Safety and Efficacy of Ketogenic Diet in the Management of Multiple Sclerosis: A Systematic Review

This systematic review examines the safety and efficacy of ketogenic diets (KD) in multiple sclerosis (MS) management. Following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched five major databases through April 2025, identifying six relevant studies published between 2017 and 2024. These studies, predominantly focusing on relapsing-remitting MS, demonstrate consistent benefits of ketogenic interventions across multiple domains. Findings suggest KD normalizes gut microbiome composition, reduces pro-inflammatory markers (ALOX5, COX1, COX2), improves body composition with favorable changes in adipokines (decreased leptin, increased adiponectin), and enhances clinical outcomes, including fatigue, depression, sleep quality, and quality of life measures. Objective neurological improvements were observed in Expanded Disability Status Scale (EDSS) scores, walking ability, and manual dexterity. Adherence rates were notably high, with benefits partially persisting after intervention completion. The metabolic shift induced by ketosis may provide alternative neuronal energy substrates, reduce oxidative stress, and attenuate neuroinflammation. Despite limitations including small sample sizes and study heterogeneity, these preliminary findings suggest KDs represent a promising adjunctive approach in MS management, addressing both inflammatory and neurodegenerative components of the disease. Larger, controlled trials with longer follow-up periods are warranted to establish long-term safety and efficacy profiles.