ArticleFrontiers in cellular neuroscience2018
Comparison of Three Clinical Trial Treatments for Autism Spectrum Disorder Through Multivariate Analysis of Changes in Metabolic Profiles and Adaptive Behavior.
Article in Frontiers in cellular neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06623227 (Randomized, Placebo-controlled, Double-blind Study of Increasing Total Antioxidant Capacity with Vitamin E and C in Two Cohorts of Patients with Autism Spectrum Disorders), which is not on this map. Cited by 9 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Randomized, Placebo-controlled, Double-blind Study of Increasing Total Antioxidant Capacity with Vitamin E and C in Two Cohorts of Patients with Autism Spectrum Disorders
Who cites it
9 citing papers in PubMed, 20 citations in OpenAlex.
- Medical treatment of autism spectrum disorder in children: Current evidence, controversies, and clinical challenges.World journal of clinical pediatrics · 2026Article
- Metabolomic Signatures of Autism Spectrum Disorder.Journal of personalized medicine · 2022Article
- Multivariate Analysis of Metabolomic and Nutritional Profiles among Children with Autism Spectrum Disorder.Journal of personalized medicine · 2022Article
- Central Nervous System Metabolism in Autism, Epilepsy and Developmental Delays: A Cerebrospinal Fluid Analysis.Metabolites · 2022Article
- A Personalized Multidisciplinary Approach to Evaluating and Treating Autism Spectrum Disorder.Journal of personalized medicine · 2022Review
- Towards a Multivariate Biomarker-Based Diagnosis of Autism Spectrum Disorder: Review and Discussion of Recent Advancements.Seminars in pediatric neurology · 2020Review
- The Key Role of Purine Metabolism in the Folate-Dependent Phenotype of Autism Spectrum Disorders: An In Silico Analysis.Metabolites · 2020Article
- The Role of Lipidomics in Autism Spectrum Disorder.Molecular diagnosis & therapy · 2020Review
- Inheritance of HLA-Cw7 Associated With Autism Spectrum Disorder (ASD).Frontiers in psychiatry · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Several studies associate autism spectrum disorder (ASD) pathophysiology with metabolic abnormalities related to DNA methylation and intracellular redox homeostasis. In this regard, three completed clinical trials are reexamined in this work: treatment with (i) methylcobalamin (MeCbl) in combination with low-dose folinic acid (LDFA), (ii) tetrahydrobiopterin, and (iii) high-dose folinic acid (HDFA) for counteracting abnormalities in the folate-dependent one-carbon metabolism (FOCM) and transsulfuration (TS) pathways and also for improving ASD-related symptoms and behaviors. Although effects of treatment on individual metabolites and behavioral measures have previously been investigated, this study is the first to consider the effect of interventions on a set of metabolites of the FOCM/TS pathways and to correlate FOCM/TS metabolic changes with behavioral improvements across several studies. To do so, this work uses data from one case-control study and the three clinical trials to develop multivariate models for considering these aspects of treatment. Fisher discriminant analysis (FDA) is first used to establish a model for distinguishing individuals with ASD from typically developing (TD) controls, which is subsequently evaluated on the three treatment data sets, along with one data set for a placebo, to characterize the shift of FOCM/TS metabolism toward that of the TD population. Treatment with MeCbl plus LDFA and, separately, treatment with tetrahydrobiopterin significantly shifted the metabolites toward the values of the control group. Contrary to this, treatment with HDFA had a lesser, though still noticeable, effect whilst the placebo group showed marginal, but not insignificant, variations in metabolites. A second analysis is then performed with non-linear kernel partial least squares (KPLS) regression to predict changes in adaptive behavior, quantified by the Vineland Adaptive Behavior Composite, from changes in FOCM/TS biochemical measurements provided by treatment. Incorporating the 74 samples receiving any treatment, including placebo, into the regression analysis yields an
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.