Could the ketogenic diet offer hope in management of neurological diseases?

The ketogenic diet (KD) is a nutritional model that includes high fat, moderate protein, and low carbohydrate (less than 50 g). The “KD ratio” is used to determine the amount of macronutrients in the diet. In classical KD with the ratio of 3:1 or 4:1, 85–90% of the energy is provided from dietary fat. In addition to classical KD, the modified Atkins diet, low glycemic index therapy, and medium-chain triglyceride diet have also been used, and in some studies, ketosis has been achieved with exogenous ketone supplements. KD has long been recognized as a successful dietary approach in the treatment of refractory epilepsy. It is known that KD may also be effective in other neurological diseases such as Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, and migraine through various mechanisms such as providing an alternative energy source for neurons, reducing inflammation and oxidative stress, stimulating neurotransmitter synthesis and regulation of microbiota, etc. However, existing evidence is insufficient to make definitive conclusions about the effect of the KD on neurological diseases other than epilepsy due to the short intervention time, the small sample size, and the heterogeneity in the study methods. Considering factors such as genetics, endocrine differences, timing, and diet composition, it is important to apply and follow precision nutrition programs to increase the benefits of KD and reduce its side effects. In this review, the mechanisms of the KD on neurological diseases, recent evidence on the use of the KD in neurological diseases other than epilepsy, the limitations and difficulties in the literature on the KD, and the contraindications of the KD were discussed in detail.