Introduction: There are a number of well-established risk factors for multiple sclerosis (MS). Other factors, however, showed conflicting or inconsistent results. Here, we examine some factors that are unique to or more practiced in Saudi Arabia (SA) and the Arab region such as waterpipe tobacco smoking (WTS), face veiling, raw milk (RM) and camel milk (CM) consumption, and tuberculosis (TB) infection in addition to other traditional factors. Methods: This is a sex- and age-matched case-control study in which we used a structured questionnaire to examine the relation between a number of factors and exposures and the risk of MS. Three hundred MS patients and 601 controls were included. Data were analyzed across different statistical models using logistic regression adjusting for age, sex, marital status, duration of breastfeeding, age first joining school, coffee consumption, and face exposure. Results: Cigarette smoking (OR = 1.79, [95% CI: 1.01–3.17], p = 0.047), WTS (OR = 2.25, [95% CI: 1.21–4.15], p = 0.010), and CM consumption (OR = 2.50, [95% CI: 1.20–5.21], p = 0.014) increased the risk of MS, while performing hajj (OR = 0.47, [95% CI: 0.34–0.67], p = 0.001), TB infection (OR = 0.29, [95% CI: 0.11–0.78], p = 0.015), face veiling (OR = 0.32, [95% CI: 0.23–0.47], p = 0.001), and coffee consumption (OR = 0.67, [95% CI: 0.49–0.89], p = 0.008) appeared to be associated with decreased risk. No association was found between fast food, processed meat, soft drinks, animal milk (other than camel), or RM consumption and the risk of MS. Conclusion: The results of this case-control study confirm that different means of tobacco smoking are associated with increased risk of MS. It also sheds more light on the complex association between infections and MS.

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