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

Sun, Chongde; Zou, Mingyang; Zhao, Dong; Xia, Wei; Wu, Lijie

doi:10.3390/nu8060337

Cited by 58 publications

(37 citation statements)

References 44 publications

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“…Numerous studies have reported that dysfunctional folate-methionine pathway enzymes may play an important role in the pathophysiology of autism [5]. In such children, a three-month folic acid supplementation has been shown to improve autistic features, particularly cognition and communication [6], as was the case in our patient. We undertook rapid evaluation, with early intervention, and evaluated our patient's response using CARS, which is a 15-point behavioral rating scale developed to both identify autism as well as define the severity of the disorder [7].…”

Section: Discussionsupporting

confidence: 78%

Clinical Relevance of Methylenetetrahydrofolate Reductase Genetic Testing in Autism: A Case Report of Successful Clinical Outcome

Fadila¹,

Suman²,

Kumar³

et al. 2021

Cureus

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Autism spectrum disorder is an emerging public health issue. The core features of autism spectrum disorder are persistent impairment in reciprocal social communication and interaction and restricted, repetitive patterns of behavior or interests. We now know that it encompasses disorders previously referred to as early infantile autism, childhood autism, Kanner autism, high-functioning autism, atypical autism, Asperger disorder, childhood disintegrative disorder, and pervasive developmental disorder not otherwise specified. While it is agreed that the etiology of autism spectrum disorder is largely unknown, certain environmental and genetic factors may be responsible for the disease. In particular, emerging evidence has suggested the role of C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene as a possible risk factor. We present the case of a two-year-old boy with high risk for autism who was found on advanced investigation to have heterozygous polymorphism for MTHFR. This prompted us to add folic acid to his therapeutic regime. He was treated with high-dose folic acid along with conventional intervention, and went on to make excellent recovery. We conclude that pharmacological intervention has the potential to improve outcome in a subgroup of autistic children.

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Section: Discussionsupporting

confidence: 78%

Clinical Relevance of Methylenetetrahydrofolate Reductase Genetic Testing in Autism: A Case Report of Successful Clinical Outcome

Fadila¹,

Suman²,

Kumar³

et al. 2021

Cureus

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“…As for neurodegenerative diseases, one hypothesis of the significance of HHcy in the etiology of ASD is that Hcy is a powerful excitotoxin, and its metabolic products can cause damage in some proteins, generating "abnormal toxin proteins" and inducing an autoimmune response [125]. Some studies on the neurotoxicity of Hcy have demonstrated that Hcy can induce neuronal damage, causing activation of N-methyl-d-aspartate (NMDA) receptors and cell loss through excitotoxicity as well as apoptosis [124][125][126][127][128][129][130][131]. Additionally, Fulceri et al [127] observed that autistic children often have gastrointestinal disorders and/or are picky eaters, and these factors could lead to an inadequate dietary intake, altered nutrient absorption, and micronutrient deficiency, particularly vitamin B deficiency, which causes increased plasma Hcy levels and worsening of autism.…”

Section: Hhcy and Autism Spectrum Disorder (Asd)mentioning

confidence: 99%

“…On the basis of the relationship between low folate levels, HHcy, and autism, Sun et al [131] in an intervention study demonstrated that supplementation with 800 µg/day of folic acid in children (mean age 52.00 ± 13.13 months) improved autism symptoms related to receptive language, cognitive verbal/preverbal, sociability, affective expression, and communication, and that this treatment also improved the concentration of folic acid, reduced Hcy plasma levels, and normalized glutathione redox metabolism. These results, according to Józefczuck et al [132], suggest serum Hcy levels as a useful biomarker for diagnosis of autism spectrum disorder in children as well as for the efficacy of treatment.…”

Section: Hhcy and Autism Spectrum Disorder (Asd)mentioning

confidence: 99%

Homocysteine: Its Possible Emerging Role in At-Risk Population Groups

Azzini

Ruggeri

Polito

2020

IJMS

109

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Increased plasma homocysteine is a risk factor for several pathological disorders. The present review focused on the role of homocysteine (Hcy) in different population groups, especially in risk conditions (pregnancy, infancy, old age), and on its relevance as a marker or etiological factor of the diseases in these age groups, focusing on the nutritional treatment of elevated Hcy levels. In pregnancy, Hcy levels were investigated in relation to the increased risk of adverse pregnancy outcomes such as small size for gestational age at birth, preeclampsia, recurrent abortions, low birth weight, or intrauterine growth restriction. In pediatric populations, Hcy levels are important not only for cardiovascular disease, obesity, and renal disease, but the most interesting evidence concerns study of elevated levels of Hcy in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Finally, a focus on the principal pathologies of the elderly (cardiovascular and neurodegenerative disease, osteoporosis and physical function) is presented. The metabolism of Hcy is influenced by B vitamins, and Hcy-lowering vitamin treatments have been proposed. However, clinical trials have not reached a consensus about the effectiveness of vitamin supplementation on the reduction of Hcy levels and improvement of pathological condition, especially in elderly patients with overt pathologies, suggesting that other dietary and non-dietary factors are involved in high Hcy levels. The importance of novel experimental designs focusing on intra-individual variability as a complement to the typical case–control experimental designs and the study of interactions between different factors it should be emphasized.

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“…The pathway of cysteine and methionine cycle, folate(vitamin B9) metabolism, and Hcy transsulfuration are interrelated and constitute the folate-related metabolism together [27]. The folate-related pathway has a critical role in cell proliferation, DNA synthesis, immune function, and neural development [28]. Vitamin B6 and B12 are cofactors of these biological processes.…”

Section: Discussionmentioning

confidence: 99%

Alterations in Gut Vitamins and Amino Acids Metabolism are Associated with Symptoms and Neurodevelopment of Children with Autism Spectrum Disorders

Zhu

Hua

Yang

et al. 2020

Preprint

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Background Accumulated evidence have supported metabolic disturbance may be associated with the pathogenesis of autism spectrum disorders (ASD). Despite abnormalities of some shared metabolic pathways, specific differential compounds are inconsistent in studies, which made a challenge to elucidate the role of metabolism in the mechanism of ASD. Besides, few researches have assessed the correlation between gut metabolites with symptoms of ASD. Objectives The present study aimed to evaluate the gut metabolomic profiles of children with ASD and to analyze potential interaction between gut metabolites with symptoms and neurodevelopment of ASD children. Methods In this cross-sectional case-control study, 120 aged 2–6 years ASD children and 60 sex and age matched typically developing (TD) children were included. Autistic symptoms were assessed with the Autism Behavior Checklist (ABC), Childhood Autism Rating Scale (CARS), and the Social Responsiveness Scale (SRS). Neurodevelopment was assessed with the Gesell Developmental Scale (GDS). Fecal samples were analyzed by untargeted liquid chromatography-mass spectrometry (LC-MS) methods, then systematic bioinformatic analyses were performed to characterize the gut metabolomic profiles of ASD and TD children. The correlations between metabolites and clinical assessment scores were assessed using Spearman correlation. Results ASD children exhibit gut metabolism perturbation compared with TD children. A total of 96 differential metabolites between the ASD and TD groups were identified, with 35 increased and 61 decreased in ASD group. The metabolic disturbance of ASD involved in multiple vitamins and amino acids metabolism pathways, with the strongest enrichment identified for tryptophan metabolism, retinol metabolism, cysteine and methionine metabolism, and vitamin digestion and absorption. The imbalanced gut metabolites are significantly correlated to symptoms and neurodevelopment of ASD children. Limitations This cross-sectional study revealed a correlation, but do not allow to prove causation of symptoms and gut metabolites outcome. The disease specificity of the metabolomic disturbance need to be evaluated in future studies.Conclusions ASD children have altered gut metabolite profiles compared with TD children, which mainly involved in multiple vitamins and amino acids metabolism pathways. Notably, vitamins metabolism abnormalities may play roles in the disturbance of amino acids metabolism. Imbalanced gut metabolites are related to symptoms and neurodevelopment of ASD children. Our findings provided an improved understanding of perturbations of metabolome networks in ASD.

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

Cited by 58 publications

References 44 publications

Clinical Relevance of Methylenetetrahydrofolate Reductase Genetic Testing in Autism: A Case Report of Successful Clinical Outcome

Clinical Relevance of Methylenetetrahydrofolate Reductase Genetic Testing in Autism: A Case Report of Successful Clinical Outcome

Homocysteine: Its Possible Emerging Role in At-Risk Population Groups

Alterations in Gut Vitamins and Amino Acids Metabolism are Associated with Symptoms and Neurodevelopment of Children with Autism Spectrum Disorders

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