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Dietary therapies: A worldwide phenomenon
Epilepsy Research (2012) 100, 205—209
journal homepage: www.elsevier.com/locate/epilepsyres
Dietary therapies: A worldwide phenomenon Eric H. Kossoff a,∗, Roberto H. Caraballo b, Tuschka du Toit c, Heung Dong Kim d, Mark T. MacKay e, Janak K. Nathan f, Sunny G. Philip g a
The John M. Freeman Pediatric Epilepsy Center, Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, MD, United States b Department of Neurology, Hospital de Pediatría Prof Dr Juan P Garrahan, Buenos Aires, Argentina c Private Practice, Pretoria, South Africa d Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, South Korea e Department of Pediatrics, Royal Children’s Hospital, Melbourne, Australia f Department of Neurology, Shushrusha Hospital, Mumbai, India g Department of Neurology, Birmingham Children’s Hospital, Birmingham, United Kingdom Received 3 January 2011; received in revised form 9 May 2011; accepted 9 May 2011
KEYWORDS Ketogenic; Diet; Epilepsy; International; Edinburgh; Worldwide
Summary At the 2010 Global Symposium on the Dietary Treatments for Epilepsy and other Disorders held in Edinburgh, there was an opening evening 75-min session to highlight the similarities and differences in the use of the ketogenic diet worldwide. Speakers from seven distinct regions of the world briefly presented their successes as well as challenges in using dietary therapies. Additionally, future clinical and research goals for each area were discussed. This article summarizes these talks and the use of the ketogenic diet worldwide. © 2011 Elsevier B.V. All rights reserved.
Introduction The ketogenic diet (KD) and other dietary therapies are at a turning point in history. Never before in the world has there been this level of research and clinical use (Kossoff and McGrogan, 2005). This dramatic increase in the past two decades was evident by the attendance at the 2nd International Symposium on Dietary Therapies held in Edinburgh, Scotland. Although this meeting was held in the United Kingdom, and the previous meeting in 2008 in the United States, the attendees were well-represented from many other coun-
∗ Corresponding author. Tel.: +1 410 955 4259; fax: +1 410 614 2297. E-mail address: [email protected] (E.H. Kossoff).
tries on all continents except Antarctica. This evident global perspective can be further noted in the international variety of speakers throughout the meeting and this supplement. Recognizing the international experience present at the meeting, the organizing committee chose to begin the conference with an evening session consisting of brief, 10-min lectures from KD clinical experts from several countries. Speakers were asked to discuss the current status of dietary treatments in their region of the world including clinical experience and insights as well as their own unique difficulties. These lecturers, the authors of this article, were asked to comment on North America, Europe, Africa, Australia, Asia, South America, and India (Fig. 1). Most speakers gave a perspective from their own country on these continents, and their country of origin is listed in the subsequent sections as well.
0920-1211/$ — see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.eplepsyres.2011.05.024
206 What was clear to all of those in attendance was that (1) there are many possible ways to implement the KD with adjustments to the ‘‘traditional’’ KD often made to adapt for children in different cultures and regions, (2) most centers are actively trying to expand the use of the KD to countries in their continents that do not offer the KD currently, and (3) the entire world is having difficulties grappling with limited hospital and dietitian resources, especially in light of the recent economic downturn.
North America (United States of America) The birthplace of the KD in 1921, the use of dietary treatments continues to increase in popularity in the United States. Additional ‘‘alternative’’ diets such as the modified Atkins diet (Kossoff et al., 2006), created in Baltimore, and the low-glycemic index treatment, created in Boston (Pfeifer and Thiele, 2005) have added to parental interest in dietary treatments. Only seven states, mostly in the Midwest regions, appear to our knowledge not to have ketogenic diet centers, with most large US cities having even more than one ketogenic diet center. The Charlie Foundation (www.charliefoundation.org) and their KetoCalculator program (www.ketocalculator.com) are available to parents in the United States over the Internet and have continued to make the diet easier and more widely available, with a 4-fold reported increase in usage of the KetoCalculator program over the past 5 years (personal communication, Beth Zupec-Kania). At the American Epilepsy Society’s annual meeting, the KD special interest group is usually well attended. Insurance companies typically do reimburse neurologists and dietitians for starting the KD as an inpatient. Although widely used in Canada, the rest of North (and Central) America is not as well represented. It does not appear to be available in Mexico and much of the Caribbean. A KD center in Honduras has just started using the modified Atkins diet without a dietitian (Kossoff et al., 2008). At this center, a neurologist has translated dietary treatment information into Spanish and has provided it to parents. This may be one avenue to making dietary therapies more available in these resource-poor countries. However, even in the United States, there are still difficulties in making the diet available to some families. Adults and adolescents are not typically referred, and some child neurology practices are still late to refer children despite very intractable epilepsy in many cases. A study of child neurologists in South Carolina from 2008 found that only 36% of those surveyed use the KD ‘‘frequently after numerous antiepileptic drugs have failed’’ (Mastriani et al., 2008). Of the remainder, 16% ‘‘never’’ use it, 24% ‘‘rarely’’, 24% ‘‘only as a last resort’’. Possible solutions to improve referrals include more lectures at the Child Neurology Society annual meeting, including the KD in US medical school curriculum, and continued activism by the Charlie Foundation.
Europe (United Kingdom) The use of dietary therapies, including the KD, modified Atkins diet, and the MCT oil diet has been well established in Europe for many decades now. Some of the earliest work in the modern era was published in the United King-
E.H. Kossoff et al. dom and evaluated the MCT diet in a multicenter design (Schwartz et al., 1989). Just recently, the first published randomized trial of the KD showed statistical significance over continued anticonvulsants and has raised awareness worldwide (Neal et al., 2008). As a result of Matthew’s Friends (www.matthewsfriends.org), a parent-support group, the use of dietary therapies has expanded significantly throughout the United Kingdom. In fact, this symposium was sponsored and organized with the large assistance of Ms. Emma Williams and Matthew’s Friends. European countries are also using the diet as well as engaged in clinical research. Specifically, Germany, Denmark, Poland, and Scandinavian countries have had ketogenic diet symposium in recent years. A 1-day KD session has been sponsored by SHS Germany annually and held in Fulda Germany as part of a larger pediatric neurology conference. There is also interest in the modified Atkins diet (Miranda et al., 2011) and using diets in adults (Carrette et al., 2008) in Europe. Multicenter trials are ongoing in countries in Europe and have been completed in Germany (Klepper et al., 2004) and Italy (Coppola et al., 2002). Despite the varying cultures and foods, Europe is probably one of the fastest growing regions of the world in ketogenic diet popularity. Parts of Eastern Europe, however, do not universally offer the KD, requiring families to travel to Germany, Poland, or Greece at times. This may change in the near future.
Australia Australia has a population of approximately 22 million people and children less than 15 years comprise approximately 4.3 million. Subspecialist pediatric care is centralized and pediatric neurological services are predominantly located in capital cities in each state. The KD first was used to treat children with epilepsy in Australia in the late 1960s at the Royal Children’s Hospital in Melbourne (Hopkins and Lynch, 1970), but it is now offered as a treatment option in all major pediatric teaching hospitals throughout Australia. Limited dietetic resources restrict access to the KD and it is usually reserved for children with medically refractory epilepsy in whom epilepsy surgery is not an option. A survey was recently conducted of pediatric neurologists and dietitians across nine tertiary pediatric centers; all except one located in State capital cities. Queensland has a joint epilepsy service across two hospitals. Five centers have multidisciplinary programs to streamline care of children treated with the KD, which include development of clinical pathways for inpatient initiation and standardized diagnostic protocols for the early detection and treatment of potential complications. Multidisciplinary outpatient clinics have been developed in five centers to ensure patients receive a balanced overview of the KD prior to commencement of treatment and that their progress is closely monitored by a team which consists of a neurologist, epilepsy nurse specialist, and dietician. One hundred and three children with medically refractory epilepsy are currently being treated with the KD across the country. The amount of pediatric dietetic time allocated to managing these patients ranges from 0 to 32 h/week. All except one center offers the classical long chain triglyceride KD, 5 use the medium chain triglyceride KD, and three
Dietary therapies: A worldwide phenomenon
207
Figure 1 Countries offering the ketogenic diet worldwide (adapted from Kossoff and McGrogan, 2005) at this time. Stars represent centers discussing the ketogenic diet in the Edinburgh ‘‘International’’ seminar session and authoring this manuscript.
offer the Modified Atkins Diet. Five of 9 centers initiate one child per month with all except one admitting children for commencement of the KD. Only one-third of centers fast children at KD initiation, with the remainder following a non-fasting protocol previously described by Bergqvist et al. (2005). In summary, there is considerable variability in practice across Australia, but there is a move towards adopting the international guidelines (Kossoff et al., 2009) to optimize and standardize management of children treated with the KD. Limited dietetic resources is the rate limiting step for most centers in implementing standardized management protocols and increasing availability of the KD for Australian children with epilepsy.
South Asia (India) The ketogenic diet (KD) was introduced in Mumbai, India in 1996 by Dr. Janak Nathan who was trained by at the Johns Hopkins Hospital by Dr. John Freeman (Freeman et al., 2006). This center has been using the diet in all age groups and over 230 children and adults have been treated to date (Nathan et al., 2009). Since that time, the foods have been successfully changed to suit the Indian cuisine and our center has published a book with 100 Indian recipes. Also, it has changed the diet to a non-fasting and non-hospitalization version. The side effect of high lipid levels often seen in this high fat KD has also been successfully addressed with a simple introduction of a mixed-oil KD that gives 4 meals with the following fat composition saturated fatty acid: monounsaturated fatty acids: polyunsaturated fatty acids of 1:2:1. The use of soy has also helped in this and other minor ways. Lower ketogenic ratios such as 1:1 are being used and appear to be successful in maintaining a urine ketone level
of 80—160 mg/dl and possibly of equal efficacy for seizure control. Research underway in India has started to investigate the relevance of blood ketones, the types of fat used, and the modified Atkins diet for infantile spasms. In the last 4 years, 24 teams of a single doctor and dietitian have been trained in Mumbai and are offering the KD across India. In the International symposium of dietary therapies in Edinburgh, 9 posters were presented from 4 centers across India, including a large center in New Delhi. An Indian ketogenic diet workshop will be held in Mumbai in November 2011.
East Asia (South Korea) The KD was started for treating intractable childhood epilepsy from 1995 in Korea. Since a traditional carbohydrate-enriched dietary culture is as dominant in Korea as other Asian countries, there was significant initial resistance to accept the diet from families. Breaking this resistance was most important to spread its usability (Seo and Kim, 2008). Improving tolerability and efficacy has been critical in order to make the KD successful despite this cultural resistance. Our group has published several articles regarding improving efficacy and safety, such as developing a nonfasting protocol, evaluating the short-term and long-term complications of the KD, studying efficacy in infantile spasms and other epileptic conditions according to underlying etiology, utilizing the modified Atkins diet (of interest due to increased ability to use rice and more sharing of foods), and widening the indications for the KD to now include certain mitochondrial respiratory chain complex deficiencies (Kang et al., 2007a,b). The KD has been included as a main session in several Asian scientific congresses in the last 3 years in order to
208 encourage scientific and clinical interest. The application and use of KD keeps increasing in many Asian countries with more successful outcomes and less resistance from family members and physicians.
Africa (South Africa) Although the number of cases of intractable epilepsy is staggering in South Africa, no statistics exist. Since there are no official KD centers in any of the provinces in South Africa, no formal indication of the number of children on the ketogenic or alternative diets, and the success thereof, exist. Few patients have access to the KD, mainly due to the limited number of dieticians that implement the diet in private practice, as well as the small number of referring doctors. In most cases, children are not admitted to hospital prior to initiation of the diet. Parents are educated in detail about the diet (KD, modified Atkins diet, and adapted low glycemic index treatment are all used) and given a home glucometer to measure glucose levels, especially in young children to monitor hypoglycemia. In general, the KD is initiated with a lower ratio (which is increased as needed) with children reaching full ketosis within approximately 2 days. Supplementation includes L-carnitine, a carbohydrate free multivitamin and mineral, essential fatty acids, and probiotics. Blood ketones as well as blood glucose values are used to obtain optimal seizure control. Due to the ‘‘rainbow nation’’ characteristic of South Africa, cultural differences prove to be one of the main obstacles that hinder success, especially since the majority of South African’s staple food is starch (maize meal). Dieticians have to have a broad knowledge of different cultures, culturally accepted food items as well as financial implications in order to make a wise decision regarding what diet to use.
South America (Argentina) In the 1970s, child neurologists were the first to use the KD in the treatment of refractory epilepsy and began in Argentina and Brazil. Over the past years, the KD has also been introduced in other countries, such as Uruguay, Chile, Ecuador, and Colombia. In most centers, the classic KD is used and patients are not always hospitalized. The modified Atkins diet is also used, especially in adolescent patients. Throughout Argentina, the country of this author, there are many centers working with the KD. Research has shown the benefit of the KD for Dravet syndrome specifically (Fejerman et al., 2005). In Brazil, due to its large population, we believe that many other centers, besides just those in Sao Pablo and Rio de Janeiro, should implement the KD. This is starting to occur, and currently two centers in Goina and Recife are being trained in its use. Uruguay and centers in Chile are using the KD with good results and have been doing so for over a decade. More recently, Ecuador and Colombia are starting to use the KD. However, we believe an effort should be made to introduce the KD in all countries in South America, including Paraguay, Venezuela, Peru, Bolivia, and Guyana, who do not to our knowledge offer dietary treatments at this time.
E.H. Kossoff et al.
Summary Dietary treatments are increasing in popularity worldwide. Many regions are interested in adapting the KD to their particular cultures and religions, with growing interest in starting the diet without a fasting period and as an outpatient. Alternative diets such as the modified Atkins diet and low glycemic index treatments may allow for the additional flexibility needed in some of these regions. All areas of the world are struggling with limited resources (especially dietitians) and addressing the problem of countries (or states) that do not yet offer the diet (and then how to provide treatment for children in those areas safely). We expect to have a similar mini-symposium of international presentations at the next conference, with updates from these regions on their progress, and hopefully inclusion of centers in regions not represented such as Central America, Middle East, and Southeast Asia.
References Bergqvist, A.G., Schall, J.I., Gallagher, P.R., Cnaan, A., Stallings, V.A., 2005. Fasting versus gradual initiation of the ketogenic diet: a prospective, randomized clinical trial of efficacy. Epilepsia 46, 1810—1819. Carrette, E., Vonck, K., de Herdt, V., Dewaele, I., Raedt, R., Goossens, L., Van Zandijcke, M., Wadman, W., Thadani, V., Boon, P., 2008. A pilot trial with modified Atkins’ diet in adult patients with refractory epilepsy. Clin. Neurol. Neurosurg. 110, 797—803. Coppola, G., Veggiotti, P., Cusmai, R., Bertoli, S., Cardinali, S., Dionisi-Vici, C., Elia, M., Lispi, M.L., Sarnelli, C., Tagliabue, A., Toraldo, C., Pascotto, A., 2002. The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience. Epilepsy Res. 48, 221—227. Fejerman, N., Caraballo, R., Cersosimo, R., 2005. Ketogenic diet in patients with Dravet syndrome and myoclonic epilepsies in infancy and early childhood. Adv. Neurol. 95, 299—305. Freeman, J.M., Kossoff, E.H., Kelly, M.T., Freeman, J.B., 2006. The Ketogenic Diet: A Treatment for Epilepsy in Children and Others, 4th ed. Demos, New York. Hopkins, I.J., Lynch, B.C., 1970. Use of ketogenic diet in epilepsy in childhood. Aust. Paediatr. J. 6, 25—29. Kang, H.C., Lee, Y.M., Kim, H.D., Lee, J.S., Slama, A., 2007a. Safe and effective use of the ketogenic diet in children with epilepsy and mitochondrial respiratory chain complex defects. Epilepsia 48, 82—88. Kang, H.C., Lee, H.S., You, S.J., Kang du, C., Ko, T.S., Kim, H.D., 2007b. Use of a modified Atkins diet in intractable childhood epilepsy. Epilepsia 48, 182—186. Klepper, J., Leiendecker, B., Riemann, E., Baumeister, F.A., 2004. The ketogenic diet in German-speaking countries: update 2003. Klin. Padiatr. 216, 277—285. Kossoff, E.H., McGrogan, J.R., 2005. Worldwide use of the ketogenic diet. Epilepsia 46, 280—289. Kossoff, E.H., McGrogan, J.R., Bluml, R.M., Pillas, D.J., Rubenstein, J.E., Vining, E.P., 2006. A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy. Epilepsia 47, 421—424. Kossoff, E.H., Dorward, J.L., Molinero, M.R., Holden, K.R., 2008. The modified Atkins diet: a potential treatment for developing countries. Epilepsia 49, 1646—1647. Kossoff, E.H., Zupec-Kania, B.A., Amark, P.E., Ballaban-Gil, K.R., Bergqvist, A.C.G., Blackford, R., Buchhalter, J.R., Caraballo,
Dietary therapies: A worldwide phenomenon R.H., Cross, J.H., Dahlin, M.G., Donner, E.J., Jehle, R.S., Klepper, J., Kim, H.D., Liu, Y.M.C., Nation, J., Nordli Jr., D.R., Pfeifer, H.H., Rho, J.M., Stafstrom, C.E., Thiele, E.A., Turner, Z., Veggiotti, P., Vining, E.P.G., Wheless, J.W., Wirrell, E.C., 2009. Charlie Foundation, and the practice committee of the Child Neurology Society optimal clinical management of children receiving the ketogenic diet: recommendations of the international ketogenic diet study group. Epilepsia 50, 304—317. Mastriani, K.S., Williams, V.C., Hulsey, T.C., Wheless, J.W., Maria, B.L., 2008. Evidence-based versus reported epilepsy management practices. J. Child Neurol. 23, 507—514. Miranda, M.J., Mortensen, M., Povlsen, J.H., Nielsen, H., Beniczky, S., 2011. Danish study of a modified Atkins diet for medically intractable epilepsy in children: can we achieve the same results as with the classical ketogenic diet? Seizure 20, 151—155.
209 Nathan, J.K., Purandare, A.S., Parekh, Z.B., Manohar, H.V., 2009. Ketogenic diet in Indian children with uncontrolled epilepsy. Indian Pediatr. 46, 669—673. Neal, E.G., Chaffe, H., Schwartz, R.H., Lawson, M.S., Edwards, N., Fitzsimmons, G., Whitney, A., Cross, J.H., 2008. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 7, 500—506. Pfeifer, H.H., Thiele, E.A., 2005. Low glycemic-index treatment: a liberalized ketogenic diet for treatment of intractable epilepsy. Neurology 65, 1810—1812. Schwartz, R.H., Eaton, J., Bower, B.D., Aynsley-Green, A., 1989. Ketogenic diets in the treatment of epilepsy: short-term clinical effects. Dev. Med. Child Neurol. 31, 145—151. Seo, J.H., Kim, H.D., 2008. Cultural challenges in using the ketogenic diet in Asian countries. Epilepsia 49 (Suppl. 8), 50—52.
journal homepage: www.elsevier.com/locate/epilepsyres
Dietary therapies: A worldwide phenomenon Eric H. Kossoff a,∗, Roberto H. Caraballo b, Tuschka du Toit c, Heung Dong Kim d, Mark T. MacKay e, Janak K. Nathan f, Sunny G. Philip g a
The John M. Freeman Pediatric Epilepsy Center, Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, MD, United States b Department of Neurology, Hospital de Pediatría Prof Dr Juan P Garrahan, Buenos Aires, Argentina c Private Practice, Pretoria, South Africa d Department of Pediatrics, Severance Children’s Hospital, Yonsei University College of Medicine, Seoul, South Korea e Department of Pediatrics, Royal Children’s Hospital, Melbourne, Australia f Department of Neurology, Shushrusha Hospital, Mumbai, India g Department of Neurology, Birmingham Children’s Hospital, Birmingham, United Kingdom Received 3 January 2011; received in revised form 9 May 2011; accepted 9 May 2011
KEYWORDS Ketogenic; Diet; Epilepsy; International; Edinburgh; Worldwide
Summary At the 2010 Global Symposium on the Dietary Treatments for Epilepsy and other Disorders held in Edinburgh, there was an opening evening 75-min session to highlight the similarities and differences in the use of the ketogenic diet worldwide. Speakers from seven distinct regions of the world briefly presented their successes as well as challenges in using dietary therapies. Additionally, future clinical and research goals for each area were discussed. This article summarizes these talks and the use of the ketogenic diet worldwide. © 2011 Elsevier B.V. All rights reserved.
Introduction The ketogenic diet (KD) and other dietary therapies are at a turning point in history. Never before in the world has there been this level of research and clinical use (Kossoff and McGrogan, 2005). This dramatic increase in the past two decades was evident by the attendance at the 2nd International Symposium on Dietary Therapies held in Edinburgh, Scotland. Although this meeting was held in the United Kingdom, and the previous meeting in 2008 in the United States, the attendees were well-represented from many other coun-
∗ Corresponding author. Tel.: +1 410 955 4259; fax: +1 410 614 2297. E-mail address: [email protected] (E.H. Kossoff).
tries on all continents except Antarctica. This evident global perspective can be further noted in the international variety of speakers throughout the meeting and this supplement. Recognizing the international experience present at the meeting, the organizing committee chose to begin the conference with an evening session consisting of brief, 10-min lectures from KD clinical experts from several countries. Speakers were asked to discuss the current status of dietary treatments in their region of the world including clinical experience and insights as well as their own unique difficulties. These lecturers, the authors of this article, were asked to comment on North America, Europe, Africa, Australia, Asia, South America, and India (Fig. 1). Most speakers gave a perspective from their own country on these continents, and their country of origin is listed in the subsequent sections as well.
0920-1211/$ — see front matter © 2011 Elsevier B.V. All rights reserved. doi:10.1016/j.eplepsyres.2011.05.024
206 What was clear to all of those in attendance was that (1) there are many possible ways to implement the KD with adjustments to the ‘‘traditional’’ KD often made to adapt for children in different cultures and regions, (2) most centers are actively trying to expand the use of the KD to countries in their continents that do not offer the KD currently, and (3) the entire world is having difficulties grappling with limited hospital and dietitian resources, especially in light of the recent economic downturn.
North America (United States of America) The birthplace of the KD in 1921, the use of dietary treatments continues to increase in popularity in the United States. Additional ‘‘alternative’’ diets such as the modified Atkins diet (Kossoff et al., 2006), created in Baltimore, and the low-glycemic index treatment, created in Boston (Pfeifer and Thiele, 2005) have added to parental interest in dietary treatments. Only seven states, mostly in the Midwest regions, appear to our knowledge not to have ketogenic diet centers, with most large US cities having even more than one ketogenic diet center. The Charlie Foundation (www.charliefoundation.org) and their KetoCalculator program (www.ketocalculator.com) are available to parents in the United States over the Internet and have continued to make the diet easier and more widely available, with a 4-fold reported increase in usage of the KetoCalculator program over the past 5 years (personal communication, Beth Zupec-Kania). At the American Epilepsy Society’s annual meeting, the KD special interest group is usually well attended. Insurance companies typically do reimburse neurologists and dietitians for starting the KD as an inpatient. Although widely used in Canada, the rest of North (and Central) America is not as well represented. It does not appear to be available in Mexico and much of the Caribbean. A KD center in Honduras has just started using the modified Atkins diet without a dietitian (Kossoff et al., 2008). At this center, a neurologist has translated dietary treatment information into Spanish and has provided it to parents. This may be one avenue to making dietary therapies more available in these resource-poor countries. However, even in the United States, there are still difficulties in making the diet available to some families. Adults and adolescents are not typically referred, and some child neurology practices are still late to refer children despite very intractable epilepsy in many cases. A study of child neurologists in South Carolina from 2008 found that only 36% of those surveyed use the KD ‘‘frequently after numerous antiepileptic drugs have failed’’ (Mastriani et al., 2008). Of the remainder, 16% ‘‘never’’ use it, 24% ‘‘rarely’’, 24% ‘‘only as a last resort’’. Possible solutions to improve referrals include more lectures at the Child Neurology Society annual meeting, including the KD in US medical school curriculum, and continued activism by the Charlie Foundation.
Europe (United Kingdom) The use of dietary therapies, including the KD, modified Atkins diet, and the MCT oil diet has been well established in Europe for many decades now. Some of the earliest work in the modern era was published in the United King-
E.H. Kossoff et al. dom and evaluated the MCT diet in a multicenter design (Schwartz et al., 1989). Just recently, the first published randomized trial of the KD showed statistical significance over continued anticonvulsants and has raised awareness worldwide (Neal et al., 2008). As a result of Matthew’s Friends (www.matthewsfriends.org), a parent-support group, the use of dietary therapies has expanded significantly throughout the United Kingdom. In fact, this symposium was sponsored and organized with the large assistance of Ms. Emma Williams and Matthew’s Friends. European countries are also using the diet as well as engaged in clinical research. Specifically, Germany, Denmark, Poland, and Scandinavian countries have had ketogenic diet symposium in recent years. A 1-day KD session has been sponsored by SHS Germany annually and held in Fulda Germany as part of a larger pediatric neurology conference. There is also interest in the modified Atkins diet (Miranda et al., 2011) and using diets in adults (Carrette et al., 2008) in Europe. Multicenter trials are ongoing in countries in Europe and have been completed in Germany (Klepper et al., 2004) and Italy (Coppola et al., 2002). Despite the varying cultures and foods, Europe is probably one of the fastest growing regions of the world in ketogenic diet popularity. Parts of Eastern Europe, however, do not universally offer the KD, requiring families to travel to Germany, Poland, or Greece at times. This may change in the near future.
Australia Australia has a population of approximately 22 million people and children less than 15 years comprise approximately 4.3 million. Subspecialist pediatric care is centralized and pediatric neurological services are predominantly located in capital cities in each state. The KD first was used to treat children with epilepsy in Australia in the late 1960s at the Royal Children’s Hospital in Melbourne (Hopkins and Lynch, 1970), but it is now offered as a treatment option in all major pediatric teaching hospitals throughout Australia. Limited dietetic resources restrict access to the KD and it is usually reserved for children with medically refractory epilepsy in whom epilepsy surgery is not an option. A survey was recently conducted of pediatric neurologists and dietitians across nine tertiary pediatric centers; all except one located in State capital cities. Queensland has a joint epilepsy service across two hospitals. Five centers have multidisciplinary programs to streamline care of children treated with the KD, which include development of clinical pathways for inpatient initiation and standardized diagnostic protocols for the early detection and treatment of potential complications. Multidisciplinary outpatient clinics have been developed in five centers to ensure patients receive a balanced overview of the KD prior to commencement of treatment and that their progress is closely monitored by a team which consists of a neurologist, epilepsy nurse specialist, and dietician. One hundred and three children with medically refractory epilepsy are currently being treated with the KD across the country. The amount of pediatric dietetic time allocated to managing these patients ranges from 0 to 32 h/week. All except one center offers the classical long chain triglyceride KD, 5 use the medium chain triglyceride KD, and three
Dietary therapies: A worldwide phenomenon
207
Figure 1 Countries offering the ketogenic diet worldwide (adapted from Kossoff and McGrogan, 2005) at this time. Stars represent centers discussing the ketogenic diet in the Edinburgh ‘‘International’’ seminar session and authoring this manuscript.
offer the Modified Atkins Diet. Five of 9 centers initiate one child per month with all except one admitting children for commencement of the KD. Only one-third of centers fast children at KD initiation, with the remainder following a non-fasting protocol previously described by Bergqvist et al. (2005). In summary, there is considerable variability in practice across Australia, but there is a move towards adopting the international guidelines (Kossoff et al., 2009) to optimize and standardize management of children treated with the KD. Limited dietetic resources is the rate limiting step for most centers in implementing standardized management protocols and increasing availability of the KD for Australian children with epilepsy.
South Asia (India) The ketogenic diet (KD) was introduced in Mumbai, India in 1996 by Dr. Janak Nathan who was trained by at the Johns Hopkins Hospital by Dr. John Freeman (Freeman et al., 2006). This center has been using the diet in all age groups and over 230 children and adults have been treated to date (Nathan et al., 2009). Since that time, the foods have been successfully changed to suit the Indian cuisine and our center has published a book with 100 Indian recipes. Also, it has changed the diet to a non-fasting and non-hospitalization version. The side effect of high lipid levels often seen in this high fat KD has also been successfully addressed with a simple introduction of a mixed-oil KD that gives 4 meals with the following fat composition saturated fatty acid: monounsaturated fatty acids: polyunsaturated fatty acids of 1:2:1. The use of soy has also helped in this and other minor ways. Lower ketogenic ratios such as 1:1 are being used and appear to be successful in maintaining a urine ketone level
of 80—160 mg/dl and possibly of equal efficacy for seizure control. Research underway in India has started to investigate the relevance of blood ketones, the types of fat used, and the modified Atkins diet for infantile spasms. In the last 4 years, 24 teams of a single doctor and dietitian have been trained in Mumbai and are offering the KD across India. In the International symposium of dietary therapies in Edinburgh, 9 posters were presented from 4 centers across India, including a large center in New Delhi. An Indian ketogenic diet workshop will be held in Mumbai in November 2011.
East Asia (South Korea) The KD was started for treating intractable childhood epilepsy from 1995 in Korea. Since a traditional carbohydrate-enriched dietary culture is as dominant in Korea as other Asian countries, there was significant initial resistance to accept the diet from families. Breaking this resistance was most important to spread its usability (Seo and Kim, 2008). Improving tolerability and efficacy has been critical in order to make the KD successful despite this cultural resistance. Our group has published several articles regarding improving efficacy and safety, such as developing a nonfasting protocol, evaluating the short-term and long-term complications of the KD, studying efficacy in infantile spasms and other epileptic conditions according to underlying etiology, utilizing the modified Atkins diet (of interest due to increased ability to use rice and more sharing of foods), and widening the indications for the KD to now include certain mitochondrial respiratory chain complex deficiencies (Kang et al., 2007a,b). The KD has been included as a main session in several Asian scientific congresses in the last 3 years in order to
208 encourage scientific and clinical interest. The application and use of KD keeps increasing in many Asian countries with more successful outcomes and less resistance from family members and physicians.
Africa (South Africa) Although the number of cases of intractable epilepsy is staggering in South Africa, no statistics exist. Since there are no official KD centers in any of the provinces in South Africa, no formal indication of the number of children on the ketogenic or alternative diets, and the success thereof, exist. Few patients have access to the KD, mainly due to the limited number of dieticians that implement the diet in private practice, as well as the small number of referring doctors. In most cases, children are not admitted to hospital prior to initiation of the diet. Parents are educated in detail about the diet (KD, modified Atkins diet, and adapted low glycemic index treatment are all used) and given a home glucometer to measure glucose levels, especially in young children to monitor hypoglycemia. In general, the KD is initiated with a lower ratio (which is increased as needed) with children reaching full ketosis within approximately 2 days. Supplementation includes L-carnitine, a carbohydrate free multivitamin and mineral, essential fatty acids, and probiotics. Blood ketones as well as blood glucose values are used to obtain optimal seizure control. Due to the ‘‘rainbow nation’’ characteristic of South Africa, cultural differences prove to be one of the main obstacles that hinder success, especially since the majority of South African’s staple food is starch (maize meal). Dieticians have to have a broad knowledge of different cultures, culturally accepted food items as well as financial implications in order to make a wise decision regarding what diet to use.
South America (Argentina) In the 1970s, child neurologists were the first to use the KD in the treatment of refractory epilepsy and began in Argentina and Brazil. Over the past years, the KD has also been introduced in other countries, such as Uruguay, Chile, Ecuador, and Colombia. In most centers, the classic KD is used and patients are not always hospitalized. The modified Atkins diet is also used, especially in adolescent patients. Throughout Argentina, the country of this author, there are many centers working with the KD. Research has shown the benefit of the KD for Dravet syndrome specifically (Fejerman et al., 2005). In Brazil, due to its large population, we believe that many other centers, besides just those in Sao Pablo and Rio de Janeiro, should implement the KD. This is starting to occur, and currently two centers in Goina and Recife are being trained in its use. Uruguay and centers in Chile are using the KD with good results and have been doing so for over a decade. More recently, Ecuador and Colombia are starting to use the KD. However, we believe an effort should be made to introduce the KD in all countries in South America, including Paraguay, Venezuela, Peru, Bolivia, and Guyana, who do not to our knowledge offer dietary treatments at this time.
E.H. Kossoff et al.
Summary Dietary treatments are increasing in popularity worldwide. Many regions are interested in adapting the KD to their particular cultures and religions, with growing interest in starting the diet without a fasting period and as an outpatient. Alternative diets such as the modified Atkins diet and low glycemic index treatments may allow for the additional flexibility needed in some of these regions. All areas of the world are struggling with limited resources (especially dietitians) and addressing the problem of countries (or states) that do not yet offer the diet (and then how to provide treatment for children in those areas safely). We expect to have a similar mini-symposium of international presentations at the next conference, with updates from these regions on their progress, and hopefully inclusion of centers in regions not represented such as Central America, Middle East, and Southeast Asia.
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