Background: The prevalence of multiple sclerosis (MS) has been increasing worldwide in recent years, especially among females. The same increasing trends are even observed in East Asian countries, where the prevalence of MS is relatively low compared with Northern European ancestries. Whether the environmental risk factors for MS are shared between Asian and North European ancestries, and the types of environmental factors that contribute to the low and recent increase in MS prevalence in Asian countries remain unknown. This study provides the first comprehensive survey of environmental risks for MS in East Asia. Methods: Patients with MS were recruited from the Department of Neurology at Kyushu University Hospital, Japan between 01 April 2017 and 31 March 2018. Healthy controls (HCs) were recruited by public notification. All participants were residents of Kyushu Island and were required to complete medical history and lifestyle questionnaires. Dietary data were collected using a Food Frequency Questionnaire comprising intake of approximately 140 food and beverage items in the past 1 year. One hundred and three patients with MS and 124 healthy controls (HCs) completed the questionnaires. Age at onset and disability score measured by the Kurtzke Expanded Disability Status Scale (EDSS) were obtained from medical records. Results: Frequency of obesity (body mass index 25 kg/m(2)) at present time was higher in MS patients than in HCs (19.4% vs. 7.4%, p = 0.009), while body mass index at age 18-20 years did not differ between the two groups. Frequency of current or ex-smokers was higher in MS patients than in HCs (50.5% vs. 22.8%, p < 0.0001) and disability measured by the EDSS was more severe in MS patients with active smoking history than in patients without such history (p = 0.006 after adjusting for sex). Passive smoking after age 16 years was also a risk factor for MS (odds ratio: 1.31, 95% confidence interval: 1.05-1.63, p = 0.015). Longer sunlight exposure in early childhood was a protective factor for MS (odds ratio: 0.65 during summer and 0.71 during winter at age 6-10 years; 0.71 during summer and 0.72 during winter at age 11-15 years). MS patients had earlier age of menarche than HCs (mean: 12.4 years vs. 12.9 years, p = 0.031). Intake of grains was lower in MS patients than in HCs, with intake of rice in particular being significantly lower in MS patients than in HCs (mean: 235.2 g/day vs. 280.6 g/day, p = 0.006). Previously reported foods associated with MS in Northern European ancestries were not replicated in Japanese people. Conclusion: Smoking and earlier age of menarche are positively associated and sunlight exposure in early childhood is negatively associated with MS in Japanese people as shown in Caucasians. Intake of steamed short-grain white rice, a staple food in Japan, is newly found to be negatively associated with MS in Japanese people. Although the causality is unclear because the participants were prevalent cases, these environmental factors may be involved in the rising prevalence of MS in Japanese females.
