High-fat, low-carbohydrate (ketogenic) diets (KDs) have been used clinically for the treatment of epilepsy for at least 85 years. Clinical indications for initiating such a diet, some of the side effects likely to occur during diet administration and indications for maintenance of the diet and strategies for its discontinuation are considered, largely from the perspective of treating the epileptic patient. Although the diet has most often been used for pediatric patients, recent experience has shown that it can be effective for use with adolescents and adults. The efficacy of dietary treatment of epilepsy has been extended beyond the classical 4:1 LCT (long-chain triglyceride) diet to modified Atkins and low glycemic index diets. Efficacy is most often limited by non-compliance. Among the key variables during administration of such diets are variations in the level of ketonemia, the degree of hypoglycemia and the level of hyperlipidemia. Any or all of these variables may be part of the mechanisms by which KDs reduce seizure incidence and/or severity. Several candidate mechanisms linking diet to the alteration of central nervous system excitability are identified.Lipid catabolism occurs within mitochondria and consumption of KDs leads to increased proliferation and increased size of mitochondria, reflecting increased oxidative stress. Production of reactive oxygen species (ROS) under such conditions is minimized by an increased expression of uncoupling proteins (UCPs) and has consequences for calcium sequestration within the mitochondrial matrix and cytosol. All have potential for diminishing neuronal hyperexcitability. The state of oxidative phosphorylation and ATP/ADP production may affect membrane excitability by altering the activity of the Na/K ATPase or KATP/ADP channels. Classical high-fat diets include elevated levels of polyunsaturated fatty acids (PUFAs), which may inhibit both Na+ and Ca++ channels and activate tandem-pore potassium (K2p) channels. The net effects of any of these changes will depend upon the identity of the neuronal or glial populations most affected. For example, decreased excitation of excitatory neurons and increased excitation of inhibitory neurons would both act to reduce seizures. A working theoretical model incorporating many of the factors considered in this chapter is proposed.

Table of Contents:
Preface; Introduction; Clinical Use of A Ketogenic Diet; Key Variables of Ketogenic Diet Treatment; Dietary Mechanisms of Seizure Protection; Dietary Implications for Preventing Epilepsy; Dietary Treatment for other Neurological Disorders; Conclusion; Index.