Does Omega-3 Help After All in Autism Spectrum Disorder? An Update Systematic Review and Meta-Analysis of Randomized Trials
Abstract
BACKGROUND/OBJECTIVES: Autism Spectrum Disorder (ASD) affects approximately 60 × 104 incident cases, 283.3 × 105 prevalent cases, and 43.1 × 105 DALYs globally and is frequently accompanied by irritability, hyperactivity, and social withdrawal linked to low-grade neuroinflammation. Omega-3 supplementation is among the most common complementary approaches used by families, but clinical evidence remains inconsistent, and prior meta-analyses have relied on a single outcome instrument. This study aimed to evaluate the efficacy of omega-3 supplementation on ASD-associated behavioral symptoms by harmonizing outcomes across multiple validated instruments.
METHODS: Twelve randomized controlled trials (number of studies per domain: k = 6-12) were identified through a systematic search of ten databases (CRD420261390092). Outcomes from eight instruments (ABC, CGI-I, BASC-2, SRS/SRS-2, GARS-2, CARS/SDQ, VABS/PLS-4/PDDBI, and CBCL) were mapped onto five behavioral domains: Irritability, Lethargy/Social Withdrawal, Stereotypy, Hyperactivity, and Inappropriate Speech/Communication. Random-effects models (REML, Knapp-Hartung adjustment) pooled Hedges' g for each domain, with fixed-effects, subgroup, and PET-PEESE publication-bias sensitivity analyses.
RESULTS: Significant pooled effects favoring omega-3 supplementation were observed for Irritability (g = -0.287, 95% CI [-0.562, -0.013], p = 0.043) and Inappropriate Speech/Communication (g = -0.213, 95% CI [-0.363, -0.063], p = 0.010).…
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