Children with genetic causes of epilepsy, including Dravet syndrome, were more than five times more likely to have fewer seizures after following a ketogenic diet, known as keto, for one year, according to a new study.
Across all types of hard-to-treat epilepsy, nearly three-quarters of patients responded to the low-carbohydrate and high-fat diet.
Responders were generally younger than nonresponders, but were older at the time of seizure onset. They also had less frequent seizures before the diet. At the same time, nonresponders were more likely to take more anti-seizure medications before starting the keto diet.
These findings highlight “the importance of early intervention and age in predicting the success of dietary treatments for [genetic epilepsy syndromes],” the researchers wrote.
The study, “Short-term effectiveness and side effects of ketogenic diet for drug-resistant epilepsy in children with genetic epilepsy syndromes,” was published in the journal Frontiers in Neurology.
Studying the effects of the keto diet in children with genetic causes of epilepsy
Nearly all cases of Dravet syndrome, a type of severe epilepsy characterized by prolonged seizures in the first year of life, are caused by mutations in the SCN1A gene. The seizures may be triggered by illness, fever, a warm bath, or warm weather, particularly in the disease’s early phases.
Because seizures associated with Dravet are typically resistant to standard anti-seizure medications, alternative approaches, such as the keto diet, have been suggested. The high-fat, low-carbohydrate, and limited protein diet is thought to promote a switch in the body’s preferred energy source. Instead of glucose sugar, which is derived from carbs, fatty bodies called ketones become the main source of energy.
A previous review of several clinical trials involving more than 1,000 children and adolescents concluded that the keto diet was effective at reducing seizure frequency in drug-resistant epilepsy.
Still, data describing the efficacy of the keto diet in drug-resistant patients with genetic epilepsy syndromes like Dravet are sparse.
In this study, a research team from Saudi Arabia and Qatar enrolled 77 children under the age of 14 with various types of epilepsy to follow a keto diet for one year. Of this group, about 55% were boys.
About 10% of children had Dravet syndrome, while nearly one-fifth had Lennox-Gastaut syndrome. Other clinical syndromes included West syndrome and GLUT1 deficiency syndrome, each affecting about 5% of patients, as well as unclassifiable encephalopathy with genetic mutations, seen in 18% of the group.
Alongside standard care, the children were slowly introduced to the keto diet, with each patient’s dietary plan carefully designed using keto meals and formula. Diet efficacy was assessed at three, six, and 12 months, and patients were classified as either seizure-free, responders, or nonresponders. Responders had at least 50% fewer seizures at any stage, while nonresponders had less than that.
75% of Dravet patients had fewer seizures after a year on the keto diet
Data showed that about 71% of participants responded to the keto diet. Responders were younger, with a mean age of about 7.5, while nonresponders were nearly 9 years old on average. Children who responded to the diet also had an older mean age at seizure onset (22 vs. 9 months). Response rates between sexes didn’t differ.
Of the 28 patients who had monthly seizures before starting the keto diet, nearly 90% achieved seizure improvement. Moreover, almost 60% of those with weekly seizures improved.
Among those with daily seizures, one-third showed some reduction or control in their seizure activity, but they still had daily seizures.
Our findings indicate a significant improvement in seizure control, especially among younger patients and those with a later onset of seizures.
All patients who either did not use any anti-seizure medications or were on a single medication had fewer seizures after a year on the diet. In addition, 80% of those on two medications had improved seizure control, while 63% of patients using three or more medications achieved an improvement.
Seizure reductions were seen in nearly three-quarters of patients with an abnormal brain MRI and an abnormal electroencephalogram, which measures the brain’s electrical activity.
Fewer seizures were observed in 93% of Lennox-Gastaut syndrome cases, followed by 79% of those with unclassifiable encephalopathies and 75% of those with Dravet.
Compared with before the diet, seizure control significantly rose for patients with confirmed genetic causes of epilepsy (18.75% to 60.77%) and structural causes of epilepsy (22% to 55%). Patients with infectious and unknown causes did not significantly improve after the keto intervention.
In an adjusted statistical analysis, patients with genetic causes of epilepsy were more than five times more likely to respond to the keto diet. In contrast, those taking three or more anti-seizure medications were almost 80% less likely to achieve a response.
Adverse events were reported by 35 patients. The most common was constipation, reported by 26% of the group, followed by irritability and nausea, affecting about 14% and 9% of the patients, respectively. Additional events included vomiting, weight loss, fatigue, hypoglycemia (low blood sugar), nutritional deficiencies, kidney stones, and pancreatitis. None of the participants discontinued the diet due to adverse events.
“Our findings indicate a significant improvement in seizure control, especially among younger patients and those with a later onset of seizures,” the researchers concluded. “Patients with specific genetic mutations responded well to [the keto diet],” and “[anti-seizure medications] used before starting [keto] is crucial in predicting response.”
