Ruoxuan Huang, Yiu-Wing Kam
Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental condition associated with long-term cognitive, behavioral, and social impairment. Given concerns about medication side effects and variability in treatment response, polyunsaturated fatty acid (PUFA) supplementation has been proposed as an adjunctive intervention. This meta-analysis evaluated the efficacy of polyunsaturated fatty acid (PUFA) supplementation, primarily omega-3 (ω-3) fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]), in improving ADHD symptoms and explored potential moderators, including intervention duration, dosage, and outcome measurement tools. A systematic search of six databases identified 16 randomized controlled trials eligible for quantitative synthesis. Effect sizes were calculated as standardized mean differences using Hedges' g and pooled using random-effects models. Overall, PUFA supplementation was associated with a small, borderline statistically significant improvement in ADHD outcomes (g = - 0.24, 95% confidence interval - 0.48 to - 0.00), with substantial heterogeneity across studies. Stratified analyses indicated stronger effects on performance-based cognitive assessments than on subjective behavioral rating scales. No significant linear associations were observed between treatment effect and intervention duration or total PUFA dosage. These findings suggest that PUFA supplementation may provide modest, context-dependent benefits but is unlikely to serve as a standalone treatment. Further biomarker-informed and longer-term trials are needed to clarify its clinical role. This review was registered in PROSPERO (registration number: CRD420261350342).