List of Research for Folic Acid (5-MTHF, Folate, Folinic Acid, Leucovorin) as an Autism Treatment

5-Methyltetrahydrofolate (5-MTHF), Folate, Folic Acid, Folinic Acid, and Leucovorin & Autism Research List

2012 Research

Cerebral Folate Receptor Autoantibodies in Autism Spectrum Disorder

  • Provides overview of cerebral folate deficiency and folate receptor autoantibodies (FRAs) in autism
  • Studied concentrations of folate receptor autoantibodies (FRAs) in individuals with autism
  • Also studied the impact of leucovorin calcium on attention, receptive and expressive language, stereotypical behavior, and verbal communication

2011 Research

Vitamin Supplementation Reduces the Level of Homocysteine in the Urine of Autistic Children

  • Included 30 children with autism spectrum disorders
  • Focused on the effect of supplementation with folic acid combined with vitamins B6 and B12 on homocysteine urine levels compared to supplementation with only vitamins B6 and B12

Autism Speaks: Meeting on Folate Metabolism and Autism Spectrum Disorders, March 19-20, 2009, Washington, DC

  • No research summary available

2010 Research

Folate and Methionine Metabolism in Autism: a Systematic Review

  • A review article
  • Provides overview of folate metabolism and folate-methionine cycle in relation to autism
  • Review included 18 studies, 5 of which focused on interventions used to correct folic acid levels in individuals with autism

2009 Research

Efficacy of Methylcobalamin and Folinic Acid Treatment on Glutathione Redox Status in Children with Autism

  • An open-label trial
  • Included 40 children with autism spectrum disorders
  • Focused on effect of treatment with methylcobalamin and folinic acid on glutathione redox status and transmethylation/transsulfuration metabolites

2005 Research

Cerebral Folate Deficiency with Developmental Delay, Autism, and Response to Folinic Acid

  • A case study
  • Individual with autism had low levels of 5-methyltetrahydrofolate (5-MTHF) in the cerebral spinal fluid
  • Discusses impact of treatment with folate on cerebral spinal fluid levels of 5-MTHF

2004 Research

Metabolic Biomarkers of Increased Oxidative Stress and Impaired Methylation Capacity in Children with Autism

  • Treatment portion of study was an open-label study
  • Treatment intervention included 8 children with autism spectrum disorders
  • Studied the impact of folinic acid supplementation (combined with betaine or betaine and methylcobalamin) on transmethylation and transsulfuration pathways

2002 Research

Autism, an Extreme Challenge to Integrative Medicine. Part 2: Medical Management

  • A review article
  • Provides a brief summary of folic acid as an autism treatment

1988 Research

Controversies in the Treatment of Autistic Children: Vitamin and Drug Therapy

  • A review article
  • Briefly discusses high-dosage folic acid as an autism treatment

1986 Research

Folic Acid as an Adjunct in the Treatment of Children with the Autism Fragile-X Syndrome (AFRAX)

  • A double-blind, placebo-controlled crossover study
  • Included 4 children with autism fragile-X syndrome
  • Focused on the impact of supplementation with folic acid on behavior

1981 Research

Folic Acid and B12 in Autism and Neuropsychiatric Disturbances of Childhood

  • No research summary available

List of Research for Folic Acid as an Autism TreatmentAdditional Resources:

Autism Research: Response to Folinic Acid in Cerebral Folate Deficiency

Autism Research:

Low Levels of 5-Methytetrahydrofolate (5-MTHF) in Brain Corrected by Treatment with Folinic Acid in Girl with Autism
Case Study of Autistic Girl Looked at Folinic Acid to Treat Low Cerebral Levels of Folic Acid

Low levels of folate in the brain and spinal cord have been found in many children with autism.  Often these low cerebral levels of folate exist despite normal levels of folate being found in the rest of the body.  A 2005 case report describes such a situation.  The report was published in an article titled Cerebral Folate Deficiency with Developmental Delay, Autism, and Response to Folinic Acid.

The case report is of a 6-year-old girl who had a developmental delay and autism.  She also showed psychomotor regression, seizures, and mental retardation.  These conditions were found in connection with low levels of cerebral 5-methyltetrahydrofolate (5-MTHF) despite folate and vitamin B12 levels being normal in the other areas of her body.  Since levels of 5-MTHF and vitamin B12 were normal in all areas except the brain, it was assumed that she was experiencing cerebral folate deficiency.

The child received treatment with folinic acid and was re-evaluated at 3 months.  Labs showed that cerebral levels of 5-MTHF had corrected during that time period.  It was found that her motor skills and seizures improved significantly.  However, areas of communication and socialization continued to be severely impaired and represented more classical autism spectrum disorder symptoms.  Her cognitive abilities also continued to be severely impaired.

The authors state that this case represents a situation where poor transport of folate into the cerebral spinal fluid likely played a key role in some of this individual’s symptoms.  All attempts to identify the cause of the poor transport did not result in finding the source of the folate deficiency.  However, the authors state that the improvements seen in some symptoms and lab values with folinic acid treatment suggest that folinic acid may be very beneficial in certain types of autism and developmental delays.

The case report was published on March 22, 2005 in Neurology.

Additional Information:

Autism Research: Autoimmunity to Folate Receptors and Lack of Cerebral Folate in Autism

Autism Research:

The Effect of Folate Receptor Autoantibodies Studied in Terms of Brain Fluid Levels of 5-MTHF (A Form of Folinic Acid)
Research Studies Folate Receptor Autoantibodies and Cerebrospinal Fluid Levels of 5-MTHF (A Form of Folic Acid)

Poor movement of folate into the central nervous system (CNS) has been found in at least two types of autism spectrum disorders.  One of these is infantile low-functioning autism with neurological abnormalities.  Previous to this study, little was known about the role that folate receptor autoimmunity played in the reduced movement of folate into the CNS in autism.  This study attempted to find the impact that folate receptor autoantibodies play in preventing folate from crossing into the CNS.  The findings were published in an article titled Folate Receptor Autoimmunity and Cerebral Folate Deficiency in Low-Functioning Autism with Neurological Deficits.

The study included 25 participants with autism, including individuals with and without neurological deficits.  Several labs were drawn for the study.  These labs include serum folate, cerebrospinal fluid 5-methyltetrahydrofolate (5-MTHF, a form of folate), and serum folate receptor autoantibodies that block folate movement into the CNS.

The study found that all participants had normal levels of serum folate (i.e. folate not found in the brain or cerebrospinal fluid).  However, 23 out of 25 individuals had low cerebrospinal fluid levels of 5-MTHF.  The research also found that 19 out of 23 of these patients had low cerebrospinal fluid levels of 5-MTHF due to folate receptor autoantibodies (i.e. the autoantibodies prevented the folate from being transported from the serum into the cerebrospinal fluid).

The participants were then given oral folinic acid (a form of folic acid).  After 12 months, the cerebrospinal fluid levels of 5-MTHF normalized and the individuals experienced either partial or full recovery.

The authors suggest that folate receptor autoimmunity may be an important cause of reduced CNS folate levels.  The authors also state that screening for folate receptor autoantibodies may play an important role in preventing and treating children with infantile low-functioning autism.

The article was epublished in Neuropediatrics in December 2007.

Additional Information:


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