An international panel of experts has published the first set of recommendations based on current clinical practices and scientific evidence for using ketogenic diet therapies (KDTs) in adults with drug-resistant epilepsy.
Just as in children with epilepsy, KDTs can be safe and effective in adults with epilepsy but should only be undertaken with the support of medical professionals trained in their use, the group says.
“Motivation is the key to successful KDT adherence,” first author Mackenzie Cervenka, MD, director of the Adult Epilepsy Diet Center, Johns Hopkins University School of Medicine, Baltimore, Maryland, told Medscape Medical News.
“Patients who are autonomous require self-motivation and having a strong support structure is important as well. For those patients who are dependents, their caregivers need to be motivated to manage their diet,” said Cervenka.
The guidelines were published online October 30 in Neurology Clinical Practice.
Novel in Adult Neurology
KDTs are high fat, low-carbohydrate, and adequate protein diets that induce fat metabolism and ketone production. Despite its use as an effective antiseizure therapy since the 1920s, KDT remains novel in adult neurology.
Furthermore, while there are established guidelines for KDTs to reduce seizures in children, there were no formal recommendations for adults, until now.
Drawing on the experience of experts at 20 centers using KDTs in more than 2100 adults with epilepsy in 10 countries, Cervenka and an international team developed recommendations on use of KDTs in adults.
The panel notes, “with a relatively mild side effect profile and the potential to reduce seizures in nearly 60% of adults with drug-resistant epilepsy, KDTs should be part of the repertoire of available options.”
KDTs are appropriate to offer to adults with seizure types and epilepsy syndromes for which these treatments are known to be effective in children, they say.
These include tuberous sclerosis complex, Rett syndrome, Lennox-Gastaut syndrome, glucose transporter type 1 deficiency syndrome (G1DS), genetic generalized epilepsies, and focal epilepsies due to underlying migrational disorders and resistant to antiseizure medication.
However, adults with drug-resistant focal epilepsy should be offered surgical evaluation first, given the higher anticipated rate of seizure freedom via this route, the panel says.
A Focus on Compliance
Experts at nearly all of the centers report using two or more KDTs. Ninety percent use the modified Atkins diet, 84% use the classic ketogenic diet, and 63% use the modified ketogenic diet and/or low glycemic index treatment.
More than half of the centers (58%) use medium-chain triglyceride oil in combination with another KDT to boost ketone body production.
The most important factors influencing the choice of KDT are ease of diet application for the patient (100%) and patient and/or caregiver preference, home setting, and mode of feeding (90% each).
The panel recommends that KDTs be tailored to fit the needs of the individual, taking into account his or her physical and mental characteristics, underlying medical conditions, food preferences, type and amount of support from family and others, level of self-sufficiency, feeding habits, and ease of following the diet.
“Most of the differences between the child and adult recommendations have to do with compliance. Often, it’s more of a challenge for adults than for children,” said Cervenka.
The panel recommends providing adult patients with recipe ideas, individualized training on the ketogenic diet lifestyle from a dietitian or nutritionist, and guidance for meal planning and preparation before starting the diet. This will provide the greatest likelihood of success, as patients often report difficulties coping with carbohydrate restriction, they note.
“In pediatric practice, positive responders typically remain on KDT for 2 years before considering weaning. KDT in adults is not time-limited. However, a minimum of 3 months of KDT is recommended before any judgment of response is made,” the panel advises.
The panel points out the absolute metabolic contraindications and cautions related to feeding difficulties, gastrointestinal dysfunction, and digestion remain the same for both children and adults.
However, they add that a range of common adult conditions such as hyperlipidemia, heart disease, diabetes, low bone density, and pregnancy “bring additional consideration, caution, and monitoring to KDT use.”
The guidelines also call for pre-KDT biochemical studies to screen adults for pre-existing abnormalities and establish a reference for comparing follow-up results after 3, 6, and 12 months, and then annually or as needed.
They also note that metabolic studies such as urine organic acid and serum amino acid levels are generally not needed in adults unless there is a strong clinical suspicion for an underlying metabolic disorder.
Updated genetic evaluation may also be considered in adults with intellectual disability and epilepsy of unknown etiology. Serial bone mineral density scans may be obtained every 5 years.
The guidelines also call for ketone monitoring (blood βHB or urine AA) during the early months of KDT as an objective indication of KDT compliance and biochemical response.
Dietary adjustments should focus on optimizing the treatment response, minimizing side effects, and maximizing sustainability.
Adults on a KDT should also be advised to take multivitamin and mineral supplements and drink plenty of fluids.
However, the panel says further evidence is needed to guide recommendations on use of KDTs in other neurologic conditions.
The research had no targeted funding. Cervenka has reported receiving grants from Nutricia, Vitaflo, BrightFocus Foundation, and Army Research Laboratory; honoraria from the American Epilepsy Society, The Neurology Center, Epigenix, LivaNova, and Nutricia; royalties from Demos; and consulting for Nutricia, Glut1 Deficiency Foundation, and Sage Therapeutics. Disclosures for the other authors are listed in the article.
Neurol Clin Pract. Published online October 30, 2020. Abstract