randomized pilot study, 40 patients with relapsingremitting MS were randomized to receive 10,400 IU or 800 IU cholecalciferol daily for 6 months. Assessments were performed at baseline and 3 and 6 months.Results: Mean increase of 25-hydroxyvitamin D levels from baseline to final visit was larger in the high-dose group (34.9 ng/mL; 95% confidence interval [CI] 25.0-44.7 ng/mL) than in the lowdose group (6.9 ng/mL; 95% CI 1.0-13.7 ng/mL). Adverse events were minor and did not differ between the 2 groups. Two relapses occurred, one in each treatment arm. In the high-dose group, we found a reduction in the proportion of interleukin-17T cells (p 5 0.03), and effector memory CD4 1 T cells (p 5 0.021) with a concomitant increase in the proportion of central memory CD41 T cells (p 5 0.018) and naive CD4 1 T cells (p 5 0.04). These effects were not observed in the low-dose group.Conclusions: Cholecalciferol supplementation with 10,400 IU daily is safe and tolerable in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects in MS, which include reduction of interleukin-17 production by CD41 T cells and decreased proportion of effector memory CD41 T cells with concomitant increase in central memory CD4 1 T cells and naive CD4 1 T cells. Classification of evidence:This study provides Class I evidence that cholecalciferol supplementation with 10,400 IU daily is safe and well-tolerated in patients with MS and exhibits in vivo pleiotropic immunomodulatory effects. 6,7 These observations may reflect the pleiotropic immunomodulatory effects of vitamin D, involving the innate and adaptive immune system. 7-9The majority of studies examining the immunologic effects of vitamin D have been conducted either in vitro or in animal models, and human studies have employed differing methods and produced discrepant results. [10][11][12] The immunologic effects of high-dose compared to lowdose vitamin D in patients with MS remain unclear. We also sought to confirm that cholecalciferol at 10,000 IU daily is well-tolerated in patients with MS.

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“…The main mechanism of the disease seems to be an autoimmune inflammatory reaction mediated by various components of the immune system [2]. …”

Section: Introductionmentioning

confidence: 99%

“…The vitamin D level has an inverse association with the risk of developing MS and the degree of a patient's disability [11,12]. It has complex effects in modulating the immune response in MS, mainly by decreasing the proinflammatory lymphocytes [2,11]. It regulates the transcription of IL-10 gene [13].…”

Section: Introductionmentioning

confidence: 99%

Short-Term Effect of High-Dose Vitamin D on the Level of Interleukin 10 in Patients with Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Ashtari¹,

Toghianifar²,

Zarkesh-Esfahani

et al. 2015

Neuroimmunomodulation

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Background: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system. Vitamin D has been related to the prevention of MS and to modulating its course. Recent studies have shown the safety of high-dose vitamin D in MS. Objective: This study compared the effects of high-dose vitamin D on interleukin 10 (IL-10) levels in MS patients in a double-blind, randomized clinical trial. Methods: Ninety-four patients with relapsing remitting MS (RRMS) were randomized into a treatment and a placebo group. Both groups received conventional MS treatment. The intervention group received 50,000 IU of vitamin D every 5 days for 3 months. IL-10 was measured at baseline and after 3 months. Results: Serum levels of IL-10 were (median ± IQR): 12.58 ± 11.97 and 10.97 ± 9.97 pg/ml in the intervention and placebo groups, respectively, at baseline (p = 0.161); after 3 months, these levels were 13.76 ± 18.95 and 11.31 ± 19.63 pg/ml, respectively (p = 0.158). The IL-10 level increased significantly after receiving high-dose vitamin D for 3 months (β = 0.737, p = 0.015 and R² = 0.91). Conclusion: IL-10 levels increased significantly in RRMS patients after taking high-dose vitamin D₃ for 3 months. High-dose vitamin D might be useful in promoting an anti-inflammatory state in RRMS patients.

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Cholecalciferol Plus Calcium Suppresses Abnormal PBMC Reactivity in Patients with Multiple Sclerosis

Abstract: MS-associated, abnormal T cell reactivities were suppressed in vivo by cholecalciferol at serum 25(OH)D concentrations higher than 100 nmol/liter.

Cited by 73 publications

References 46 publications

Environmental modifiable risk factors for multiple sclerosis: Report from the 2016 ECTRIMS focused workshop

Environmental modifiable risk factors for multiple sclerosis: Report from the 2016 ECTRIMS focused workshop

Safety and immunologic effects of high- vs low-dose cholecalciferol in multiple sclerosis

Short-Term Effect of High-Dose Vitamin D on the Level of Interleukin 10 in Patients with Multiple Sclerosis: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

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