**1. Introduction**

Attention Deficit Hyperactivity Disorder (ADHD) is a common neurodevelopmental disorder in children and adolescents, which may persist into adulthood. A meta-analysis of 102 prevalence studies found that the worldwide prevalence estimate for ADHD among children and adolescents under the age of 18 years is 3.4% (CI 95% 2.6–4.5) [1].

ADHD is characterized by three core symptoms, namely, inattention, hyperactivity, and impulsivity. The symptoms must be present in different settings and be both impairing and age inappropriate. ADHD is frequently comorbid with other psychiatric disorders and a substantial burden to the affected children and their families [2]. Long-term studies have revealed that a diagnosis of ADHD is associated with lower educational achievements and significant higher prevalence of, e.g., injury, substance abuse, unemployment, and delinquency [3–8].

A wide variety of treatments such as pharmacological and psychosocial interventions are used for the management of ADHD. There is some evidence for the short-term effectiveness of certain non-pharmacological interventions and pharmacological treatments [9–11]. However, some patients and parents are concerned with the use of pharmaceuticals for the treatment of ADHD, and initiation of pharmacological treatment may be linked with a certain degree of reluctance due to side-effects. Investigations of other interventions such as diet or nutritional supplements are therefore necessary.

Based on evidence from epidemiological studies and animal models, the rationale for using polyunsaturated fatty acids (PUFAs) as a treatment option for ADHD is promising. Studies have found that a deficiency of essential fatty acids positively correlates with ADHD symptoms [12]. Supporting the evidence that PUFAs may play a role in brain disorders, essential fatty acids have shown to regulate neurotransmitter and immune functions via the modulation of lipid rafts signaling platforms on the cell membrane in addition to having an anti-inflammatory inhibition of the free radical generation and oxidative stress [13–15].

The objective of this systematic review and meta-analysis was to systematically identify and critically assess the current evidence from clinical trials concerning the administration of supplementation with PUFAs for the treatment of ADHD among children and adolescents (6–18 years). Specifically, we sought to evaluate the effect of supplementation with PUFAs on ADHD core symptoms and behavioral difficulties, rated by both parent and teachers. Furthermore, we sought to investigate the impact on quality of life as well as the occurrence of side effects including diarrhea, gastrointestinal discomfort, and nausea.

The systematic review and meta-analysis were based on an update of the results from a Danish national clinical guideline published in 2018 by the Danish Health Authority.
