NUTRITION MANAGEMENT
KETOGENIC DIETS FOR EPILEPSY: PAST, PRESENT AND FUTURE
This article provides us with a timeline of the ketogenic diet, how it originated and how it has developed over the years, highlighting a 2017 survey that assessed the impact of NICE guidance. A STEP BACK IN TIME
Reports of starvation associated with a reduction or cessation of seizures in people with epilepsy, date as far back as the Hippocrates era. Centuries later, in the Gospels, Mark (9.29, King James Version) described a boy with seizures, which only ‘prayer and fasting’ could cure. In the early 1920s, Dr Wilder, from the Mayo Clinic, proposed to mimic the state of starvation and produce ketosis with a high-fat, low-carbohydrate diet.1 This led to the introduction of the socalled ‘classical ketogenic diet (KD)’, typically with a 4:1 ratio of grams of fat to grams of protein and carbohydrate, as a treatment for people with epilepsy. The initial enthusiasm for the KD was ousted by the discovery of diphenylhydantoin in 1938 and the advent of new easy-to-administer anti-epileptic drugs (AEDs). Although widely used, concerns were quickly raised regarding adverse side effects of these drugs. In the 1970s, in an attempt to make dietary treatment more palatable, Huttenlocher introduced the MediumChain Triglyceride (MCT) KD.2 Based on the premise that MCTs are more ketogenic per calorie, the MCT KD, which originally derived 60% of its calories from MCT oil, allowed a greater bulk of protein and carbohydrate compared with the predominantly long-chain classical KD. A modified MCT KD was later developed, designed to minimise gastrointestinal side effects, which derived 30% of its calories from MCT oil and 41% from long-chain fats.3
KDs experienced a new lease of life in 1994 following NBC-TV’s Dateline report on Charlie Abrahams, who became seizure-free with KD treatment started at Johns Hopkins Hospital, Baltimore. The Charlie Foundation was then formed by Charlie’s father, the film director Jim Abrahams, helping to further publicise dietary treatment in the public and academic domains with the film First Do No Harm in 1997, and supporting the first multicentre prospective study of the classical KD.4 To this day, the foundation continues to provide information for professionals and families regarding KDs.
Dr Natasha Schoeler, UCL Great Ormond Street Institute of Child Health
Kirsty Martin-McGill, University of Liverpool and University of Chester
THE NOUGHTIES
In the early 2000s, Dr Eric Kossoff from Johns Hopkins Hospital, published on the use of the Atkin’s diet as a treatment for epilepsy5 and, later, on the development of the KD variant, the Modified Atkin’s Diet (MAD).6 The MAD was intended as a more liberal alternative to the classical KD, with fats ‘encouraged’ rather than specifically measured and protein ‘unlimited’. In 2005, colleagues from Massachusetts General Hospital published on a further ‘liberalised’ dietary regimen, the Low Glycaemic Index Treatment (LGIT), which aimed to minimise the increase of blood glucose following food consumption rather than producing ketones per se.7 The LGIT allowed a greater intake of carbohydrate (around 60% of total energy) compared with other KD types, with only low-glycaemic index foods allowed.
Victoria Whiteley, Royal Manchester Children’s Hospital
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NUTRITION MANAGEMENT In 2008, the first randomised controlled trial (RCT) of classical and MCT KDs to treat drugresistant epilepsy, was undertaken at Great Ormond Street Hospital for Children, London. 38% of children aged two to 16 achieved ≥50% seizure reduction after three months of dietary treatment, compared with 6% controls.8 No difference in effectiveness was found between the classical and MCT KDs.9 This study changed the perceptions of dietary treatment for epilepsy and KDs became more widely available in clinical practice. In 2000, there were 22 centres and 101 patients following KDs in the UK,10 increasing to 28 centres and 152 patients in 2010.11 74% of patients followed the classical KD in 2010 and the remainder followed the MCT KD, despite the aforementioned trend in modified versions of the KD from the USA. PRESENT DAY: THE UK PICTURE AND BEYOND
In 2017, the Ketogenic Dietitians Research Network (KDRN) undertook a survey in the UK and Ireland to assess the impact of the 2012 updated NICE guidance, recommending that children and young people with refractory epilepsy should be referred for consideration of a KD.12 The results demonstrated a 77% increase in services compared with 2000, with patient numbers reaching 754 (KDRN, submitted for publication). Whilst NICE guidance only supports the use of KDs in children, there have also been developments in adult services, with the establishment of seven adult centres. Despite the rapid increase in services and increased availability of the diet, there is ongoing demand for patients to be considered for dietary treatment: 31 centres reported a waiting list (range 1-49 patients) with 267 patients in total
waiting to start a KD. The main reasons stated for limited service capacity included inadequate funding for dietetic, nursing and medical time. This highlights the need for continued improvements in services nationally and an increasing number of KD dietitians supported by charity funding via The Daisy Garland and Matthew’s Friends. The 2017 survey showed that classical and MCT KDs are still in use, but use of the MCT KD has significantly declined and a new diet variant, termed ‘modified ketogenic diet’ (MKD) has been introduced.37 MKD in the UK and Ireland is a hybrid KD, adopting principles from other established KD protocols (predominantly high fat and low carbohydrate), but there is little research into its efficacy or cost-effectiveness. MAD is not in use in the UK and Ireland; LGIT was said to be used in 13 patients, predominantly adults. Additional MCT can be added to each of the dietary protocols as a fine-tuning tool to improve ketosis and seizure reduction. This is reflective of the overall trend in ketogenic practice of allowing more flexibility, but still achieving optimal clinical outcomes. There is now a growing body of evidence to support the use of KDs, particularly for children with refractory epilepsy,13 with a developing interest in the use of KDs for status epilepticus,14 although further research is required in this area. There is controlled evidence to show that the benefits of KDs expand beyond seizure control, with improvements in activity, productivity and anxiety in children.15 Our understanding of which epilepsy syndromes and metabolic conditions are likely to respond well to KDs is also improving. These include glucose transporter type 1 deficiency syndrome, pyruvate dehydrogenase deficiency,
4TH ANNUAL PROGRAMME OF KETOGENIC DIETARY THERAPY LEARNING AND NETWORKING EPILEPSY • DIABETES • NEURO-ONCOLOGY • WORKSHOPS
4TH – 6TH JUNE 2019 www.mfclinics.com/keto-college 30
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NUTRITION MANAGEMENT
There is controlled evidence to show that KDs can positively impact cognition in people with epilepsy. epilepsy with myoclonic-atonic seizures, infantile spasms, tuberous sclerosis complex and Dravet syndrome.16 The use of KDs in adults is growing in popularity following the publication of two recent trials,17,18 both of which illustrated a ‘moderate’ improvement in seizure control, although limited by small sample sizes. An adequately-powered RCT would be of benefit in this population to investigate both clinical and cost effectiveness. With the increase in use of KDs and the growing body of evidence supporting their efficacy in epilepsy, national and international guidelines have, and continue to be, produced. This includes an updated international consensus statement on use of KDs for children with epilepsy, with advice ranging from who is eligible for consideration of a KD, prevention and treatment of adverse effects and how to discontinue dietary treatment.16 Specific guidance has also been published on use of KDs in infants19 and work is underway on guidelines for the use of KDs in parenteral nutrition and within an intensive care setting for status epilepticus. As the indications for and number of patients on KD has increased, so has the number of prescribable products available to support patients, families and professionals. Products now include a specific formula for infants (Nutricia’s KetoCal 3:1) and for adults (Nutricia’s KetoCal 2.5:1 LQ), cereal bars and ready meals (Ketoclassic range by Ketocare) and a chocolate pudding (Keyo by Vitaflo International Ltd). There has also been development of online support tools including EKM, MyKetogenicDiet (Vitaflo International Ltd) and Myketoplanner (Nutricia Metabolics), aiming to improve compliance and accessibility to KDs.
FORWARD FACING
Use, and the potential uses of KDs is expanding, both for epilepsy and beyond. Following a plethora of case series over the past few decades, a nationwide RCT is currently underway to determine the efficacy of the classical KD in infants.20 Evidence, although preliminary, is also mounting for use of KDs in cancer,21,22 neurodegenerative diseases,23 Alzheimer’s disease,24 autism spectrum disorder25 and migraines,26,27 to name but a few. There is continued interest in the potential mechanisms of action of KDs, with the ultimate aim of making dietary treatment easier and more accessible. There is particular focus on medium chain fatty acids,28 including decanoic acid29,30 and triheptanoin,31 and the role of the gut microbiota32 at present. In addition, enhancing understanding of predictors of response to KDs continues to be at the forefront of research interests, with particular regard to genetics,33 epilepsy syndromes and seizures types34,35 and biochemical parameters.36 The UK and Ireland’s contribution to KD research is ever-mounting with the creation of national groups, such as KDRN, promoting communication, idea and resource-sharing and supporting dietitian-led research and international collaborations. CONCLUSION
KDs are more accessible than ever. However, in this rapidly developing field of dietetics, further research is required. Networks, such as KDRN, are essential in fostering research collaborations, clinical support systems and promoting the excellent work of ketogenic dietitians. www.NHDmag.com May 2019 - Issue 144
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