Overview of diet and autoimmune demyelinating optic neuritis: a narrative review

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TL;DR

This narrative review examines the relationship between diet and autoimmune demyelinating optic neuritis (ADON), the most common visual complication in multiple sclerosis (MS). The authors synthesize evidence from preclinical and human studies showing that whole-food diets rich in anti-inflammatory omega-3 fatty acids and fiber, while low in ultra-processed foods and pro-inflammatory fats, may reduce ADON risk and severity through mechanisms involving T-cell modulation, gut microbiome health, and reduced systemic inflammation. Despite promising preliminary data, no published human studies have specifically addressed dietary impacts on ADON, highlighting a critical gap in clinically validated nutritional recommendations for this condition.

Full summary

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**Background:** Autoimmune diseases affect 5% to 8% of the US population, with rising incidence attributed partly to environmental factors such as diet. Autoimmune demyelinating optic neuritis (ADON) is the most prevalent visual complication in people with multiple sclerosis (pwMS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated diseases (MOG-AD). ADON affects approximately 50% of pwMS and is the first demyelinating event (FDE) for about 20%. The review focuses on MS-associated ADON and the potential of nutritional interventions, as most dietary intervention data come from the MS literature.

**Methods:** This is a narrative review synthesizing evidence from preclinical experimental autoimmune encephalomyelitis (EAE) models and human observational and interventional studies. The authors searched PubMed for diet and MS literature and reviewed cellular/molecular mechanisms of MS-ADON, including IL-17-secreting T cells, CD8+ T cells, astrocytes, B cells, macrophages/microglia, and infiltrating cell types in ADON lesions. Dietary studies in animal models and human MS dietary studies were reviewed, including impacts on FDEs, foods associated with improved or worsened MS, and various dietary patterns.

**Key Results:** In EAE models, a fatty acid cocktail of eight fatty acids (palmitic, oleic, stearic, linoleic, α-linolenic, γ-linolenic, eicosapentaenoic, and docosahexaenoic acids) prevented RGC apoptosis and restored myelinated fibers. α-lipoic acid dramatically reduced MOG35-55-EAE-induced axonal injury in optic nerves, reduced CD4+ T lymphocytes and CD11b+ macrophages/microglia infiltrates, and prevented inner retinal layer thinning and vision loss. A weight-stabilizing ketogenic diet prevented optic neuritis onset and motor deficits in EAE mice and improved visual and motor function within 4 days when initiated after symptom onset.

In human studies, the Ausimmune Study showed higher yogurt, non-processed red meat, and fish consumption associated with decreased odds of FDE. The Mediterranean diet and other healthy dietary patterns also associated with reduced odds of FDE. Pro-inflammatory diets enriched in added sugars and ultra-processed foods were associated with increased FDE odds. Higher fiber, fruits, vegetables, and healthy fat intake was positively associated with most health outcomes. A 5-year longitudinal study showed a high prudent diet score associated with reduced relapse risk in early MS. A cross-sectional study among 2063 adults with MS revealed a link between higher adherence to Australian dietary guidelines and lower relapse risk, disability, disease activity, and higher quality of life. A multi-center prospective cohort study in pediatric MS reported each 10% increase in energy intake from fat, particularly saturated fat, increased relapse risk, while each additional cup equivalent of vegetables decreased relapse risk. A 6-month randomized controlled trial of the Mediterranean diet reduced EDSS progression compared with controls among women with MS. A recent study showed 6 months of an adapted ketogenic diet reduced serum neurofilament light chain (sNFL), a biomarker of MS severity. However, two prospective cohort studies among 56,867 Danish adults and 185,000 US women found no association between diet quality and MS risk, though MS incidence was only 0.2% in both studies.

**Clinical Implications:** The authors propose five dietary guidelines that may prove efficacious for MS-ADON: (1) whole foods while reducing ultra-processed foods, as ultra-processed food consumption associates with increased FDE likelihood and MS severity; (2) diets enriched in omega-3 anti-inflammatory fatty acids and limited in omega-6 pro-inflammatory fatty acids, with fish consumption associated with a 23% decreased risk of MS; (3) sufficient fermentable and non-fermentable fiber to support a healthy gut microbiome; (4) dietary patterns that reduce biomarkers of MS disease severity, such as ketogenic diets that reduce sNFL; and (5) identification and elimination of potential autoimmune-exacerbating dietary antigens. The authors note that disease-specific dietary recommendations are highly desired by pwMS and that therapeutic diets may be customizable based on personal preferences, culture, costs, and health status. They acknowledge that not all trials have yielded clear findings and that cross-sectional associations can be confounded by disability burdens that preclude acquiring and preparing healthy foods.