The ketogenic diet has been in clinical use for over 80 years, primarily for the symptomatic treatment of epilepsy. A recent clinical study has raised the possibility that exposure to the ketogenic diet may confer long-lasting therapeutic benefits for patients with epilepsy. As the underlying mechanisms become better understood, it will be possible to develop alternative strategies that produce similar or even improved therapeutic effects without the need for exposure to an unpalatable and unhealthy, high-fat diet. The ketogenic diet is a high-fat content diet in which carbohydrates are nearly eliminated so that the body has minimal dietary sources of glucose. Fatty acids are thus an obligatory source of cellular energy production by peripheral tissues and also the brain. During high rates of fatty acid oxidation, large amounts of acetyl-CoA are generated. These exceed the capacity of the tricarboxylic acid cycle and lead to the synthesis of the three ketone bodies within liver mitochondria. In the absence of glucose, the preferred source of energy particularly of the brain, the ketone bodies are used as fuel in extrahepatic tissues.
While the connection between diet and physical health has long been understood, the roll of diet in brain health is a lesser known. While physical and mental health are often perceived as separate concepts, they are completely interrelated. Many symptoms thought to be physical can often be attributed to psychological influences. Mental illnesses are often debilitating and can manifest in a myriad of ways, including mood swings, delusions, dementia, and death. Treating these conditions are a major financial burden in the U. Nearly 1 in 5 adults is diagnosed with a mental illness each year. Brain and Metabolism — a C ase for Keto. The cause of mental illness can be rooted deep in the cells of the brain.
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Data from clinical and preclinical studies indicate that these diets restrict glycolysis and increase fatty acid oxidation, actions which result in ketosis, replenishment of the TCA cycle i. Further, there is mounting evidence that the KD and its variants can impact key signaling pathways that evolved to sense the energetic state of the cell, and that help maintain cellular homeostasis. That diet and nutrition should influence brain function should not be altogether surprising and much clinical and laboratory data exist linking disturbances in energy metabolism to a variety of clinical disorders 5, 9, Fundamentally, any disease in which the pathogenesis is affected by disturbances in cellular energy utilization, and this could apply to almost every known medical condition, would potentially be amenable to treatments that restore normal metabolism. Further, as there is increasing evidence for diet-induced epigenetic mechanisms contributing causally to the development of common chronic diseases 11, 12, greater knowledge of processes and players such as DNA methylation, histone modifications, and noncoding microRNAs will be needed to understand the relationships between energy dysregulation and therapeutic strategies to counter such impairment 11, However, it is important to recognize that much of the data discussed herein remain preliminary in nature. The use of dietary manipulations to treat epilepsy, in particular controlling seizures through sustained fasting, dates back to the time of Hippocrates 15 — In modern times, reports of modifying diets to treat seizures emerged in the early 20th century both in France and in the United States 15, 17 — Importantly, in the s, several researchers made significant discoveries regarding the physiological changes associated with the anti-seizure effects of starvation. At Harvard Medical School, Drs.