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Ketogenic Diet: New Hope for Infants Battling Drug-Resistant Epilepsy


A ketogenic diet, which is low in carbohydrates and high in fat, shows promise as an alternative treatment option for infants with drug-resistant epilepsy, finds a new study led by researchers at UCL and Great Ormond Street Hospital for Children (GOSH).

Keto diet

Results from the Ketogenic Diet in Infancy (KIWE) trial, outlined in The Lancet Neurology, was the first in the world to compare the impact of a ketogenic diet to further anti-seizure medication for infants aged one to 24 months with drug-resistant epilepsy.

The researchers investigated whether the diet could reduce seizure frequency, compared with further anti-seizure medication. To do this, they recruited 136 infants across 19 centres in the UK, between 2015 and 2021 who were undergoing standard epilepsy treatments.

Of the patients, 78 infants started a ketogenic diet and 53 started an additional anti-seizure medication, in addition to their standard treatments.

The team recorded the number of seizures each patient had, both before they started the ketogenic diet or additional anti-seizure medication, and for the first eight weeks after starting their new treatment. Participants were also followed for up to 12 months – and all serious adverse events that resulted in hospitalisation or loss of life, such as infection or an increase in seizures, were recorded.

The phase clinical 4 trial found both treatment options to be effective for reducing seizures in infants.

The median number of seizures experienced by those in the ketogenic diet group was five, whereas those on anti-seizure medication had a median number of three seizures.

At eight weeks, 11% of the infants on the ketogenic diet were seizure-free compared to 13% in the anti-seizure medication group.

Likewise, a similar number of infants with at least one serious adverse event was reported in both groups – 51% in the keto diet group and 45% in the anti-seizure medication group.

The researchers also found that there was no significant difference in the quality of life and neurodevelopment experienced by both groups.

Lead author, Dr Natasha Schoeler (UCL Great Ormond Street Institute of Child Health and GOSH), said: “There is no evidence to show that there is a difference between the effectiveness of a ketogenic diet and further anti-seizure medication in infants with drug-resistant epilepsy.

“To be classed as drug-resistant, adequate trials of two anti-seizure medications must have already failed to control seizures. Going on a ketogenic diet gives families a feeling of empowerment over their treatment and gives paediatric neurologists an alternative route of care.

“We can’t overpromise and say that a ketogenic diet is better than another drug. However, it should be considered as another treatment option.”

A ketogenic diet is high in protein and light on carbohydrates. It alters the body’s metabolism, directing it to draw on body fat as its primary fuel source, mimicking one physiological effect of starvation even though the individual is fully nourished. The switch from carbohydrates to fat for body fuel is known as ketosis.

Those on the trial were given a strict classic ketogenic diet, calculated by a paediatric dietitian and usually based on a ratio of between 2:1 and 4:1 grams of fat to grams of carbohydrate and protein.

Dr Schoeler said: “The diet is very strict and all recipes are made by dietitians. This means that everything must be weighed out properly. However, there are also prescribable products that some infants can eat too – so it is palatable.

“It depends on the family, but it is generally easier for children to start the diet when they are young.

“They may have to stay on the diet for around two years but then we can have a conversation about coming off it. Previous research in children shows that around 75-80% maintain the response after stopping the ketogenic diet, if they become seizure-free whilst on the diet.”

Senior author, Professor Helen Cross (UCL Great Ormond Street Institute of Child Health and GOSH), said: “‘This study was a real collaborative effort amongst ketogenic diet centres in the UK, demonstrating this therapy should be considered as a second line treatment option in infants with epilepsy alongside other standard anti-seizure medication.”

The research was funded by the National Institute for Health and Care Research (NIHR), Nutricia Advanced Medical Nutrition and Young Epilepsy.

Patient story

Ace, 10, from Brighton, started having partial epilepsy seizures when she was just 14 weeks old.

Despite being put on sodium valproate medication the seizures continued to worsen and, at 5 months, Ace developed infantile spasms – a severe type of epilepsy that usually occurs under the age of two years and causes stiffening of the body and jerky movements of the head, arms or legs.

When Ace was 12 months she was diagnosed with a SCN8A gene mutation – a condition that causes developmental delays and learning difficulties, as well as also being a common cause of drug-resistant epilepsy in children.

Ace was put on high-dose steroids. But they failed to control her seizures, so she started on the anti-epilepsy drug, vigabatrin.

Ace’s mum, Rai, said: “None of these treatments worked – Ace, who is non-verbal, was still having seizures up to 10 times a day, and the side effects of the medications were making her tired, floppy and unable to stay awake.”

When Ace was 18 months old, the family were referred to GOSH from the Royal London Hospital.

Ace and her mum RaiRai says: “The consultant at GOSH decided to try combining the steroid therapy with the vigabatrin – while this stopped Ace’s infantile spasms, she reverted back to the nonconvulsive episodic seizures which were happening daily.”

When Ace was two years old, the GOSH epilepsy team and the dietetic team at GOSH and the UCL Great Ormond Street Institute of Child Health agreed that Ace should try a ketogenic diet as a treatment option.

Rai explained: “Before the ketogenic diet, Ace was seizing daily but within a few months the change in her was incredible.

“Quite quickly we also saw her interest in her surroundings improving and she’d start kicking toys in her pram, looking in mirrors, rolling on the floor – all the developmental milestones that weren’t there before. Her daily seizures had reduced to a mild seizure occurring about once a month.”

Ace stopped the ketogenic diet when she was eight, and now she manages her epilepsy with the lowest optimal dose of oxcarbazepine and a small does of clonazepam before bedtime.

Rai said: “Ace has been having normal foods since, and has been stable. In fact, for the past few months she hasn’t had any seizures.

“We’ve been mind-blown by how lucky we’ve been with Ace – I know it may not benefit all patients but the ketogenic diet has really improved our daughter’s quality of life.

“I hope that other families who want to access the diet for their children with drug-resistant epilepsy are able to.”

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