Baseline omega-3 nutritional status and supplementation response in pediatric attention-deficit/hyperactivity
Xiao Fu1,2, Ling Feng1,2, Mingyan Jiang1,2
1Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, China.
Insights
Omega-3 supplementation may improve attention-deficit/hyperactivity disorder (ADHD) symptoms in children, especially those with low baseline omega-3 levels. Further research is needed to confirm these findings for clinical guidance.
Area of Science:
- Nutritional Neuroscience
- Pediatric Psychiatry
- Evidence Synthesis
Background:
- Efficacy of omega-3 polyunsaturated fatty acid (PUFA) supplementation for attention-deficit/hyperactivity disorder (ADHD) shows high variability.
- Baseline omega-3 nutritional status is hypothesized to influence treatment response.
Purpose of the Study:
- To investigate if baseline omega-3 nutritional status explains variability in omega-3 supplementation response in pediatric ADHD.
- To synthesize evidence from randomized controlled trials (RCTs) stratifying outcomes by baseline biomarker status.
Main Methods:
- Systematic review and meta-analysis of PRISMA guidelines, registered in PROSPERO (CRD420251218861).
- Searched PubMed, Embase, PsycINFO, and CENTRAL up to December 2025 for RCTs in children/adolescents with ADHD.
- Synthesized data using random-effects meta-analysis, comparing low-baseline vs. normal/high or unstratified baseline groups.
Main Results:
- Seven RCTs (10 estimates) were included. Overall pooled effect of omega-3 was small (SMD = 0.21, p=0.017) with moderate heterogeneity.
- Subgroup analysis revealed a larger effect in the low-baseline group (SMD = 0.52, p < 0.001, I² = 0%) compared to normal/high or unstratified groups (SMD = 0.03, p = 0.77).
- Stratification by baseline biomarkers reduced heterogeneity and indicated differential treatment effects.
Conclusions:
- Omega-3 supplementation response in pediatric ADHD may depend on baseline nutritional status.
- Current evidence is limited and preliminary; definitions of low baseline status varied across studies.
- Larger, prospectively stratified RCTs with harmonized biomarker assessments are required for clinical recommendations.
Introduction:
High heterogeneity characterizes the efficacy of omega-3 polyunsaturated fatty acid (PUFA) supplementation for attention-deficit/hyperactivity disorder (ADHD). This study aimed to examine whether baseline omega-3 nutritional status may partly explain variability in supplementation response.
Methods:
We conducted a PRISMA-compliant systematic review and meta-analysis registered in PROSPERO (CRD420251218861). PubMed, Embase, PsycINFO, and CENTRAL were searched from inception to December 2025. Eligible studies were randomized controlled trials (RCTs) of omega-3 supplementation in children and adolescents with ADHD that reported baseline nutritional biomarkers, such as erythrocyte EPA/DHA, and efficacy outcomes stratified or otherwise separable according to baseline biomarker status. Data were synthesized using random-effects meta-analysis of standardized mean differences (SMDs), with a prespecified categorical subgroup analysis comparing low-baseline versus normal/high or unstratified baseline estimates.
Results:
Seven RCTs, contributing 10 analytical estimates, were included. The overall pooled analysis showed a small statistically significant effect of omega-3 supplementation (SMD = 0.21, 95% CI: 0.04-0.38; p= 0.017), with moderate heterogeneity (I 2 = 38.7%). Stratification by baseline biomarkers was associated with lower within-subgroup heterogeneity and suggested differential treatment effects by baseline status (χ2 = 10.44, df = 1, p = 0.0012). The low-baseline subgroup (k = 4) showed a larger estimated effect (SMD = 0.52, 95% CI: 0.28-0.76; p < 0.001; I 2 = 0%), whereas the normal/high or unstratified baseline subgroup (k = 6) did not show a statistically significant effect (SMD = 0.03, 95% CI: -0.15-0.21; p = 0.77; I 2 =).
Discussion:
Omega-3 supplementation response in pediatric ADHD may vary according to baseline nutritional status. However, the evidence base remains limited to seven RCTs, and definitions of low baseline status differed across trials according to biomarker matrix and study-specific thresholds. These findings should therefore be interpreted as preliminary and hypothesis-generating. Larger, prospectively stratified RCTs using harmonized biomarker assessments and standardized baseline cut-offs are needed before biomarker-guided omega-3 supplementation can be recommended for clinical nutritional guidance.
Systematic Review Registration:
PROSPERO https://www.crd.york.ac.uk/PROSPERO/view/CRD420251218861, identifier CRD420251218861.
