Table 2.

Beneficial therapeutic effects of KD in different diseases and defined biological mechanisms, which could be involved in advantages of KD

Type of KD tested	Disease	Effect	Involved biological mechanisms allegedly derived by KD
Fasting Classic ketogenic diet	Refractory epilepsy	Seizure protection [22, 39, 68]	Increase gamma-aminobutyric acid (GABA) Decrease glutamate pH alteration affecting excitability GABA Microbiota profile reshape
Caloric restriction Classic ketogenic diet Fasting periods	Obesity	Weight loss and metabolic profile improvement [48, 68–73]	Appetite suppression by ketone bodies Gut microbiota profile and its metabolites change Beiging of white adipose tissue Brown adipose tissue activation (increase uncoupling protein UCP1 expression) Loss of fat (not lean mass) Increase metabolic cost of gluconeogenesis Increase lipogenesis and decrease lipolysis Metabolic improvements, browning and fat loss associated with microbiota remodelling
Caloric restriction Classic ketogenic diet	DT2	Improve insulin sensitivity and glycaemic control [68, 74, 75]	Decrease inflammation Reduce insulin Lipid profile improvement Decrease body weight, glycaemia, glycosylated haemoglobin, triglyceride level and LDL cholesterol Increased HDL cholesterol levels Greater weight loss than other diets in the short term Remarkable metabolic improvement Reduced or even withdrawn antidiabetic treatment
Classic ketogenic diet Ketone supplements	Alzheimer	Improve motor performance and cognition [30, 76–78]	Compensate for the deficiency in glucose metabolism Decrease glutamate Increase GABA Decrease reactive oxygen species (ROS) Decrease Inflammation Enhancing metabolism Metabolic state improvement Increase neurovascular integrity Application of theory brain-gut-microbiota axis
Classic ketogenic diet	Multiple Sclerosis	Normalized concentrations of the colonic microbiome [36]	Restore colonic microbiome Application of theory brain-gut-microbiota axis
Classic ketogenic diet	Autism	Mitigate some of the neurological symptoms associated with Autism Spectrum Disorder [35, 79]	Application of theory brain-gut-microbiota axis
Fasting	Cardiovascular	Improve cardiovascular health [80]	Supply of ketone bodies to the heart where KBs are efficiently oxidized Synergic actions between butyrate production by gut bacteria and circulating high blood ketones Application of theory gut–heart metabolic axis
Caloric Restriction Classic ketogenic diet	Cancer	Tumor growth decrease Increase survival patient [67, 81–83]	Cancer cell starvation (glucose privation reduce energy production of cancer cells) Repress Warburg effect Decrease inflammation Decrease insulin and insulin growing factor Decrease angiogenesis Decrease PI3K/Akt signalling (a known pathway involved in carcinogenesis) Increase apoptosis Affect tumor epigenetic Avoid cachexia (inhibition of muscle and body weight loss) Sensitize cancer cells to oncological treatment