The Therapeutic Role of Ketogenic Diet in Neurological Disorders

Abstract

The ketogenic diet (KD) is a high-fat, low-carbohydrate and adequate-protein diet that has gained popularity in recent years in the context of neurological diseases (NDs). The complexity of the pathogenesis of these diseases means that effective forms of treatment are still lacking. Conventional therapy is often associated with increasing tolerance and/or drug resistance. Consequently, more effective therapeutic strategies are being sought to increase the effectiveness of available forms of therapy and improve the quality of life of patients. For the moment, it seems that KD can provide therapeutic benefits in patients with neurological problems by effectively controlling the balance between pro- and antioxidant processes and pro-excitatory and inhibitory neurotransmitters, and modulating inflammation or changing the composition of the gut microbiome. In this review we evaluated the potential therapeutic efficacy of KD in epilepsy, depression, migraine, Alzheimer's disease and Parkinson's disease. In our opinion, KD should be considered as an adjuvant therapeutic option for some neurological diseases.

Keywords: Alzheimer’s disease; Parkinson’s disease; depression; epilepsy; ketogenic diet; migraine; neurological disorders.

Figure 1

Comparison of selected modifications of the ketogenic diet and their macronutrient ratios. Classic KD- Classic Ketogenic Diet; MAD- High-Protein Ketogenic Diet; MCTD- Medium-Chain Triglycerides Diet; LGIT- Low Glycaemic Index Treatment.

Figure 2

Ketogenesis. Fatty acids undergo the process of β-oxidation in the liver, resulting in the formation of ketone bodies. These are then transported to the blood vessels and then to the neurons where, after conversion to acetyl-CoA, they enter the TCA cycle. The alternative energy source compensates for the smaller contribution of glucose to the ATP yield. (HMG-CoA: 3-hydroxy-3-methyl glutaryl-CoA; HMG-CoA synthetase: 3-hydroxy-3-methyl glutaryl-CoA synthetase; HMG-CoA lyase: 3-hydroxy-3-methyl glutaryl-CoA lyase; ACA: acetoacetate; D-βHB: D-β-hydroxybutyrate; TCA: tricarboxylic acid cycle).

Figure 3

Amino acid metabolism in the brain. During ketosis, the amount of glutamate is increased. This may contribute to the increased flow through the TCA cycle.

Figure 4

The potential role of the ketogenic diet/nutritional ketosis in neurological disorders. The large amount of ketone bodies formed during a low-carbohydrate, high-fat diet may have a beneficial effect on many of the pathological processes found in neurological diseases, thus potentially offering beneficial adjuvant therapy. (IL-1β: interleukin 1β; IL-6: interleukin 6; TNF-alpha: tumour necrosis factor alpha; HCA-2: hydroxycarboxylic acid 2; NRPL: NOD-like receptor family pyrin domain containing 3 inflammasome; HDAC: histone deacetylases; BDNF: brain-derived neurotrophic factor; GABA: gamma-aminobutyric acid; Aβ: amyloid β).