Shortcomings of the Ketogenic Diet
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In this edition, I would like to share a summary of a recent publication by Dr. Joerg Klepper and colleagues. Dr. Klepper is the Medical Director of Aschaffenburg Children’s Hospital in Aschaffenburg, Germany, and an esteemed and very engaged member of our Medical and Scientific Advisory Board.
The title of the publication is: “Not always the magic bullet” – Insufficient seizure control by ketogenic dietary therapies in Glut1 Deficiency Syndrome.
The goal of this publication was to better understand why ketogenic dietary therapy (KDT), despite being the standard of care for GLUT1 Deficiency for more than 30 years, does not fully control epilepsy in a growing number of patients, even when adequate ketosis is achieved.
Study
The study followed 53 patients with GLUT1 Deficiency over 23 years (2000–2023) who were treated with KDT. Of these, 44 patients had epilepsy and were evaluated for:
- How well seizures were controlled with KDT
- Whether adding antiseizure medications (ASMs) improved seizure control
- Brain activity using electroencephalograms (EEG)
- Genetic and clinical factors
Key Findings
KDT works well for many, but not for everyone.
About 61% of patients with epilepsy experienced a greater than 90% reduction in seizures with KDT alone. These patients were classified as responders.
Adding antiseizure medication can help some patients.
About 39% of patients did not achieve adequate seizure control with diet alone and required the addition of ASMs. These patients were classified as non-responders.
The most commonly used ASMs included ethosuximide and levetiracetam. However, no single medication was found to be clearly superior.
It is difficult to predict who will respond to KDT.
The study examined several factors that might influence response to KDT, including age at diagnosis, type of diet (classic ketogenic diet, Modified Atkins Diet, or others), seizure type, and genetic variants in the SLC2A1 gene. None of these factors predicted treatment response, highlighting the complexity of the condition and the uniqueness of each patient’s experience.
EEG slowing may be a potential indicator of treatment response.
The authors identified that a specific EEG feature, called “EEG background slowing,” improved only in patients whose seizures were well controlled on the diet. EEG slowing refers to brain activity that is slower than expected for a person’s age and may reflect underlying brain dysfunction.
This finding suggests that improvement in EEG slowing could potentially serve as a marker for effective seizure control with KDT in GLUT1 Deficiency.
Take-Home Messages
- KDT works for many, but not all, patients with GLUT1 Deficiency
- close to one-third of patients continue to have seizures despite appropriate treatment
- adding antiseizure medications can help some patients
- more research is needed to predict who will respond to KDT
- KDT remains the standard of care, but some patients do not fully respond even with good adherence
- managing GLUT1 Deficiency often requires a combination of treatment strategies
- there is a need for new therapies that address all symptoms and improve quality of life
We thank Dr. Klepper and his colleagues for his work and dedication to our patients and our community!
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