medwireNews: A classic ketogenic diet that is high in fat and low in carbohydrate could be considered a treatment option for infants aged up to 2 years who, despite trying at least two antiseizure medications, continue to experience four or more seizures a week, suggest researchers.
While a ketogenic diet was no better than further antiseizure medication in reducing the median number of daily seizures, “it was numerically similar in efficacy and tolerability,” and “appeared safe to use in this age group,” report Helen Cross (UCL Great Ormond Street Institute of Child Health, UK) and colleagues in The Lancet Neurology.
The researchers conducted a phase 4 randomized controlled trial, enrolling 136 infants aged 1–24 months (mean age 1.16; 55% boys) with a confirmed diagnosis of epilepsy, all of whom were having four or more seizures in a week that had failed to respond to at least two previous antiseizure medications.
Following a 1–2-week observation period during which no changes were made to existing antiseizure medication, 78 of the infants were randomly assigned to follow a classic ketogenic diet, based on a ratio of fat to carbohydrate and protein of between 2:1 and 4:1. The other 58 instead received further antiseizure medication, depending on their seizure type, epilepsy syndrome, and what drugs had previously been used. Emergency seizure treatment continued as required in both groups.
During weeks 6 to 8, the average number of seizures per day was similar in the ketogenic diet and antiseizure medication groups, at a median of 5 and 3, respectively, giving a nonsignificant incidence rate ratio of 1.33 in favor of antiseizure medication.
At 8 weeks, the proportion of infants who were classed as treatment responsive, defined as having at least a 50% improvement from baseline in seizure frequency, was 44% with the ketogenic diet and 40% with antiseizure medication, at a nonsignificant odds ratio (OR) of 1.21. By this point, 11% of the infants on a ketogenic diet were seizure-free compared with 13% of those on medication; a nonsignificant difference with an OR of 0.88.
Despite the similar seizure frequency in the two groups, Cross and team note that 50% of infants in the antiseizure group had to change the number or dose of their concurrent medications, compared with just 14% of those in the ketogenic diet group, “suggesting that infants on a ketogenic diet may have been more clinically stable,” they say.
Serious adverse events occurred in 51% of patients in the ketogenic diet group and 45% of those taking further antiseizure medication. There were three deaths, all of which occurred among infants on the ketogenic diet, but none were considered related to treatment.
Cross et al point out that “[m]any parents or guardians viewed a ketogenic diet as positive, even if it did not stop their child’s seizures,” perceiving their child’s health to be much better at 12 months than at baseline. The investigators add that “[a] ketogenic diet might also improve some aspects of quality-of-life and neurodevelopment, but further trials are needed with larger cohorts at 12-month follow-up.”
In a comment accompanying the study, Manisha Patel, from the University of Colorado Anschutz Medical Campus School of Medicine in Aurora, USA, says the findings fill “an important gap in the knowledge about ketogenic diets,” but she highlights that major research goals remain, including gaining a better understanding of the mechanisms underlying these diets to identify novel therapeutic targets, and optimizing them to achieve better compliance.
She concludes that “[t]he future for metabolism-based therapies looks bright, but further clinical studies are needed to ascertain the effects of ketogenic diets and other metabolism-based therapies, not only on seizures, but also on comorbidities and quality of life.”
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Lancet Neurol 2023; 22: 1113–1124
Lancet Neurol 2023; 22: 1088–1089