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, as well as 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 ketosis, 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 were not fully understood as of 2018.

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 Mayo Clinic 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%. Wilder's diet is almost identical to the protocol used at Johns Hopkins.

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. 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, and many practitioners regarded it as a holistic or alternative treatment for epilepsy.

Interest in the ketogenic diet was reawakened in the mid-1990s, when the father of a two-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 healthcare 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.

Matthew's Friends is a clinic and charity in the United Kingdom that specializes in ketogenic dietary therapies. Founded in 2004, it now includes Matthew's Friends Canada and Matthew's Friends New Zealand. Its website includes ketogenic diet recipes as well as medical information about the diet.

Demographics

As of 2018, epilepsy affected an estimated 65 million persons worldwide. Only a small minority of these patients used the ketogenic diet, however, as about 60% of patients controlled their epilepsy with medications, and most of the remainder benefited from surgery. The ketogenic diet is used primarily by the 20% of patients who do not respond to any of three or more anticonvulsant drugs.




Keto food pyramid chart.





Keto food pyramid chart.
(Sudowoodo/Shutterstock.com)

Description

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 provides a ratio of 4 parts fat to 1 part protein and carbohydrate combined. Infants, toddlers, and adolescents are usually started on a 3:1 ratio. Individual patients may require ratios ranging from 2.5:1 to 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) can 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 a dietitian so that the child can have a treat that will not 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.

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 to tailor the special diet to the child's growth needs. 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:

Potential side effects of the classic ketogenic diet

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 1,500 calories per day, is as follows:

Resources are available 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. Popular newer items for the children's ketogenic diet include Egg Beaters and the Ross carbohydrate-free formula, which can be used to make shakes.

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; 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 2002, 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 their 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:

Other variations of the ketogenic diet

MODIFIED KETOGENIC DIET. According to the Charlie Foundation, the modified ketogenic diet is one in which the ratio of fats to non-fats is 2:1 or even 1:1 rather than the 4:1 ratio of the classic ketogenic diet.

MCT DIET. The MCT diet is one in which the long-chain triglycerides (LCTs) contained in normal dietary fats are replaced by medium-chain triglycerides or MCTs. Researchers in the 1960s discovered that MCTs produce more ketone bodies per unit of energy than LCTs. In 1971, a neurologist named Peter Huttenlocher (1931–2013) devised a ketogenic diet in which an emulsion of coconut oil was mixed in a 1:2 ratio with skim milk and sipped during the meal or added to food. The MCT oil provides about 60% of the calories in the diet but allows more protein and carbohydrate than the classic ketogenic diet. It is less popular in the United States, however, because the MCT coconut oil emulsion is more expensive than other dietary fats and is not covered by insurance.

The MCT version of the ketogenic diet has been used in Germany since 1995 on a case-by-case basis to treat patients with brain cancer.

LOW GLYCEMIC INDEX TREATMENT (LGIT). The LGIT version of the ketogenic diet was introduced at Massachusetts General Hospital in 2002 as an attempt to maintain the stable levels of blood sugar attained on the classic ketogenic diet using a less restrictive dietary regimen. In addition to allowing patients to be treated on an outpatient basis without constant monitoring by a dietitian, the LGIT allows more carbohydrates than either the classic ketogenic diet or the modified Atkins diet; however, the carbohydrates consumed must have a glycemic index below 50, which still excludes such favorites as sweets, pasta, and bread. Although the LGIT allows more variety in meals than the classic ketogenic diet, about a quarter of families report that it is too difficult to follow on a long-term basis.

Function

The function of ketogenic diets is therapeutic—improved control of seizures in children, adolescents, and some adults with epilepsy; treatment of rare metabolic disorders (pyruvate dehydrogenase deficiency and glucose transporter type 1 deficiency syndrome); and slowed progression of such other diseases as amyotrophic lateral sclerosis. Ketogenic diets were used as of 2018 on an experimental basis to treat patients diagnosed with brain cancer, childhood autism, Alzheimer's disease, depression, type 2 diabetes, and Parkinson's disease. There was also some evidence that the diet had protective effects in patients with traumatic brain injuries and stroke.

More recently, some researchers have tried ketogenic diets as a weight loss regimen in adults at risk of type 2 diabetes and cardiovascular disorders associated with obesity. As of 2018, the results of ketogenic diets in these groups of patients were mixed; some evidence indicated that ketogenic diets increased the risk of insulin resistance and nonalcoholic fatty liver disease in overweight adults.

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 nearly normal lives.

Patients with cancer, 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 and regular appointments with a registered dietitian. 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.

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. Some evidence indicates that the ketogenic diet can slow the progression of ALS.
Anticonvulsant—
A drug given to prevent or control seizures.
Atkins diet—
A low-carbohydrate diet that was popularized in the early 2000s as a weight-loss diet. A modified version of the Atkins diet appears to be helpful to patients with epilepsy who cannot tolerate the food restrictions of the classic ketogenic diet.
Double-blind study—
A study in which neither the researchers nor the subjects know the identity of the people in the experimental and control groups during the course of the research.
Glucose transporter type 1 deficiency syndrome—
A genetic metabolic disorder characterized by a lack of the protein that transports glucose across the blood-brain barrier. Children with the disorder typically develop seizures within a few months of birth.
Glycemic index (GI)—
A measurement of the speed at which the body converts carbohydrates in foods to blood glucose. The more rapidly a food's carbohydrates are converted to glucose, the higher its GI. Only foods with a GI below 50 are allowed on the LGIT version of the ketogenic diet.
Ketone bodies—
A group of three compounds (acetoacetic 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. Many older studies of the ketogenic diet have been longitudinal studies.
Medium-chain triglycerides (MCTs)—
Fatty acids with shorter carbon chains that are absorbed more readily than long-chain triglycerides and speed up the process of fat burning on a ketogenic diet. The most common dietary sources of MCTs are coconut oil and palm kernel oil.
Pyruvate dehydrogenase deficiency—
A rareX-linked genetic disorder that may take either a metabolic or a neurological form. Children with the neurological form often develop seizures and may be treated with a ketogenic diet.

Risks

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% reduction in seizures within six months. Half of that group will show greater than 90% improvement, with about 15% completely seizure free. Many families are able to taper or completely eliminate the use of anticonvulsant medications.

As of 2018, there wsa no way to predict ahead of time whether a child would respond to the diet. It was recommended that the child follow the diet for a period of two to six months before deciding that it was not working. Ineffectiveness was the single most common reason for discontinuing the diet, although some people discontinued it because they could not tolerate the foods allowed, even after fine-tuning, or because of side effects. The Johns Hopkins program reported that about half of the children who began the ketogenic diet in their treatment center were 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:

QUESTIONS TO ASK YOUR DOCTOR

The MCT version of the ketogenic diet is reported to have a higher rate of diarrhea, vomiting, and other gastrointestinal complaints than the classic ketogenic diet even though it allows for a more varied menu and meals that are easier to prepare. These side effects are the major reason it is less popular in North America than other ketogenic diets.

Research and general acceptance

The 4:1 ketogenic diet was the subject of a number of longitudinal studies in the years immediately following Dr. Wilder's initial case report in 1921. Although research lagged in the years after World War II, interest in the diet has increased significantly since the 1990s. As of early 2018, 121 clinical trials of ketogenic diets had been registered with the National Institutes of Health (NIH); 66 of those trials were being conducted in the United States. In addition to continuing to study ketogenic diets as treatment for refractory epilepsy in adults as well as children, researchers worldwide were investigating these diets as treatments for many different types of cancer, as adjunctive therapies for stroke rehabilitation, as weight loss regimens to prevent type 2 diabetes and cardiovascular disease in overweight patients, and as treatments for pyruvate dehydrogenase deficiency and glucose transporter type 1 deficiency syndrome.

Most clinical trials of ketogenic diets involved either the classic diet or the modified Atkins diet. Only 13 studies worldwide were trials of the MCT ketogenic diet, and all but two were being conducted outside the United States, with research being done in the United Kingdom, Germany, and Canada.

See also Atkins diet ; Bodybuilding diet ; Coronary heart disease ; High-fat, low-carb diets ; TLC diet .

Resources

BOOKS

Farooqui, Tahira, and Akhlaq A. Farooqui, eds. Diet and Exercise in Cognitive Function and Neurological Diseases. Hoboken, NJ: Wiley-Blackwell, 2015.

Kossoff, Eric H., Zahava Turner, Sarah Doerrer, et al. The Ketogenic and Modified Atkins Diets: Treatments for Epilepsy and Other Disorders. 6th ed. New York: Demos Health, 2016.

Masino, Susan A., ed. Ketogenic Diet and Metabolic Therapies: Expanded Roles in Health and Disease. New York: Oxford University Press, 2017.

PERIODICALS

Abbasi, Jennifer. “Interest in the Ketogenic Diet Grows for Weight Loss and Type 2 Diabetes.” JAMA 319, no. 3 (January 16, 2018): 215–17.

Chung, H. Y., and Y. K. Park. “Rationale, Feasibility, and Acceptability of Ketogenic Diet for Cancer Treatment.” Journal of Cancer Prevention 22, no. 3 (September 2017): 127–34.

Gupta, L., D. Khandelwal, S. Kalra, et al. “Ketogenic Diet in Endocrine Disorders: Current Perspectives.” Journal of Postgraduate Medicine 63, no. 4 (October/December 2017): 242–51.

Kosinski, Christophe, and François R. Jornayvaz. “Effects of Ketogenic Diets on Cardiovascular Risk Factors: Evidence from Animal and Human Studies.” Nutrients 9, no. 6 (May 19, 2017): 517.

Lambrechts, Danielle A., Reina J. A. de Kinderen, Hans S. H. Vles, et al. “The MCT-Ketogenic Diet as a Treatment Option in Refractory Childhood Epilepsy: A Prospective Study with 2-Year Follow-Up.” Epilepsy and Behavior 51 (October 2015): 261–66.

McDonald, Tanya J. W., Elizabeth V. Ratchford, Bobbie J. Henry-Barron, et al. “Impact of the Modified Atkins Diet on Cardiovascular Health in Adults with Epilepsy.” Epilepsy and Behavior 79 (February 2018): 82–86.

Rezaei, S., M. Kavoosi, M. Mahmoudi, et al. “Efficacy of Low Glycemic Index Treatment in Epileptic Patients: A Systematic Review.” Acta Neurologica Belgica (January 24, 2018): 1–11.

Walczyk, Thomas, and Jeannette Y. Wick. “The Ketogenic Diet: Making a Comeback.” The Consultant Pharmacist 32, no. 7 (July 1, 2017): 388–96.

WEBSITES

Johns Hopkins Medicine Health Library. “Seizures and Epilepsy in Children.” Johns Hopkins University. https://www.hopkinsmedicine.org/healthlibrary/conditions/adult/pediatrics/epilepsy_and_seizures_in_children_90,p02621

Kossoff, Eric. “Ketogenic Diet.” Epilepsy Foundation. https://www.epilepsy.com/learn/treating-seizures-andepilepsy/dietary-therapies/ketogenic-diet (accessed May 5, 2018).

Kossoff, Eric, ed. Keto News. Epilepsy Foundation. https://www.epilepsy.com/learn/seizure-and-epilepsy-news/keto-news (accessed May 5, 2018). This section of the Epilepsy Foundation website contains articles about the ketogenic diet, both tips about adjusting to it and news about recent research.

Matthew's Friends. “Keto Therapies.” MatthewsFriends.org . https://www.matthewsfriends.org/keto-therapies (accessed May 5, 2018).

Roehl, Kelly, and Sarika L. Sewak. “Practice Paper: Classic and Modified Ketogenic Diets for Treatment of Epilepsy.” Academy of Nutrition and Dietetics. http://www.eatrightpro.org/resource/practice/position-andpractice-papers/practice-papers/practice-paper-classicand-modified-ketogenic-diets-for-treatment-of-epilepsy (accessed May 5, 2018).

ORGANIZATIONS

Academy of Nutrition and Dietetics, 120 S. Riverside Plaza, Ste. 2190, Chicago, IL, 60606-6995, (312) 899-0040, (800) 877-1600, amacmunn@eatright.org, http://www.eatright.org .

Charlie Foundation for Ketogenic Therapies, 515 Ocean Ave., #602N, Santa Monica, CA, 90402, (310) 393-2347, https://www.charliefoundation.org/contact , https://www.charliefoundation.org .

Epilepsy Foundation, 8301 Professional Place East, Suite 200, Landover, MD, 20785, (301) 459-3700, (800) 332-1000, Fax: (301) 577-2684, ContactUs@efa.org, https://www.epilepsy.com .

Johns Hopkins Ketogenic Diet Center, 1800 Orleans St., Baltimore, MD, 21287, (410) 955-9441, (410) 955-4259, https://www.hopkinsmedicine.org/neurology_neurosurgery/centers_clinics/epilepsy/pediatric_epilepsy/ketogenic_diet.html .

Matthew's Friends Charity and Clinics, St. Piers Lane, Lingfield, United KingdomSurrey, RH7 6PW, +44(01342) 836571, Fax: +44(01342) 837792, enq@matthewsfriends.org, https://www.matthewsfriends.org .

Rebecca J. Frey, PhD

  This information is not a tool for self-diagnosis or a substitute for professional care.