Role of Ketogenic Diets in Multiple Sclerosis and Related Animal Models: An Updated Review

Abstract

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.

Immune Modulatory Effects of Ketogenic Diet in Different Disease Conditions

“…Kim et al (2012) showed the favorable effect of KD correlated with decreased inflammation markers of brain in an experimental autoimmune encephalomyelitis (EAE) murine model [119]. KD could rescript crucial characteristics of MS pathogenesis through enriched CNS bioenergetics, and ketosis supported the expression of antioxidant pathways and lowered effector cell related protection [123]. KD is allied with a neuroprotective activity imparted by an enhanced sirtuin 1, (SIRT1-a participant of class III HDACs), expression in numerous cell types in the CNS [124][125][126].…”

The Role of Ketogenic Diet in the Treatment of Neurological Diseases

“…Currently, a body of objective evidence that suggests a potentially favourable effect of the ketogenic diet in the treatment of MS is available. It can affect the course and prophylaxis of the disease while simultaneously offering safety of use and feasibility [ 201 ]. Taking into account the demyelination processes observed in MS, an effect of the ketogenic diet is suggested for the possible reconstruction and repair of the myelin sheaths.…”

A metabolome-wide Mendelian randomization study prioritizes causal circulating metabolites for multiple sclerosis

“…Our MR analysis supports the causal roles of these metabolites in the development of MS. Notably, the higher circulating levels of ketone bodies (i.e., acetoacetate and acetone) may reflect a protective shift in energy metabolism in MS patients, and ketogenic diets have shown suggestive benefits for MS patients 43 . It is of great interest to investigate the roles of ketone bodies in the development of MS, in addition to its treatment.…”