The goal of the work described here was to determine the effect of high-dose n-3 fatty acids (eicosapentanoic acid+docosahexanoic acid, fish oil) on several outcomes in subjects with refractory epilepsy, including seizure severity, seizure frequency, cardiac risk factors, and heart rate variability, in a pilot, exploratory planning trial.

Pilot, randomized, double-blind two-period crossover clinical trial of high-dose fish oil (9600 mg of fish oil/day, 2880 mg of n-3 fatty acids) in 11 subjects with refractory seizures. Outcomes included seizure frequency, seizure severity, lipid panel, and heart rate variability as measured by SDNN and SDANN (defined as the standard deviation of all normal R-R intervals for 1h, and the standard deviation of all R-R intervals in each successive 5-min epoch, respectively).

Preliminary data identified trends towards lower seizure severity, lower triglycerides, higher HDL, and increased SDNN/SDANN in those with low SDNN/SDANN at baseline (Spearman's correlation=-0.65, P=0.03). No positive effect on seizure frequency was identified.

Further study of the effect of n-3 fatty acids is indicated in people with epilepsy, as favorable trends were identified on cardiac risk factors (triglycerides) and in a subgroup with low heart rate variability (low SDNN/SDANN), a marker of sudden death risk. To our knowledge, this is the first trial to explore the beneficial effects of n-3 fatty acids on cardiac risk factors and heart rate variability in people with epilepsy.