The Effect of a Mediterranean Diet on Quality of Life in Multiple Sclerosis Patients

Currently, there is no definite cure for MS. The current treatments may slow down the degree of disease activity and improve the prognosis of the patients. Yet, still many patients suffer from a decrease in the QoL. The lack of a cure and the reduced QOL raise interest among patients, physicians, and researchers regarding nutritional approaches that may improve the condition of the patients . Indeed, a higher EDSS score has been correlated with poor diet quality. The Western diet, characterized by a high intake of saturated fats, omega-6 fatty acids, and a high proportion of refined carbohydrates, may lead to the activation of pro-inflammatory immune pathways and is therefore not recommended. The Med-Diet is beneficial in preventing heart diseases, and outcomes of a decrease in inflammation processes are evident .Thus, the Med-Diet might have an additive beneficial effect with the current disease-modifying drugs (DMTs) in improving disease severity . Furthermore, the Med-Diet is easy for lifelong adherence compared to the various diets investigated in MS (e.g., ketogenic diets, gluten-free, very low-fat, and fasting-mimicking diets), which require careful clinical monitoring . In addition, Recent studies have shown that the Med-Diet positively affects MS fatigue . Whereas people with MS (pwMS) are highly interested in diet as a potential protective factor against disability and improving QOL and other MS symptoms , empirical evidence remains unclear, limiting the possibility of evidence-based nutritional recommendations. Finally, even though the Med-Diet is known for its anti-inflammatory effect, its exact mechanism and effect on MS progression are still not fully understood. Hence, this study will highlight the potential effects and pathways of Med-Diet to improve the QoL of MS patients.

1. Study Design: A single-blind, randomized controlled, single-center study.
2. MS patients, men and women, Aged 18-70 with confirmed MS diagnosis based on 2017 Mcdonald criteria, fulfilling the eligibility criteria.
3. Baseline data (Time 0 - T0) Socioeconomic and lifestyle information on smoking, physical activity, and medical information regarding disease type and activity. Moreover, Baseline, three months, six months, and 12-month (T0, T3, T6, T12) assessments of: questionnaires: Mediterranean adherence diet questionnaire (I- MEDAS), MS Quality of Life-54 (MSQoL-54), Patient Health Questionnaire (PHQ-9), Fatigue Severity Scale Questionnaire (FSS). Anthropometric measurements: height, weight, waist circumference, bioelectrical impedance analysis, including fat mass and fat-free mass, Hand grip strength. Clinical assessment: A note on the appearance of relapses from the previous visit, EDSS, SDMT, Blood test for complete blood count, chemistry, levels of vitamins D and vitamin B12, CRP, fatty acid composition in red blood cell membranes , neurofilament light chain (NfL), and carotenoids plasma concentration. Food intake will be measured using food diaries, adherence to Med-Diet will be measured using the I-MEDAS .
4. Length of intervention- 6 months. Follow-up will occur immediately after the intervention (T6) and 6 months after the intervention (T12). The main outcome variable will be QOL as measured by the MSQoL-54 questionnaire.
5. The interventions will occur in the Neuroimmunology and Multiple Sclerosis Unit at Tel Aviv Sourasky Medical Center.
6. Methods (Sample size and its justification should be included \& available equipment/means)
7. All eligible patients fulfilling the eligibility criteria will be contacted by study personnel after approval from the treating physician and asked to come for a baseline meeting and explanation of study procedures. Those meeting all inclusion criteria and willing to provide informed consent will be enrolled.
8. Randomization: Individuals will be randomized to intervention or control groups by stratified randomization, where the stratification will be by the severity of the disease as measured by EDSS ( EDSS ≤3, EDSS>3) and sex. To obtain population representativeness and based on the difference between sexes in the disease prevalence, participants will be randomized separately with a ratio of two women per man in the study.
9. Sample size: Based on the average score (mean±SD) of 58.2±21.9 detected in the QoL54 MS questionnaire, to achieve a mean difference between the groups of 10 points in the questionnaire and 80% power, a sample of 77 participants per group is needed. With an anticipated discontinuation/dropout rate, 81 participants per group are needed overall 162 participants
10. Statistical analysis: The investigators will further be able to ensure sufficient power for a multivariate regression model according to the following criteria: The model will include four covariates, which will yield an R-squared of at least .070. It will include one variable (study group), which will yield an increment of .050. The total R-squared for the five variables in the model will be at least .120. With the given sample size of 160 and alpha set at .05, the study will have a power of 0.84