Polyunsaturated fatty acid supplementation for drug-resistant epilepsy


Approximately 25% to 30% of all people with epilepsy continue to have seizures despite taking two or more medications in adequate doses. This condition is called drug-resistant or refractory epilepsy. Different treatments, including the use of vitamins and other supplements, are being tested to see if they can help to improve the control of seizures in this group.


We searched for studies that tested the effects of supplementation with polyunsaturated fatty acids (PUFAs) compared to placebo in the treatment of seizures in people with drug-resistant epilepsy, in addition to their routine antiepileptic medications.

Key results

We identified only three randomised trials, which included 155 persons in total (85 adults and 70 children). Two of these studies included only adults and were conducted in more developed countries (US and UK) while the third study involved only children and was conducted in Egypt. In the study involving only children, after 12 weeks of treatment there were more children who were free of seizures in the group that received PUFAs than in the group that received a placebo (pills that do not contain active substance). Likewise, the proportion of children who had a 50% reduction in the number of seizures was higher in the group that received PUFAs than in the group that received placebo. The two studies involving adults did not estimate the number of participants who were free from seizures after the treatment. The analyses of the two studies involving adults showed no differences in the proportion of participants that had a 50% reduction in the number of seizures (low-quality evidence), the mean frequency of seizures, quality of life or side effects, compared to those who received a placebo.


The existing evidence, which consists of only three small studies, is not enough to support the use of PUFA supplementation in addition to routine antiepileptic medications to improve seizure control or quality of life in people with drug-resistant epilepsy.

The evidence is current to 5 November 2015.

Authors' conclusions: 

In view of the limited number of studies and small sample sizes, there is not enough evidence to support the use of PUFA supplementation in people with refractory epilepsy. More trials are needed to assess the benefits of PUFA supplementation in the treatment of drug-resistant epilepsy.

Read the full abstract...

An estimated 1% to 3% of all individuals will receive a diagnosis of epilepsy during their lives, which corresponds to approximately 50 million affected people worldwide. The real prevalence is possibly higher because epilepsy is underreported in developing countries. Although most will achieve adequate control of their disease though the use of medication, approximately 25% to 30% of all those with epilepsy are refractory to pharmacological treatment and will continue to have seizures despite the use of two or more agents in adequate dosages. Over the last decade, researchers have tested the use of polyunsaturated fatty acid (PUFA) supplements for the treatment of refractory epilepsy, with inconsistent results. There have also been some concerns about the use of omega-3 PUFA compounds because they reduce platelet aggregation and could, in theory, cause bleeding.


To assess the effectiveness and tolerability of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid-EPA and docosahexanoic acid-DHA) in the control of seizures in people with refractory epilepsy.

Search strategy: 

We searched the Cochrane Epilepsy Group Specialised Register (from inception up to November 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (2015, issue 11), MEDLINE (1948 to November 2015), EMBASE (1980 to November 2015), SCOPUS (1823 to November 2015); LILACS (Literatura Latino-Americana e do Caribe de Informação em Ciências da Saúde) (1982 to November 2015); ClinicalTrials.gov; World Health Organization (WHO) International Clinical Trials Registry Platform (November 2015). No language restrictions were imposed. We contacted study authors for additional and unpublished information and screened the reference lists of retrieved citations for potentially eligible studies not identified through the electronic search.

Selection criteria: 

All randomised and quasi-randomised studies using PUFAs for the treatment of drug-resistant epilepsy.

Data collection and analysis: 

Two review authors were involved in study selection, data extraction and quality assessment of the included trials. The following outcomes were assessed: seizure freedom, seizure reduction, improvement in quality of life, potential adverse effects, gastrointestinal effects, drop-out rates and changes in plasma lipid profile. Primary analyses were by intention to treat.

Main results: 

Eight studies were identified as potentially relevant; three fulfilled the selection criteria and were included in the review. Two placebo-controlled, double blind trials involving adult participants were conducted in developed countries, while one placebo-controlled, single blind trial involving children was conducted in a developing country (Egypt). Bromfield 2008 randomised 27 American adults to receive 2.2 g/day of omega-3 PUFAs (EPA:DHA in a 3:2 ratio) or placebo. Yuen 2005 randomised 58 people in the UK to approximately 1.7 g/day omega-3 PUFAs (1g EPA and 0.7g DHA) or placebo. Reda 2015 randomised 70 Egyptian children to receive 3 ml/day of 1200 mg fish oil (providing 0.24 g DHA and 0.36 g EPA) or placebo. The three studies recruited a total of 155 subjects (85 adults and 70 children); 78 of them (43 adults and 35 children) were randomised to PUFAs and 77 (42 adults and 35 children) to placebo. All participants were followed for up to 12 weeks. Seizure freedom was reported by only one study, with a high risk of bias, involving exclusively children. The risk estimate for this outcome was significantly higher in the children receiving PUFA compared to the control group (risk ratio (RR) 20.00, 95% confidence interval (CI) 2.84 to 140.99, 1 study, 70 children). Similarly, PUFA supplementation was associated with a significant difference in the proportion of children with at least 50% reduction in seizure frequency (RR 33.00 95% CI 4.77 to 228.15, 1 study with a high risk of bias, 70 children). However, this effect was not observed when the data from two studies including adult participants were pooled (RR 0.57, 95% CI 0.19 to 1.75, I² 0%, 2 studies, 78 participants, low-quality evidence). One of our three primary outcomes (adverse effects related to bleeding) was not assessed in any of the studies included in this review. There were no significant differences between the PUFA and control groups in relation to gastrointestinal effects (RR 0.78, 95% CI 0.32 to 1.89, 2 studies, 85 participants, low-quality evidence).

Supplementation with PUFA did not produce significant differences in mean frequency of seizures, quality of life or other side effects.