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.
Highlights
Introduction A deficiency of omega3 polyunsaturated fatty acids
Overall (n = 92), we found that youth on EPA improved more than youth on placebo in focused attention (CPT variability, effect size (ES) = 0.38, confidence interval (CI) = −0.05 to 0.80, p = 0.041) but less than those on placebo in impulsivity
As 51 out of 92 participants had comorbid oppositional defiant disorder (ODD), and children with Attention Deficit Hyperactivity Disorder (ADHD) and ODD tend to be generally less responsive to pharmacological treatment[28], we tested whether this improvement in attention was present in a subgroup analysis of these 51 participants; and we found that, as in the whole group, youth on EPA improved more than youth on placebo in focused attention (ES = 0.66, CI = 0.07 to 1.23, p = 0.025)
Summary
Brain and body[2], and have been closely associated with cognitive function[3] and academic performance[4]. Our recent meta-analysis has shown that youth with ADHD have lower blood levels of DHA, EPA and total n-3 PUFAs, when compared with typically developing youth[1]. Meta-analysis report that stimulants are tolerated and effective treatments for youth with ADHD, Chang et al Translational Psychiatry (2019)9:303 these drugs have side effects that need monitoring, such as insomnia, risk of abuse, and changes in blood pressure, heart rate and body weight[7,8,9,10]. N-3 PUFAs have a very good tolerability and safety profile, and may be a preferable treatment option for youth with ADHD.
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