IntroductionFive to eight percent of the world population currently suffers from at least one autoimmune disorder. Despite multiple immune modulatory therapies for autoimmune demyelinating diseases of the central nervous system, these treatments can be limiting for subsets of patients due to adverse effects and expense. To circumvent these barriers, we investigated a nutritional intervention in mice undergoing experimental autoimmune encephalomyelitis (EAE), a model of autoimmune-mediated demyelination that induces visual and motor pathologies similar to those experienced by people with multiple sclerosis (MS).MethodsEAE was induced in female and male mice and the impact of limiting dietary carbohydrates by feeding a ketogenic diet (KD) enriched in medium chain triglycerides (MCTs), alpha-linolenic acid (an omega-3 fatty acid), and fiber was evaluated in both a preventive regimen (prior to immunization with MOG antigen) and an interventional regimen (following the onset of symptoms). Motor scores were assigned daily and visual acuity was measured using optokinetic tracking. Immunohistochemical analyses of optic nerves were done to assess inflammatory infiltrates and myelination status. Fatty acid and cytokine profiling from blood were performed to evaluate systemic inflammatory status.ResultsThe KD was efficacious when fed as a preventive regimen as well as when initiated as an interventional regimen following symptom onset. The KD minimally impacted body weight during the experimental time course, increased circulating ketones, prevented motor and ocular deficits, preserved myelination of the optic nerve, and reduced infiltration of immune cells to optic nerves. The KD also increased anti-inflammatory-associated omega-3 fatty acids in the plasma and reduced select cytokines in the circulation associated with EAE-mediated pathological inflammation.DiscussionIn light of ongoing clinical trials using dietary strategies to treat people with MS, these findings support that a KD enriched in MCTs, omega-3 fatty acids, and fiber promotes a systemic anti-inflammatory milieu and ameliorates autoimmune-induced demyelinating visual and motor deficits.

5-8% of the world population currently suffers from at least one autoimmune disorder. Despite multiple immune modulatory therapies for autoimmune demyelinating diseases of the CNS, these treatments are restricted to subsets of patients. To overcome these barriers, we investigated a nutritional intervention in mice undergoing experimental autoimmune encephalomyelitis (EAE). This model of autoimmune-mediated demyelination induces visual and motor pathologies similar to those experienced by patients with multiple sclerosis. Here, we report that limiting dietary carbohydrates by feeding mice a well-formulated ketogenic diet (WFKD) enriched in medium chain triglycerides, alpha-linolenic acid, and fiber protects from EAE-induced optic neuritis and motor deficits. The WFKD increased circulating ketones but did not cause weight gain while preserving visual acuity and motor function in both female and male EAE mice. Immunohistochemistry of optic nerves revealed that the WFKD preserved oligodendrocytes and reduced infiltrating T cells and macrophages. The WFKD also increased anti-inflammatory-associated omega-3 fatty acids in the plasma and reduced select cytokines in the circulation associated with inflammation and EAE pathologies. In support of ongoing clinical trials using dietary strategies to treat MS patients, these findings support that a WFKD promotes a systemic anti-inflammatory milieu that mitigates autoimmune-induced demyelinating visual and motor deficits.

This review summarizes the cellular and molecular underpinnings of autoimmune demyelinating optic neuritis (ADON), a common sequela of multiple sclerosis and other demyelinating diseases. We further present nutritional interventions tested for people with multiple sclerosis focusing on strategies that have shown efficacy or associations with disease course and clinical outcomes. We then close by discuss the potential dietary guidance for preventing and/or ameliorating ADON.