Virginia Thornley, M.D., Neurologist, Epileptologist, February 26, 2018
Doctors first took notice of the ketogenic diet working in patients with epilepsy in the 1920’s. But the exact mechanism remains unclear. One study elucidated that the ketone bodies are one of the reasons why the ketogenic diet works in patients with epilepsy. Ketosis occurs during a natural fasting state. In the ketogenic diet using high fat, the by-products of beta-oxidation of fatty acids which are beta-hydroxyacetate and acetoacetate in the blood do not correlate with patients who are doing better. Medium chain triglyceride fatty acids, which are a part of a variation of the ketogenic diet, are shown to suppress the AMPA receptors which subserve the excitatory neurotransmitter glutamate and may change energy use of the cell through mitochondrial processes (1).
Ketogenic diet and adverse effects
Some patients have difficulty adhering to the diet which makes it difficult to use. Common side effects because of the high-fat content are diarrhea, constipation, nausea, transient increase in lipemic values. Variations of the ketogenic diet are sometimes used to offset these side effects and reduce the non-compliance.
Some ketogenic variants
Ketogenic diet variants include modified Atkins diet, low glycemic index treatment, and medium chain diet. The ketogenic diet consists of 4:1 ratio of fat to carbohydrates shifting metabolism to the use of ketone bodies as a source of energy. A lower ratio is sometimes employed called the modified ketogenic diet with a 3:1 or 2:1 ratio of fat to carbohydrates. In the modified ketogenic diet, the palatability is improved and avoids the gastrointestinal symptoms associated with the ketogenic diet such as nausea. With the modified Atkins diet, carbohydrates are restricted to 10-20 grams a day, or a 1-2:1 ratio of protein to fat plus carbohydrates. In the low glycemic index treatment, carbohydrates are limited to 40-60 grams while 50-60% of the diet is fat and 20-30% is from protein. The medium-chain triglyceride diet employs oils as a supplement such as coconut oil. The palatability of these diets improve patient compliance and lessen the side effects of the ketogenic diet. Some patients also used the diets to incidentally lose weight in addition to treating seizures (2).
Effectiveness of the ketogenic diet and ketogenic diet variants
One study summarizing studies on patients using the classic ketogenic diet found that 50% of patients out of 206 had a >50% reduction of seizures using the classic ketogenic diet. Older patients seemed to benefit less. In the modified Atkins diet, seizures were reduced in younger patients with more frequent seizures. Patients tended to drop out because of the side effects, lack of perceived effectiveness and because of the restrictions in the diet. Patients greater than 12 years old were less adherent to the diet (3).
It is possible that the protective effects of the ketogenic diet are related to the medium chain triglyceride fatty acids and not the ketone bodies.
1. Augustin, et al, “Mechanism of action for medium-chain triglyceride ketogenic diet and metabolic disorders,” Lancet Neurology, 2018, Jan., 84-93.
2. McDonald, et al, “Ketogenic diets for adults with highly refractory epilepsy,” Epilepsy Currents, 2017, Nov.-Dec., 17(6):346-350.
3. Payne, et al, “The ketogenic and related diets in adolescents and adults-a review,” Epilepsia, 2011, Oct., 52(11):1941-1948.