Abstract
<title>Abstract</title> <p> Folate-related metabolic dysregulation has emerged as a key pathological mechanism and therapeutic target in Autism Spectrum Disorder (ASD). While various forms of folate supplementation are utilized as adjunct therapies, their specific impact on core ASD symptoms remains clinically debated. This meta-analysis synthesized high-quality randomized controlled trials to clarify the effects of folinic acid on core ASD symptoms. A systematic search of PubMed, Web of Science, Embase, Cochrane Library, Scopus, and EBSCO was conducted through February 2026. Although our search strategy was designed to encompass all folate-based interventions, the eligible high-quality evidence identified was restricted exclusively to folinic acid. Furthermore, subgroup analyses assessed efficacy in language, social interaction, motor skills, and adaptive behavior. A total of five randomized controlled trials were included in this meta analysis. Folinic acid did not significantly improve overall symptom severity compared with placebo [SMD = -0.62, 95% CI (-1.34 to 0.11), <italic>p</italic> = 0.094; <italic>I²</italic> = 43.2%]. Subgroup analyses showed a significant benefit for language and communication [SMD = -0.32, 95% CI (-0.58 to -0.06), <italic>p</italic> = 0.015; <italic>I²</italic> = 0%], while effects on social interaction, motor skills, and adaptive behavior were not significant. In conclusion, folinic acid showed no clear overall benefit for ASD. Benefits appeared most evident in language and communication, whereas evidence for other domains remained inconclusive. Further large-scale and long-term randomized controlled trials are warranted to definitively establish the overall therapeutic benefit and confirm the reliability of these findings. </p>