Stopping keto diet triggers drug toxicity in 2 Dravet kids, report says
Diet suppressed valproic acid blood levels, which rose when eating changed
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Two children with Dravet syndrome developed severe toxicity from the anti-seizure medicine valproic acid after stopping the ketogenic diet, a case study reported.
The study, the first to report the issue, showed that the diet suppressed valproic acid blood levels in both children, which rose sharply once the diet ended.
“This complication has not been reported in previous literature,” and highlights “the need for monitoring [valproic acid] levels during [ketogenic diet] therapy and wean,” the researchers wrote.
They described the cases in a report, “The Ketogenic Diet Wean as a Trigger for Valproate Toxicity: Lessons from Two Cases,” published in Pediatric Neurology.
Dravet is a severe form of epilepsy marked by seizures beginning in the first year of life alongside a range of Dravet symptoms involving developmental, motor, cognitive, and behavioral issues. Children with the condition are often treated with valproic acid, an anti-seizure medication. Non-medication approaches include the ketogenic diet, a high-fat, low-carbohydrate, limited-protein diet that can help reduce seizure frequency.
Drug-diet interactions
The ketogenic diet generates ketone bodies that may increase levels of nerve cell signaling molecules and boost the number of mitochondria, the cell’s main energy producers.
Interactions between the diet and the medication are increasingly being recognized. Valproic acid levels have been shown to drop on the diet, and the drug can suppress the production of ketone bodies. Both therapies can also affect liver function, and switching from liquid medications to tablets may change how much medicine the body absorbs.
A research team at the Hospital for Sick Children in Toronto reported on two children with Dravet who developed valproic acid toxicity after stopping the ketogenic diet.
In one case, a 23-month-old girl was receiving multiple anti-seizure medications: valproic acid, clobazam (sold as Onfi, Sympazan and generics), and levetiracetam (sold as Keppra and others).
In April 2025, she was admitted with status epilepticus, a prolonged seizure. She began a classic ketogenic diet at a 2:1 ketogenic ratio (two grams of fat for every one gram of combined protein and carbohydrate). Her initial liver and kidney tests were normal. All medicines were switched to tablet forms, and her liquid valproic acid was replaced with divalproex sodium tablets (Depakote and generics).
In June of that year, she experienced recurrent seizures, prompting an increase in the ketogenic diet ratio to 2.25:1. After a subsequent admission for status epilepticus, divalproex was again increased. However, she was admitted again in September with status epilepticus and low VPA levels. Doctors suspected poor tablet absorption, so they increased divalproex even further.
Because the girl’s seizures continued, the family requested that she be weaned from the ketogenic diet, which was fully stopped by December. But in January 2026, she was back with fatigue, declining mobility, and poor appetite.
Tests showed low counts of all blood cell types, with mildly elevated liver enzymes, suggesting liver injury. Valproic acid levels were in the toxic range, so the team discontinued divalproex, and the girl gradually improved and was discharged.
The other patient was a 3-year-old boy who was also being treated with several anti-seizure medications: valproic acid, levetiracetam, clobazam, and Diacomit (stiripentol). He began the ketogenic diet at 14 months of age in March 2024, with his initial liver and kidney tests within the normal range.
Valproic acid and levetiracetam were switched to tablets. A ketogenic diet was started at a 1.25:1 ratio due to signs of drug-resistant epilepsy.
Despite signs of ketone bodies in the urine, his seizures had worsened by September, so divalproex was increased further. Two weeks later, blood tests showed mildly elevated liver enzymes. Although free valproic acid was higher than normal, total valproic acid was within the therapeutic range.
Because of limited benefit and difficulty sustaining the diet, the boy was weaned from the ketogenic diet beginning in November. He was fully out of ketosis by March 3 of the following year, but by March 25, he was admitted with somnolence (unusual sleepiness). Tests showed toxic levels of valproic acid.
Doctors reduced divalproex and optimized levetiracetam, which rapidly lowered valproic acid blood levels. At discharge in April 2025, the boy’s valproic acid values were even lower; he gradually improved and was discharged.
Possible reasons the ketogenic diet may lower valproic acid levels include enhanced liver metabolism, altered gut absorption, or changes in protein binding associated with ketone body production, the researchers suggested.
In children with Dravet syndrome, “anticipating rising [valproic acid] levels as ketosis wanes may help prevent severe toxicity,” they wrote.
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