Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial

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Abstract

Autism spectrum disorders (ASD) are recognized as a major public health issue. Here, we evaluated the effects of folic acid intervention on methylation cycles and oxidative stress in autistic children enrolled in structured teaching. Sixty-six autistic children enrolled in this open-label trial and participated in three months of structured teaching. Forty-four children were treated with 400 μg folic acid (two times/daily) for a period of three months during their structured teaching (intervention group), while the remaining 22 children were not given any supplement for the duration of the study (control group). The Autism Treatment Evaluation Checklist (ATEC) and Psychoeducational Profile-third edition (PEP-3) were measured at the beginning and end of the treatment period. Folic acid, homocysteine, and glutathione metabolism in plasma were measured before and after treatment in 29 autistic children randomly selected from the intervention group and were compared with 29 age-matched unaffected children (typical developmental group). The results illustrated folic acid intervention improved autism symptoms towards sociability, cognitive verbal/preverbal, receptive language, and affective expression and communication. Furthermore, this treatment also improved the concentrations of folic acid, homocysteine, and normalized glutathione redox metabolism. Folic acid supplementation may have a certain role in the treatment of children with autism.

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Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism.

S. Jill James, Paul Cutler, Stepan Melnyk … (2004)

Autism is a complex neurodevelopmental disorder that usually presents in early childhood and that is thought to be influenced by genetic and environmental factors. Although abnormal metabolism of methionine and homocysteine has been associated with other neurologic diseases, these pathways have not been evaluated in persons with autism. The purpose of this study was to evaluate plasma concentrations of metabolites in the methionine transmethylation and transsulfuration pathways in children diagnosed with autism. Plasma concentrations of methionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), adenosine, homocysteine, cystathionine, cysteine, and oxidized and reduced glutathione were measured in 20 children with autism and in 33 control children. On the basis of the abnormal metabolic profile, a targeted nutritional intervention trial with folinic acid, betaine, and methylcobalamin was initiated in a subset of the autistic children. Relative to the control children, the children with autism had significantly lower baseline plasma concentrations of methionine, SAM, homocysteine, cystathionine, cysteine, and total glutathione and significantly higher concentrations of SAH, adenosine, and oxidized glutathione. This metabolic profile is consistent with impaired capacity for methylation (significantly lower ratio of SAM to SAH) and increased oxidative stress (significantly lower redox ratio of reduced glutathione to oxidized glutathione) in children with autism. The intervention trial was effective in normalizing the metabolic imbalance in the autistic children. An increased vulnerability to oxidative stress and a decreased capacity for methylation may contribute to the development and clinical manifestation of autism.

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Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism

Daniel Rossignol, Richard Frye (2014)

Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders that are defined solely on the basis of behavioral observations. Therefore, ASD has traditionally been framed as a behavioral disorder. However, evidence is accumulating that ASD is characterized by certain physiological abnormalities, including oxidative stress, mitochondrial dysfunction and immune dysregulation/inflammation. While these abnormalities have been reported in studies that have examined peripheral biomarkers such as blood and urine, more recent studies have also reported these abnormalities in brain tissue derived from individuals diagnosed with ASD as compared to brain tissue derived from control individuals. A majority of these brain tissue studies have been published since 2010. The brain regions found to contain these physiological abnormalities in individuals with ASD are involved in speech and auditory processing, social behavior, memory, and sensory and motor coordination. This manuscript examines the evidence linking oxidative stress, mitochondrial dysfunction and immune dysregulation/inflammation in the brain of ASD individuals, suggesting that ASD has a clear biological basis with features of known medical disorders. This understanding may lead to new testing and treatment strategies in individuals with ASD.

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Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study.

Flora Tassone, Jaana Hartiala, Hooman Allayee … (2012)

Periconceptional folate is essential for proper neurodevelopment. Maternal folic acid intake was examined in relation to the risk of autism spectrum disorder (ASD) and developmental delay (DD). Families enrolled in the CHARGE (CHildhood Autism Risks from Genetics and Environment) Study from 2003 to 2009 were included if their child had a diagnosis of ASD (n = 429), DD (n = 130), or typical development (TD; n = 278) confirmed at the University of California Davis Medical Investigation of Neurodevelopmental Disorders Institute by using standardized clinical assessments. Average daily folic acid was quantified for each mother on the basis of dose, brands, and intake frequency of vitamins, supplements, and breakfast cereals reported through structured telephone interviews. Mean (±SEM) folic acid intake was significantly greater for mothers of TD children than for mothers of children with ASD in the first month of pregnancy (P1; 779.0 ± 36.1 and 655.0 ± 28.7 μg, respectively; P T variant genotypes. A trend toward an association between lower maternal folic acid intake during the 3 mo before pregnancy and DD was observed, but not after adjustment for confounders. Periconceptional folic acid may reduce ASD risk in those with inefficient folate metabolism. The replication of these findings and investigations of mechanisms involved are warranted.

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Journal

Journal ID (nlm-ta): Nutrients

Journal ID (iso-abbrev): Nutrients

Journal ID (publisher-id): nutrients

Title: Nutrients

Publisher: MDPI

ISSN (Electronic): 2072-6643

Publication date (Electronic): 07 June 2016

Publication date Collection: June 2016

Volume: 8

Issue: 6

Electronic Location Identifier: 337

Affiliations

[1 ]Department of Children’s and Adolescent Health, Public Health College of Harbin Medical University, Harbin 150081, China; suncaihong2003@ 123456163.com (C.S.); mingyangshine@ 123456sina.com (M.Z.)

[2 ]Zhejiang Provincial Center For Disease Prevention and Control, Hangzhou 310009, China; dzhao@ 123456cdc.zj.cn

Author notes

[* ]Correspondence: xiawei1023@ 123456126.com (W.X.); wulijiehyd@ 123456126.com (L.W.); Tel.: +86-451-87502867

[†]

These authors contributed equally to this work.

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Publisher ID: nutrients-08-00337

DOI: 10.3390/nu8060337

PMC ID: 4924178

PubMed ID: 27338456

SO-VID: 32eb723e-6c08-4c72-ab83-c5f633de8133

License:

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license ( http://creativecommons.org/licenses/by/4.0/).

Efficacy of Folic Acid Supplementation in Autistic Children Participating in Structured Teaching: An Open-Label Trial

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Karger: Nutrition and Dietetics

Most cited references 38

Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism.

Evidence linking oxidative stress, mitochondrial dysfunction, and inflammation in the brain of individuals with autism

Maternal periconceptional folic acid intake and risk of autism spectrum disorders and developmental delay in the CHARGE (CHildhood Autism Risks from Genetics and Environment) case-control study.

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