38. The Origins of the Ketogenic Diet: Epilepsy
Lesson 38 of Masterclass With Masterjohn: Energy Metabolism
The ketogenic diet was first proposed by Russell M. Wilder at the Mayo Clinic in 1921. The goal was to mimic the the physiology of fasting in a way that was more sustainable over time than completely abstaining from food. The application was to treat epilepsy. The use of fasting to treat epilepsy dates back to the era of Hippocrates, but at the turn of the 20th century physicians were documenting its effects more clearly and new methods of chemical analysis were revealing that ketone bodies were peed out in the urine during fasting. Wilder proposed that acetoacetate acted as an anesthesia on the brain and thereby blunted the occurrence of seizures.
Wilder was an expert in diabetes, and the predominant view at that time was that diabetes should be treated with dietary measures to suppress ketogenesis, thereby preventing diabetic ketoacidosis, while using only the minimum carbohydrate necessary for this purpose to reduce stress on the pancreas. Wilder took the work on the anti-ketogenic diet used in diabetes and turned it on its head to develop the ketogenic diet to treat epilepsy. This high-fat, moderate protein, low-carbohydrate diet proved remarkably effective at the time, with initial reports of the Mayo Clinic suggesting that 95% of patients benefited and that almost all of them could be treated without the need for drugs. Within a few years, the Mayo reports were revised to suggest that approximately half of patients with good compliance benefited, and that almost a quarter of the total patient pool had to be excluded from their analysis due to poor compliance. Still, it was remarkably effective in the responders and it is the only dietary treatment that has ever been shown to treat epilepsy without medicine.
Ketogenic Diets fell by the wayside in the 40s through the 90s, but the late 90s and early 00s saw a resurgence in their use to treat epilepsy, and research on their effects mushroomed. Today, there are seven randomized controlled trials showing their benefits. These studies suggest that a large subsection of children who do not respond well to antiepileptic drugs do respond well to the ketogenic diet. Studies tend to estimate these children are 20-50% of the patient pool, though some studies suggest even higher rates. Preliminary evidence suggests similar efficacy in adults, and similar efficacy in children for several less strict diets, such as the MCT oil diet, the modified Atkins diet, and the low-glycemic index, low-carbohydrate diet.
Why are the ketogenic diet and these related diets effective? We’ll tackle the mechanisms in our next lesson, and that will serve as the bridge to evaluating the efficacy of the ketogenic diet for many other conditions.
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