Twenty-one studies (including four placebo-controlled and three prospective, controlled) treated individuals with autism spectrum disorders (ASD) using d,l-leucovorin. d,l-Leucovorin was found to significantly improve communication with medium-to-large effect sizes and have a positive effect on core ASD symptoms and associated behaviors (attention and stereotypy) in individual studies with large effect sizes. Furthermore, adverse effects of these treatments were mild, with the most common being aggression in 9.5% of the participants.

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