KETOGENIC DIET THERAPY
When I was first asked to take over as the dietitian for the ketogenic diet program at York Hospital in York, PA I was more than reluctant. A diet relying on a specific mathematical calculation for each bite, a lengthy list of possible complications, along with a medically fragile population to work with was completely intimidating. Over 10 years of helping families manage this important diet therapy and seeing the significant benefits, laid the foundation for my increasing comfort level and competence in this medical therapy.
While the ketogenic diet for intractable epilepsy has continued to grow in acceptance, including a randomized controlled trial in 2008, medical professionals and the lay public remain skeptical regarding this high fat, moderate protein, low carbohydrate approach. I wrote the following article six years ago for a magazine for dietitians, but the article was later rejected by the editor who had originally approved the topic stating it was “too controversial” for dietitians. I hope you enjoy hearing about how dietitian’s in children’s hospitals across the country help families find success with keto.
Ketogenic Diet Therapy & The Dietitian’s Vital Role
Julie Stefanski MEd, RDN, CSSD, LDN, CDE
‘Does this diaper cream contain any carbs?’
This is just one of the unique questions a dietitian may field in an average day helping clients achieve success on the ketogenic diet. Food allergies aside, there aren’t many therapeutic diets in existence that require families to weigh every gram of food their child consumes, monitor every milliliter of liquid, and even specify for parents what brand of sunscreen to purchase. This is the reality though, for families and adults controlling their seizures through the ketogenic diet or alternative diet therapies for epilepsy.
While some believe fasting or a fasting-like state was used to treat seizures as far back as Biblical times, the therapeutic ketogenic diet as an option for treating Epilepsy is attributed to Dr. Russel Wilder, MD, of the Mayo Clinic in 1921. With the discover of Valproic Acid post-World War II, interest and use of the ketogenic diet fell out of favor with neurologists in all, but a few medical centers. Seizures are typically treated with anti-epileptic medications (AEDs), but it’s estimated that one-third of seizure conditions cannot be controlled through medications alone (Kwan, 2001). For patients with certain types of seizures, surgery, implantation of a vagal nerve stimulator or diet therapy are the limited treatment options.
Ketone bodies, specifically acetone, acetoacetate, and beta-hydroxybutyrate, are created by the liver as an alternate fuel source in the presence of starvation. Although the body is not starving on the ketogenic diet, carbohydrate is restricted low enough that the body must turn to fat as a main source of energy. The classic ketogenic diet is calculated in a ratio of fat compared to protein plus carbohydrate (2:1, 3:1, or 4:1). This diet ratio can only be achieved through precise meal and snack calculations and measurement of food using a gram scale.
Dr. Eric Kossoff, Associate Professor of Neurology and Pediatrics and Medical Director of The Ketogenic Diet Center at Johns Hopkins Hospital in Baltimore, Maryland is one of the international leaders in the push for use of and research behind low carbohydrate diets for disease treatment. “Families typically turn to the diet when seizures are not being controlled by medications, usually after 2-3 drugs have been tried and failed.” For certain medical conditions including infantile spasm and GLUT1 deficiency syndrome, a genetic condition in which glucose is impaired in crossing the blood brain barrier, the ketogenic diet is recommended as a first-line treatment (Kossoff, 2008).
Failing medications often means that seizures are not reduced or sometimes even increase. Parents though must also deal with side effects of medications which can include significant changes in behavior, altered physical abilities to perform daily activities, disruption of sleep patterns, and a person’s appetite can be affected with a decrease or increase. In intractable epilepsy parents may have to use a “rescue medication” such as rectally administered Diastat to stop uncontrolled seizures. The outlook for seizure control is grim once several AEDs have failed, as research has shown that typically once three different medications have been tried its not likely that trying a fourth or fifth will be effective.
Most dietitians know the ketogenic diet is all about the fat. At the typically highest ratio of 4:1, meals, snacks or formula provide 90% of calories from fat. A three year old for example would receive a little less than 1000 calories per day calculated at 80 to 90% of DRI for age, but in actuality the goal is individualized by each dietitian based on factors including weight gain pattern, medical conditions, and activity level. Unlike ketogenic diets proposed for weight loss children do not lose or gain a significant amount of weight if calories from fat are provided to meet total calories needs.
Children on diet therapy still receive adequate protein for growth, but protein is also tightly controlled. For the 1000 calorie diet given as an example, that leads to less than 9 grams of total carbohydrate per day at a 4:1 ratio. Fiber is subtracted from most counted carbs, but sugar alcohols (which are often avoided) are not. That would equal about 95 grams of fat per day which can be consumed as sources such as heavy cream, butter, oils, nuts, cheese, bacon, or avocado.
A fluid goal, rather than a limit, is used to ensure adequate hydration with ketosis. Given that most children consume at least 100 to 200 grams of carbohydrate per day, with such a low level of carbohydrates treats such as candy, soda, and crackers are eliminated, but also grain foods such as rice, pasta, bread and cereal do not fit into such a tight diet restriction. This change can be shocking for families to even contemplate let alone carry out.
As research and application of the ketogenic diet grew it was found that diet guidelines could be loosened slightly and still achieve seizure reduction. Newer approaches to diet therapies for seizures include the Modified Atkins Diet (MAD) and the Low Glycemic Index (LGI) diet. Both of these diets focus on the restriction of dietary carbohydrate to a certain level, typically 10 to 15 grams of carbohydrate per day for MAD or on LGI, 50 to 60 grams of low-glycemic index carbs. Food is not weighed on a gram scale and nutrition facts labels or other databases are used to calculate carbohydrate intake. Initiation of these diets does not require a hospitalization. These diets are often used for teenagers and adults as opposed to the ketogenic diet.
Kossoff, co-author of Ketogenic Diets: Treatments for Epilepsy and Other Disorders has helped thousands of families effectively use dietary treatment as an intervention to improve seizure control. Despite his belief in the benefits of the ketogenic diet he adds, “The diet is a medical therapy, it has real and sometimes severe side effects. They are often manageable and do not require the diet to be stopped, however, with these risks the diet should be followed along closely by a neurologist and preferably a dietitian as well.”
HOW IS THE KETOGENIC DIET INITIATED?
According to Danine Mele-Hayes RD, Ketogenic Dietitian with the Epilepsy & Brain Mapping Program at Huntington Memorial Hospital in Pasadena, CA, who has been working with clients on the ketogenic diet since 1995, “A patient must be evaluated by a neurologist or epileptologist before being referred to the ketogenic diet program. If the physician does not have a ketogenic diet program at his facility, then he will be less likely to discuss this option with his patient. Several families have stressed their concern about not receiving information about this option earlier. Most neurologists will try using anti-seizure medications first. The ketogenic diet and associated diets are not generally the first choice, though exceptions exist.”
Before diet therapy is initiated serum levels including a complete blood count, liver and renal function, lipid profile, carnitine, AED medication levels, and plasma amino acid levels are routinely checked along with urinalysis for calcium, creatinine, and organic acids to rule out any underlying metabolic or other illnesses which would categorize this high fat diet as inappropriate.
With any of the low carbohydrate diet approaches, the role of the dietitian is paramount for a successful transition. Mele-Hayes explains that, “Several teaching sessions are scheduled with the dietitian prior to initiating the classic ketogenic diet or modified forms. We review a wide range of subjects including basic principles, food preparation, complications of the diet, lists of hidden carbohydrates (ie. medications, lotions), label reading, fluid guidelines, collecting urinary and/or blood ketones, lab protocols, vitamin and mineral supplementation, sick day schedule, fine-tuning and even problem shooting.” Krystyna Skowronski, MS, RD, Clinical Dietitian with DMC Children's Hospital of Michigan relates a similar approach. “Once pre-diet labs are drawn to check for underlying metabolic disorders and nutrient deficiencies, I meet with the patient and his/her family in clinic and complete a full nutrition assessment. We discuss what meals will look like and how they are prepared; we discuss efficacy, possible complications and risk factors, plus expected duration of the diet. My role is imperative on our keto team. I handle the bulk of the diet and help to educate the physicians and NPs about the diet.”
The ketogenic diet in many facilities requires a hospitalization of 3 to 5 days in order to monitor the body’s response to ketosis, provide intravenous sugar-free fluids if needed, and educate families on meal preparation. With possible acute side effects including acidosis, GI dysfunction, constipation, and long term effects of poor growth, kidney stones, hyperlipidemia, osteoporosis, or even pancreatitis, how did the neurology community decide that this was a viable option for patients?
In the late 1990’s a growing body of research showed that just over half of children tried on the ketogenic diet had a 50% or more improvement in seizures. These results were comparable to the outcomes of some medications (Freeman, 1998). Despite retrospective studies demonstrating effective use of the ketogenic diet, due to the nature of the diet such as the types of food, portion sizes, etc., it was difficult for researchers to even conduct the gold standard of a doubly blinded clinical trial. The first blinded, crossover study of the ketogenic diet was published in Epilepsia in 2009. This study was carried out by both groups starting out with a fasting period, and then glucose or saccharin was added to a ketogenic diet received by children with Lennox-Gastaut syndrome. There was only a slight difference in parent reported seizures and no difference in EEG results. Ketosis was not completely eliminated in the saccharin group and it was felt that the design of the study could be improved upon (Freeman, 2009).
AND FINALLY....THE GOLD STANDARD OF CONFIRMATION
The randomized control trial conducted by Neal et. al in England and published in 2008 showed more evidence that the ketogenic diet was an effective treatment. The research team used the same ketogenic diet in both the control and experimental group, but started the control group on the KD three months after the first group. 28 children (38%) in the diet group had greater than 50% reduction in seizures compared with four (6%) of children in the control group. Five children (7%) in the ketogenic diet group had greater than 90% seizure reduction. None of the children in the control group had this type of result. Ten children did not stay in the study due to intolerance and many of the common side effects such as constipation, vomiting, lack of energy, and hunger were documented (Neal, 2008).
A Cochrane Database review published in 2012 which focused on four randomized research studies, echoed the major problem inherent in KD therapy. Although, their review concluded that the KD resulted in a beneficial reduction in seizure occurrence and a comparable effect to some medications, the high incidence of families unable to stick with the diet lowers the efficacy of actually using it with success. The authors pointed to less restrictive diets such as the Modified Atkins and Low Glycemic Index diets as possibly having just as effective outcomes with better attrition rates (Levy, 2012).
Beth Leonberg MS, RDN, CSP, FAND, LDN, Editor-in-chief of The Academy of Nutrition and Dietetics Pediatric Nutrition Care Manual and Assistant Clinical Professor and Didactic Program Director in the Department of Nutrition Sciences at Drexel University agreed that the ketogenic diet is considered a valid therapy approved by the Academy of Nutrition and Dietetics. Leonberg shared, “I had no reservations about including the ketogenic diet in the Pediatric Nutrition Care Manual since it has been safely used for decades. It has been proven to be a very effective means for treating and managing intractable seizures in some children. Although it should not be undertaken without appropriate education and monitoring, when administered to patients whose families have been thoroughly trained by a team of physicians, nurses and dietitians, typically at a tertiary care center, it's use can be truly life changing. There is some debate about the level of restriction needed, and the effectiveness of various types of diets in achieving ketogenesis, but the underlying principle is well supported.”
Use of KD therapy has grown in part by the positive outcomes produced by experts in KD therapy, but also through work done by organizations such The Charlie Foundation and Matthew’s Friends. The Charlie Foundation, a non-profit organization celebrating twenty years of fighting for respect for the diet and its benefits, has had a significant impact on both families and practitioners who support patients on diet therapy.
Jim and Nancy Abrahams found out about the diet in 1994 when no other options, including multiple drugs or surgery, had helped their son Charlie. Coming across the diet in a textbook, the family wondered why the KD was not available at more facilities. Charlie eventually had success on the diet through working with staff at Johns Hopkins. Abrahams later went on to write, direct and produce a movie in 1997 called First Do No Harm. This movie, still available for purchase on the Charlie Foundation website, starred Meryl Streep and was based on a true story about another child who eventually became seizure-free while on the ketogenic diet.
Beth Zupec Kania, RD, CD, mentor to many ketogenic dietitians, is a nutrition consultant for The Charlie Foundation and owner of Ketogenic Seminars and has trained staff on administering the ketogenic diet in over 130 hospitals in ten different countries. The Charlie Foundation offers support through expert advice, materials for diet education, supplies, and recipes. The KetodietCalculator©, a web based program for dietitians which is supported by funds fromThe Charlie Foundation, was the brain child of Zupec-Kania. Dietitians are now able to save hours of time in meal calculations while helping families serve a greater variety of meal options and still stay within the parameters of the ketogenic ratio. The Ketodietcalculator© program which was designed by Zupec-Kania along with LifeTime Computing, Inc. allows dietitians to customize private, personalized profiles for their clients. Dietitians can provide a password to their clients so that families and dietitians can plan the meals, snacks, and fluid schedules together. The program also provides carbohydrate content for many commonly used medications.
AVOIDING SIDE EFFECTS
“Many factors may affect dietary compliance including the patient's age, eating habits prior to diet, medications that suppress appetite, medical conditions, etc,” explained Mele-Hayes. Trouble shooting issues often falls to the RDN. Mele-Hayes added, “If a patient has GERD prior to the diet, his challenge may be tolerating some of the high fat foods such as heavy whipping cream. I may design a meal plan which omits certain trigger foods to establish tolerance upon initiation. A school age child on an athletic team may be challenged when the team goes out for pizza after the game. Our dietitian and social worker will provide support for this child by offering suggestions for diet compliance during social events. The parents of a two year old, who is a picky eater prior to the diet, may be challenged with identifying high fat food preferences. The dietitian will work with the parents to suggest creative meal plan ideas that the child may find palatable.”
With the growing interest in low carbohydrate diets, the safest approach for both adults and children is working with licensed healthcare practitioners experienced in the possible real and serious side effects of the diet. Laura Cramp, RD, LD, CNSC, a clinical nutrition manager and ketogenic diet specialist for Children’s National Health System in Washington, DC has used ketogenic diet therapies so far for glioblastoma, diabetes, GLUT-1 deficiency, pyruvate dehydrogenase complex deficiency and thiamine pyrophosphokinase-1 deficiency. Although she mainly works with children she has provided help for managing the diet for a handful of adults over the last seven years.
Cramp doesn’t believe that families should try this on their own, “It is too risky to induce ketosis without medical monitoring and the rate of failure is higher because they won’t have the support when things get tough.”
A trained team works to teach parents how to avoid kidney stones by supplementing with potassium citrate or assuring adequate water intake on a daily basis, use of interventions for constipation, prescribing adequate vitamin and mineral supplementation, and monitoring for the possible side effects.
When nearly all dairy products are eliminated, and fruits and vegetables are severely limited, appropriate supplementation is necessary to maintain normal growth and immune system functioning. Skowronski adds, “The diet is not nutritionally complete and is especially lacking in calcium and vitamin D, therefore supplementation is essential to prevent nutritional deficiencies and future complications.” Cramp also emphasizes the importance of proper implementation and monitoring, “The diet is deficient in vitamins and minerals, so supplementation is necessary. In some cases, we provide extra calcium and vitamin D to account for increased risk for bone mineral deficiency from low weight bearing activity and use of AEDs.” Minimum supplementation typically includes a sugar free vitamin and mineral complex containing selenium, calcium, vitamin D3, and sometimes fish oil, carnitine, table salt or Morton lite salt, or baking soda are also encouraged based on lab work.
Registered Dietitian Nutritionists working this closely with the neurologists need to be aware of the side effects of concurrent anti-epileptic drug (AED) use too. Mele-Hayes explains that, “if a patient is on zonisamide or topiramate prior to KD initiation, the child may be having a lack of appetite or acidosis. Ketosis, as well as, some anti-epileptic medications may suppress appetite and increase acidosis. We may recommend smaller, more frequent meals or a nutritional supplement, between meals to encouraged adequate intake or the neurologist may reduce a medication to help with acidosis.”
IMPACT OF DIETITIANS
“While a ketogenic diet is a great tool to help control seizures; planning meals and the time that it takes to prepare them is a significant challenge. It takes a lot of good and open communication with families to make it successful,” said Skowronski. Mele-Hayes agreed, “The RD plays a vital role in the success of a ketogenic diet program. One main responsibility is to assure adequate nutrition while on this therapy. This requires us to assess and communicate any medical or nutritional concerns with the ketogenic diet team.” In recent years, some inventive chefs and mothers of children on diet therapy have brought more palatability and support to families struggling to find keto-friendly alternatives to their children’s favorite foods. Dawn Martinez, author of the Keto Cookbook, has partnered with the Charlie Foundation to produce tasty recipes including flax breads, pancakes created from nut flours, and sauces featuring coconut oil and stevia.
Although this labor intensive work for RDNs includes multiple phone calls and emails with families which is often non-billable time, the KD can offer RDNs a feeling of satisfaction. “Helping patients with the diet is very time intensive, time which I often don’t have in my schedule. Working so closely with the families, I become close with parents and children. It is tough when the diet doesn’t work, but when it does, it is best feeling,” agreed Cramp.
Dr. Kossoff, who works closely with several dietitians at Johns Hopkins added, “Dietitians are critical for the classic ketogenic diet and helpful for keeping patients compliant and happy on the modified Atkins diet.” Cramp adds, “The ketogenic diet is a unique way to treat epilepsy, but it is not a “miracle diet.” It is just another treatment option for epilepsy, with its own side effects and down sides. The future of the KD is bright in that the uses for KD are expanding and the palatability and tolerability of the diet is improving. The use of modified Atkins diet and Low Glycemic index treatment allow for a wider variety of options for patients that may not succeed on the KD as well.”
The trend towards acceptance in the medical community still has challenges, but according to Dr. Kossoff, “Neurologists absolutely ARE using the diet – they are not discouraging it as they did 20-30 years ago. There are ketogenic diet centers everywhere in the USA and most of the countries of the world. The diet is being increasingly used for nonepilepsy indications (e.g. cancer, Alzheimer’s, autism), in adults, and as an early/first line therapy, especially for infantile spasms.”
For Becca Gillmore of Pennsylvania, the diet has become an important component of her daughter’s care in the last two years. Four year old, Gracie, who deals with multiple medical conditions in addition to epilepsy, receives the ketogenic diet entirely via feeding tube. Gillmore shared, “A parent told me the ketogenic diet did nothing for their child and I was worried before we started. Now, Gracie only has seizures when she is sick. The diet is the best thing we’ve done for her. Someone who doesn’t know Gracie well, might not notice it, but for the first time in her life she smiled for us. That has been worth all the efforts of the diet.”
The Charlie Foundation to Help Cure Pediatric Epilepsy: http://www.charliefoundation.org/
Matthews Friends: Dietary Treatments for Epilepsy: http://www.matthewsfriends.org/
Freeman JM, et al. The efficacy of the ketogenic diet-1998: a prospective evaluation of intervention in 150 children. Pediatrics. 1998 Dec;102(6):1358-63.).
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Kossoff EH, Hedderick EF, Turner Z, Freeman JM. A case-control evaluation of the ketogenic diet versus ACTH for new-onset infantile spasms. Epilepsia. 2008;49(9):1504.
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