Volume 31, Issue 2 (7-2022)                   JGUMS 2022, 31(2): 166-179 | Back to browse issues page

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Saadat S, Saberi A. Environmental Risk Factors in Multiple Sclerosis: A Narrative Review. JGUMS 2022; 31 (2) :166-179
URL: http://journal.gums.ac.ir/article-1-2382-en.html
Environmental Risk Factors in Multiple Sclerosis: A Narrative Review
Sajjad Saadat1 , Alia Saberi * 2
1- Neuroscience Research Center, Guilan University of Medical Sciences, Rasht, Iran.
2- Department of Neurology, Poursina Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran. , alia.saberi1@gmail.com
Keywords: Epidemiology, Environmental risk factors, Multiple Sclerosis
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Introduction
Multiple sclerosis (MS) is one of the most common chronic autoimmune diseases and a progressive disease of the central nervous system with a prevalence of more than 2.8 million worldwide [2, 1]. The high and increasing prevalence of this disease is mostly among the people aged 20-40 years [4, 3]. MS is a multidimensional heterogeneous disease with varying clinical manifestations [5] that occurs mainly in the form of sensory and motor symptoms [6] and impairs physical, mental and social functioning [7]. Despite recent advances in epidemiological studies and molecular immunology research on MS, it is still unknown which and how risk factors are involved in the pathogenesis of MS [8]. Although a latitude-related risk variation in MS has been accepted [9], variability in MS risk is a more complex phenomenon that may be associated with interregional variations [10] which possibly results from the interaction between several genetic and unspecified environmental factors [11]. Changes in lifestyle and environmental factors increase the risk of MS [12, 13]. Therefore, knowledge of environmental factors can help develop more effective preventive measures for this disease [14]. This study aims to review the environmental risk factors of MS.
Methods
In this review study, a search was conducted in databases such as PubMed, Scopus, ScienceDirect, Google Scholar and Magiran on articles published in Persian and English from 2000 to 2021 using the keywords Multiple Sclerosis, MS, Environmental Risk Factors and Epidemiology.  The case studies, letters to the editor, interventional studies, studies with only available abstracts, studies with unclear methodology and data analysis were excluded. Finally, after reviewing the abstracts and the full texts of the eligible articles, their results were presented in a narrative and analytical manner.
Results
The findings of the studies showed that genetic factors increase the risk of developing MS and when relatives are primarily infected with MS, the risk is even up to 30%. On the other hand, the studies showed that genes with human leukocyte antigen and white people are more susceptible to MS. The risk of developing MS gradually increases with the increase of age and reaches its peak at the age of 30. However, the peak prevalence of MS is shifting to older ages. It is more common in women globally due to the severe hormonal changes they experience throughout their lives. On the other hand, men have shown faster progression and worse consequences of the disease. 
The prevalence of MS is very low in geographical areas close to the equator; with an increase in geographical latitude, the prevalence of MS increases by 5 and 10 times. In recent years, MS in Iran has become more prevalent; Isfahan city has become one of the regions with the highest risk of MS in Asia and the Pacific. Migration-related studies showed that changes in geographical location can significantly affect the risk of MS. Infection with Einstein-Barr virus after adolescence associated with the destruction of myelin in the central nervous system (CNS) can also increase the risk of MS by up to 15 times. Furthermore, the results of studies reported that direct and indirect exposure to tobacco smoke not only increases the risk of developing MS but also increase the risk of developing neutralizing antibodies against the biologics used for the treatment. Moreover, some studies reported that increased exposure to air pollutants may increase the susceptibility to transmissible infections and consequently the risk of MS recurrence in infected individuals. Moreover, the increase in vitamin D (as a strong moderator of the immune system) by exposure to sunlight and supplementation can play a role in preventing and controlling the MS. The consumption of tea, coffee and alcohol have been introduced as factors that reduce the risk and progression of MS. Working night shifts can cause sleep deprivation and suppression of melatonin which can play a role in the pathogenesis of MS. Exposure to stressful and unexpected life events also increases the risk of MS by 17-30%. On the other hand, obesity in adolescence, premature birth, head trauma in childhood, migraine, intestinal inflammation, use of microwave ovens, prolonged exposure to chemicals and industrial solutions, high family economic status, pregnancy and lack of breastfeeding, high salt intake, changes in intestinal microbiota, and child birth in summer and early autumn were some of the risk factors that need to be further investigated.
Discussion
The purpose of this study was to examine the environmental risk factors of MS. The results showed that the age of 20-40 years, female gender, birth season, and air pollution are important risk factors affecting the onset and exacerbation of the disease in MS patients. Moreover, circadian disruption, geographical latitude and distance from the equator, infection to viruses, and metabolic and psychological factors could increase the risk of MS. Immigration, Einstein-Barr virus infection, alcohol and coffee consumption, vitamin D levels, and smoking were also factors that can affect the genetic susceptibility to MS. However, evidence for the other environmental risk factors of MS is limited. The mentioned factors seem to be synergistic, and the risk of developing MS among those exposed to more than one of these factors is higher. 
Having Knowledge of important risk factors of MS and understanding how and when these factors are involved can help develop preventive strategies to reduce the MS prevalence. The health care providers are recommended to pay attention to these factors to reduce the prevalence of MS, especially in high-risk areas of Iran, by providing preventive programs. Further studies are recommended on the impact of environmental factors on the course of MS.

Ethical Considerations
Compliance with ethical guidelines
In this study, no experiments on human or animal models were conducted. Therefore, there was no need for ethical clearance.

Funding
This study did not receive any funding from any public, commercial, or nonprofit funding organizations.

Authors' contributions
Study concept and design: Alia Saberi, Sajjad Saadat; Drafting of the manuscript: Sajjad Saadat; Critical revision of the manuscript for important intellectual content, funding acquisition, supervision: Alia Saberi.

Conflicts of interest
The authors declared no conflict of interest.

Acknowledgements
The authors appreciate the support of the Clinical Research Development Unit of Poursina Hospital.


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Review Paper: Research | Subject: Special
Received: 2021/07/9 | Accepted: 2022/05/22 | Published: 2022/07/1
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