Medical Research Summaries

Take a look at our sources through our research summaries or view information directly from the source.

Summary of ASD and folate, nutritional interventions

“Factors Predisposing for Autism”

Autism Spectrum Disorder (ASD) prevalence (the degree to which something is widespread) has tripled this century, such that over 2% of children in the US are autistic. There are some common variables that may increase the likelihood of an ASD diagnosis. This article summarizes factors that contribute to ASD risk, including genetic, environmental and lifestyle factors. Oxidative stress exposure (an imbalance in the body between free radicals and antioxidants that lead to cell and tissue damage) and cerebral folate deficiency (CFD)(a lack of folate in the brain) may increase the risk of ASD. Proper nutritional habits can mitigate the effects of oxidative stress and CFD, and include supplemental folate (vitamin B9), eating fruits and vegetables naturally high in folate, and elimination of cow’s milk from the diet to reduce folate receptor antibodies being produced by the body.Di

gnosis, Intervention and Treatment Strategies”

“Cerebral Folate Deficiency Syndrome: Early Diagnosis, Intervention and Treatment Strategies”
This article explains Cerebral Folate Deficiency (CFD) syndrome, which is a condition that can occur when the brain does not get enough folate, a type of vitamin B9. This can cause problems with thinking, movement, and development. If this condition is caught early and treated with the introduction of folate (vitamin B9) to one’s diet, symptoms may improve significantly. 
Ramaekers & Quadros 2022: Cerebral Folate Deficiency Syndrome: Early Diagnosis, Intervention and Treatment Strategies

“Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis”
This article discusses the role of folate receptor alpha autoantibodies in Autism Spectrum Disorder (ASD) and how they may cause cerebral folate deficiency (a lack of folate to the brain). It reviews how a folinic acid called leucovorin might help improve symptoms in individuals with ASD who have these autoantibodies. The study suggests that leucovorin could be a beneficial treatment option for some people with ASD.
Rossignol & Frye 2021: Cerebral Folate Deficiency, Folate Receptor Alpha Autoantibodies and Leucovorin (Folinic Acid) Treatment in Autism Spectrum Disorders: A Systematic Review and Meta-Analysis

Clinical trials showing improvement of ASD symptoms with leucovorin

“Folinic Acid Improves Verbal Communication in Children with Autism and Language Impairment: a Randomized Double-Blind Placebo-Controlled Trial”
This article summarizes the results of a well-controlled clinical study that concluded that children with autism and language impairment saw improvements in verbal communication skills after introducing folinic acid dietary supplements.
Frye et al 2016: Folinic Acid Improves Verbal Communication in Children with Autism and Language Impairment: a Randomized Double-Blind Placebo-Controlled Trial

“Folinic Acid Improves the Score of Autism in the EFFET Placebo-Controlled Randomized Trial”
This article studied a small group of children with Autism Spectrum Disorder (ASD) and showed that folinic acid is effective in improving the Autism Diagnostic Observation Schedule (ADOS) score of these children. Their social interaction and communication improved after 12 weeks when folinic acid was introduced to their daily routines.
Renard et al 2019: Folinic Acid Improves the Score of Autism in the EFFET Placebo-Controlled Randomized Trial.

“A Milk-Free Diet Downregulates Folate Receptor Autoimmunity in Cerebral Folate Deficiency Syndrome”
This article explores the impact of a milk-free diet on those with cerebral folate deficiency syndrome (CFDS). In CFDS, where decreased folate transport to the central nervous system is a key issue, researchers found that autoantibodies against the folate receptor (FR) play a significant role. These autoantibodies hinder the transport of folate and are linked to the clinical response of patients to folinic acid therapy. Interestingly, the autoantibodies can cross-react with milk folate receptors from different species.

This study intervened with a milk-free diet in 12 children with CFDS, resulting in a significant decrease in autoantibody levels over 3 to 13 months. Conversely, reintroducing milk to 9 of these children led to a significant increase in autoantibody levels over 6 to 14 weeks. In contrast, 12 other children with CFDS who maintained a normal diet experienced a notable increase in autoantibody levels over 10 to 24 months. The study suggests that combining a milk-free diet with folinic acid therapy could help lower autoantibody levels and may be beneficial for managing CFDS in these patients.
Ramaekers et al 2008: A Milk-Free Diet Dowregulates Folate Receptor Autoimmunity in Cerebral Folate Deficiency Syndrome.

Review of critical periods and impact of stress in ASD development.

“Neurodevelopment with Low Nutritional Folate Increases Childhood Autism”
This article discusses how a deficiency in folate, a B9 vitamin, during pregnancy might affect a child’s development and increase the risk of autism. Low levels of folate can lead to changes in brain development, which could be linked to autism. Ensuring pregnant women receive enough folate might help reduce this risk, and children with autism may see significant improvements in their symptoms if they take supplemental folate in the first five years of life. 
Ayoub 2023: Neurodevelopment with Low Nutritional Folate Increases Childhood Autism

“Stress and Folate Impact Neurodevelopmental Disorders”
This article discusses how stress and low levels of folate, a B9 vitamin, can affect fetal brain development and potentially increase the risk of neurodevelopmental disorders (disorders that influence how the brain functions). Researchers found that high stress and insufficient folate during pregnancy can harm a child’s brain, and may cause developmental disorders such as autism or Attention-Deficit/Hyperactivity Disorder (ADHD). Taking steps to manage stress and ensure adequate folate intake may help to prevent these issues. 
Ahmavaara & Ayoub 2023: Stress and Folate Impact Neurodevelopmental Disorders


“Critical Periods in the Neurodevelopment of Autism”
Autism Spectrum Disorder (ASD) affects about 2% of children and leads to challenges with behavior and communication. Many children with ASD produce an antibody that blocks folate from getting into the brain, causing a folate shortage that may worsen their symptoms. Studies show that giving ASD children a special form of folate can help improve their communication, suggesting that starting folate supplements early, even before birth, might reduce ASD symptoms. 
Ayoub & Lam 2023: Critical Periods in the Neurodevelopment of Autism.

Trial showing children with the folate receptor antibodies have parents with the same antibody

“Folate Receptor Autoantibodies are Prevalent in Children Diagnosed with Autism Spectrum Disorder, their Normal Siblings and Parents”
Folate deficiency can impact brain development in babies, and a specific antibody that blocks folate transport is often found in families with autism. In a study of families with autistic children, this antibody was found in most of the affected children, their siblings, and their parents. The presence of this antibody might be passed down through families and can contribute to autism when combined with other factors.
Quadros et al 2018: Folate Receptor Autoantibodies are Prevalent in Children Diagnosed with Autism Spectrum Disorder, their Normal Siblings and Parents