Effect of the ketogenic diet in excitable tissues

In the last decade Ketogenic Diet (KD) came to light as a potential treatment for a wide range of diseases, from neurological to metabolic disorders, thanks to a beneficial role mainly related to its anti-inflammatory properties. The high-fat, carbohydrate-restricted regimen causes changes in the metabolism leading, through the β-oxidation of fatty acids, to the hepatic production of ketone bodies (KBs), used by many extrahepatic tissues as energy fuels. Once synthetized, KBs move through the systemic circulation and reach all the tissues of the organism, affecting their functions and playing pleiotropic roles acting directly and indirectly on various targets as ion channels and neurotransmitters. Moreover, they can operate as signalling metabolites and epigenetic modulators. Therefore, it is limiting to consider that the clinical condition of each single patient could improve after a KD regimen based on its localized effects; rather it is more complete to think about how KBs might affect the organism as a whole. In this minireview, we tried to summarize the recent knowledge of the effects of KBs on various tissues, with a particular attention to the excitable ones, namely the nervous system, heart and muscles.