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These included: Expressive communication Personal and domestic daily living skills Interpersonal skills Play-leisure skills Coping social skills Other clinical improvements observed with B12 included improvements in: Sleep Gastrointestinal symptoms Hyperactivity Tantrums Nonverbal intellectual quotient Vision Eye contact Echolalia Stereotypy Anemia Nocturnal enuresis (bed wetting) Adverse events with B12 identified by meta-analysis included: Hyperactivity (11.9%) Irritability (3.4%) Trouble sleeping (7.6%) Aggression (1.8%) Worsening behaviors (7.7%) But adverse effects were generally few, mild, not serious, and not significantly different compared to placebo

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Additional mechanistic studies demonstrated that both dihexa and Nle 1 -AngIV, its parent compound, were effective stimulators of hippocampal synaptogenesis, thus providing a rational explanation for their procognitive activities