Studies Of Associations Between Disability In Multiple Sclerosis, Skin Type, Gender And Ultraviolet Radiation
Woolmore JA, Stone M, Pye EM, Partridge JM, Boggild M, Young C, Jones PW, Fryer AA, Hawkins CP, Strange RC
Mult Scler 2007 Apr;13(3):369-75
Keele University Medical School, University Hospital of North Staffordshire, Keele Multiple Sclerosis Research, Human Genomics Research Group, Institute of Science and Technology in Medicine, Stoke on Trent, Staffordshire, UK
Recent studies suggest UltraViolet Radiation (UVR)/Vitamin D is protective against the development of Multiple Sclerosis (MS).
We determined if outcome in MS is associated with the surrogate for host pigmentation, skin type, and parameters of UVR exposure.
We used a validated questionnaire to determine skin type and UVR exposure during childhood (0-16 years), and early adult life (17-40 years), in 448 Caucasians with MS.
Outcome was assessed using the Kurtzke Expanded Disability Status Score (EDSS) and Multiple Sclerosis Severity Scale (MSSS).
We studied the association of skin type and exposure with dichotomized values of EDSS (< and > or = 6) and MSSS (continuous variable) using logistic and linear regression analyses, respectively.
Sex, onset age and MS duration were significantly associated with outcome in all patients.
In 169 females with established disease (> or = 10 years), sun sensitive skin types 1 and 2 were associated with reduced risk of EDSS > or = 6 (odds ratio = 0.50; 95% CI = 0.26-0.97), and higher MSSS values (coefficient = -0.86; 95% CI = -1.67 to -0.05).
Parameters of UVR exposure were not significantly associated with outcome. These preliminary data show an association between skin type and disability in female MS patients.
They are compatible with independent studies suggesting that exposure mediates MS pathogenesis via Vitamin D. Further studies are required to properly assess these potentially important findings.
1,25-DihydroxyVitamin D3 Reverses Experimental Autoimmune Encephalomyelitis By Inhibiting Chemokine Synthesis And Monocyte Trafficking
Pedersen LB, Nashold FE, Spach KM, Hayes CE
J NeuroSci Res 2007 Aug 15;85(11):2480-90
University of Wisconsin-Madison, Department of BioChemistry, College of Agricultural and Life Sciences, Madison, Wisconsin, USA
Multiple Sclerosis (MS) is a complex NeuroDegenerative Disease whose pathogenesis involves genetic and environmental risk factors leading to an aberrant, NeuroAntigen-specific, CD4+ T Cell-mediated Autoimmune Response.
In support of the hypothesis that Vitamin-D3 may reduce MS risk and severity, we found that Vitamin-D3 and 1,25-DihydroxyVitamin D3 (1,25-(OH)2D3) inhibited induction of Experimental Autoimmune Encephalomyelitis (EAE), an MS model.
To investigate how 1,25-(OH)2D3 could carry out anti-inflammatory functions, we administered 1,25-(OH)2D3 or a placebo to mice with EAE.
And subsequently analyzed clinical disease, Chemokines, Inducible Nitric Oxide Synthase (iNOS), and recruitment of dye-labeled Monocytes.
The 1,25-(OH)2D3 treatment significantly reduced clinical EAE severity within 3 days.
Sharp declines in Chemokines, inducible iNOS, and CD11b+ Monocyte recruitment into the Central Nervous System (CNS) preceded this clinical disease abatement in the 1,25-(OH)2D3-treated animals.
The 1,25-(OH)2D3 did not directly and rapidly inhibit Chemokine synthesis in vivo or in vitro.
Rather, the 1,25-(OH)2D3 rapidly stimulated activated CD4+ T-Cell Apoptosis in the CNS and Spleen. Collectively, these results support a model wherein inflammation stimulates a natural anti-inflammatory feedback loop.
The activated inflammatory cells produce 1,25-(OH)2D3, and this hormone subsequently enhances the Apoptotic death of inflammatory CD4+ T-Cells, removing the driving force for continued inflammation.
In this way, the sunlight-derived hormone could reduce the risk of chronic CNS inflammation and Autoimmune-mediated NeuroDegenerative Disease.
Copyright 2007 Wiley-Liss, Inc.
Vitamin D Levels In People With Multiple Sclerosis And Community Controls In Tasmania, Australia
van der Mei IA, Ponsonby AL, Dwyer T, Blizzard L, Taylor BV, Kilpatrick T, Butzkueven H, McMichael AJ
J Neurol 2007 May;254(5):581-90
Menzies Research Institute, Private Bag 23, Hobart, Tasmania, 7001, Australia. Ingrid
Adequate 25(OH)D levels are required to prevent adverse effects on bone health. Population-based data on factors associated with 25(OH)D levels of people with MS have been lacking.
To examine the prevalence and determinants of Vitamin D insufficiency in a population-based sample of MS cases and controls, and to compare 25(OH)D status between MS cases and controls, taking into account case disability.
We conducted a population based case-control study in Tasmania, Australia (latitude 41-43 degrees S):
On 136 prevalent cases with MS confirmed by Magnetic Resonance Imaging and 272 community controls, matched on sex and year of birth.
Measurements included Serum 25(OH)D, sun exposure, skin type, dietary Vitamin D intake and disability including EDSS.
A high prevalence of Vitamin D insufficiency was found in MS cases and controls.
Among MS cases, increasing disability was strongly associated with lower levels of 25(OH)D and with reduced sun exposure.
Cases with higher disability (EDSS > 3) were more likely to have Vitamin D insufficiency than controls (OR = 3.07 (1.37, 6.90) for 25(OH)D < /= 40 nmol/l), but cases with low disability were not (OR = 0.87 (0.41, 1.86)).
The strong associations between disability, sun exposure and Vitamin D status indicate that reduced exposure to the sun, related to higher disability:
May contribute to the high prevalence of Vitamin D insufficiency found in this population-based MS case sample.
Active detection of Vitamin D insufficiency among people with MS and intervention to restore Vitamin D status to adequate levels should be considered as part of the clinical management of MS.
Assessment Of 25-HydroxyVitamin-D And 1,25-DihydroxyVitamin-D3 Concentrations In Male And Female Multiple Sclerosis Patients And Control Volunteers
Barnes MS, Bonham MP, Robson PJ, Strain JJ, Lowe-Strong AS, Eaton-Evans J, Ginty F, Wallace JM
Mult Scler 2007 Jun;13(5):670-2
Northern Ireland Centre for Food and Health (NICHE), University of Ulster, Coleraine BT52 1SA, Northern Ireland, UK
Populations with insufficient ultraviolet exposure and who consume diets low in Vitamin-D have low Vitamin-D status (plasma 25-HydroxyVitamin-D (25(OH)D) concentrations) and a reported higher incidence of Multiple Sclerosis (MS).
The active form of Vitamin-D, 1,25-DihydroxyVitamin-D3 (1,25(OH)2D3), is an effective AntiInflammatory molecule. No research to date has assessed 1,25(OH)2D3 concentrations in individuals with MS.
In this study, Plasma concentrations of 25(OH)D, 1,25(OH)2D3 and
ParaThyroid Hormone (PTH) were measured in 29 individuals with MS and 22 age- and sex-matched control volunteers.
There were no significant differences in Plasma PTH, 25(OH)D and 1,25(OH)2D3 concentrations between individuals with MS and control volunteers.
Women with MS had significantly higher 25(OH)D and 1,25(OH)2D3 concentrations than men with MS (79.1+/-45.4 versus 50.2+/-15.3 nmol/L, P=0.019 and 103.8+/-36.8 versus 70.4+/-28.7 pmol/L, P=0.019, respectively).
There was a significant positive correlation between 25(OH)D and 1,25(OH)2D3 concentrations in all subjects (r = 0.564, P = 0.000), but secondary analysis revealed that the correlation was driven by women with MS (r = 0.677, P = 0.001).
Significant sex differences in Vitamin-D metabolism were observed and were most marked in individuals with MS, suggesting that Vitamin-D requirements may differ between the sexes, as well as by underlying disease state.