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Prescribing a ketogenic diet (KD) is a century-old dietary intervention mainly used in the context of intractable epilepsy. The classic KD and its variants regained popularity in recent decades, and they are considered potentially beneficial in a variety of neurological conditions other than epilepsy. Many patients with multiple sclerosis have attempted diet modification for better control of their disease, whereas evidence thus far remains insufficient to recommend a specific diet for these patients. The results of three pilot clinical trials of KD therapy for multiple sclerosis, as well as several related studies, have been reported in recent years. The preliminary findings suggest that KD is safe, feasible, and potentially neuroprotective and disease-modifying for patients with multiple sclerosis. Research on corresponding rodent models also lent support to the efficacy of KD in the prevention and treatment of experimental autoimmune encephalomyelitis and toxin-induced inflammatory demyelinating condition in the brain. Furthermore, the animal studies yielded mechanistic insights into the molecular mechanisms of KD action in relevant situations, paving the way for precision nutrition. Herein we review and synthesize recent advances and also identify unresolved issues, such as the roles of adipokines and gut microbiota, in this field. Hopefully this panoramic view of current understanding could inform future research directions and clinical practice with regard to KD in MS and related conditions.

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