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Ketogenic Diets

Definition

Ketogenic diets are a group of high-fat, moderate-protein, and very low-carbohydrate diets given to treat some children and adolescents with epilepsy, and some adults with epilepsy and other diseases. The name ketogenic refers to the increased production of ketone bodies as a result of this special diet. Ketone bodies are three compounds that are formed during the metabolism of fats and are ordinarily excreted in the urine. An abnormally high level of ketone bodies is called keto-sis, and this condition is the goal of the ketogenic diet. It is thought that ketosis helps to control the frequency and severity of epileptic seizures, even though the reasons for this effect are not fully understood as of 2007.

Origins

It has been known since Biblical times that some people with epilepsy were helped by prolonged periods of fasting, with good results. In earlier periods of history, children were kept on clear liquids for as long as two or three weeks until their seizures improved. This type of fasting, however, was obviously not sustainable as a long-term treatment. In 1921, a doctor at the MayoClinic named R. M. Wilder devised a diet for patients with epilepsy that was intended to mimic the biochemical changes that take place during fasting—ketosis, acidosis, and dehydration. Dr. Wilder’s ketogenic diet provided 10–15 grams of carbohydrates per day, 1 gram of protein for each kilogram of the patient’s body weight, and the remaining calories from fat. The calorie level was 75% of the normal daily allowance for the patient’s weight, and fluids were restricted to 80 percent. Wilder’s diet was almost identical to the protocol used at Johns Hopkins in 2007.

Until the late 1930s, the Mayo Clinic ketogenic diet was used to treat adults as well as children with epilepsy. In 1938, however, the first anticonvulsant drug—phenytoin (Dilantin)—was introduced, and was quickly followed by others. As of the early 2000s, there are 20 different anticonvulsant medications given to patients with epilepsy. After these medications were introduced, people were less interested in the ketogenic diet; many doctors considered it unnecessary or too much trouble. The number of hospitals that used it as therapy fell off sharply, while many practitioners regarded it as a “holistic” or even “alternative” treatment for epilepsy.

Interest in the ketogenic diet was reawakened in the mid-1990s, when the father of a 2-year-old with seizures that had not responded to any medications or surgical procedures read about the diet in medical textbooks. He started his son on the ketogenic diet with very good results; the child stopped having seizures and was able to discontinue his medications. The father then established the Charlie Foundation, which continues to provide information and guidance about the ketogenic diet to parents, dietitians, and other health care professionals. Since 1994, the diet has been generally accepted by doctors; it is used in about 40 countries around the world for the treatment of childhood epilepsy. The costs of the diet are reimbursed by most insurance carriers in the United States.

Classic ketogenic diet (Johns Hopkins protocol)

The ketogenic diet used at the Johns Hopkins Pediatric Epilepsy Center is commonly considered the standard or classic form of this diet. Its usual protocol for children between the ages of 3 and 12 years provides a ratio of 4 parts fats to 1 part protein and carbohydrates combined. Infants, toddlers, and adolescents are usually started on a 3:1 ratio. Individual patients may require ratios ranging from 2.5:1 to.

Potential side effects of the Classic Ketogenic Diet.

✔ Abnormally high levels of blood lipids after discontinuing the diet

✔ Decreased bone density

✔ Dehydration

✔ Growth retardation caused by protein deficiency

✔ Inflammation of the pancreas

✔ Kidney stones or gallstones

✔ More frequent infections due to a weakened immune system

✔ Nausea, vomiting, or constipation

✔ Protein deficiency, causing growth retardation

✔ Menstrual irregularities

✔ Vitamin and mineral deficiency

(Illustration by GGS Information Services/Thomson Gale.).

5:1; these ratios are worked out by fine-tuning the diet once the child has been started on it.

PREPARATION. The most important aspect of preparation for the ketogenic diet is deciding whether it will benefit the child. Most doctors prefer not to use it if the child is taking medications that are effective in controlling seizures without producing severe side effects. If, however, the child has tried two or more anticonvulsants without success, or is having serious side effects from the drugs, the ketogenic diet offers a chance to have a more normal life. It helps if the child is not a fussy eater and is willing to try foods that he or she might not ordinarily choose. The child also must be capable of self-control, as eating only a few cookie crumbs or anything else containing sugar (including toothpaste and other oral care products), will break the effect of the diet and possibly bring on a seizure.

Another important aspect of preparation is commitment on the part of the entire family. It takes considerable time and care to measure food portions, test the child’s urine at home, watch for possible side effects, and keep a balance between the needs of the epileptic child and the food preferences of other family members. Parties and holiday meals may require some advice from the dietitian so that the child can have a treat that won’t break the diet and will allow him or her to enjoy the meal or party with other friends or family members.

INITIAL FAST. The classic ketogenic diet begins with placing the child on a 24- to 48-hour fast followed by a stay of several days as a hospital inpatient, so that his or her body fluids can be measured and possible side effects monitored. The reason for the fast is to force the body to exhaust its glucose supply and begin burning stored fat for energy. The foods that are given after the fast are intended to keep the process of fat burning going by providing slightly fewer calories than the body needs and providing 80% of those calories in the form of fat.

KEY TERMS

Amyotrophic lateral sclerosis (ALS)—A rare progressive and eventually fatal disease affecting the nerve cells that control movement. It is also known as Lou Gehrig’s disease. As of the early 2000s, there is some evidence that the ketogenic diet can slow the progression of ALS.

Anticonvulsant—Adrug given toprevent or control seizures.

Double-blind study—A study in which neither the researchers nor the subjects know the identity of the persons in the experimental and control groups during the course of the research.

Ketone bodies—A group of three compounds (ace-toacetic acid, acetone, and beta-hydroxybutyric acid) that are formed in an intermediate stage of fat metabolism and excreted in the urine. Measuring the level of ketone bodies in the urine of a patient on the ketogenic diet is the primary way of assessing the diet’s effectiveness.

Ketosis—An abnormally high level of ketone bodies in the blood or urine, produced when the body begins to burn fat for energy instead of glucose (sugar).

Longitudinal study—A clinical study in which the researchers follow the same group of patients over a period of time. Most studies of the ketogenic diet have been longitudinal studies.

Prior to coming to the hospital, the child’s food records are kept over a three-day period so that the doctors will know the average daily calorie intake in order to tailor the special diet to the child’s need for growth. The goal is to maintain the child’s body mass index at the 50th percentile. The amount of protein in the diet is based on the child’s age, kidney function, and stress factors. While the child is in the hospital, the parents are given a four-day educational program to help them understand the diet and give them practice in preparing meals as well as monitoring the child.

The Johns Hopkins schedule for the child’s hospital stay is as follows:.

  • Sunday (night before admission): Child begins fasting at home in the evening.
  • Day 1 (Monday): Child is admitted to the hospital; fasting continues; fluid intake is restricted; and blood glucose is monitored every 6 hours
  • Day 2 (Tuesday): Child is given “eggnog” for dinner (1/3 of the maintenance calorie allotment for dinner); blood glucose checks are discontinued. The parents are asked to start checking the child’s urine ketone levels. Ketone levels should be between 80 and 160 mg/dL when the diet is working properly.
  • Day 3 (Wednesday): Breakfast and lunch are given as eggnog (1/3 of the maintenance calorie allotment for those meals); dinner (more eggnog) is increased to 2/3 maintenance level.
  • Day 4 (Thursday): Breakfast and lunch are given at 2/3 maintenance level; dinner is the child’s first full ketogenic meal (not eggnog).
  • Day 5 (Friday): After a full ketogenic breakfast, the child’s prescriptions are reviewed, follow-up is arranged, and the child is discharged from the hospital.

Some hospital programs do not require fasting to initiate the child’s diet. Follow-ups for most children take place at three-month intervals, although infants may be seen monthly. Children must take multivitamins and mineral supplements (particularly calcium) while on the ketogenic diet. Anticonvulsant medications are usually continued for the first few months of the diet, but may be given in lower dosages if the child responds well to the diet, or even discontinued altogether.

SAMPLE MENUS. A typical day’s menu for a child on the standard 4:1 ratio diet, allowing 1500 calories per day:

  • Breakfast: egg with bacon, made with heavy whipping cream and butter, plus an apple
  • Snack: peanut butter mixed with butter
  • Lunch: tuna salad made with celery, mayonnaise, and heavy whipping cream, served with lettuce
  • Snack: keto yogurt (made with heavy whipping cream, sour cream, strawberries, and artificial sweetener)
  • Dinner: cheeseburger with lettuce and green beans
  • Snack: keto custard (heavy whipping cream, egg, and pure unsweetened vanilla flavoring)

A computer program is available (listed in the resources below) to help parents and dietitians devise menus that will take the individual child’s food preferences into account as well as keep the meal selections within the correct nutritional ratio.

TAPERING AND TERMINATION. The ketogenic diet is a long-term diet but is not intended for indefinite use in children. Most children who respond favorably to it remain on it about two years. The diet must not be stopped abruptly, however; most doctors recommend that parents slowly start to add regular foods to the child’s menu to see whether the seizures are still controlled.

Sanggye Paik Hospital diet

The Sanggye Paik Hospital diet is a version of the ketogenic diet developed in Korea for the treatment of Asian children, whose diets typically contain much less fat than the diets of Western children. The Sanggye Paik protocol does not require an introductory fast and introduces high-fat foods to the patient’s diet gradually, although it uses the same 4:1 ratio of fats to protein and carbohydrates as the Johns Hopkins protocol. It is reported to have the same proportion of successes in patients as the Johns Hopkins ketogenic diet.

Modified Atkins diet

In 2003 the Johns Hopkins treatment center initiated a case series of six children and adults who used a modified version of the Atkins diet to control seizures rather than the classic 4:1 ketogenic diet. These patients were not admitted to the hospital; did not have to fast at the beginning of the diet; did not have calories, protein, or fluid intake restricted; were limited to 10-grams of carbohydrates per day; and were encouraged to eat foods rich in fats. Half the patients showed a marked reduction in seizures.

Based on this initial success, the Johns Hopkins doctors drew up a modified Atkins diet protocol for a group of 20 children, as follows:

  • A carbohydrate counting guide is given to the patient’s family
  • Carbohydrate intake is limited to 10g per day for the first month
  • A generous intake of fats in the form of mayonnaise, butter, oils, heavy cream, etc. is encouraged, although precise amounts are not defined
  • Clear carbohydrate-free fluids and calories are unrestricted
  • The patient is given a low-carbohydrate multivitamin and a calcium supplement
  • Ketones in the urine are checked twice a week and weight once a week
  • Low-carbohydrate store-bought products (shakes, snack bars, etc.) are discouraged for at least the first month
  • The patient is given a complete blood test and metabolic workup every three months

Of the 20 patients, two-thirds had a significant reduction in seizures, 9 were able to reduce medication dosages, and none developed kidney stones.

Function

The function of ketogenic diets is therapeutic— improved control of seizures in children, adolescents, and some adults with epilepsy; treatment of some other rare metabolic disorders; and slowing the progression of such other diseases as amyotrophic lateral sclerosis.

Benefits

The benefits of the ketogenic diet are improved seizure control without the need for large doses of anticonvulsant drugs with their associated side effects. Patients who respond well to the diet are able to lead more nearly normal lives. Patients with amyotrophic lateral sclerosis or other disorders being treated experimentally with a ketogenic diet may benefit by having their disease progress at a slower rate even when a cure is not possible.

Precautions

The most important precaution to note is that the ketogenic diet is not a do-it-yourself nutritional regimen. It is a serious form of therapy and requires careful medical supervision as well as parental monitoring. Patients on the diet must be followed by an experienced treatment team, usually based in a specialized epilepsy treatment center. Even though the diet may seem like a more “natural” way to control seizures than taking medications, it is based on a highly unnatural selection of foods and forces the body to obtain its necessary energy in an unusual way.

Another important precaution is preventing the child from accidentally ingesting sugar in over-the-counter medications, toothpastes, mouthwashes, or similar products. A list of sugar-free products can be found in PDF format on the Charlie Foundation website.

Success rate

Not all patients respond to the ketogenic diet. According to the Johns Hopkins treatment center, about half the children who begin the classic ketogenic diet will have at least a 50-percent reduction in seizures within 6 months. Half of that group will show greater than 90-percent improvement, with about 15% completely seizure-free. Many families are able to taper or completely eliminate the use of anticonvulsant medications.

As of the early 2000s, there is no way to predict ahead of time whether a child will respond to the diet. It is recommended that the child follow the diet for a period of 2-6 months before deciding that it isn’t working. Ineffectiveness is the single most common reason for children’s discontinuing the diet, although some discontinue it because they cannot tolerate the foods allowed even after fine-tuning, or because of side effects. The Johns Hopkins program reports that about half the children who begin the ketogenic diet in their treatment center are still using it a year later.

Side effects

Because the 4:1 ketogenic diet is an unnatural way to obtain nutrition, it has some potential side effects. Reported adverse effects in patients using the classic ketogenic diet include:

  • Growth retardation caused by protein deficiency
  • Vitamin and mineral deficiencies
  • Nausea, vomiting, or constipation
  • Abnormally high levels of blood lipids after discontinuation of the diet
  • Kidney stones or gallstones. Parents are taught to monitor the child’s urine for blood as well as ketone levels, because blood in the urine is often an early sign of kidney stone formation
  • More frequent infections due to a weakened immune system
  • Inflammation of the pancreas
  • Dehydration
  • Decreased bone density
  • Menstrual irregularities (in adolescent and adult females)

Research and general acceptance

Another area of recent research is the use of the ketogenic diet in the treatment of other disorders. It appears to be beneficial in the treatment of patients with glucose transporter defects (genetically transmitted disorders in which glucose in the blood cannot cross the blood-brain barrier) and a few other inborn metabolic disorders. In 2006 a group of researchers at Mount Sinai School of Medicine in New York reported that the diet shows promise in slowing the progression of amyotrophic lateral sclerosis, a progressive and fatal disease of the nerve cells that control movement.

BOOKS

“Carbohydrate Metabolism Disorders.” Chapter 296, Section 19 in the Merck Manual of Diagnosis and Treatment, 18th ed. Edited by Mark H. Beers and Robert Berkow. Whitehouse Station, NJ: Merck, 2007.

Freeman, John M., et al. The Ketogenic Diet: A Treatment for Children and Others with Epilepsy, 4th ed. New York: Demos, 2007.

“Seizure Disorders.” Chapter 214, Section 16 in the Merck Manual of Diagnosis and Treatment, 18th ed. Edited by Mark H. Beers and Robert Berkow. Whitehouse Station, NJ: Merck, 2007.

PERIODICALS

Benbadis, Selim R., MD, and William O. Tatum IV, DO. “Advances in the Treatment of Epilepsy.” American Family Physician 64 (July 1, 2001): 91–106.

Coppola, G., P. Veggiotti, R. Cusmai, et al. “The Ketogenic Diet in Children, Adolescents and Young Adults with Refractory Epilepsy: An Italian Multicentric Experience.” Epilepsy Research 48 (February 2002): 221–227.

Freeman, J. M., E. H. Kossoff, and A. L. Hartman. “The Ketogenic Diet: One Decade Later.” Pediatrics 119 (March 2007): 535–543.

Hartman, A. L., and E. P. Vining. “Clinical Aspects of the Ketogenic Diet.” Epilepsia 48 (January 2007): 31–42.

Kang, H. C., and H. D. Kim. “Diet Therapy in Refractory Pediatric Epilepsy: Increased Efficacy and Tolerabil-ity.” Epileptic Disorders 8 (December 2006): 309–316. This article describes the development of the Sanggye Paik Hospital ketogenic diet.

Kang, H.C., H. S. Lee, S. J. You, et al. “Use of a Modified Atkins Diet in Intractable Childhood Epilepsy.”Epilepsia 48 (January 2007): 182–186.

Kossoff, E. H., J. R. McGrogan, R. M. Bluml, et al. “A Modified Atkins Diet is Effective for the Treatment of Intractable Childhood Epilepsy.” Epilepsia 47 (February 2006): 421–424.

Turner, Zahava, RD, and Eric H. Kossoff, MD. “The Ketogenic and Atkins Diets: Recipes for Seizure Control.”Practical Gastroenterology (June 2006): 53–64.

Zhao, Z., D. J. Lange, A. Voustianiouk, et al. “A Ketogenic Diet as a Potential Novel Therapeutic Intervention in Amyotrophic Lateral Sclerosis.” BMC Neuroscience 7 (April 3, 2006): 29.

VIDEOS AND COMPUTER PROGRAMS

Abrahams, Jim, and Meryl Streep (narrator). Introductory Video to the Ketogenic Diet. This is a video for parents of children with epilepsy using the ketogenic diet. It shows step-by-step meal preparation, food choices for the diet, and frank discussions of parents’ initial concerns as well as problems that families encounter in adhering to the diet. To order the video, parents should send a written letter and a check for $10 to cover shipping and handling costs to The Charlie Foundation at the address given below.

Ketogenic Diet Program, Epilepsy Association of Maryland. Ketogenic Diet Computer Program. This is a computer program for dietitians and parents to help plan meals for a child on a ketogenic diet. It is a Windows-based program requiring an IBM-compatible machine. The computer disk can be purchased ($150 for dietitians, $75 for parents, plus $5 fee for shipping and handling) at the following address: Ketogenic Diet Program, c/o Epilepsy Association of Maryland, 300 East Joppa Road, Suite 1103, Towson, MD 21286-3018. Telephone: (410) 828-7700.

OTHER

Epilepsy Foundation. General Information about the Ketogenic Diet. Landover, MD: Epilepsy Foundation, 2007. Available online at http://www.epilepsyfoundation.org/answerplace/Medical/treatment/diet/ (accessed March 28, 2007).

National Institute of Neurological Disorders and Stroke (NINDS). NINDS Summer Program—Erika Williams. “Stimulus Train Induced Bursting as an In Vitro Model of Epilepsy,” January 11, 2007. This is an updated report on research being conducted to determine which metabolic compounds produced in the bodies of patients on ketogenic diets may be responsible for controlling seizures. Available online at http://www.ninds.nih.gov/jobs_and_training/summer/2006_students/Abstract_Erika_Williams.htm (accessed March 28, 2007).

National Institute of Neurological Disorders and Stroke (NINDS). Seizures and Epilepsy: Hope through Research. Bethesda, MD: NINDS, 2004. Available online at http://www.ninds.nih.gov/disorders/epilepsy/detail_epilepsy.htm.

ORGANIZATIONS

The Charlie Foundation to Help Cure Pediatric Epilepsy. 1223 Wilshire Boulevard, Suite 815, Santa Monica, CA 90403. Telephone: (800) FOR-KETO or (310) 395-6751. Website: http://www.charliefoundation.org

Epilepsy Foundation. 8301 Professional Place, Landover, MD 20785. Telephone: (800) 332-1000. Website: http://www.epilepsyfoundation.org

Johns Hopkins Pediatric Epilepsy Center, Meyer 2-147, The Johns Hopkins Hospital, 600 North Wolfe Street, Baltimore, MD 21287-7247. Telephone: (410) 955-9100. Website: http://www.neuro/jhml.edu/Epilepsy/keto.html.

National Institute of Neurological Disorders and Stroke (NINDS) Brain Resources and Information Network (BRAIN). P. O. Box 5801, Bethesda, MD 20824. Telephone: (800) 352-9424. Website: http://www.ninds.nih.gov.

U. S. Food and Drug Administration (FDA). 5600 Fishers Lane, Rockville, MD 20857-0001. Telephone: (888) INFO-FDA. Website: http://www.fda.gov/

Rebecca J. Frey, PhD.


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