Interview with Edward Bromfield, MD

The therapeutic benefit of fish oils as a treatment for epilepsy is largely anecdotal. Several years ago, Edward Bromfield, MD, Neurology, Brigham and Women's Hospital, Boston, and Associate Professor of Neurology, Harvard Medical School, began a study of omega-3 fatty acids for the treatment of refractory epilepsy.

Dr. Bromfield told us that as a result of an article on, "I began getting emails, some of which described fairly impressive anecdotes in terms of the effects of fish oil on epilepsy."

He added: "We were also quite enthusiastic, because our early analysis looked only at the open-label phase of the study, and results were encouraging, with several patients achieving a 50% or more decrease in seizure frequency relative to baseline. However, when we completed the study and analyzed the double-blinded portion, where neither we nor the patients knew whether they were taking fish oil or the mineral oil placebo, there was no significant difference regarding change in seizure frequency relative to baseline. And we did not even see an encouraging trend."

Dr. Bromfield undertook a new study – a randomized trial of polyunsaturated fatty acids (PUFAs) – with colleagues from Brigham and Women's Hospital and Boston University. The results of this research were presented by his colleagues at the recent annual meeting of the American Epilepsy Society.

Study methodology for new randomized trial

In the PUFA study, 27 adults with uncontrolled epilepsy, defined as those who had at least 4 seizures per month, were randomized 1:1, double-blinded, to PUFA [eicosapentanoic acid (EPA) plus docosahexanoic acid (DHA), 2.2 mg/d in a 3:2 ratio] or placebo (mineral oil).

According to the research abstract, "Following a 4-week prospective baseline and 1-week titration phase, subjects entered a 12-week treatment period. Quality of life was assessed (QOLIE-31) before and after treatment. Upon completion, subjects had the opportunity to participate in a 1-month open-label PUFA trial."

Results regarding seizures

Of the 27 subjects who were randomized, 21 persons completed the study, and 19 completed the open-label phase. Those who did not remain in the study were excluded for various reasons ranging from non-compliance to increased seizures. The study noted that enrolled subjects took between 1 to 3 antiepileptic drugs daily. During the double-blind portion of the study, "seizure frequency increased 6% on PUFA and decreased 12% on placebo (p=0.21). On the other hand, of 19 subjects completing the 4-week open-label PUFA trial, 15 experienced fewer seizures than during baseline (p=0.02), 5 by at least 50%; 4 of these 5 subjects had previously been on placebo."

In addition, QOLIE-31 scores did not show any significant difference between treatments, and there was no evidence of interactions of PUFA with seizure medications, except for lamotrigine, which declined by a mean of 17% among 6 patients.


The researchers concluded that PUFA was not superior to a placebo as treatment for intractable epilepsy for their subjects. During an interview with, Dr. Bromfield said, "Although this was a small pilot study, it has led us to believe that if we were to continue the study, we needed to think about using different fatty acid preparations, or perhaps higher doses - we used 2.2 gm of fatty acids per day, with an EPA:DHA ratio of 3:2."

Dr. Bromfield pointed out that there was a similar study by Alan Yuen and colleagues in the United Kingdom (Yuen AWC et al. Epilepsy Behav 2005;7:253-8). "This group," he said, "found that a polyunsaturated fatty acid preparation similar to ours seemed to have a positive effect during the first 6 weeks of the trial, but that this effect was lost in the second 6 weeks."

"Although our study did not find a similar transient effect during the blinded portion, this kind of effect could have explained the positive results we saw in the open-label portion, at least for patients who had previously been randomized to placebo - as could the so-called placebo effect."

He added: "Our study, along with that of Yuen et al., provides evidence that typical fish oil capsules may not be as helpful as we had hoped, and suggest that other preparations or other doses will need to be studied if the encouraging results of animal studies are to be transferred to the clinic. Or we need to design a new study with higher fish oil doses."

Dr. Bromfield emphasized that "Although our study was small, if people have obtained good results using fish oil capsules or similar preparations, they can continue using them despite our negative results, especially since the safety profile seems excellent. At this point, however, we do not have sufficient information to recommend a specific polyunsaturated fatty acid treatment."


The study, Randomized Trial of Polyunsaturated Fatty Acids for Refractory Epilepsy, was conducted by ¹Edward Bromfield, ¹Barbara Dworetzky, ²Shelley Hurwitz, ¹Zina Eluri, ¹Lara O'Brien, ¹Sonia Replansky, and ³David Mostofofsky at the following institution(s) ¹Neurology, Brigham and Women's Hospital, Boston, MA; ²Medicine, Brigham and Women's Hospital, Boston, MA; and ³Psychology, Boston University, Boston, MA.

Authored By: 
Rita Watson MPH
Edward Bromfield MD
Authored Date: