Triglyceride supplements shows promise in refractory epilepsy


By Mardi Chapman

28 Mar 2019

Prof Patrick Kwan

Adding medium chain triglycerides (MCTs) or triheptanoin to the diet to ameliorate metabolic deficiencies in treatment-resistant epilepsy may have a protective effect on focal unaware seizures,  Australian research suggests.

A  small prospective study conducted at the the Royal Melbourne Hospital found that adding MCTs to the diet appeared feasible, safe and tolerated.

The study, led by Dr Karin Borges, Head of the Neurological Disorders and Metabolism Laboratory, University of Queensland, comprised 34 patients with epilepsy who experienced at least two seizures per 28 days  despite treatment with at least one antiseizure drug. They were randomised to either an MCT (triglycerides of octanoate or decanoate) or triheptanoin (triglycerides of heptanoate) taken in an oil form at three daily meals.

Patients were given a titration scheme to increase their dose over a period of three weeks to 35% of energy intake (based on 4-day food diaries), a maximum of 100 mL or their maximal tolerated dose in the case of gastrointestinal disturbances.

A 12-week maintenance phase was followed by down titration over three weeks and cessation of treatment.

The study found an encouraging 50% reduction in seizure frequency in five of 11 (45%) participants treated with MCTs and specifically focal unaware seizures.

One of nine (11%) patients who completed the trial treated with triheptanoin also had a 50% reduction in seizure frequency.

However two participants experienced a doubling of their seizures on treatment – one participant with epilepsy following viral encephalitis taking MCTs and another with ventricular heterotopia in the triheptanoin treatment arm.

There were no correlations between triglyceride dose and seizure control.

Diarrhoea, stomach cramps, and abdominal pain were the most commonly reported adverse events but 56-65% of patients were able to tolerate the treatment. Weight gain averaged about 2 kg.

Dr Borges and co-investigators including Professor Patrick Kwan, Head of Epilepsy at the Royal Melbourne Hospital, said the study opened up a possible new metabolic treatment option for epilepsy without the down sides of dietary restriction associated with ketogenic or modified Atkins diets.

The rationale for using triglycerides in epilepsy was based on evidence for impaired glucose metabolism being a factor in some seizures. In some individuals, the tricarboxylic acid (TCA) cycle may be disrupted, leading to localised shortages of ATP as well as carbons to produce lipids and amino acids in the brain.

“This may contribute dysregulation of neuronal signaling and subsequent seizure generation,” they wrote.

“Larger placebo-controlled studies are necessary to confirm these antiseizure effects in adults and children and we propose to first focus on adults with focal unaware seizures,” they suggested.

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