Vitamin D status is associated with relapse rate in pediatric‐onset multiple sclerosis

Mowry, Ellen M.; Krupp, Lauren; Milazzo, Maria; Chabas, Dorothée; Strober, Jonathan B.; Belman, Anita; McDonald, Jamie; Oksenberg, Jorge R.; Bacchetti, Peter; Waubant, Emmanuelle

doi:10.1002/ana.21972

Cited by 316 publications

(257 citation statements)

References 33 publications

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“…Our study shows a clear relationship between vitamin D status and the relapse rate of RRMS patients, as previously reported in several association studies [Van der Mei et al 2007;Smolders et al 2008b;Mowry et al 2010;Simpson et al 2010], but our study is the first so far to observe this finding after systematic vitamin D supplementation. Furthermore, the global quantitative effect of the DSL increase on the relapse reduction found here (13.7% decrease in IR for every 10 nmol/l increase in DSL in the multivariate analysis) confirms the quantitative predictions made in two recent association studies [Mowry et al 2010;Simpson et al 2010], in which broadly similar figures were reported in RRMS patients, most of whom were not being supplemented with vitamin D. It should be noted that in one of these studies [Simpson et al 2010], most of the patients were also under first-line IMT, as in our cohort. However, the fundamental difference between our study and these previous studies is that almost all of our patients have to a greater or lesser extent eventually benefited from the vitamin D effect thanks to active, systematic supplementation.…”

Section: Relationship Between the Relapse Rate And Vitamin D Statussupporting

confidence: 91%

Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation

Pierrot‐Deseilligny

Rivaud-Péchoux

Clerson

et al. 2012

Ther Adv Neurol Disord

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Abstract:Background: Vitamin D could play a protective role in multiple sclerosis. Methods:In an observational, uncontrolled study, vitamin D3 supplementation (3010 IU/day on average) was given to 156 consecutive patients with relapsing-remitting multiple sclerosis, under first-line immunomodulatory therapy and with initial 25-OH-D serum level lower than 100 nmol/l (40 ng/ml). Relapses were determined for 29.1 ± 8.4 months during vitamin D and 29.8 ± 10.1 months before supplementation. The 25-OH-D level was measured before supplementation and several times during supplementation. The incidence rate of relapses before and during supplementation was estimated using negative binomial regression models with follow-up durations as offset terms. The incidence rate and incidence rate ratio of relapses at various 25-OH-D levels were also calculated using negative binomial regression models. Results: In 76 patients, immunomodulatory therapy preceded vitamin D supplementation (by 4.2 ± 2.7 years) and in 80 patients both treatments were started simultaneously. Under supplementation, the 25-OH-D level increased from 49 ± 22 nmol/l to 110 ± 26 nmol/l on average. Pooling data collected before and during supplementation, we found a significant strong inverse relationship between the relapse incidence rate and the 25-OH-D level (p < 0.0001), suggesting that vitamin D did indeed influence the relapse rate. Results of univariate, bivariate and multivariate analyses were analogous: in the multivariate model adjusted for age, disease duration and previous use of immunomodulatory therapy, every 10 nmol increase in 25-OH-D level was associated with a reduction in the relapse incidence rate of 13.7%. Dividing iteratively the population made up of pooled periods into two subgroups according to the 25-OH-D levels, the relapse incidence rate ratio decreased as the 25-OH-D level increased up to 110 nmol/l, but a plateau effect was observed beyond this limit. Conclusion: Further studies are warranted for accurate quantification of the vitamin D effect.

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Section: Relationship Between the Relapse Rate And Vitamin D Statussupporting

confidence: 91%

Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation

Pierrot‐Deseilligny

Rivaud-Péchoux

Clerson

et al. 2012

Ther Adv Neurol Disord

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“…Serum 25(OH) vitamin D (25OHD) levels were measured using chemiluminescence assay as previously described (Heartland Assays, Ames, IA) 26. 25OHD levels were used to adjust analyses because they are associated with risk of MS onset and MS outcomes, such as relapse and possibly disability 26, 27…”

Section: Methodsmentioning

confidence: 99%

“…25OHD levels were used to adjust analyses because they are associated with risk of MS onset and MS outcomes, such as relapse and possibly disability 26, 27…”

Section: Methodsmentioning

confidence: 99%

Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course

Nourbakhsh

Bhargava

Tremlett

et al. 2018

Ann Clin Transl Neurol

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ObjectiveTo determine if altered tryptophan (Trp) metabolism is associated with MS risk or disease severity in children.MethodsParticipants with pediatric‐onset MS and clinically isolated syndrome (CIS) within 4 years of disease onset and healthy controls underwent collection of serum. Longitudinal disability and processing speed measures and relapse data were collected in cases. Global metabolomics were conducted in 69/67 cases/controls. Targeted Trp measurement was performed in a discovery group (82 cases, 50 controls) and a validation group (92 cases, 50 controls), while functional gut microbiome analysis was done in 17 cases. Adjusted logistic, linear and negative binomial regression and Cox‐proportional hazard models were used.ResultsUsing global metabolomics data, higher relative abundances of Trp and indole lactate, a known gut microbiota‐derived Trp metabolite, were associated with lower risk of MS. In cases, higher relative abundances of gut microbiota‐derived Trp metabolites were associated with lower disability and higher processing speed scores and higher relative abundance of kynurenine was associated with higher relapse rate. Using targeted tryptophan measures, in the discovery and validation groups, each 1 mcg/mL increase in serum Trp level was associated with 20% (95% CI: 4–34%) and 32% (95% CI: 16–44%) decrease in adjusted odds of having MS, respectively. A lower relative abundance of gut microbial genes involved in Trp catabolism was associated with higher relapse risk.InterpretationTrp metabolism by the gut microbiota and the kynurenine pathway may be relevant to the risk of MS in children as well as MS activity and severity.

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“…After MS onset, serum 25(OH)D 3 concentration declines [91] , and hypovitaminosis D is observed throughout the course of the disease, even in a clinically isolated syndrome (CIS) [92][93][94] . Thus, the studies measuring 25(OH)D 3 concentration in patients with MS are uninformative in deciding whether vitamin D can decrease the risk of MS [95,96] .…”

Section: Vitamin D and Msmentioning

confidence: 99%

Role of vitamin D in immune responses and autoimmune diseases, with emphasis on its role in multiple sclerosis

Zhang

2010

Neurosci. Bull.

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Vitamin D status is associated with relapse rate in pediatric‐onset multiple sclerosis

Abstract: Lower serum 25-hydroxyvitamin D(3) levels are associated with a substantially increased subsequent relapse rate in pediatric-onset multiple sclerosis or clinically isolated syndrome, providing rationale for a randomized controlled trial of vitamin D supplementation.

Cited by 316 publications

References 33 publications

Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation

Relationship between 25-OH-D serum level and relapse rate in multiple sclerosis patients before and after vitamin D supplementation

Altered tryptophan metabolism is associated with pediatric multiple sclerosis risk and course

Role of vitamin D in immune responses and autoimmune diseases, with emphasis on its role in multiple sclerosis

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