Baseline omega-3 nutritional status and supplementation response in pediatric attention-deficit/hyperactivity disorder: a systematic review and biomarker-stratified meta-analysis
Fu X, Feng L, Jiang M, Li J
Frontiers in public health · 2 citations
How it was studied
- Design
- Meta-analysis (indexed by PubMed)
- Studied in
- People
- Main outcome
- Health markers and function
Who paid for it
- Funding
- Independent funding
- University or hospital
- Sichuan University
Based on 1 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2026-06-22 · Front Public Health · vol. 14 · p. 1844881
- Publisher
- Frontiers Media
- Cited
- 1 citation · more than 89% of similar papers · 2.5× the field average
- References
- 39 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Attention Deficit Hyperactivity Disorder · Sleep and related disorders · Down syndrome and intellectual disability research
- Keywords
- Baseline (sea), Subgroup analysis, Meta-analysis, Randomized controlled trial, Biomarker, Clinical trial
- MeSH
- humans, fatty acids, omega-3, attention deficit disorder with hyperactivity, nutritional status, dietary supplements, adolescent, child, randomized controlled trials as topic, biomarkers
4 authors
From CN
- Xiao FuSichuan University; West China Second University Hospital of Sichuan University
- Ling FengSichuan University; West China Second University Hospital of Sichuan University
- Mingyan Jiang · correspondingSichuan University; West China Second University Hospital of Sichuan University
- Jinrong Li · correspondingSichuan University; West China Second University Hospital of Sichuan University
Abstract
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 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.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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