Vitamin D and multiple sclerosis hospital admissions in Scotland. Is serum vitamin D levels associated with disability in patients with newly diagnosed multiple sclerosis? What is needed to keep persons with multiple sclerosis vitamin D-sufficient throughout the year? A phase I/II dose-escalation trial of vitamin D3 and calcium in multiple sclerosis Therapeutic Effect of Vitamin D3 in Multiple Sclerosis Patients Lower serum vitamin D levels are associated with a higher relapse risk in multiple sclerosis Cytokine profile in patients with multiple sclerosis following vitamin D supplementation Safety and T Cell Modulating Effects of High Dose Vitamin D3 Supplementation in Multiple Sclerosis Vitamin D as an early predictor of multiple sclerosis activity and progression. Vitamin D intake and incidence of multiple sclerosis Vitamin D levels in Hispanics with multiple sclerosis Effect of dietary advice and n‐3 supplementation in newly diagnosed MS patients Vitamin D-mediated immune regulation in Multiple Sclerosis Vitamin D status and effect of low-dose cholecalciferol and high-dose ergocalciferol supplementation in multiple sclerosis Vitamin D, pregnancy, breastfeeding, and postpartum multiple sclerosis relapses. Polyunsaturated fatty acids and the risk of multiple sclerosis Monthly Ambient Sunlight, Infections and Relapse Rates in Multiple Sclerosis Impact of Vitamin A Supplementation on Disease Progression in Patients with Multiple Sclerosis. Anti-Epstein–Barr virus antibodies as serological markers of multiple sclerosis: a prospective study among United States military personnel Multiple sclerosis: decreased relapse rate through dietary supplementation with calcium, magnesium and vitamin D. A randomised placebo controlled exploratory study of vitamin B-12, lofepramine, and L-phenylalanine (the “Cari Loder regime”) in the treatment of multiple sclerosis Treatment of multiple sclerosis with lofepramine, L-phenylalanine and vitamin B(12): mechanism of action and clinical importance: roles of the locus coeruleus and central noradrenergic systems. A randomised, double blind, placebo controlled trial with vitamin D3 as an add on treatment to interferon β-1b in patients with multiple sclerosis
It is now acknowledged that seasonality is a main feature of the complex neurological disorder multiple sclerosis ( MS ) . Having a spring birthday and being exposed to low levels of sunshine significantly increase the risk of MS later in life.1,2 Although global environment is dominated by seasonality , the observation that vitamin D status is inversely associated with risk of MS later in life and that vitamin D regulates the expression of a large number of MS associated genes , strongly indicate that ultra-violet ( UV ) light exposure and consequent effects on vitamin D production are involved in MS etiology.3,4 Intriguingly this essential hormone appears to also play an important role in influencing MS disease course . Studies have shown an inverse association between 25-hydroxyvitamin D ( 25-OH-D ) levels and clinical MS severity and relapse rate.5 Furthermore , in a recent prospect i ve investigation of a large cohort of MS patients , vitamin D status inversely correlated with relapses over the subsequent 6 months.6 Similar Background Although the precise etiology of multiple sclerosis ( MS ) is unknown , it seems that both genetic and environmental factors are important . Recent studies suggest that low serum vitamin D levels are important environmental factor in MS . The aim of this study was to compare the serum levels of vitamin D between MS patients and healthy subjects , and to determine its association with disability  in MS patients . Methods In this cross-sectional study , a total of 52 patients with MS were r and omly recruited and matched for age and sex with 52 healthy subjects .  Demographic characteristics and serum vitamin D levels for both groups , as well as duration of disease Exp and ed Disability Status Scale ( EDSS ) for MS patients were evaluated . Statistical analysis was performed by independent sample s t-test and multiple linear regression analysis . Results The mean serum vitamin D levels were 26.5 ± 16.3 ng/ml in MS patients vs. 37.1 ±19.7 in healthy subjects ( P = 0.003 ) . A linear regression analysis showed no significant association between vitamin D levels and EDSS score of patients with MS ( P = 0.345 ) , after adjusting for the covariates . Conclusion Our findings did not suggest a protective association for serum vitamin D levels against disability in MS patients 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 D3 supplementation on vitamin D status . A 96-week r and omized controlled trial was performed to assess the effect of supplementation with 20,000 IU of vitamin D3 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 Objective : Low vitamin D status has been associated with multiple sclerosis ( MS ) prevalence and risk , but the therapeutic potential of vitamin D in established MS has not been explored . Our aim was to assess the tolerability of high-dose oral vitamin D and its impact on biochemical , immunologic , and clinical outcomes in patients with MS prospect ively . Methods : An open-label r and omized prospect i ve controlled 52-week trial matched patients with MS for demographic and disease characteristics , with r and omization to treatment or control groups . Treatment patients received escalating vitamin D doses up to 40,000 IU/day over 28 weeks to raise serum 25-hydroxyvitamin D [ 25(OH)D ] rapidly and assess tolerability , followed by 10,000 IU/day ( 12 weeks ) , and further downtitrated to 0 IU/day . Calcium ( 1,200 mg/day ) was given throughout the trial . Primary endpoints were mean change in serum calcium at each vitamin D dose and a comparison of serum calcium between groups . Secondary endpoints included 25(OH)D and other biochemical measures , immunologic biomarkers , relapse events , and Exp and ed Disability Status Scale ( EDSS ) score . Results : Forty-nine patients ( 25 treatment , 24 control ) were enrolled [ mean age 40.5 years , EDSS 1.34 , and 25(OH)D 78 nmol/L ] . All calcium-related measures within and between groups were normal . Despite a mean peak 25(OH)D of 413nmol/L , no significant adverse events occurred . Although there may have been confounding variables in clinical outcomes , treatment group patients appeared to have fewer relapse events and a persistent reduction in T-cell proliferation compared to controls . Conclusions : High-dose vitamin D ( ∼10,000 IU/day ) in multiple sclerosis is safe , with evidence of immunomodulatory effects . Classification of evidence : This trial provides Class II evidence that high-dose vitamin D use for 52 weeks in patients with multiple sclerosis does not significantly increase serum calcium levels when compared to patients not on high-dose supplementation . The trial , however , lacked statistical precision and the design requirements to adequately assess changes in clinical disease measures ( relapses and Exp and ed Disability Status Scale scores ) , providing only Class level IV evidence for these outcomes Multiple sclerosis ( MS ) is an inflammatory disease in which the myelin sheaths around the axons of the central nervous system are damaged . The damage leads to demyelination and scarring as well as a broad spectrum of signs and symptoms . The epidemiological data suggest a possible influence of vitamin D as an immunomodulatory agent on multiple sclerosis susceptibility as well as on clinical course of the disease . We investigated the effects of short-term vitamin D3 therapy on Iranian patients with MS . In a prospect i ve r and omized controlled trial study , 62 MS patients received 300,000 IU/month vitamin D3 or placebo as intramuscular injection for 6 months . Our results showed no significant difference between the treatment and the control groups in the exp and ed disability status scale scores and number of gadolinium-enhancing lesions during the 6-month treatment period . After 6 months , the levels of cell proliferation in the vitamin D treatment group were significantly lower than the control group . Also , the levels of transforming growth factor-beta and interleukin-10 in the vitamin D treatment group were significantly higher than the control group . This result suggests that vitamin D therapy may help prevent the development of MS and could be a useful addition to the therapy Objective : There is increasing evidence that vitamin D can be protective against the development of multiple sclerosis ( MS ) , but it may also be beneficial for the clinical course of the disease . Our objective was to prospect ively investigate if 25-hydroxy-vitamin D ( 25-OH-D ) levels are associated with exacerbation risk in MS in a study with frequent serum measurements . Methods : This was a prospect i ve longitudinal study in 73 patients with relapsing-remitting MS .  Blood sample s for 25-OH-D measurements were taken every 8 weeks . Associations between 25-OH-D levels and exacerbation rates were assessed using Poisson regression ( generalized estimating equations ) with the individual serum levels as time-dependent variable . Results : During follow-up ( mean 1.7 years ) , 58 patients experienced a total of 139 exacerbations . Monthly moving averages of 25-OH-D levels were categorized into low ( < 50 nmol/L ) , medium ( 50–100 nmol/L ) , and high ( > 100 nmol/L ) levels . Exacerbation risk decreased significantly with higher serum vitamin D levels : respective relative exacerbation rates for the medium and high-level category as compared to the low-level category were 0.7 and 0.5 ( p value for trend : p = 0.007 ) . The association between 25-OH-D concentrations and exacerbation rate was log linear without a threshold . With each doubling of the serum 25-OH-D concentration the exacerbation rate decreased by 27 % ( 95 % confidence interval 8%–42 % , p = 0.008 ) . Conclusions : Our finding that higher vitamin D levels are associated with decreased exacerbation risk in relapsing-remitting MS suggests a beneficial effect of vitamin D on disease course in MS . However , the possibility of reverse causality can not be ruled out completely . R and omized intervention studies are therefore needed to investigate the effect of vitamin D supplementation in MS Multiple sclerosis ( MS ) patients were r and omized , in a double blind design , and placed into either a vitamin D supplemented group or a placebo control group . As expected , serum 25-hydroxyvitamin D levels increased significantly following 6 month vitamin D supplementation ( 17+/-6 ng/ml at baseline to 28+/-8 ng/ml at 6 months ) . Vitamin D supplementation also significantly increased serum transforming growth factor (TGF)-beta 1 levels from 230+/-21 pg/ml at baseline to 295+/-40 pg/ml 6 months later . Placebo treatment had no effect on serum TGF-beta 1 levels . Tumor necrosis factor (TNF)-alpha , interferon (IFN)-gamma , and interleukin (IL)-13 were not different following vitamin D supplementation . IL-2 mRNA levels decreased following vitamin D supplementation but the differences did not reach significance . Vitamin D supplementation of MS patients for 6 months was associated with increased vitamin D status and serum TGF-beta 1 Background A poor vitamin D status has been associated with a high disease activity of multiple sclerosis ( MS ) . Recently , we described associations between vitamin D status and peripheral T cell characteristics in relapsing remitting MS ( RRMS ) patients . In the present study , we studied the effects of high dose vitamin D3 supplementation on safety and T cell related outcome measures . Methodology /Principal Findings Fifteen RRMS patients were supplemented with 20 000 IU/d vitamin D3 for 12 weeks . Vitamin D and calcium metabolism were carefully monitored , and T cell characteristics were studied by flowcytometry . All patients finished the protocol without side-effects , hypercalcaemia , or hypercalciuria . The median vitamin D status increased from 50 nmol/L ( 31–175 ) at week 0 to 380 nmol/L ( 151–535 ) at week 12 ( P<0.001 ) . During the study , 1 patient experienced an exacerbation of MS and was censored from the T cell analysis . The proportions of ( naïve and memory ) CD4 + Tregs remained unaffected . Although Treg suppressive function improved in several subjects , this effect was not significant in the total cohort ( P = 0.143 ) . An increased proportion of IL-10 + CD4 + T cells was found after supplementation ( P = 0.021 ) . Additionally , a decrease of the ratio between IFN-γ+ and IL-4 + CD4 + T cells was observed ( P = 0.035 ) . Conclusion / Significance Twelve week supplementation of high  dose vitamin D3 in RRMS patients was well tolerated and did not induce decompensation of calcium metabolism . The skewing towards an anti-inflammatory cytokine profile supports the evidence on vitamin D as an immune-modulator , and may be used as outcome measure for upcoming r and omized placebo-controlled trials . Trial Registration Clinical trials.gov IMPORTANCE It remains unclear whether vitamin D insufficiency , which is common in individuals with multiple sclerosis ( MS ) , has an adverse effect on MS outcomes . OBJECTIVES To determine whether serum concentrations of 25-hydroxyvitamin D ( 25[OH]D ) , a marker of vitamin D status , predict disease activity and prognosis in patients with a first event suggestive of MS ( clinical ly isolated syndrome ) . DESIGN , SETTING , AND PARTICIPANTS The Betaferon/Betaseron in Newly Emerging multiple sclerosis For Initial Treatment study was a r and omized trial originally design ed to evaluate the impact of early vs delayed interferon beta-1b treatment in patients with clinical ly isolated syndrome .  Serum 25(OH)D concentrations were measured at baseline and 6 , 12 , and 24 months . A total of 465 of the 468 patients r and omized had at least 1 25(OH)D measurement , and 334 patients had them at both the 6- and 12-month ( seasonally asynchronous ) measurements . Patients were followed up for 5 years clinical ly and by magnetic resonance imaging . MAIN OUTCOMES AND MEASURES New active lesions , increased T2 lesion volume , and brain volume on magnetic resonance imaging , as well as MS relapses and disability ( Exp and ed Disability Status Scale score ) . RESULTS Higher 25(OH)D levels predicted reduced MS activity and a slower rate of progression . A 50-nmol/L ( 20-ng/mL ) increment in average serum 25(OH)D levels within the first 12 months predicted a 57 % lower rate of new active lesions ( P < .001 ) , 57 % lower relapse rate ( P = .03 ) , 25 % lower yearly increase in T2 lesion volume ( P < .001 ) , and 0.41 % lower yearly loss in brain volume ( P = .07 ) from months 12 to 60 . Similar associations were found between 25(OH)D measured up to 12 months and MS activity or progression from months 24 to 60 . In analyses using dichotomous 25(OH)D levels , values greater than or equal to 50 nmol/L ( 20 ng/mL ) at up to 12 months predicted lower disability ( Exp and ed Disability Status Scale score , -0.17 ; P = .004 ) during the subsequent 4 years . CONCLUSIONS AND RELEVANCE Among patients with MS mainly treated with interferon beta-1b  , low 25(OH)D levels early in the disease course are a strong risk factor for long-term MS activity and progression Background : A protective effect of vitamin D on risk of multiple sclerosis ( MS ) has been proposed , but no prospect i ve studies have addressed this hypothesis . Methods : Dietary vitamin D intake was examined directly in relation to risk of MS in two large cohorts of women : the Nurses ’ Health Study ( NHS ; 92,253 women followed from 1980 to 2000 ) and Nurses ’ Health Study II ( NHS II ; 95,310 women followed from 1991 to 2001 ) .  Diet was assessed at baseline and up date d every 4 years thereafter . During the follow-up , 173 cases of MS with onset of symptoms after baseline were confirmed . Results : The pooled age-adjusted relative risk ( RR ) comparing women in the highest quintile of  total vitamin D intake at baseline with those in the lowest was 0.67 ( 95 % CI = 0.40 to 1.12 ; p for trend = 0.03 ) . Intake of vitamin D from supplements was also inversely associated with risk of MS ; the RR comparing women with intake of ≥400 IU/day with women with no supplemental vitamin D intake was 0.59 ( 95 % CI = 0.38 to 0.91 ; p for trend = 0.006 ) . No association was found between vitamin D from food and MS incidence . Conclusion : These results support a protective effect of vitamin D intake on risk of developing MS Vitamin D has been associated with multiple sclerosis ( MS ) and several markers of disease state in whites . There are limited reports of vitamin D ’s influence in MS in ethnic groups , such as in Hispanics . In this study , we compared vitamin D levels in  Hispanics and whites with MS and tried to determine whether season or increasing disability influence hypovitaminosis D in Hispanics with MS .  Serum 25-hydroxyvitamin D [ 25(OH)D ] levels and clinical characteristics were compared in a cross-sectional sample of Hispanics ( n = 80 ) and whites ( n = 80 ) with MS recruited from the University of Southern California . Serum 25(OH)D levels were significantly lower in Hispanics than whites with MS ( mean and st and ard deviation 25.1 ± 9.4 and 37.3 ± 19.8 ng/ml , respectively ; p < 0.001 ) . Hispanics were significantly more likely than whites to be  vitamin D insufficient ( ≤30 ng/ml ; 70 vs. 41 % , respectively ; p < 0.001 ) and deficient ( ≤20 ng/ml ; 40 vs. 14 % , respectively , p < 0.001 ) . In Hispanics , serum 25(OH)D levels were not influenced by season ( p = 0.8 ) or higher physical disability ( EDSS ≥6 , p = 0.7 ) . We found that the relationship between vitamin D and MS differs by Hispanic ethnicity . Hypovitaminosis D was significantly more common among Hispanics than among whites with MS , and the majority of Hispanics were vitamin D insufficient . Interestingly , there was no association between vitamin D levels and season or increasing disability in the Hispanics . Our findings imply that factors influencing vitamin D levels and possibly vitamin D  requirements may vary by ethnicity in patients with MS . These results should be confirmed in larger , prospect i ve multi-ethnic cohort studies Objective – To investigate whether supplementation with fish oil given together with dietary advice and vitamin supplementation influenced the clinical outcome in newly diagnosed multiple sclerosis ( MS ) patients . Material and methods – Sixteen consecutive , newly diagnosed patients with multiple sclerosis were recruited to an open intervention study . They were given dietary advice and supplemented with 0.9 g/day of long‐chain marine fatty acids and vitamins . The patients were followed for 2 years with respect to dietary habits , blood parameters and neurological assessment including exacerbation rate . Results – There was a significant reduction in the mean annual exacerbation rate and the mean Exp and ed Disability Status Scale ( EDSS ) as compared to pre‐ study values . The plasma total phospholipid n‐3 fatty acids increased and n‐6 fatty acids decreased significantly . Conclusions – The results suggest that fish oil supplementation given together with vitamins and dietary advice can improve clinical outcome in patients with newly diagnosed MS Although Vitamin D is best known as a modulator of calcium homeostasis , it also has immune modulating potential . A protective effect of Vitamin D on Multiple Sclerosis ( MS ) is supported by the reduced risk associated with sun exposure and use of Vitamin D supplements . Moreover , high circulating levels of Vitamin D have been associated with lower risk of MS . To gain more insight into putative regulatory mechanisms of Vitamin D in MS pathogenesis , we studied 132 Hispanic patients with clinical ly definite MS , 58 with relapsing remitting MS ( RR MS ) during remission , 34 RR MS patients during relapse , and 40 primary progressive MS cases ( PP MS ) . Sixty healthy individuals matched with respect to place of residence , race/ethnicity , age and gender served as controls  . Levels of 25(OH ) Vitamin D and 1,25(OH)(2 ) Vitamin D  , measured by ELISA were significantly lower in RR MS patients than in controls . In addition , levels in patients suffering relapses were lower than during remissions . By contrast , PP MS patients showed similar values to controls . Proliferation of both freshly isolated CD4 + T cells and MBP-specific T cells was significantly inhibited by 1,25(OH)(2 ) Vitamin D. Moreover , activated Vitamin D enhanced the development of IL-10 producing cells , and reduced the number of IL-6 and IL-17 secreting cells . Notably , VDR expression was induced by 1,25(OH)(2 ) Vitamin D in both activated and resting cells . Interestingly , T cells were able to metabolize 25(OH ) Vitamin D into biologically active 1,25(OH)(2 ) Vitamin D , since T cells express 1α-hydroxylase constitutively . Finally , 1,25(OH)(2 ) Vitamin D also increased the expression and biological activity of IDO , triggering significant increase in the number of CD4+CD25 + T regulatory cells . Collectively , these findings suggest that 1,25(OH)(2 ) VitaminD plays an important role in T cell homeostasis during the course of MS , suggesting correction of its deficiency may be useful during treatment of the disease Background Vitamin D is important for bone health and immune regulation , and has been shown to be low in multiple sclerosis ( MS ) . We sought to determine the effect of over the counter low dose cholecalciferol ( LDC ) and high dose ergocalciferol ( HDE ) on the vitamin D levels in MS patients . Methods We retrospectively evaluated serum 25-hydroxy-vitamin D [ 25(OH)D ] levels of 199 patients ( CIS , n = 32 ; RRMS , n = 115 ; PPMS , n = 10 ; SPMS , n = 16 ; Transverse Myelitis ( TM ) , n = 9 ; other neurological diseases , n = 16 ) attending our clinic between 2004 and 2008 . We examined the change in  25(OH)D levels in 40 MS patients who took either LDC ( ≤800 IU/day ) or HDE ( 50,000 IU/day for 7 - 10 days , followed by 50,000 IU weekly or biweekly ) . Results The average 25(OH)D level was 71 ± 39 nmol/L ( Mean ± SD ) , and 167(84 % ) patients had insufficient levels ( ≤100 nmol/L ) of 25(OH)D. The patients supplemented with LDC did not have a significant increase in their 25(OH)D levels . However , 25(OH)D levels increased by 42 nmol/L ( P = 0.01 ) in the patients originally taking LDC and then prescribed HDE . Optimal levels ( ≥100 nmol/L ) were only achieved in less than 40 % of patients . Conclusions We conclude that large numbers of patients with MS and TM in our cohort are deficient in vitamin D. HDE significantly elevated 25(OH)D levels in MS patients and was more effective at increasing 25(OH)D levels than LDC . Prospect i ve studies are required to determine appropriate dosing regimen to achieve optimal levels in the majority of MS patients and to ascertain the safety , immunological response , and ultimately the clinical efficacy of vitamin D replacement therapy OBJECTIVE To determine whether low levels of 25-hydroxyvitamin D ( 25[OH]D ) contribute to the increased risk of postpartum multiple sclerosis ( MS ) relapses . DESIGN Prospect i ve cohort study . SETTING Out patients identified through membership records of Kaiser Permanente Northern California or Stanford University outpatient neurology clinics . PATIENTS Twenty-eight pregnant women with MS . INTERVENTIONS We prospect ively followed up patients through the postpartum year and assessed exposures and symptoms through structured interviews .  Total serum 25(OH)D levels were measured using the DiaSorin Liaison Assay during the third trimester and 2 , 4 , and 6 months after giving birth . The data were analyzed using longitudinal multivariable methods . MAIN OUTCOME MEASURES Levels of 25(OH)D and relapse rate . RESULTS Fourteen ( 50 % ) women breastfed exclusively , and 12 women ( 43 % ) relapsed within 6 months after giving birth . During pregnancy , the average 25(OH)D levels were 25.4 ng/mL ( range , 13.7 - 42.6 ) and were affected only by season ( P=.009 ) . In contrast , in the postpartum period , 25(OH)D levels were significantly affected by breastfeeding and relapse status . Levels of 25(OH)D remained low in the exclusive breastfeeding group , yet rose significantly in the nonexclusive breastfeeding group regardless of season ( P=.007 , unadjusted ; P=.02 , adjusted for season ) . By 4 and 6 months after childbirth , 25(OH)D levels were , on average , 5 ng/mL lower in the women who breastfed exclusively compared with the nonbreastfeeding group ( P=.001 ) . CONCLUSIONS Pregnancy and exclusive breastfeeding are strongly associated with low 25(OH)D levels  in women with MS . However , these lower vitamin D levels were not associated with an increased risk of postpartum MS relapses . These data suggest that low vitamin D in isolation is not an important risk factor for postpartum MS relapses Background : Results from previous studies on polyunsaturated fatty acid ( PUFA ) intake and multiple sclerosis ( MS ) risk are conflicting . Objective : To prospect ively investigate the association between dietary intake of PUFA and MS risk . Methods : We followed 80,920 women from Nurses ’ Health Study ( 1984–2004 ) and 94,511 women from Nurses ’ Health Study II ( 1991–2009 ) who reported on diet using a vali date d food frequency question naire every 4 years and identified 479 incident MS cases during follow-up . We used Cox regression to estimate hazard ratios ( HRs ) and 95 % confidence intervals ( CIs ) , for the effect of PUFA intake on MS risk adjusting for age , latitude of residence at age 15 , ancestry , cigarette smoking , supplemental vitamin D intake , body mass index , and total energy intake . Results : Higher intake of total PUFA at baseline was associated with a lower risk of MS ( HR top vs bottom quintile : 0.67 , 95 % CI : 0.49–0.90 , p trend = 0.01 ) . Among the specific types of PUFA , only α-linolenic acid ( ALA ) was inversely associated with MS risk ( HR top vs bottom quintile : 0.61 , 95 % CI : 0.45–0.83 , p trend = 0.001 ) . The long-chain fatty acids eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) were not associated with MS risk . Conclusion : Low dietary PUFA intake may be another modifiable risk factor for MS Background : Monthly variation in multiple sclerosis ( MS ) relapses has been found . The relationship between seasonal environmental factors , infections , serum vitamin D [ 25(OH)D ] and MS relapses is undetermined . Methods : We prospect ively followed a population -based cohort of relapsing-remitting ( RR ) MS patients in Southern Tasmania for a mean 2.3 years ( January 2002–April 2005 ) . Associations between monthly ambient environmental factors , estimated serum 25(OH)D , upper respiratory tract ( URT ) infections and relapse rates were examined using weighted Pearson ’s correlation and linear regression . Results : Of 199 definite MS patients , 142 had RRMS . The lowest relapse rate of 0.5 per 1,000 days ( 95 % CI : 0.2–1.3 ) occurred in February ( mid-late summer ) versus the March – January RR of 1.1 per 1,000 days ( 95 % CI : 0.9–1.3 ; p = 0.018 , weighted regression ) . Monthly relapse rates correlated with : ( 1 ) prior erythemal ultraviolet radiation ( EUV ) : lagged 1.5 months , r = –0.32 , p = 0.046 ; ( 2 ) URT infection rate : no lag , r = 0.39 , p = 0.014 ; ( 3 ) 25(OH)D : no lag , r = –0.31 , p = 0.057 . The association between URT infections and relapses was reduced after adjustment for monthly EUV . Conclusions : Relapse rates were inversely associated with EUV and serum 25(OH)D levels and positively associated with URT infections . The demonstrated lag between EUV but not 25(OH)D and relapse rates is consistent with a role for EUV-generated 25(OH)D in the alteration of relapse rates . Future work on the association between URT infections and relapses should be considered in the context of ultraviolet radiation and vitamin BACKGROUND Many studies have shown that active vitamin A derivatives suppress the formation of pathogenic T cells in multiple sclerosis ( MS ) patients . The aim of the present study is to determine the impact of vitamin A on disease progression in MS patients . METHODS A total of 101 relapsing-remitting MS ( RRMS ) patients were enrolled in a 1-year placebo-controlled r and omized clinical trial . The treated group received 25000 IU/d retinyl palmitate for six month followed by 10000 IU/d retinyl palmitate for another six month . The results of the exp and ed disability status scale ( EDSS ) and multiple sclerosis functional composite ( MSFC ) were recorded at the beginning and the end of the study . The relapse rate was recorded during the intervention . Patients underwent baseline and follow up brain MRIs . RESULTS The results showed " Mean ± SD " of MSFC changes in the treated group was ( -0.14 ± 0.20 ) and in the placebo group was ( -0.31 ± 0.19 ) . MSFC was improved significantly ( P < 0.001 ) in the treatment group . There were no significant differences between the " Mean ± SD " of EDSS changes in the treated ( 0.07 ± 0.23 ) and placebo ( 0.08 ± 0.23 ) groups ( P = 0.73 ) . There were also no significant differences between the " Mean ± SD " of annualized relapse rate in the treated group ( -0.36 ± 0.56 ) and placebo ( -0.53 ± 0.55 ) groups ( P = 0.20 ) . The " Mean ± SD " of enhanced lesions in the treatment ( 0.4 ± 1.0 ) and in the placebo ( 0.2 ± 0.6 ) groups were not significantly different ( P = 0.26 ) . Volume of T2 hyperintense lesions " Mean ± SD " was not significantly different between treatment ( 45 ± 137 ) and placebo ( 23 ± 112 ) groups after intervention ( P = 0.23 ) . CONCLUSION Vitamin A  improved total MSFC score in RRMS patients , but it did not change EDSS , relapse rate and brain active lesions Background : Elevated Epstein – Barr virus ( EBV ) antibody titers are risk factors for multiple sclerosis ( MS ) , but the strength and consistency of this association are not well characterized . Objectives : The objectives of this study were to determine whether this association is confounded by vitamin D or modified by gender or race , and the usefulness of EBV nuclear antigen ( EBNA ) antibodies as a marker for MS . Methods : We conducted a prospect i ve study among US military personnel .  Antibody titers against EBV antigens  were measured in serum sample s from 222 individuals who developed MS and 444 age , sex , and race/ethnicity matched controls . Conditional logistic regression was used to estimate relative risks . Results : MS risk increased with increasing titers of anti-EBNA complex ( p < 10−9 ) and anti-EBNA-1 ( p = 5.8 × 10−9 ) titers . MS risk was 36-fold higher among individuals with anti-EBNA complex IgG titers ≥320 than among those with titers < 20 ( 95 % confidence interval [ CI ] 9.6–136 ) , and 8-fold higher among those with anti-EBNA-1 ≥320 than among those with anti-EBNA-1 < 20 ( 95 % CI 2.6–23 ) . These associations were consistent across gender and race/ethnicity groups and independent from 25-hydroxyvitamin D levels . Areas under the receiver operating characteristic ( ROC ) curves were 0.67 for EBNA complex and 0.65 for EBNA-1 . Conclusions : Serum titers of pre-onset anti-EBNA antibodies are strong , robust markers of MS risk and could be useful in an MS risk score A group of young patients having multiple sclerosis was treated with dietary supplements containing calcium , magnesium and vitamin D for a period of one to two years . The experimental design employed self-pairing : the response of each patient was compared with his/her own case history as control . The number of exacerbations observed during the program was less than one half the number expected from case histories . No side effects were apparent . The dietary regimen may offer a new means of controlling the exacerbation rate in MS , at least for younger patients . The results tend to support a theory of MS which states that calcium and magnesium are important in the development , structure and stability of myelin Objective : To determine whether combination therapy with lofepramine , L-phenylalanine , and intramuscular vitamin B-12 ( the “ Cari Loder regime ” ) reduces disability in patients with multiple sclerosis . Methods : A placebo controlled , double blind , r and omised study carried out in five United Kingdom centres on out patients with clinical ly definite multiple sclerosis , measurable disability on Guy 's neurological disability scale ( GNDS ) , no relapse in the preceding six months , and not on antidepressant drugs . Over 24 weeks all patients received vitamin B-12 , 1 mg intramuscularly weekly , and either lofepramine 70 mg and L-phenylalanine 500 mg twice daily , or matching placebo tablets . Outcome was assessed using the GNDS , the Kurtzke exp and ed disability status scale ; the Beck depression inventory , the Chalder fatigue scale , and the Gulick MS specific symptom scale . Results : 138 patients were entered , and two were lost from each group . There was no statistically significant difference between the groups at entry or at follow up . Analysis of covariance suggested that treated patients had better outcomes on four of the five scales used . Both groups showed a reduction of 2 GNDS points within the first two weeks , and when data from all time points were considered , the treated group had a significant improvement of 0.6 GNDS points from two weeks onwards . Conclusions : Patients with multiple sclerosis improved by 2 GNDS points after starting vitamin B-12 injections . The addition of lofepramine and L-phenylalanine added a further 0.6 points benefit . More research is needed to confirm and explore the significance of this clinical ly small difference In a r and omized , placebo-controlled double-blind trial a combination of lofepramine , phenylalanine and vitamin B(12 ) was found to be effective in relieving the symptoms of multiple sclerosis ( MS ) .  The effect occurred within 2 - 4 weeks , and improved all types of symptoms in all types of MS . The combination was also effective in relieving symptoms in patients with chronic pain and chronic fatigue .  We hypothesize that the action of this combined therapy may relate to activation of the noradrenergic locus coeruleus/lateral tegmentum ( LC/LT ) system which has the potential to influence the functioning of large areas of the brain and spinal cord Objectives To study the safety and efficacy of vitamin D3 as an add on therapy to interferon β-1b ( IFNB ) in patients with multiple sclerosis ( MS ) . Methods 1 year , double blind , placebo controlled , r and omised study in 66 MS patients . The primary outcomes were T2 burden of disease ( BOD ) on MRI scans , proportion of patients with serum levels of 25-hydroxyvitamin D ( 25(OH)D ) ≥85 nmol/l or intact parathyroid hormone ( PTH ) ≤20 ng/l , and number of adverse events . Secondary outcomes were number of MRI enhancing T1 lesions and new T2 lesions , annual relapse rate , changes in the Exp and ed Disability Status Scale score , timed 25 foot walk test and timed 10 foot t and em walk tests . Results Median change in BOD was 287 mm3 in the placebo group and 83 mm3 in the vitamin D group ( p=0.105 ) . Serum levels of 25(OH)D increased from a mean of 54 ( range 19–82 ) nmol/l to 110 ( range 67–163 ) nmol/l in the vitamin D group . 84 % of patients reached a serum 25(OH)D level > 85 nmol/l in the vitamin D group and 3 % in the placebo group ( p<0.0001 ) . Patients in the vitamin D group showed fewer new T2 lesions ( p=0.286 ) and a significantly lower number of T1 enhancing lesions ( p=0.004 ) , as well as a tendency to reduced disability accumulation ( p=0.071 ) and to improved timed t and em walk ( p=0.076 ) . There were no significant differences in adverse events or in the annual relapse rate . Conclusion Vitamin D3 add on treatment to IFNB reduces MRI disease activity in MS . Trial registration number EudraCT number 2007 - 001958 - 99 and Clinical TrialsGov number NCT01339676
To sum up , low vitamin D  levels are associated with an increased risk of MS
To estimate the associations between vitamin D status and multiple sclerosis ( MS ) .