The ketogenic diet became popular as a therapy for epilepsy in the 1920s and 30s. It was developed to provide an alternative to non-mainstream fasting, which had demonstrated success as an epilepsy therapy. However, the diet was eventually largely abandoned due to the introduction of new anticonvulsant therapies. Although it emerged that most cases of epilepsy could be effectively controlled using these medications, they still failed to achieve epileptic control in around 20% to 30% of epileptics. For these individuals, and particularly children with epilepsy, the diet was re-introduced as a technique for managing the condition.

The role of fasting in the treatment of disease has been known to mankind for thousands of years and was studied in detail by ancient Greek physicians and ancient Indian physicians. An early treatise in the Hippocratic Corpus, “On the Sacred Disease,” describes how alterations in diet played a role in epilepsy management. The same author also describes in “Epidemics” from the collection, how a man was cured of epilepsy when he abstained completely from consuming food or drink.

The first modern scientific study into fasting as a cure for epilepsy was conducted in France, in 1911. At the time, potassium bromide was used to treat epileptics, but this agent slowed patients’ mental capabilities.. Instead, twenty epilepsy patients followed a low-calorie, vegetarian food plan that was combined with fasting. Two patients showed significant improvements, although most could not adhere to the dietary restrictions. However, the diet was found to improve the patient’s mental abilities compared with the effects of taking potassium bromide.

Also during the early 20th Century, an American called Bernarr Macfadden, popularised the idea of fasting as a means of restoring health. His student osteopath, Hugh Conklin, introduced fasting as a treatment method for controlling epilepsy. Coklin proposed that epileptic seizures were caused by a toxin secreted in the intestine and suggested that fasting for 18 to 25 days could cause the toxin to dissipate. His epileptic patients were put on a “water diet,” which he reported cured 90% of children with the condition and 50% of adults. Analysis of the study that was performed later showed that, in fact, 20% of Coklin’s patients became seizure-free, while 50% demonstrated some improvement. The fasting therapy was soon adopted as part of mainstream therapy for epilepsy and in 1916, Dr McMurray reported to the New York Medical Journal that he had successfully treated epileptic patients by prescribing a fast, followed by a diet free of starch and sugar since 1912.

It was in 1921 that endocrinologist Rollin Woodyatt noted that three water-soluble compounds, acetone, β-hydroxybutyrate and acetoacetate (together called ketone bodies) were produced by the liver as a result of starvation or if they followed a diet rich in fat and low in carbohydrates. Russel Wilder from the Mayo Clinic called this the “ketogenic diet” and used it as a treatment for epilepsy, also in 1921.

Further research in the 1960s showed that more ketones are produced by medium-chain triglycerides (MCTs) per unit of energy because they are transported quickly to the liver via the hepatic portal vein, as opposed to the lymphatic system. In 1971, Peter Huttenlocher devised a ketogenic diet where 60% of the calories came from MCT oil, which allowed more protein and carbohydrates to be included compared with the original ketogenic diet, meaning parents could prepare more enjoyable meals for their children with epilepsy. Many hospitals also adopted the MCT diet in place of the original ketogenic diet, although some used a combination of the two.