The Role of Ketogenic Diet in the Treatment of Neurological Diseases

Abstract

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.

Keywords: Alzheimer’s disease (AD); Parkinson’s disease (PD); anti-inflammatory; brain; epilepsy; high fat; inflammatory; ketogenic; ketogenic diet; ketone bodies; low carb; migraine; multiple sclerosis (MS); neuroinflammation; neurological diseases; neurone; neuroplasticity; neurotransmitters; nutrition; prevention; treatment.

Figure 1

The number of publications for the entry “ketogenic diet neurological disease” in the PubMed base in the period from 1 January 1948 to 17 November 2022. Date of search: 17 November 2022.

Figure 2

Potential mechanisms of the ketogenic diet effect in neurological diseases. GABA: Gamma-Aminobutyric Acid; BBB: blood–brain barrier; Cx43: connexin-43; MCT: monocarboxylate transporters; GLUT: glucose transporters; LRP1: LDL receptor-related protein 1; P-gp: glycoprotein P; PICALM: phosphatidylinositol binding clathrin assembly protein; IL-1β: interleukin-1β; IL-6: interleukin-6; TNF-α: tumor necrosis factor α; ALOX5: arachidonate 5-lipoxygenase gene; COX1: cyclooxygenase 1; COX2: cyclooxygenase 2; iNOS: inducible nitric oxide synthase; IL-2: interleukin-2; IL-4: interleukin 4; NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells; PPARγ: peroxisome proliferator-activated receptor γ; HIF-1α: hypoxia-induced factor 1α; Sirt1: sirtuin 1; mTORC1: mammalian target of rapamycin complex 1; mLST8: mammalian lethal with SEC13 protein 8; PRAS40: proline-rich Akt substrate of 40 kDa; mTOR: mammalian target of rapamycin. The above figure was created with BioRender.com, accessed on 23 November 2022. Agreement number: TF24OJVLEL.