The initiation and prevention of multiple sclerosis

Department of Nutrition, Harvard School of Public Health, 677 Huntington Avenue, Boston, MA 02115, USA.
Nature Reviews Neurology (Impact Factor: 15.36). 10/2012; 8(11). DOI: 10.1038/nrneurol.2012.198
Source: PubMed


Although strong genetic determinants of multiple sclerosis (MS) exist, the findings of migration studies support a role for environmental factors in this disease. Through rigorous epidemiological investigation, Epstein-Barr virus infection, vitamin D nutrition and cigarette smoking have been identified as likely causal factors in MS. In this Review, the strength of this evidence is discussed, as well as the potential biological mechanisms underlying the associations between MS and environmental, lifestyle and dietary factors. Both vitamin D nutrition and cigarette smoking are modifiable; as such, increasing vitamin D levels and smoking avoidance have the potential to substantially reduce MS risk and influence disease progression. Improving our understanding of the environmental factors involved in MS will lead to new and more-effective approaches to prevent this disease.

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    • "Strong epidemiological evidence supports the role of vitamin D in reducing MS relapses (Ascherio et al., 2012). Strikingly, vitamin D levels are higher during spring and summer, when relapse occurrence in MS patients peaks. "
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    ABSTRACT: Seasonal changes in disease activity have been observed in multiple sclerosis, an autoimmune disorder that affects the CNS. These epidemiological observations suggest that environmental factors influence the disease course. Here, we report that melatonin levels, whose production is modulated by seasonal variations in night length, negatively correlate with multiple sclerosis activity in humans. Treatment with melatonin ameliorates disease in an experimental model of multiple sclerosis and directly interferes with the differentiation of human and mouse T cells. Melatonin induces the expression of the repressor transcription factor Nfil3, blocking the differentiation of pathogenic Th17 cells and boosts the generation of protective Tr1 cells via Erk1/2 and the transactivation of the IL-10 promoter by ROR-α. These results suggest that melatonin is another example of how environmental-driven cues can impact T cell differentiation and have implications for autoimmune disorders such as multiple sclerosis.
    Cell 09/2015; 162(6):1338-1352. DOI:10.1016/j.cell.2015.08.025 · 32.24 Impact Factor
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    • "Actually, MS has a multifactorial nature and various environmental factors or metabolic conditions may have a role in its development (Ascherio, 2013): viral infections (Ascherio et al., 2012; Venkatesan and Johnson, 2014), heavy metal poisoning (Latronico et al., 2013; Zanella and Roberti di Sarsina, 2013), smoking (Jafari and Hintzen, 2011), childhood obesity (Munger, 2013), low vitamin D status (Ascherio et al., 2014), or incorrect lifestyle, including wrong dietary habits (Riccio, 2011; Riccio et al., 2011; Riccio and Rossano, 2013). "
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    ABSTRACT: The question whether dietary habits and lifestyle have influence on the course of multiple sclerosis (MS) is still a matter of debate, and at present, MS therapy is not associated with any information on diet and lifestyle. Here we show that dietary factors and lifestyle may exacerbate or ameliorate MS symptoms by modulating the inflammatory status of the disease both in relapsing-remitting MS and in primary-progressive MS. This is achieved by controlling both the metabolic and inflammatory pathways in the human cell and the composition of commensal gut microbiota. What increases inflammation are hypercaloric Western-style diets, characterized by high salt, animal fat, red meat, sugar-sweetened drinks, fried food, low fiber, and lack of physical exercise. The persistence of this type of diet upregulates the metabolism of human cells toward biosynthetic pathways including those of proinflammatory molecules and also leads to a dysbiotic gut microbiota, alteration of intestinal immunity, and low-grade systemic inflammation. Conversely, exercise and low-calorie diets based on the assumption of vegetables, fruit, legumes, fish, prebiotics, and probiotics act on nuclear receptors and enzymes that upregulate oxidative metabolism, downregulate the synthesis of proinflammatory molecules, and restore or maintain a healthy symbiotic gut microbiota. Now that we know the molecular mechanisms by which dietary factors and exercise affect the inflammatory status in MS, we can expect that a nutritional intervention with anti-inflammatory food and dietary supplements can alleviate possible side effects of immune-modulatory drugs and the symptoms of chronic fatigue syndrome and thus favor patient wellness. © The Author(s) 2015.
    ASN Neuro 02/2015; 7(1). DOI:10.1177/1759091414568185 · 4.02 Impact Factor
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    • "Multiple sclerosis (MS) is an inflammatory disease of the central nervous system often affecting young adults [1]. Several environmental exposures have been associated with increased risk of developing MS, the best established are infection with Epstein-Barr virus (EBV), low levels of vitamin D and smoking [2]. The genetic background of MS is complex, and both HLA and non-HLA genes are known to influence the disease susceptibility [3]. "
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    ABSTRACT: Background Several environmental exposures, including infection with Epstein-Barr virus, low levels of vitamin D and smoking are established risk factors for multiple sclerosis (MS). Also, high hygienic standard and infection with parasites have been proposed to influence MS risk. The aim of this study was to investigate the influence of various environmental exposures on MS risk in a Norwegian cohort, focusing on factors during childhood related to the hygiene hypothesis.MethodsA questionnaire concerning environmental exposures, lifestyle, demographics and comorbidity was administrated to 756 Norwegian MS patients and 1090 healthy controls. Logistic regression was used to calculate odds ratio (OR) with 95% confidence interval (CI) for the risk of MS associated with the variables infectious mononucleosis, severe infection during childhood, vaccination and animals in the household during childhood. Age, gender, HLA-DRB1*15:01, smoking and infectious mononucleosis were included as covariates. General environmental exposures, including tobacco use, were also evaluated.ResultsInfectious mononucleosis was confirmed to be significantly associated with increased MS risk, also after adjusting for the covariates (OR¿=¿1.79, 95% CI: 1.12-2.87, p¿=¿0.016). The controls more often reported growing up with a cat and/or a dog in the household, and this was significant for ownership of cat also after adjusting for the covariates (OR¿=¿0.56, 95% CI: 0.40-0.78, p¿=¿0.001). More patients than controls reported smoking and fewer patients reported snuff use.Conclusions In this Norwegian MS case¿control study of environmental exposures, we replicate that infectious mononucleosis and smoking are associated with increased MS risk. Our data also indicate a protective effect on MS of exposure to cats during childhood, in accordance with the hypothesis that risk of autoimmune diseases like MS may increase with high hygienic standard.
    BMC Neurology 10/2014; 14(1):196. DOI:10.1186/s12883-014-0196-x · 2.04 Impact Factor
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