Summary:
ADHD is a common neurodevelopmental disorder characterised by difficulties with attention, impulsivity, and hyperactivity. Although stimulant and non-stimulant medications are considered first-line treatments, some children experience adverse effects, limited benefit, or there is parental concerns about long-term use. As a result, alternative treatment approaches are being explored. This systematic review and meta-analysis of randomised controlled trials investigated whether baseline omega-3 biomarker levels influenced the effectiveness of omega-3 supplementation in paediatric ADHD. Seven randomised controlled trials were included. Omega-3 supplementation produced a small but statistically significant improvement in ADHD-related outcomes. When participants were grouped according to baseline omega-3 status, larger treatment effects were observed in those with low baseline omega-3 levels, while no significant benefit was found in participants with normal or high baseline levels. The findings suggest that baseline omega-3 status may influence response to supplementation in children and adolescents with ADHD. However, the evidence remains limited, and further large, well-designed randomised controlled trials are required before biomarker-guided omega-3 supplementation can be recommended in clinical practice.
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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 (I2 = 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; I2 = 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; I2 =).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.
Article Publication Date: 22/06/2026
DOI: 10.3389/fpubh.2026.1844881
