*3.2. Review of the Evidence*

The populations in the included studies consisted of children with ADHD in the age group ranging from 6–18 years. The interventions consisted of supplements with polyunsaturated fatty acids with either omega 3, omega 6, or combined supplements with both types of fatty acids. The interventions lasted between 8 weeks to 12 months. In some studies [38,49,55], the children were also in medical treatment in both the intervention group and the placebo group, whereby fatty acid treatment was investigated as an active add-on treatment in the intervention group. Information on study identification, baseline characteristics, intervention, control, reported outcomes, and the authors' conclusion is presented in Supplementary Material.

#### 3.2.1. Primary Outcomes

The primary outcomes were reported in 24 studies [29,32,34,35,37–42,44–56] and were based on information from 1755 participants. The results showed no clinically relevant effect was found on the primary outcome parent-rated ADHD core symptoms (SMD: −0.17; 95% CI: −0.32, −0.02) (Figure 3), corresponding to a mean difference on the Parent ADHD rating scale of −1.85 (95% CI: −3.49, −0.22) calculated from the endpoint SD in the control group of Cornu et al., 2018 [51]. The Parent ADHD rating scale ranges from 0 to 54, and thus the result is equivalent to a decrease of 3.4% on the scale (MCID is estimated to a decrease of 30% [19–21]), nor was there any effect found on teacher-rated ADHD core symptoms (k = 10; SMD: −0.06; 95% CI: −0.31, 0.19) [27,29,32,33,35,41,45,50,53] (Figure 4).


**Figure 3.** Forest plot of comparison: PUFA vs. placebo, outcome: parent-reported core symptoms (end of treatment). Green square indicates summary estimates of the individual studies. Black diamond indicates total summary effect estimate.


**Figure 4.** Forest plot of comparison: polyunsaturated fatty acids (PUFA) vs. placebo, outcome: teacher-reported core symptoms (end of treatment). Green square indicates summary estimates of the individual studies. Black diamond indicates total summary effect estimate.

#### 3.2.2. Secondary Outcomes

There was no clinically significant effect on behavioral difficulties, neither when the outcomes were rated by parents (k = 7; SMD: −0.02; 95% CI: −0.17, 0.14) [29,32,35,44,50,52,54] (Figure 5) nor by teachers (k = 5; SMD: −0.04; 95% CI: −0.35, 0.26) [29,32,35,39,50] (Figure 6).


**Figure 5.** Forest plot of comparison: PUFA vs. placebo, outcome: parent-reported behavioral difficulties (end of treatment). Green square indicates summary estimates of the individual studies. Black diamond indicates total summary effect estimate.


**Figure 6.** Forest plot of comparison: PUFA vs. placebo, outcome: teacher-reported behavioral difficulties (end of treatment). Green square indicates summary estimates of the individual studies. Black diamond indicates total summary effect estimate.

> Only two studies [32,52] examined the effect of the intervention on quality of life, with no significant effect (SMD: 0.01; 95% CI: −0.29, 0.31) (Figure 7).

**Figure 7.** Forest plot of comparison: PUFA vs. placebo, outcome: quality of life (longest follow-up time (minimum 3 months after end of treatment)). Green square indicates summary estimates of the individual studies. Black diamond indicates total summary effect estimate.

> Additionally, there were no differences between the intervention group compared to the placebo group regarding the three selected side effects: diarrhea (k = 5, RR: 1.08; 95% CI: 0.32, 3.63 and RD: −0.00; 95% CI: −0.04, 0.03) [29,42,49,50,55], gastrointestinal discomfort (k=4; RR: 0.72; 95% CI: 0.27, 1.88 and RD: −0.01; 95% CI: −0.04, 0.03) [42–44,55], and nausea (k = 6, RR: 0.99; 95% CI: 0.41, 2.38 and RD: 0.01; 95% CI: −0.02, 0.03) [29,32,33,42,43,49,55] (Figure 8).


**Figure 8.** Forest plot of comparison: PUFA vs. placebo, outcome: side effects (end of treatment). Blue square indicates summary estimates of the individual studies. Black diamond indicates total summary effect estimate.
