Abstracts

Nutritional studies suggest the Western diet is deficient in omega-3 fatty acids (FA). FA have important roles in determining optimal structural and functional properties of neuronal membranes. Deficiency of FA may contribute to chronic epilepsy. Studies have shown that the FA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), applied extracellularly raised stimulatory thresholds of CA1 neurones. Infusions of EPA and DHA were equipotent in raising seizure thresholds in a rat seizure model. Other studies show that pro-inflammatory mediators are elevated in models of epilepsy, whilst increasing anti-inflammatory mediators appear to have anticonvulsant effects. EPA reduces pro-inflammatory mediators by inhibiting PLA2 and COX2 enzymes and is itself metabolised to form anti-inflammatory prostaglandins. In an open study, 5 patients were given 2.3g of DHA and 0.9 g of EPA daily. Three patients became seizure free and 2 had a greater than 50% seizure reduction at the end of the 6-month trial [Epilepsia 2002; 43(1):103-104]. Patients with chronic epilepsy and learning disability were randomised and received capsules of EPA (1g) and DHA (0.7g) daily or placebo (mixed vegetable oils) in a 12-week double blind study. All patients were then given active medication in a 12-week open maintenance phase. Seizure counts, adverse events, antiepileptic drug (AED) and red blood cell (RBC) FA concentrations were assessed during the study. UCL ethics committee gave approval for the study. Fifty-eight patients were randomised, one patient (on placebo) was withdrawn, hence 30 received active and 27 placebo (age19-65 vs 20-63; males 43% vs 82%, mean no AEDs 2.8 vs 2.4 ). A significantly (p[lt]0.05, CI 1.5% to 36% [17%]) greater proportion on active showed at least a 50% seizure reduction in the first 6 weeks of treatment but not in the second 6 weeks. Analysis of covariance showed a trend (p=0.087) towards a greater reduction in total seizures in the active group in the first 6 weeks only. There were no relevant changes in mean AED concentrations. RBC FA concentrations showed a large increase in EPA and DHA in the active group and a much smaller increase on placebo. There were very few reports of adverse events ( active 4, placebo 4). Status epilepticus occurred in one patient each on active and placebo (withdrawn from trial). One patient (also taking aspirin and naproxen) with a drop in haemoglobin concentration was withdrawn during the open phase. In this study, FA supplementation appears to reduce seizures transiently in the first 6 weeks of treatment. Further studies are required to assess higher FA doses and longer treatment periods. (Supported by Seven Seas Ltd. UK provided study medication.)