Elsevier

Epilepsy & Behavior

Volume 7, Issue 2, September 2005, Pages 253-258
Epilepsy & Behavior

Omega-3 fatty acid supplementation in patients with chronic epilepsy: A randomized trial

https://doi.org/10.1016/j.yebeh.2005.04.014Get rights and content

Abstract

Animal studies and a preliminary clinical observation suggest that nutritional supplementation with long chain omega-3 fatty acids (omega-3 FAs) may be useful in the nonpharmacological treatment of patients with epilepsy. Omega-3 FAs increase seizure thresholds, and lower inflammatory mediators, which are increased in patients with epilepsy. In this first randomized, placebo-controlled parallel group trial of omega-3 FA supplementation with 1 g eicosapentaenoic acid (EPA) and 0.7 g docosahexaenoic acid (DHA) daily, 57 patients completed a 12-week double-blind phase. Seizure frequency was reduced over the first 6 weeks of treatment in the supplement group, but this effect was not sustained. The supplementation produced a significant increase in EPA and DHA concentrations and a reciprocal fall in arachidonic and linoleic acid concentrations. No change in serum AED concentrations was detected. Further studies are required to examine different omega-3 FA preparations, different doses, longer treatment duration, and larger sample sizes.

Introduction

Nonpharmacological treatment strategies for the management of refractory epilepsies are increasingly being considered. The use of diet in the treatment of epilepsy has recently been reviewed [1]. Nutritional studies [2], [3] suggest that the Western diet is deficient in long-chain omega-3 fatty acids (omega-3 FAs) but not omega-6 fatty acids. Dietary intake of FA affects the fatty acid composition of neuronal cell membrane phospholipids. FA can modulate electrical signal transduction mechanisms, by affecting ion channel functions and receptor systems [4]. The omega-3 FAs, eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3), derived mainly from fish oil, are the ones incorporated into neuronal phospholipids. Pharmacology studies show that EPA and DHA applied extracellularly raise the stimulatory thresholds of CA1 neurons in hippocampal slices [5], and infusions of EPA and DHA are equipotent in raising seizure thresholds in the male Wistar rat [6]. Furthermore, prolonged oral administration of α-linolenic acid and linoleic acid in a 1:4 mixture protects rats from having seizures in four different epilepsy models [7]. Pharmacology studies also show that the omega-6 FA arachidonic acid (AA) inhibits sodium currents and synaptic transmission [8]. Hence AA may also have an impact on seizures.

Other studies demonstrate the role of inflammatory mediators in epilepsy: proinflammatory mediators are elevated in models of epilepsy [9], [10] and in patients [11] with epilepsy, whereas increasing anti-inflammatory mediators appear to have anticonvulsant effects [10]. EPA reduces pro-inflammatory mediators by inhibiting PLA2 [12] and COX2 [13] enzymes and is itself metabolized to form anti-inflammatory prostaglandins. Increasing omega-3 FA intake has been shown to lower plasma inflammatory markers [14].

Hence, there is some evidence from animal studies that omega-3 FA may increase seizure thresholds. The studies on inflammatory markers also suggest that EPA can reduce these markers, which may lead to reduced seizures. A very small open clinical observation [15] further supports examining the potential effect of EPA and DHA on chronic epilepsy in a well-controlled trial. The present study was undertaken so as to ascertain whether or not omega-3 FA supplementation enhances seizure control.

Section snippets

Methods

This was a 12-week double-blind, placebo-controlled, parallel group trial of omega-3 FA supplementation in patients with refractory epilepsy living in a residential facility. All patients were then continued in a 12-week open maintenance phase of supplements. Patients were entered if their 12-week retrospective seizure counts were clearly recorded and showed at least four epileptic seizures per month. Blood samples were taken prior to and at the end of the 12-week double-blind treatment phase

Results

Sixty-eight patients were screened, with 58 patients being randomized (Fig. 1). One patient (on placebo) was withdrawn after 20 days of treatment following an episode of status epilepticus, which necessitated multiple drug changes. One patient, on low-dose aspirin and naproxen, was withdrawn from the maintenance phase because of a drop in hemoglobin concentration thought to be due to occult bleeding. Table 1 lists patient characteristics.

A significantly greater proportion of patients taking

Discussion

Schlanger et al. [15] reported on an open clinical trial in which 5 patients took omega-3 FA supplements. Though the results were encouraging, it is not possible to draw any definitive conclusions as the observations were open, and of 21 patients entered, 16 refused to consume the bread spread. The spread used provided a proportion of DHA higher (2.3 g DHA and 0.9 g EPA daily) than found in generally available omega-3 FA supplements, which have a higher proportion of EPA.

Our double-blind

Acknowledgments

The authors thank MRC Human Nutrition Research, Cambridge, UK, for analyzing RBC and plasma fatty acid concentrations, and the National Society for Epilepsy Pharmacy for dispensing the trial medication.

Omega-3 fatty acid supplements (Maxepa capsules) and matching placebo capsules were supplied gratis by Seven Seas Ltd, UK.

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    Citation Excerpt :

    Consistent with these findings, efficacy was reported by Schlanger et al. [22] and DeGiorgio et al. on those who received a low dose of EPA & DHA [21]. In contrast, Bromfield et al. [15] and Yuen et al. [14] did not find positive outcomes. Differences in duration of the treatment period, dose of EPA and DHA, and their ratios and/or dietary and genetic backgrounds of the participants might account for the conflicting findings.

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The results of this study were first presented at the American Epilepsy Society Meeting in New Orleans in 2004.

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