External Exposome of Italian adults with Multiple Sclerosis focusing on nutrition-related inflammation: results from the cross-sectional EXPOSITION study

Background: The cause of multiple sclerosis (MS) is unknown and likely multifactorial, including genetic, environmental and lifestyle factors. Some dietary patterns have been studied in relation to MS, however the data are scarce, especially about the role of nutrients, dietary inflammation and body composition. Aims: This thesis aims to fill these gaps by assessing nutrition and lifestyle habits in people with MS, examining sex-specific differences and their associations with phase angle and diet-related inflammation. Methods: This thesis is part of the EXPOSITION cross-sectional study, which studied the exposome of people with MS living in the provinces of Milan and Pavia, Italy. Nutritional status, body composition, and lifestyle habits of people with MS (pwMS) were assessed through anthropometric measurements and bioelectrical impedance analysis (BIA) for phase angle, alongside validated questionnaires. Dietary intake was evaluated with a food frequency questionnaire and 24-hour recalls; dietary inflammatory potential with the Dietary Inflammatory Index (DII); and Mediterranean diet adherence with the MEDI-LITE score. Physical activity (IPAQ), sleep quality (PSQI), smoking status, and quality of life (MSQOL-29) were also recorded. Non-parametric tests were used for all variable comparisons, while LASSO regression was applied to explore associations and identify key predictors of phase angle and DII. Results: In total, 131 pwMS (67% women, mean age 46 years) were included in this analysis, with low disability (median EDSS 1.5) and a median phase angle of 5.35⁰. Overall dietary patterns reflected a good adherence to the Mediterranean diet (median MEDI-LITE score 11), though the population reported a highly pro-inflammatory diet (median DII 4.1). Vitamin D insufficiency was common, with a median serum 25(OH)D of 22 ng/ml despite frequent supplement use, and sleep quality was generally poor, especially among women. Regression analyses showed that higher selenium intake and physical activity were associated with higher phase angle, whereas older age and female sex predicted lower values. Additionally, higher serum 25(OH)D was independently linked to lower DII scores, suggesting a role of vitamin D in modulating the inflammatory potential of the diet. Conclusion: The results of this thesis support future personalized interventions combining anti-inflammatory diets, vitamin D levels optimization and tailored physical activity programs to improve muscle health, and consequently phase angle and overall well-being in pwMS. Longitudinal studies including participants with a wider range of disability are needed to confirm these effects and guide evidence-based strategies.