MTHFR and Autism

MTHFR and Autism

Table of Contents

    What is autism?

    Autism spectrum disorder (ASD) is a neurodevelopmental condition, which means it affects the brain and nervous system. Symptoms of autism usually appear in early childhood and there is a wide range of symptoms and severity levels among different individuals.


    Typically, people with autism struggle with many everyday situations such as communication, social interaction, and learning. They may find it difficult to respond appropriately to social cues, such as facial expressions and body language. They often take longer to understand information and engage in conversations. They also tend to have an intense focus on specific topics and may engage in repetitive behaviors. Sensory issues such as sensitivity to light, sound, taste, or touch are also common, and they may experience anxiety or distress in certain situations.


    • Diagnostic criteria for autism include persistent difficulties in social communication, such as challenges with back-and-forth conversation, nonverbal cues, and forming relationships. These behaviours must be accompanied by at least two types of restricted or repetitive behaviors, such as repetitive movements or speech, a strong need for routine, intensely focused interests, or unusual sensory responses.1


    ASD is a lifelong condition. Each child with ASD presents differently and responds differently to treatment. As children with ASD grow and become young adults, they have difficulties interacting with their peers, managing themselves on their own, and understanding the behaviors expected of them in school or at work. Early intervention at home and school can help with daily activities, and many children benefit from structured support plans.


    Early recognition and intervention are essential to help those affected manage their challenges and enhance their quality of life.

    How does methylation (and MTHFR) affect autism?

    Numerous studies have shown that the MTHFR C677T mutation is more common in people with ASD and their mothers than in the general population.2


    There is strong evidence that the MTHFR mutation may increase the risk of autism. The MTHFR enzyme is essential for converting folic acid into methylfolate, which is needed for proper DNA methylation and brain development during pregnancy.3 If a mother has an MTHFR mutation, her enzyme function is impaired, often leading to lower methylfolate levels. As DNA methylation regulates gene expression and plays a crucial role in brain development, disruptions in this process have been linked to autism.


    Research suggests that poor MTHFR activity and/or folate deficiency may contribute to autism risk. Both DNA methylation and folate metabolism are essential for brain and nervous system development, as well as overall mental health.4


    A 2024 study suggested that exposure to a common pesticide called pyrethroid (DPE) disrupts folate metabolism, which may increase the risk of neurodevelopmental disorders (NDDs), including autism. DPE is used on farms to protect crops and also in many household insecticides.


    As MTHFR is a key enzyme in folate metabolism, this may be relevant to those with and without the MTHFR mutation. The study found that DPE altered the expression of MTHFR and other folate-related proteins, suggesting that pesticide exposure may interfere with methylation processes essential for brain development. This could also explain why NDDs have increased in recent years.5


    Additionally, maternal folate supplementation helped counteract many of the behavioral effects of DPE, indicating that supporting folate metabolism—especially in individuals with MTHFR mutations—could be a potential strategy to mitigate neurodevelopmental risks.


    The MTHFR enzyme works with folate, vitamin B6, and vitamin B12 to recycle homocysteine and create methionine. If this process doesn’t happen, homocysteine can accumulate and cause damage to neurons and blood vessels, including the cerebral microvasculature. This may also contribute to the development of neurocognitive conditions such as depression, dementia, and autism.6


    Several studies also report that about 70% of children with ASD also have autoantibodies against folate receptor alpha (FRα), which prevents the breakdown of folate in the body. Further research has found that when these children are treated with folinic acid, a significant number show improvements in speech, language and social interaction.7 Folinic acid is a more biologically active form of folate and the immediate precursor to the most active form, methylfolate.


    Some research has suggested that when folate is too low, the body relies more on choline and betaine (a derivative of choline) to help recycle homocysteine and support methylation. Choline is also critical for normal brain development, and deficiencies in one-carbon metabolism during pregnancy can contribute to impaired brain development in children due to reduced or altered choline levels. Children with ASD and ADHD are found to be low in choline.8

    Treating autism with methylfolate

    Several studies have reported that mothers taking folic acid supplements during pregnancy are less likely to have children born with ASD.9 However, folic acid is not suitable for women with MTHFR mutations, as they are unable to properly convert folic acid to methylfolate.10


    Supplementing with methylfolate during pregnancy has been shown to reduce the risk of behavioural disorders linked to impaired folate metabolism. Methylfolate is the biologically active form of folate and can bypass disruptions to the breakdown of folate in the body, whether caused by MTHFR or by DPE exposure.11 In the 2024 study mentioned above, high-dose supplementation with methylfolate in rodents dramatically reduced the behavioural disorders caused by folate issues, specifically by preventing deficits in the social, communication, cognitive, and locomotor areas of the brain that are linked to autism.  The researchers concluded that the methylfolate supplementation compensated for the lack of active folate in the body and helped to normalize cerebral folate levels.12

    Treating autism with methyl B12

    Vitamin B12 is also involved in normal brain development and cognitive function, both during pregnancy and throughout life. It is related to the folate regeneration process and the conversion of folic acid to methylfolate. Deficiencies in B12 have a negative impact on cognitive function and brain development, as it is also involved in myelin synthesis.13 Myelination ensures normal communication between brain cells and networks, and is critical to structural neurodevelopment and contributes to the “social” aspects of brain function.14


    A study found that children with ASD and anemia showed behavioral improvements after treatment with doses of methyl B12 of around 1.3 mg-2.3 mg per dose (64.5 to 75 µg/kg). The results indicated that methyl B12 may improve symptoms in autism by supporting methylation and antioxidant balance. Methyl B12 supplementation was associated with improvements in key aspects of metabolic function in children with ASD, including methylation capacity and glutathione balance, which correlated with better communication, daily life activities, and social skills.15

    For autism caregivers: How to take care of yourself

    Caregivers of children with ASD are often under significant pressure.  A recent study on caregiver stress found that those relying on formal assistance reported higher emotional burdens, while those who turned to informal support (such as friends, family, and neighbors) experienced more guilt.16


    Caring for an autistic child is not easy, and caregivers are encouraged to take time for themselves where possible. Practicing self-care every day is vital to maintain mental wellbeing. Self-care is often misunderstood, especially for caregivers, who may see it as selfish or unnecessary. In reality, caring for yourself helps you better support others.


    Self-care encompasses physical, emotional, and social wellbeing. This can include getting enough sleep, eating well, exercising, talking about your feelings to people you trust, practicing mindfulness, and connecting with others outside your caring role. Even small efforts matter. Exercising for 10 minutes is better than not at all, just as talking to a friend is better than bottling your feelings up inside. The key is finding what works for you and making self-care a consistent part of your life.

    MTHFR and Autism

    Key takeaways

    • Icon The MTHFR genetic mutation has been linked to autism, a neurodevelopmental disorder.
    • Icon MTHFR can lead to low methylfolate levels. Low methylfolate during pregnancy can affect brain development of the fetus.
    • Icon Recent research suggests that methylfolate and methyl B12 supplementation may support behavioral and cognitive function in some individuals with autism.

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    Frequently Asked Questions about MTHFR and autism

    Does MTHFR cause autism?

    While MTHFR may not cause autism directly, studies show a higher incidence of MTHFR genetic mutations in people on the autism spectrum. This may be because the MTHFR enzyme deficiency impairs the conversion of folate to methylfolate, leading to low methylfolate levels. Methylfolate is a critical component of processes involved in normal brain development. However, supplementing with methylfolate during pregnancy may help to reduce the risk of a child being born with autism.17

    Can autism be caused by a genetic mutation?

    Autism has a complex genetic background, as several different genetic factors can be involved in its development. In some cases, autism is inherited from parents, while other cases result from new genetic changes that occur spontaneously and are not passed down.18 In the past decade, hundreds of genes have been identified that contribute to characteristics of autism, such as difficulty communicating, poor social cognition, and other behaviors. A 2019 study suggested that around 10-20% of ASD cases can be explained by known genetic factors, such as copy number variations (deletions/duplications of sections of DNA that can affect how genes function) SNPs, and epigenetic changes. These can all influence ASD severity and behavior.19 A 2023 study estimated that because around 800 genes and numerous genetic syndromes are linked to ASD, around 70–90% of autism cases may be genetic. Around 50% of cases have identifiable genetic changes such as chromosomal deletions, duplications, or single-gene disorders.20

    What genetic disorder looks like autism?

    Asperger's Syndrome is similar to autism, and also has a strong genetic component. Asperger’s is now a subtype within the broader ASD category, although it is considered the ‘milder’ end of the autism spectrum.21 Several genetic disorders are similar to autism or associated with autism. These include DiGeorge syndrome (also known as 22q11.2 deletion syndrome or just 22q). Around 15-20% of those with DiGeorge meet the behavioral criteria for autism, which means some but not all of those with 22q also have autism.

    References

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    2. Ayelet Orenbuch, Keren Fortis, Siraphat Taesuwan, Raz Yaffe, Marie A Caudill, Hava M Golan; "Prenatal Nutritional Intervention Reduces Autistic-Like Behavior Rates Among Mthfr-Deficient Mice"; Frontiers in neuroscience.; 2019 May

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    8. Emma Derbyshire, Michael Maes; "The Role of Choline in Neurodevelopmental Disorders—A Narrative Review Focusing on ASC, ADHD and Dyslexia"; Nutrients.; 2023 Jun

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      https://pmc.ncbi.nlm.nih.gov/articles/PMC7564482/

    11. Nilanjana Saferin, Ibrahim Haseeb, Adam M Taha, Sarah E Beecroft, Sangeetha Pillai, Asha E Neifer, Rudhasri Lakkuru, Brian P Kistler, Charlotte N Nawor, Isa Malik, Dena Hasan, Jonathan A Carlson, Kareem K Zade, Sydnee P Dressel, Eileen M Carney, Radha Shah, Shudhant Gautam, John Vergis, Kari L Neifer, Zachary V Johnson, Morgan L Gustison, F Scott Hall, James P Burkett; "Folate prevents the autism-related phenotype caused by developmental pyrethroid exposure in prairie voles"; bioRxiv : the preprint server for biology.; 2024 Dec

      https://pmc.ncbi.nlm.nih.gov/articles/PMC11623627/

    12. Nilanjana Saferin, Ibrahim Haseeb, Adam M Taha, Sarah E Beecroft, Sangeetha Pillai, Asha E Neifer, Rudhasri Lakkuru, Brian P Kistler, Charlotte N Nawor, Isa Malik, Dena Hasan, Jonathan A Carlson, Kareem K Zade, Sydnee P Dressel, Eileen M Carney, Radha Shah, Shudhant Gautam, John Vergis, Kari L Neifer, Zachary V Johnson, Morgan L Gustison, F Scott Hall, James P Burkett; "Folate prevents the autism-related phenotype caused by developmental pyrethroid exposure in prairie voles"; bioRxiv : the preprint server for biology.; 2024 Dec

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    15. Daniel A Rossignol, Richard E Frye; "The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis"; Journal of personalized medicine; 2021 Aug

      https://pubmed.ncbi.nlm.nih.gov/34442428/

    16. Amelia Rizzo, Luana Sorrenti, Martina Commendatore, Aurora Mautone, Concettina Caparello, Maria Grazia Maggio, Ahmet Özaslan, Hakan Karaman, Murat Yıldırım, Pina Filippello; "Caregivers of Children with Autism Spectrum Disorders: The Role of Guilt Sensitivity and Support"; Journal of clinical medicine.; 2024 Jul

      https://pmc.ncbi.nlm.nih.gov/articles/PMC11278243/

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      https://pmc.ncbi.nlm.nih.gov/articles/PMC11640478/

    18. Lauren Rylaarsdam, Alicia Guemez-Gamboa; "Gnetic Causes and Modifiers of Autism Spectrum Disorder"; Frontiers in cellular neuroscience.; 2019 Aug

      https://pmc.ncbi.nlm.nih.gov/articles/PMC6710438/

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    Katie Stone - Naturopath

    About the Author

    Katie is a qualified Naturopath (BNatMed) and freelance writer from New Zealand. She specializes in all things health and wellness, particularly dietary supplements and nutrition. Katie is also a dedicated runner and has completed more half-marathons than she can count!