HEAL MS: A Culturally Adapted Lifestyle Medicine Intervention Targeting Metabolic and Immune Dysregulation in Multiple Sclerosis Using Multi-Omics Profiling

Multiple sclerosis (MS) is a chronic immune-mediated disease of the central nervous system characterized by neurodegeneration, demyelination, and progressive disability. Although current treatments primarily focus on immune suppression, growing evidence indicates that non-immune mechanisms, including mitochondrial dysfunction, metabolic imbalance, and chronic systemic inflammation, play a significant role in disease progression and symptom burden. Multi-omics studies have identified disruptions in mitochondrial proteins, lipid and amino acid metabolism, and inflammatory signaling pathways in individuals with MS, suggesting that systemic metabolic processes contribute to disease activity and may represent modifiable therapeutic targets.

HEAL MS (Healthy Eating and Active Living for Multiple Sclerosis) was developed to address these upstream biological drivers through a structured lifestyle intervention integrating nutrition, physical activity, sleep optimization, and stress regulation. The program is culturally adapted for the UAE population and delivered through a hybrid model combining in-person onboarding and digital support via a bilingual (Arabic-English) mobile application that facilitates behavioral tracking, education, and participant engagement.

This study is a 24-month pilot interventional study designed to evaluate the feasibility, acceptability, and biological impact of the HEAL MS program in individuals with relapsing-remitting or progressive MS. Thirty participants will be recruited from collaborating MS clinics. The study uses a within-subject design consisting of a 12-week observation (control) period followed by a 12-week lifestyle intervention. Assessments are conducted at four timepoints: baseline, pre-intervention, post-intervention, and three months after completion of the intervention. This design allows each participant to serve as their own control, improving statistical sensitivity and reducing inter-individual variability.

The intervention targets four behavioral domains. Adaptive movement training consists of supervised small-group sessions conducted twice weekly using functional resistance exercises based on bodyweight, resistance bands, and suspension training. Exercises are designed to improve strength, neuromuscular coordination, and mitochondrial resilience while remaining scalable to accommodate MS-related fatigue and mobility limitations. The nutrition component emphasizes anti-inflammatory, nutrient-dense whole foods with a macronutrient distribution of approximately 40% carbohydrates, 30% protein, and 30% fat. Personalized calorie targets are calculated using the Mifflin-St Jeor equation, and participants receive meal delivery during the initial two weeks to facilitate adherence before transitioning to guided self-preparation. Sleep optimization focuses on circadian-aligned behavioral strategies such as consistent sleep schedules, screen-light reduction, and timing of meals and exercise. Stress regulation includes daily breath-based practices, mindfulness exercises, and vagal nerve-stimulating techniques designed to support autonomic balance. Participant engagement and adherence are supported through daily behavioral tracking using the mobile application.

The study integrates biological, clinical, and behavioral outcomes to evaluate the mechanistic impact of the intervention. Blood samples collected at each assessment will undergo routine clinical chemistry testing and high-resolution molecular profiling. Proteomic analysis will be performed using the Olink Reveal platform, enabling multiplex quantification of over 1,000 plasma proteins related to immune signaling, inflammation, oxidative stress, and metabolic regulation. Metabolomic profiling will be conducted using nuclear magnetic resonance spectroscopy to quantify approximately 250 circulating metabolic biomarkers related to mitochondrial function and systemic metabolism.