ReviewSeminars in pediatric neurology2020
Treatment of Folate Metabolism Abnormalities in Autism Spectrum Disorder.
Review in Seminars in pediatric neurology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 25 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.
Leucovorin for the Treatment of Language Impairment in Children With Autism Spectrum Disorder
Early Treatment of Language Impairment in Young Children With Autism Spectrum Disorder With Leucovorin Calcium
Treatment of Social and Language Deficits With Leucovorin for Young Children With Autism
Who cites it
25 citing papers in PubMed, 45 citations in OpenAlex.
- Safety and Efficacy of High-Dose Folinic Acid in Children with Autism: The Impact of Folate Metabolism Gene Polymorphisms.Nutrients · 2025Trial
- Characterizing features of the genetic architecture underlying autism from a multi-ancestry perspective.Molecular psychiatry · 2026Article
- HopeFOL, or FOL of problems? Leucovorin for autistic symptoms.The oncologist · 2026Review
- Tunable gene expression in zebrafish using RiboSCALE.bioRxiv : the preprint server for biology · 2026Article
- Role of Folate Metabolism in Neurodegenerative Diseases: Insight from Experimental and Clinical Studies.Current nutrition reports · 2026Review
- Folate in autism neurodevelopment.Frontiers in nutrition · 2026Review
- Redox System Dysfunction as a Key Mechanism in Autism Spectrum Disorder Pathogenesis.International journal of molecular sciences · 2025Review
- Exploring the Association Between Glucose-6-Phosphate Dehydrogenase Deficiency and Autism Spectrum Disorder: A Narrative Review.Children (Basel, Switzerland) · 2025Review
- Nutritional management and autism spectrum disorder: A systematic review.World journal of clinical pediatrics · 2024Article
- Review
- Reversal of Autism Symptoms among Dizygotic Twins through a Personalized Lifestyle and Environmental Modification Approach: A Case Report and Review of the Literature.Journal of personalized medicine · 2024Article
- Recent Advances in Folates and Autoantibodies against Folate Receptors in Early Pregnancy and Miscarriage.Nutrients · 2023Review
- Characterization of folic acid, 5-methyltetrahydrofolate and synthetic folinic acid in the high-affinity folate transporters: impact on pregnancy and development.Reproductive and developmental medicine · 2023Article
- The Rationale for Vitamin, Mineral, and Cofactor Treatment in the Precision Medical Care of Autism Spectrum Disorder.Journal of personalized medicine · 2023Review
- Potential Benefits of Anthocyanins in Chronic Disorders of the Central Nervous System.Molecules (Basel, Switzerland) · 2022Review
- Novel localization of folate transport systems in the murine central nervous system.Fluids and barriers of the CNS · 2022Article
- Shotgun Metagenomics Study Suggests Alteration in Sulfur Metabolism and Oxidative Stress in Children with Autism and Improvement after Microbiota Transfer Therapy.International journal of molecular sciences · 2022Article
- Prenatal methotrexate injection increases behaviors possibly associated with depression and/or autism in rat offspring; A new animal model for mental disorder, based on folate metabolism deficit during pregnancy.Neuropsychopharmacology reports · 2022Article
- Signalling pathways in autism spectrum disorder: mechanisms and therapeutic implications.Signal transduction and targeted therapy · 2022Review
- Multivariate Analysis of Metabolomic and Nutritional Profiles among Children with Autism Spectrum Disorder.Journal of personalized medicine · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 5 institutions in 1 country.
Funding
Abstract
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder that currently has no approved medical therapy to address core symptoms or underling pathophysiological processes. Several compounds are under development that address both underlying pathophysiological abnormalities and core ASD symptoms. This article reviews one of these treatments, d,l-leucovorin calcium (also known as folinic acid) for treatment of folate pathway abnormalities in children with ASD. Folate is a water-soluble B vitamin that is essential for normal neurodevelopment and abnormalities in the folate and related pathways have been identified in children with ASD. One of these abnormalities involves a partial blockage in the ability of folate to be transported into the brain utilizing the primary transport mechanism, the folate receptor alpha. Autoantibodies which interfere with the function of the folate receptor alpha called folate receptor alpha autoantibodies have been identified in 58%-76% of children with ASD and independent studies have demonstrated that blood titers of these autoantibodies correlate with folate levels in the cerebrospinal fluid. Most significantly, case-series, open-label, and single and double-blind placebo-controlled studies suggest that d,l-leucovorin, a reduced folate that can bypass the blockage at the folate receptor alpha by using the reduced folate carrier, an alternate pathway, can substantially improve particular symptoms in children with ASD, especially those positive for folate receptor alpha autoantibodies. This article reviews the current evidence for treating core and associated symptoms and underlying pathophysiological mechanisms in children with ASD with d,l-leucovorin.
Indexed as
Identifiers
What OpenQuestion holds
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.