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

Lin, Wei; Lin, Shan-Ju; Liao, Pei-Yin; Suresh, Divya; Hsu, Ting-Rong; Wang, Peiyu

doi:10.1093/advances/nmac065

Cited by 11 publications

(10 citation statements)

References 86 publications

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“…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.…”

Section: The Role Of the Ketogenic Diet In The Therapy Of Multiple Sc...mentioning

confidence: 99%

The Role of Ketogenic Diet in the Treatment of Neurological Diseases

2022

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Over a hundred years of study on the favourable effect of ketogenic diets in the treatment of epilepsy have contributed to a long-lasting discussion on its potential influence on other neurological diseases. A significant increase in the number of scientific studies in that field has been currently observed. The aim of this paper is a widespread, thorough analysis of the available scientific evidence in respect of the role of the ketogenic diet in the therapy of neurological diseases such as: epilepsy, Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS) and migraine. A wide range of the mechanisms of action of the ketogenic diet has been demonstrated in neurological diseases, including, among other effects, its influence on the reduction in inflammatory conditions and the amount of reactive oxygen species (ROS), the restoration of the myelin sheath of the neurons, the formation and regeneration of mitochondria, neuronal metabolism, the provision of an alternative source of energy for neurons (ketone bodies), the reduction in glucose and insulin concentrations, the reduction in amyloid plaques, the induction of autophagy, the alleviation of microglia activation, the reduction in excessive neuronal activation, the modulation of intestinal microbiota, the expression of genes, dopamine production and the increase in glutamine conversion into GABA. The studies discussed (including randomised controlled studies), conducted in neurological patients, have stressed the effectiveness of the ketogenic diet in the treatment of epilepsy and have demonstrated its promising therapeutic potential in Alzheimer’s disease (AD), Parkinson’s disease (PD), multiple sclerosis (MS) and migraine. A frequent advantage of the diet was demonstrated over non-ketogenic diets (in the control groups) in the therapy of neurological diseases, with simultaneous safety and feasibility when conducting the nutritional model.

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Section: The Role Of the Ketogenic Diet In The Therapy Of Multiple Sc...mentioning

confidence: 99%

The Role of Ketogenic Diet in the Treatment of Neurological Diseases

2022

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Ge¹,

Sun

Kiker

et al. 2022

Preprint

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Objective To prioritize circulating metabolites that likely play causal roles in the development of multiple sclerosis (MS). Methods Two-sample Mendelian randomization analysis was performed to estimate the causal effects of 571 circulating metabolites on the risk of MS. Genetic instruments for circulating metabolites were obtained from three previous genome-wide association studies (GWAS) of the blood metabolome, while genetic associations with MS were from a large GWAS by the International Multiple Sclerosis Genetics Consortium. The primary analysis was performed with the multiplicative random-effect inverse variance-weighted method, while multiple sensitivity analyses were conducted with the weighted median, weighted mode, MR-Egger, and MR-PRESSO. Results A total of 29 metabolites had suggestive evidence of causal associations with MS. Genetically instrumented levels of serine (OR = 1.56, 95% CI = 1.25-1.95), lysine (OR = 1.18, 95% CI = 1.01-1.38), acetone (OR = 2.45, 95% CI = 1.02-5.90), and acetoacetate (OR = 2.47, 95% CI = 1.14-5.34) were associated with a higher MS risk. Total cholesterol and phospholipids in large very-low-density lipoprotein were associated with a lower MS risk (OR = 0.83, 95% CI = 0.69-1.00; OR = 0.80, 95% CI = 0.68-0.95), but risk-increasing associations (OR = 1.20, 95% CI = 1.04-1.40; OR = 1.13, 95% CI = 1.00-1.28) were observed for the same two lipids in very large high-density lipoprotein. Conclusions Our metabolome-wide Mendelian randomization study prioritized a short list of circulating metabolites, such as serine, lysine, acetone, acetoacetate, and lipids, that likely have causal associations with MS.

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“…Signs of intestinal dysbiosis were observed in a group of AD rats and patients with MCI after KD consumption [37]. Intermittent fasting reduced hippocampal Aβ deposition, whereas KD worsened gut dysbiosis by increasing Proteobacteria and failed to improve memory function in an AD model of rats receiving Aβ (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35) infusion [229]. A KD also resulted in a further increase in Enterobacteriaceae among patients with MCI [205].…”

Section: Kbs and Kd As Regulators Of The Gut Microbiotamentioning

confidence: 99%

Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases

Jang,

Kim,

Lee

et al. 2023

IJMS

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Ketone bodies (KBs), such as acetoacetate and β-hydroxybutyrate, serve as crucial alternative energy sources during glucose deficiency. KBs, generated through ketogenesis in the liver, are metabolized into acetyl-CoA in extrahepatic tissues, entering the tricarboxylic acid cycle and electron transport chain for ATP production. Reduced glucose metabolism and mitochondrial dysfunction correlate with increased neuronal death and brain damage during cerebral ischemia and neurodegeneration. Both KBs and the ketogenic diet (KD) demonstrate neuroprotective effects by orchestrating various cellular processes through metabolic and signaling functions. They enhance mitochondrial function, mitigate oxidative stress and apoptosis, and regulate epigenetic and post-translational modifications of histones and non-histone proteins. Additionally, KBs and KD contribute to reducing neuroinflammation and modulating autophagy, neurotransmission systems, and gut microbiome. This review aims to explore the current understanding of the molecular mechanisms underpinning the neuroprotective effects of KBs and KD against brain damage in cerebral ischemia and neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease.

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

Cited by 11 publications

References 86 publications

The Role of Ketogenic Diet in the Treatment of Neurological Diseases

The Role of Ketogenic Diet in the Treatment of Neurological Diseases

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

Molecular Mechanisms of Neuroprotection by Ketone Bodies and Ketogenic Diet in Cerebral Ischemia and Neurodegenerative Diseases

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