Background/Objectives: Emotional dysregulation (ED) is emerging as a major contributor to functional impairment in Autism Spectrum Disorder (ASD). Although effective behavioral interventions exist, pharmacological treatments remain constrained by side effects and variable tolerability. Given their neurobiological roles that include neurotransmission, inflammation, and neuroplasticity, vitamin D and omega-3 polyunsaturated fatty acids (PUFAs) have been identified as promising candidates for modulating emotional and behavioral dysregulation. This systematic review aimed to evaluate the efficacy of combined vitamin D and omega-3 supplementation in improving emotional and behavioral regulation in individuals with ASD. Methods: This review was conducted in accordance with PRISMA guidelines. Included studies were English peer-reviewed studies involving participants with ASD that assessed combined vitamin D and omega-3 suppleupplementation with outcomes related to emotional or behavioral dysregulation. The search was restricted to 2015–2025 to ensure inclusion of recent, methodologically consistent studies and to minimize heterogeneity in diagnostic criteria and supplementation protocols. Results: Of 649 records initially screened, 3 studies met inclusion criteria: one randomized controlled trial, one observational study, and one case report, involving participants ranging from early childhood to young adulthood. Across studies, combined supplementation was associated with improvements in irritability, hyperactivity, agitation, and self-injurious behaviors. These clinical effects were accompanied by specific biochemical changes, including reductions in the AA/EPA ratio, increases in serum 25(OH)D and omega-3 indices, and decreased urinary levels of HVA and VMA. Conclusions: This review indicates that co-supplementation with vitamin D and omega-3 fatty acids may exert preliminary beneficial effects on emotional and behavioral dysregulation in individuals with ASD, potentially through anti-inflammatory and neuroregulatory mechanisms. However, the available evidence remains limited due to a small number of studies, their modest sample size, and methodological heterogeneity. Further, biomarker-driven randomized studies are needed to confirm efficacy and delineate optimal dosing strategies for application in clinics.
Berni et al. (Fri,) studied this question.