Wider use of ketogenic diet therapies for epilepsy has been backed by a review of the latest clinical evidence, which highlights the importance of early intervention in infants with epilepsy.
Published in Lancet Neurology (link here), the review found there is now good evidence for the effectiveness of ketogenic diet therapies, with trials showing that about half of individuals following a diet could achieve more than 50% seizure frequency reduction or seizure freedom.
Ketogenic diets were most helpful in children with epilepsy, where trials have shown they confer a six-fold greater likelihood of achieving seizure frequency reduction and a three-fold higher probability of seizure freedom, the review noted.
Studies in both paediatric and adult populations showed that ketogenic diet therapies allowed reduction or discontinuation of antiseizure medication, with success rates of up to 64% in reducing antiseizure medication without seizure recurrence in some groups of patients.
“Even partial antiseizure medication reduction, however, can substantially enhance [quality of life],” the review emphasised.
Early implementation of ketogenic diet therapy in childhood epilepsy, particularly before multiple antiseizure medication use, could help improve neurodevelopmental outcomes, the US-based authors said.
Factors associated with sustained antiseizure medication freedom include young age at diet initiation, achievement of seizure freedom, and metabolic causes of epilepsy such as glucose transporter type I deficiency, in which response rates exceed 70%.
“At a fundamental level, by providing alternative substrates such as ketone bodies, ketogenic diet therapies target mitochondrial function directly to help control seizures and promote neuroprotection through overlapping and synergistic mechanisms,” they wrote.
“Early intervention is crucial to prevent irreversible mitochondrial and neuronal damage, reduce the risk of developing drug resistance, and maximise ketogenic diet therapy efficacy,” they added.
While the strict regimen of a classic ketogenic diet may be too restrictive for some patients, alternatives such as the medium-chain triglyceride (MCT) ketogenic diet offered greater flexibility, palatability, and adherence, the authors said.
Other options included the modified Atkins diet and a low GI diet, which could offer significant benefits in seizure control while being more acceptable and affordable for people in areas with limited resources, such as rural areas with restricted access to ketogenic diet centres.
Basic science studies showed there were several likely mechanisms of action by which ketogenic diets could prevent seizures by shifting metabolism from glucose to ketone bodies.
“They improve mitochondrial function, reduce neuroinflammation, and modulate neurotransmitters … also affect the gut microbiome, potentially impacting neurotransmitter balance in ways that contribute to seizure control,” the authors said.
However, they cautioned that more robust trials were needed to compare effectiveness of different ketogenic diet interventions and also more studies of early ketogenic diet therapy implementation, particularly before multiple antiseizure medication use.
In the UK, the Epilepsy Society (link here) states that a ketogenic diet may help reduce seizures and is an established treatment option for children with hard to control epilepsy.
The Society advises that a ketogenic diet is usually only considered when at least two suitable medications have been tried and not worked, and must only be followed with the support of an experienced epilepsy specialist and dietitian.