Folic Acid Supplementation May Improve Autism Spectrum Disorder Symptoms

Written by Angeline A. De Leon, Staff Writer. Folic acid supplementation significantly improved autism symptoms involving sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication in children with autism.

Recent research has discovered that autism spectrum disorder (ASD), a neurodevelopmental disorder affecting communication and behavior, involves not only changes in cognitive, emotional, and social patterns, but alterations in pathophysiology as well. Children with ASD exhibit an abnormal metabolic profile, compared to healthy children, with specific alterations in folic acid (key to red blood cell formation and healthy cell growth and function), homocysteine (amino acid associated with oxidative stress at high levels), and glutathione (body’s master antioxidant) metabolism ^1-4. Ample evidence supports the notable role of folic acid in cognitive function and the link between folic acid deficiency and autistic-like behaviors ⁵. Oxidative stress, levels of which increase when there is an imbalance between inflammation levels and the body’s antioxidant capacity (redox homeostasis), is also recognized as a factor in the etiology of autism ⁶. Looking at measures of folic acid, homocysteine, and glutathione metabolism, a 2016 study ⁷ published in Nutrients investigated the effects of folic acid supplementation on core symptoms of ASD and redox homeostasis in children participating in a structured teaching program.

A total of 66 children (mean age = 54.5 months) with ASD completed the open-label trial, which involved participation in a 3-month structured teaching program (designed to reduce challenging behavior and improve communication and sensorimotor skill). Subjects were divided into two groups, one group receiving 400 µg folic acid twice daily for 3 months during the structured teaching program (n = 44) and a control group receiving no supplementation (n = 22). At baseline and at the end of the treatment period, researchers administered the autism behavior checklist (ABC), childhood autism rating scale (CARS), autism treatment evaluation checklist (ATEC), and the psychoeducational profile-third edition (PEP-3). Fasting blood samples were also collected for quantification of folic acid, homocysteine, and glutathione concentrations.

Repeated measures analysis of the ATEC and PEP-3 data revealed that the intervention significantly improved sociability (p < 0.05), as well as verbal/preverbal cognitive ability, receptive language, affective expression, and communication (p < 0.05 for all). Researchers also observed that folic acid supplementation significantly increased concentration of plasma folic acid (p < 0.05), reduced mean concentration of homocysteine (p < 0.05), and increased the ratio of total reduced glutathione to oxidized glutathione disulfide (tGSH/GSSG ratio) (p < 0.001), indicative of improved glutathione redox metabolism.

Based on study findings, researchers suggest that short-term supplementation with folic acid in children with ASD is sufficient to produce improvements in cognition and language-, expression-, and communication-related symptoms of autism. Folic acid also demonstrated the ability to favorably alter metabolic profile in children, producing improvements in folic acid and homocysteine concentrations, as well as normalizing glutathione redox metabolism. At early stages of ASD, such changes in antioxidant capacity may significantly benefit neurological development. Because the current trial was an open-label, non-randomized test, it would be critical to conduct follow-up studies using a blinded, placebo-controlled design. It would also be helpful to examine the impact of folic acid supplementation on ASD symptoms, independent of a structured teaching program, and across a spectrum of ages.

Source: Sun C, Zou M, Zhao D, et al. Efficacy of folic acid supplementation in autistic children participating in structured teaching: an open-label trial. Nutrients. 2016; 8: 337. DOI: 10.90/nu8060337.

© 2016, The American College of Clinical Pharmacology

Posted May 30, 2019.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

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