Ketosis and Seizure Control Correlational Studies

The suggestion by Wilder in 1921 that the anticonvulsant effects of fasting and the ketogenic diet were owing to the sedative effects of acetoacetate (3) reflected the belief at the time that a drug must have sedative properties to be anticonvulsant (14). It implied, however, that the ketone bodies have direct anticonvulsant effects. Not surprisingly, many studies since the time of Wilder have attempted to establish a correlation between the level of ketosis and seizure control. Overall, the...

Contents

Series Foreword by Philip A. 1 An Introduction to Seizures and Epilepsy Cellular Mechanisms Underlying Classification and Treatment Carl E. 2 History and Origin of the Ketogenic Diet James W. 3 The Ketogenic Diet The Physician's Perspective Eric H. Kossoff and John M. 4 Clinical Use of the Ketogenic Diet The Dietitian's Role Beth Zupec-Kania, Rhonda Roell Werner, and Mary L. Zupanc 63 5 How to Maintain and Support a Ketogenic Diet Program A Nursing Perspective Jeri E. Nichols Sutherling and...

Calculating Energy Requirements

The calculation of the energy requirement is aimed at achieving normal growth and development while maintaining ketosis during the course of ketogenic diet therapy. A calorie level that is too high will result in rapid weight gain. A calorie level that is too low may result in poor growth and insufficient ketosis. Experience has shown that children can grow on the ketogenic diet, but often growth occurs at a decelerated rate. The calorie level may need to be adjusted several times during the...

Brain Energetics and Metabolism

The brain requires a tremendous amount of energy for optimal function. Normally, the brain utilizes more than 20 of the body's basal oxygen consumption (in children, the percentage is an even higher). Much of this energy expenditure is used to operate ionic pumps and other cellular machinery. Ordinarily, the brain derives its energy from the aerobic oxidation of carbohydrate (mainly glucose), making it an obligate utilizer of glucose. With both generalized and focal seizure activity, the...

Adjusting the Carbohydrate

The carbohydrate value may need to be adjusted to account for nonfood sources of carbohydrate such as medications and supplements. If the sum total of the carbohydrate Sample Ketogenic Diet Prescription for a 7-yr-old Child (1300-kcal, 4 1 diet ratio) Sample Ketogenic Diet Prescription for a 7-yr-old Child (1300-kcal, 4 1 diet ratio) content from medications and supplements exceeds 500 mg, the excess amount of carbohydrate should be subtracted from the total dietary carbohydrate allowance. If...

The Nurses Role

It is the nurse's responsibility to work closely with the dietitian and the ketogenic diet physicians. It is the nurse who must schedule the routine labs and make sure that the results are seen by the physician. When a patient is having a difficulty that arises from the KD, the nurse will troubleshoot with the family to determine whether the problem is dietary or medical. Often the nurse will contact the patient's primary physician or dentist to coordinate care. If the patient is undergoing a...

Enhanced Excitability In Immature Brain

The immature brain is especially susceptible to seizures (43,44). Seizure incidence is highest during the first decade and especially during the first year of life. Several physiologic features favor enhanced neuronal hyperexcitability early in life. Ca2+ and Na+ channels, which mediate neuronal excitation, develop relatively early. Excitatory synapses tend to form before inhibitory ones. Excitatory NMDA receptors are transiently overexpressed early in postnatal development, when they are...

Fine Tuning the Ketogenic Diet

The goal of ketogenic diet therapy is to find and maintain a state of ketosis that serves to abate seizures. After a few weeks of ketogenic diet therapy, a defining pattern of ketosis will emerge. Ketosis is monitored at home by the caregiver with a urine ketone testing kit. Ketosis is usually lower in the morning and higher in the afternoon and evening. Urine ketone levels are a crude estimate of serum ketone levels and can be sufficient for determining level of ketosis on a daily basis....

Pathophysiological Events in Neuronal Network

What is happening at the neuronal network level when neurons transition from their normal firing pattern to the interictal condition and then to the ictal state Figure 5B depicts some of the physiologic features that accompany these changes. Now, rather than recording electrical activity from the surface of the brain, single electrodes are placed inside individual excitatory cortical neurons 1 and 2, thereby recording intracellular potentials. Much of our understanding of epilepsy mechanisms...

Plasma Ketone Analyses

Plasma ketone analyses provide more accurate quantifications of ketones than the urinary dipstick ketone test but also have their shortcomings. Because these analyses require a blood sample, they are invasive, and frequent blood sampling from pediatric patients presents both logistical and ethical challenges. Also, because plasma ketones are analyzed in a laboratory, there is often a delay between collecting the sample and generating the result. Finally, the analytical requirements for the...

Ketone Bodies Levels and Metabolic Roles

Figure 2 outlines the biochemical pathways by which ketone bodies are generated. P-Hydroxybutyrate is the most frequently measured ketone body. The concentration of Fig. 1. Both fasting and the ketogenic diet induce a number of common changes in the body. These include an elevation of ketone bodies in the blood and brain, a decrease in glucose utilization, and a shift in electrolytes and hormones. The identification of specific changes resulting in anticonvulsant effects has been challenging....

Collecting Food Composition Data

Food composition information should be collected and updated regularly for accuracy. Converting food value data to amounts per 100 g is necessary to perform the calculations described in these examples. Food labels are not reliable sources for precise nutrient values because manufacturers are not required to reveal nutrient values that are less than 1 g for the serving size listed on the label. The food manufacturer should be contacted to obtain accurate values for processed foods. The US...

Neurotransmitter Perturbations Via PPARa Activation

The KD may be anticonvulsant via its ability to correct disturbances in neurotrans-mitter concentrations associated with epilepsy. These include alterations in excitatory neurotransmitters such as glutamate and aspartate, inhibitory neurotransmitters such as Y-aminobutyric acid (GABA), and taurine, and or neurotransmitters such as glycine that may adopt either excitatory or inhibitory roles (41). Thus, for example, the KD decreases aspartate (42) and enhances synthesis of GABA from glutamate...

Animal Models of Ketosis

Animal models and in vitro preparations afford a number of advantages for the study of the ketogenic diet and the effects of ketosis. In animal models, blood, brain, and cerebrospinal fluid samples may be ethically obtained. Likewise, individual ketone bodies can be injected in isolation to permit the assessment of their effects on seizure threshold in the absence of the other ketone bodies. In in vitro models, voltage- or patch-clamp techniques may help to establish the molecular and cellular...

Polyunsaturated Fatty Acids PUFAs

Effects of Fatty Acids on Brain Development The critical role of fatty acids in nervous system development has been emphasized in numerous studies (for reviews, see refs. 30-33). Essential fatty acids, especially long-chain polyunsaturated fatty acids (PUFAs) of the omega-3 (ffl3 or n-3) class, are necessary for development of normal retinal and neuronal membranes (34,35) and subsequent normal behavior and cognition (36-40). PUFAs are particularly important for normal retinal and brain...

Fasting A Precursor To The Ketogenic Diet

It was not until the early twentieth century that medical use of the ketogenic diet emerged as a strategy to mimic the biochemical effects of fasting (or starvation) (Fig. 2). Guelpa and Marie, both French physicians, authored the first scientific report on the value of fasting in epilepsy (6). They reported that seizures were less severe during treatment, but no details were given. In the United States, contemporary accounts of fasting were also recorded early in the twentieth century (Table...

Ketogenic Diet in the 1990s

Use of the ketogenic diet decreased greatly until it received national media attention in October 1994, when NBC-TV's Dateline aired a program on the treatment (7,8,42,63-66). This television program was based on the true story of Charlie, a 2-yr-old with intractable myoclonic, generalized tonic, and tonic-clonic seizures (Fig. 4). A videotape presentation made later summarizes Charlie's condition in 1994 Thousands Fig. 4. Charlie Abrahams, age 4, with his parents Jim and Nancy, as they...

Perspectives On The Antiepileptic Mechanism Of Caloric Restriction

We propose that CR inhibits seizure susceptibility by shifting brain energy metabolism from glucose to ketone bodies. A CR-induced reduction in glucose utilization and increase in ketone utilization will, on the one hand, reduce the glycolytic energy reserves related to seizure activity and, simultaneously, decrease neuronal excitability through ketone metabolism. This involves multiple metabolic changes that would ultimately shift the neural environment from excitation to inhibition. An...

Inborn Errors of Metabolism in Which the KD Is Contraindicated

There are definitive contraindications to the use of the KD. These include defects in fat metabolism and disorders that require high carbohydrate contents. Failure to diagnose these disorders before starting the KD could result in significant morbidity and may be fatal. These contraindications should therefore be considered in every child before the KD treatment is started. P-Oxidation defects were first described in 1973, and since then at least 22 additional inborn errors of metabolism have...

Pre Ketogenic Diet Session

The rigors of ketogenic diet management should be discussed during the pre-keto-genic diet session. The process of food preparation and food weighing should be explained. The caregiver should be provided with the information for purchasing a scale that weighs in tenths of a gram (0.1 g). A description of the typical meals and beverages, and the requirement for the omission of carbohydrate-rich foods, should be clearly communicated. The caregiver should be informed about the appropriate foods...

Inborn Errors of Metabolism

The major use of the KD is as a treatment for intractable epilepsy. In a few inborn errors of metabolism, however, the metabolic defects in carbohydrate metabolism are bypassed by using ketone bodies as the primary energy source. We discuss these disorders because the KD, with the steady production of ketone bodies, is the treatment of choice, and early diagnosis and treatment may prolong life and reduce morbidity in these patients. 1.7.1. Facilitated Glucose Transporter Protein Deficiency...

References

In Engel JJ, Pedley TA (eds.). Epilepsy A Comprehensive Textbook, Vol. 1. Lippincott-Raven, New York, 1997, pp. 47-57. 2. Engel JJ, Pedley TA. Introduction what is epilepsy In Engel JJ, Pedley TA (eds.). Epilepsy A Comprehensive Textbook, Vol. 1. Lipponcott-Raven, New York, 1997, pp. 1-10. 3. Baumann RJ. Classification and population studies of epilepsy. In Anderson VE, Hauser WA, Penry JK, Sing CF (eds.). Genetic Basis of the Epilepsies. Raven, New York,...

Control Of Npy And Galanin Expression By Nutritional Status

The circulating hormones leptin and insulin have inhibitory effects on the expression of orexigenic neuropeptides. Leptin is a satiety hormone that is secreted by fat cells and serves as a signal of energy stores. When energy stores are abundant, leptin levels are high. Leptin decreases food intake via two mechanisms. Leptin activates preprome-lanocortin (POMC) neurons in the ARC, which release a-melanocyte-stimulating hormone (a-MSH). a-MSH stimulates cells expressing melanocortin-4 receptors,...

The Ketogenic Diet

At about the same time as the study of Cobb and Lennox, in 1921, a review article about diet adjustments and diabetes by Woodyatt stated acetone, acetic acid, and beta-hydroxybutyric acid appear in a normal subject by starvation, or a diet containing too low a proportion of carbohydrate and too high a proportion of fat. It ketoacidosis appears to be the immediate result of the oxidation of certain fatty acids in the absence of a sufficient proportion of 'oxidizing' glucose (32). Concurrently,...

Choline Enriched Diets

Choline is an amine that has been of interest for many years because of its critical role in brain development and response to injury. Choline is an essential nutrient for all mammals, and an adequate supply is particularly important during fetal development, when the organism grows rapidly (3). Pregnancy and lactation are the periods of highest dietary demands for choline, when large amounts of this compound are transferred from the mother to the offspring via placenta and milk. Choline serves...

Dietary Longchain Polyunsaturated Fatty Acids In A Ketogenic Diet Clinical Challenges

The data outlined thus far regarding LC-PUFAs can be summarized as follows 1. Supplementation exposure to LC-PUFAs may reduce seizure susceptibility. 2. Increased serum levels of LC-PUFAs have been observed in subjects consuming a KD. Although incorporating LC-PUFAs into a KD may enhance the diet's efficacy, there are several clinical challenges that must first be addressed. The optimal dosage and composition of the LC-PUFA supplement must be determined. Preliminary evidence suggests that only...

Conclusion On Ketogenic Diet

We suggest that CR may underlie the anticonvulsant mechanism of the KD and that CR alone may be an effective antiepileptic diet therapy. Moreover, the anticonvulsant action of CR may operate through the combined effects of reducing blood glucose and elevating blood ketones, thereby modulating cerebral energy metabolism. Our preclinical findings in EL mice suggest that CR may be an effective dietary therapy for some human epilepsies because CR is easy to administer and is devoid of the adverse...

Regulation by Absolute Changes in Protein HMGCS2 Concentration

At the genetic level HMGCS2 gene expression is upregulated by glucocorticoids, fatty acids, and cyclic adenosine monophosphate (cAMP) and downregulated by insulin Fig. 3. The HMGCS2 gene promoter. The promoter region is depicted by an open box for the DNA sequence upstream of the transcription start site tss and a solid box for the transcribed region downstream of the transcription start site. Abbreviations for DNA sequence elements and receptors GRE, glucocorticoid response element CRE, cAMP...

Putative Effect Of The Kd On Npy And Galanin Systems

Taken together, these data indicate that starvation conditions induce the expression of galanin and NPY. It stands to reason that these peptides would also be induced by the KD. A combination of the starvation-like phenotype, i.e., ketosis, and low glucose intake elicited by the KD would lead to decreased leptin and insulin. Low leptin and insulin levels would stimulate the activity of NPY-ergic neurons and increase NPY and galanin expression. Furthermore, because fat ingestion may enhance...

Freeman Ketogenic Diet

The Ketogenic Diet A Treatment for Epilepsy, 3rd ed. Demos, New York, 2000. 2. Musa-Veloso K, Likhodii SS, Cunnane SC. Breath acetone is a reliable indicator of ketosis in adult volunteers consuming ketogenic meals. Am J Clin Nutr 2002 76 65-70. 3. Freund G. The calorie deficiency hypothesis of ketogenesis tested in man. Metabolism 1965 14 985-990. 4. Livingston S. Dietary treatment of epilepsy. In Comprehensive Management of Epilepsy in Infancy, Childhood and...

References Of Kodama S On Ketogenic Diet At 2012

Prasad AN, Stafstrom CE, Holmes GL. Alternative epilepsy strategies the ketogenic diet, immunoglobulins, and steroids. Epilepsia 1996 37 Suppl 1 S81-S95. 2. Merritt HH, Putnam TJ. Sodium diphenylhydantoinate in the treatment of convulsive disorders. J Am Med Assoc 1938 111 1068-1073. 3. Richards RK, Everett GM. Analgesic and anticonvulsive properties of 3,5,5-trimethyloxazoliidine-2,4-dione Tridione . Fed Proc 1944 3 39. 4. Krall RL, Penry JK, White BG, Kupferberg HJ, Swinyard EA....