Ketogenic diets and protective mechanisms in epilepsy, metabolic disorders, cancer, neuronal loss, and muscle and nerve degeneration.

Ketogenic diet (KD), the "High-fat, low-carbohydrate, adequate-protein" diet strategy, replacing glucose with ketone bodies, is effective against several diseases, from intractable epileptic seizures, metabolic disorders, tumors, autosomal dominant polycystic kidney disease, and neurodegeneration to skeletal muscle atrophy and peripheral neuropathy. Key mechanisms include augmented mitochondrial efficiency, reduced oxidative stress, and regulated phospho-AMP-activated protein kinase, gamma-aminobutyric acid-glutamate, Na+/ K+ pump, leptin and adiponectin levels, ghrelin levels, lipogenesis, ketogenesis, lipolysis, and gluconeogenesis. In cancer cells, KD targets glucose metabolism, suppresses insulin-like growth factor-1 and PI3K/AKT/mTOR pathways, and reduces cancer cachexia and muscle waste and fatigue. An associated increased skeletal proliferator-activated receptor-γ coactivator-1α activity alters systemic ketone body homeostasis, contributing toward attenuated diabetic hyperketonemia. Antioxidative and anti-inflammatory properties enable KD enhance endurance and sports performances while preventing exercise-induced muscle and organ debility. KD reduces metabolic syndromes-associated allodynia and promotes peripheral axonal and sensory regeneration. This review enlightens effects of KD on various disease conditions. PRACTICAL APPLICATIONS: It is increasingly being realized that diet plays a very important role in our fight against several diseases. This can range from neurological disorders to diabetes and cancer. In this context, the potential of KD, the "High-fat, low-carbohydrate, adequate-protein" diet strategy, is increasingly being realized. In this article, we provide a comprehensive analysis of the benefits of KD against many diseases and discuss the underlying biochemical mechanisms. We hope that our write-up will stimulate further research on KD and help generate an interest for the populations to adopt this healthy diet. It can help overcome the problems associated with weight and dysregulated metabolism.