High-dose eicosapentaenoic acid (EPA) improves attention and vigilance in children and adolescents with attention deficit hyperactivity disorder (ADHD) and low endogenous EPA levels

Abstract

No studies have examined the relationship between endogenous polyunsaturated fatty acids (PUFAs) levels and treatment response to PUFAs. We conducted a 12-week, double-blind, placebo-controlled trial comparing the effects of high-dose eicosapentaenoic acid (EPA, 1.2 g) and placebo on cognitive function (continuous performance test) in n = 92 youth (age 6-18-years-old) with Attention Deficit Hyperactivity Disorder (ADHD). Blood erythrocytes PUFAs were measured before and after treatment, to examine the effects of baseline endogenous EPA levels on treatment response and the effects of EPA treatment on PUFAs levels. Secondary measures included other ADHD symptoms, emotional symptoms, and levels of plasma high-sensitivity c-reactive protein (hs-CRP) and brain-derived neurotrophic factor (BDNF). Overall, EPA group improved more than placebo group on focused attention (variability, Effect size (ES) = 0.38, p = 0.041); moreover, within youth with the lowest baseline endogenous EPA levels, EPA group improved more than placebo group in another measure of focused attention (hit reaction time, HRT, ES = 0.89, p = 0.015) and in vigilance (HRT interstimulus interval changes, HRTISIC, ES = 0.83, p = 0.036). Interestingly, EPA group improved less than placebo group in impulsivity (commission errors), both overall and in youth with the highest baseline EPA levels, who also showed less improvement in other ADHD and emotional symptoms. EPA increased blood erythrocytes EPA by 1.6-fold but not DHA levels, and did not affect hs-CRP and BDNF plasma levels. In conclusion, EPA treatment improves cognitive symptoms in ADHD youth, especially if they have a low baseline endogenous EPA level, while youth with high EPA levels may be negatively affected by this treatment.

Fig. 1. Flow chart of study recruitment.

CPT continuous performance test, EPA eicosapentaenoic acid, n number, PUFAs polyunsaturated fatty acids

Fig. 2. The effect size of EPA on cognitive function, (a) HRT, (b) HRTISIC and (c) COM, with stratification of baseline EPA levels.

a EPA have a greater effect on HRT than placebo in the Low EPA group, with an effect size of 0.89, the confidence intervals of 0.10 to 1.63, p = 0.015. There were no differences between the n-3 PUFAs group and placebo group on HRT of CPT in the overall, High EPA and Mod EPA group. b EPA have a greater effect on HRTISIC than placebo in the Low EPA group, with an effect size of 0.83, the confidence intervals of 0.05 to 1.57, p = 0.036. There were no differences between the n-3 PUFAs group and placebo group on HRT of CPT in the overall, High EPA and Mod EPA group. c The placebo group improved more on the commission errors than the placebo group in the overall, with an effect size of −0.43, the confidence intervals of −0.84 to −0.01, p = 0.025, and high EPA group, with an effect size of −0.83, the confidence intervals of −1.59 to −0.02, p = 0.022. There were no differences between the EPA group and placebo group on COM of CPT in the Mod EPA and Low EPA group. The x-axis is the effect size. Note, COM, commission errors; EPA, eicosapentaenoic acid; High EPA, EPA > 1.08%; HRT, hit reaction time; HRTISIC, HRT interstimulus interval change; Mod EPA, 0.91% < EPA < 1.08%; Low EPA, EPA < 0.91%; n number