Review ArticleDietary treatments for epilepsy: Management guidelines for the general practitioner
Research highlights
► The diet is increasing in use for both children and adults. ► Pediatricians need to be aware of diet issues in their general practice. ► Neurologists should be cognizant of indications and contraindications. ► Emergency physicians have to be able to recognize common and rare problems.
Introduction
Despite continued advancements in anticonvulsant development, approximately 30% of patients with epilepsy have refractory seizures [1], and so there remains a significant demand for additional options. Carbohydrate-restricted diets have become increasingly used as a treatment of chronic and acute epilepsy [2], [3]. Evidence from randomized, controlled trials [2], [4] and meta-analyses [5] has demonstrated that overall approximately 50% of children will respond to these diets with at least a 50% reduction in seizures. Ketogenic diets may be also effective for adult status epilepticus [6] and adult epilepsy [6], [7], and as a first-line treatment of seizures associated with glucose transporter 1 deficiency [8]. These diets are being used worldwide in many new centers [9], and based on the approximately 200 centers today offering dietary treatment, an estimated 3000 children are likely actively receiving this treatment worldwide.
These children are also cared for by pediatricians, internists, emergency department physicians, intensivists, and house officers in academic and community hospitals when general pediatric illnesses arise. Similar to all children, they may become ill, require anesthesia for surgery, and receive oral medications. Therefore, there is a need for these general practitioners worldwide to recognize emergencies and common side effects and be aware of treatment aspects unique to carbohydrate-restrictive dietary therapies. This review highlights many of the common medical issues seen in children and adults receiving dietary treatment for epilepsy.
Section snippets
Composition of dietary treatments
All dietary therapies used to treat epilepsy share the common characteristic of restricting carbohydrate intake to shift the predominant caloric source of the diet to fat [10]. Body tissues are thereby forced to catabolize fats as their primary source of energy, and the catabolism of fats results in ketones, hence the origin of the common descriptor for these therapies, “the ketogenic diet.” The precise mechanisms by which the ketogenic diet yields its anticonvulsant effect are not known, but
Pre-ketogenic diet preparations
As groups have gained experience with ketogenic diets, it has become obvious that some patients with certain epilepsy syndromes particularly benefit from this therapy, some are less likely to benefit but may merit a trial, and there are some for whom the diet is contraindicated. Appropriate screening and selection of eligible patients are imperative for best chance of success and more importantly for safety.
Acute issues during initiation of the ketogenic diet
The practice at our institution and at the majority of institutions employing the ketogenic diet is that inpatient admission is helpful and important for close monitoring of children and the intense education of their parents. This short (3- to 4-day) admission is needed for patient safety should problems arise during diet initiation and as a means to ensure completion of parental education about the diet. In select circumstances, outpatient initiation has been reported as safe [26], but it
Chronic issues with the ketogenic diet
Beyond the admission period, there are other adverse effects that may arise in children on dietary treatment (Table 3). The vast majority of inquiries and on-call issues with the ketogenic diet can be triaged and solved without an emergency room evaluation or hospital admission. Although issues with the ketogenic diet may seem at first glance more complicated than those of anticonvulsant medications, fielding a phone call or outpatient query about a possible diet-related side effect requires
Gastrointestinal complaints
The most common reported chronic complications of the ketogenic diet typically include gastrointestinal issues. Constipation is frequently associated with the ketogenic diet and can be managed by increasing dietary fiber intake, ensuring adequate carbohydrate-free fluid intake, or, if other measures fail, by prescribing carbohydrate-free laxatives such as polyethylene glycol. These children can present with abdominal distention, hematochezia (as a result of straining and rectal mucosal
Long-term issues with the ketogenic diet
Several issues require particular attention from those caring for patients on long-term use of the ketogenic diet. Typically the issues regarding hypoglycemia, constipation, acidosis, and hunger become less problematic over time. Exceptions may occur during intercurrent illnesses. In general, the long-term (over years) issues that a general practitioner needs to be aware of are related to (1) inadequate supplementation to prevent systemic deficiencies and (2) increasing risk of poor growth,
Rare reported adverse effects
Rare side effects have been described in case reports that have not been mentioned so far in this review (Table 4). These include basal ganglia changes, increased illnesses, bleeding, and other electrolyte and mineral deficiencies. The correlation between these adverse effects and the ketogenic diet has not been definitively demonstrated. However, as no centralized adverse effect registry exists for dietary treatment, as often occurs during the initial introduction of a new anticonvulsant drug
Special issues for adults
As the number of adult patients trying ketogenic diets, especially the modified Atkins diet, for epilepsy has increased, issues unique to this population have become apparent. Caloric restriction in young women can cause loss of bone density and menstrual irregularities [48]. This has been described before in women treated with the ketogenic diet for epilepsy [49]. A reduction in ketogenic diet ratio to increase carbohydrate intake and increased calories to restore a normal body mass index
Discontinuing dietary therapy
Generally, for a patient whose response to the diet is a greater than 50% reduction in seizure frequency, the typical duration of ketogenic diet therapy is 2 years, though this time frame can be extended because of irreversibility of the underlying condition (i.e., GLUT-1 deficiency) or because of robust response without significant side effects. After 2 years, it is advisable to weigh the relative benefits with potential risks for any patients receiving dietary therapy, recognizing the adverse
Conclusions
Ketogenic diet therapy is a well-tolerated, safe treatment for many forms of epilepsy and can be used in adults and children following careful screening and education. Many complications of dietary therapy are easily prevented and, when present, can be managed on an outpatient basis. In acute illness, goals of care should focus on ameliorating the illness first; maintaining the diet is a secondary yet important consideration. Gastrointestinal complaints such as constipation and gastroesophageal
Acknowledgment
The authors gratefully appreciate the idea for this review by Dr. Jong Rho. This review is thus dedicated to his house officers at Alberta Children's Hospital in Calgary, Alberta, Canada.
References (50)
- et al.
The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial
Lancet Neurol
(2008) - et al.
The effects of the ketogenic diet in refractory partial seizures with reference to tuberous sclerosis
Eur J Paediatr Neurol
(2006) - et al.
Decreased relative efficacy of the ketogenic diet for children with surgically approachable epilepsy
Seizure
(2007) - et al.
Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet
Am J Clin Nutr
(2008) - et al.
Sudden cardiac death in association with the ketogenic diet
Pediatr Neurol
(2008) - et al.
Cognitive dietary restraint: impact on bone, menstrual and metabolic status in young women
Physiol Behav
(2008) - et al.
Natural history of treated childhood-onset epilepsy: prospective, long-term population-based study
Brain
(2006) - et al.
A blinded, crossover study of the efficacy of the ketogenic diet
Epilepsia
(2009) - et al.
Efficacy of ketogenic diet in severe refractory status epilepticus initiating fever induced refractory epileptic encephalopathy in school age children (FIRES)
Epilepsia
(2010) - et al.
Efficacy of the ketogenic diet as a treatment option for epilepsy: meta-analysis
J Child Neurol
(2006)
The ketogenic diet in treatment of two adults with prolonged nonconvulsive status epilepticus
Epilepsia
Efficacy and tolerability of the modified Atkins diet in adults with pharmacoresistant epilepsy: a prospective observational study
Epilepsia
Glucose transporter 1 deficiency syndrome and other glycolytic defects
J Child Neurol
Worldwide use of the ketogenic diet
Epilepsia
State of the ketogenic diet(s) in epilepsy
Curr Neurol Neurosci Rep
Anticonvulsant mechanisms of the ketogenic diet
Epilepsia
Optimal clinical management of children receiving the ketogenic diet: recommendations of the International Ketogenic Diet Study Group
Epilepsia
Role of carnitine and fatty acid oxidation and its defects in infantile epilepsy
J Child Neurol
Efficacy of dietary treatments for epilepsy
J Hum Nutr Diet
A modified Atkins diet is effective for the treatment of intractable pediatric epilepsy
Epilepsia
Low-glycemic-index treatment: a liberalized ketogenic diet for treatment of intractable epilepsy
Neurology
The modified Atkins diet
Epilepsia
Efficacy, safety, and tolerability of the low glycemic index treatment in pediatric epilepsy
Epilepsia
GLUT1 deficiency syndrome—2007 update
Dev Med Child Neurol
Ketogenic diet in patients with Dravet syndrome
Epilepsia
Cited by (65)
Ketogenic diet in children and adolescents: The effects on growth and nutritional status
2023, Pharmacological ResearchQualitative exploration of feasibility and acceptability of the modified ketogenic dietary therapy for children with drug-resistant epilepsy in Kenya
2021, Epilepsy and BehaviorCitation Excerpt :An estimated one-third of children with epilepsy have clinical syndromes characterized by drug resistance, necessitating palliative interventions [1–3]. Global evidence indicates that dietary therapies are efficacious when offered to children with drug-resistant epilepsy, with reduction in the number of seizures, reduction in hyperactivity, and improvement in cognition reported [4]. The modified Atkins diet is a more relaxed diet to implement in comparison to the classical or medium chain triglyceride Atkins diet [5–7].
The ‘epileptic diet’- ketogenic and/or slow release of glucose intervention: A review
2020, Clinical NutritionEarly α-linolenic acid exposure to embryo reduces pentylenetetrazol-induced seizures in zebrafish larva
2019, Prostaglandins Leukotrienes and Essential Fatty AcidsCitation Excerpt :Furthermore, there are a lot of side-effects associated with the use of available antiepileptic drugs, hence they do not serve the purpose for the comprehensive management of epilepsy [2,3]. Several food-based therapies have emerged out to be an effective and efficient non-pharmacological management option for successfully achieving control over refractory epilepsy via acting through multiple mechanisms [4]. For instance, ketogenic diet has confirmed its efficacy in different epileptic animal models, as well as in clinical conditions acting by changing the main energy source to the brain.
Ketogenic Diet: Parental Experiences and Expectations
2024, Journal of Child Neurology