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Environmental Factors


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Epidemiologic studies demonstrate that environmental factors play a significant role in a person’s susceptibility to MS (Ascherio & Munger, 2007 [Part I]; Asherio & Munger, 2007 [Part II]). The following environmental factors have been associated with the risk of MS (Wingerchuk, 2011): vitamin D, infection(s), and smoking.
In their review of environmental risk factors from the perspective of timing in adult-onset MS, Handel and colleagues (2010) suggest that vitamin D influences risk early in life, that EBV acts during adolescence or early adulthood, and that smoking increases a person’s susceptibility to adult-onset MS when individuals are exposed later in life.

Epstein-Barr Virus

An array of environmental risk factors for MS have been examined over the past century.  Of those, the Epstein-Barr virus (EBV), ultra-violet light exposure and vitamin D levels, and cigarette smoking have the clearest supporting evidence (Wingerchuk, 2011).

Evidence pointing to a critical role for EBV includes:

  • A history of symptomatic infectious mononucleosis increases the MS risk more than twofold (Thacker et al, 2006).
  • Elevated serum antibody titers to EBV nuclear antigen 1(EBNA-1) precede the onset of MS (Ascherio et al, 2001) and are associated with MRI activity in established disease (Farrell et al, 2009).
  • EBV infection has been found to be a characteristic feature of the MS brain (Serafini et al, 2007)
The evidence concerning the relationship between MS and MBV isn’t conclusive, however. And these studies have been countered by other studies (Willis et al, 2009; Peferoen et al, 2010; Sargsyan et al, 2010). Read the argument in support of EBV being a requisite causative agent in the pathogenesis of MS; read the argument against EBV being a requisite causative agent in MS pathogenesis.

Epstein-Barr and brain inflammation

In 2010 an international team led by U.-C. Meier (Tzartos et al, 2012) identified clues that may help explain how the Epstein-Barr virus might contribute to the brain inflammation that occurs in MS. White matter postmortem MS tissue and control tissue were analyzed for the expression of the proinflammatory cytokine interferon α (IFNα) by immunohistochemistry, and for EBV by using EBV-encoded RNA (EBER) in situ hybridization. They found high levels of interferon alpha in active MS brain lesions, as well as neighboring immune B cells latently infected by Epstein-Barr virus, in the absence of active viral infection. These findings may point to a possible mechanism for how the virus might indirectly stimulate MS disease activity.

Vitamin D

An array of environmental risk factors for MS have been examined over the past century. Of those, the Epstein-Barr Virus, ultra-violet light exposure and vitamin D levels, and cigarette smoking have the clearest supporting evidence (Wingerchuk, 2011)

Evidence pointing to a critical role for vitamin D includes:

  • In experimental autoimmune encephalomyelitis (EAE), the animal model of MS, vitamin D supplementation prevents and slows the progression of the disease while vitamin D deficiency worsens the disease (Cantorna et al., 1996, 2000; Pedersen et al., 2007).
  • Most people with established MS have relatively low serum levels of vitamin D, and the level appears to decline over time (Nieves et al, 1994; van der Mei et al, 2007; Munger et al, 2006).
  • The risk of developing MS appears to be lower in those with relatively high intakes or relatively high blood levels of vitamin D (Munger et al, 2006; Ascherio & Munger, 2007).
  • In those with MS, high vitamin D levels have been associated with decreased risk for attacks and less severe disability (Smolders et al., 2008a; Simpson et al, 2010).
  • A pilot study (Allen et al, 2010) of the immunomodulatory effects of vitamin D in healthy individuals (n=4), who took 5000-10,000 IU/day of vitamin D over 15 weeks demonstrated a significant rise in serum 25(OH) vitamin D levels, with a corresponding increase in IL-10 production by peripheral blood mononuclear cells and a reduced frequency of Th17 cells..
  • In a one-year, double blind, randomized, placebo controlled study looking at the safety and efficacy of vitamin D3 as an add on therapy to interferon β-1b (IFNB), vitamin D3 reduced MRI disease activity (Soilu-Hӓnninen et al, 2012).
  • Results from the Betaferon/ Betaseron in Newly Emerging multiple sclerosis For Initial Treatment (BENEFIT) and the Betaferon/Betaseron Efficacy Yielding Outcomes of a New Dose in multiple sclerosis (BEYOND) studies suggest a benefit on clinical and MRI measures if patients are treated with both vitamin D and IFNβ-1b.