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.

Polygenic risk score analysis revealed shared genetic background in attention deficit hyperactivity disorder and narcolepsy

“…A recent study using an animal model of ADHD demonstrated the efficacy of core ADHD symptoms by regulating dopaminergic signaling in the brain 47 . More recently, the reduction of fatty acids in the blood 48 among children and adolescents with ADHD, and similarly, the efficacy of a high dose of eicosapentaenoic acid (EPA) for ADHD symptoms have been reported 49 . Future clinical trials using both existing and novel compounds for ADHD and narcolepsy are warranted.…”

The stress–Wnt-signaling axis: a hypothesis for attention-deficit hyperactivity disorder and therapy approaches

“…Some investigations have demonstrated that cognitive functions, such as working memory, teacher-rated behavior, and impulsivity, have improved after n-3-PUFA administration in children with ADHD [105][106][107][108][109] . In particular, EPA supplementation seems to elicit small but significant improvement in inattention and hyperactivity symptoms in ADHD patients 103,110,111 . An in vitro study has recently shown that PC12 dopaminergic cells had their viability significantly increased after n-3-PUFA administration 112 , starting with lower doses (from 100 pM).…”

Use of Non-Pharmacological Supplementations in Children and Adolescents with Attention Deficit/Hyperactivity Disorder: A Critical Review

“…In total, 20 studies focused on supplementation with PUFAs [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53] (see Table 1a): fourteen were on patients without comorbidities [34,[36][37][38][40][41][42][43][44][45][46][47]50,53], two with oppositional defiant disorder (ODD) [35,39], and four with various co-diagnoses, such as specific learning disorder, ODD, conduct disorder, tic disorder, anxiety, Tourette syndrome, or psychomotor difficulties [48,49,51,52]. Two researches [42,43] include very small samples.…”

“…These studies supplemented with various omega-3 fatty acids. In total, 18 studies provided docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) [34][35][36][37][38][39][40][41][42][44][45][46][47][48][49][50]52,53], one study provided alpha linolenic acid (ALA) [43], and one study did not specify which omega-3 was used. Three studies supplemented omega-6: one used gamma-linolenic acid (GLA) [36], while two did not specify which omega-6 was used [35,51].…”