Folate and Autism: What everyone should know.

When you think of folate, you probably picture pregnancy vitamins - that familiar advice to “take folic acid.” But did you know that folate plays a critical role in brain development,

behaviour, and speech in children with autism?

Let’s unpack a few things:

• Why folate is crucial for neurological (brain) development.

• The difference between folate and folic acid.

• The role of folate receptor alpha (FRa) and the impact of autoantibodies.

• How these factors might affect children with autism - and what you can do about it.

What is Folate and Why Does it Matter?

Folate is a B-vitamin (B9) essential for:

• DNA synthesis and repair.

• Neurotransmitter (brain chemical) production, like serotonin and dopamine.

• Detoxification.

• Methylation (the biochemical process that affects gene expression).

In the developing brain, and throughout our life, folate supports neuronal growth,

myelination, and cognitive function. Deficiencies can affect mood, learning, attention, and behaviour.

Not All Folate is Made Equal

All TGA approved prenatal supplements in Australia must contain folic acid. Most

fortified foods also contain folic acid, the synthetic version of folate. While folic acid has

been effective at preventing neural tube defects (such as spina bifida), it needs to be

converted in the liver or other tissues to its active form, 5-methyltetrahydrofolate (5-MTHF), to be used by the body.

Here’s the problem:

Some people have genetic variations of MTHFR (and many others) that impair this

conversion. Others might have immune responses that block folate’s access to the brain - no matter how much folic acid they take. Note that MTHFR does not work alone and this gene should NEVER be tested individually.

The Folate Receptor Alpha: A Gateway to the Brain

The brain is protected by the blood-brain barrier (BBB) - a tightly controlled gateway that regulates what can enter the central nervous system. Folate crosses into the brain via a special transporter caller the folate receptor alpha (FRa), located in the choroid plexus. Think it this as a locked door that opens only when the right key (5-MTHF) arrives.

Unfortunately, in some children, that door gets jammed shut.

Folate Receptor Alpha Autoantibodies (FRAAs): The Hidden Barrier

In a significant number of children with autism, the immune system produces

autoantibodies that attack the folate receptor alpha. These are called Folate Receptor

Alpha Autoantibodies (FRAAs). When this happens, folate can’t reach the brain effectively - even if the blood levels are normal.

This can lead to:

• Low cerebrospinal fluid folate (a condition called Cerebral Folate Deficiency).

• Speech delay, language regression, seizures, and motor issues.

• Increased behavioural symptoms like irritability, hyperactivity, and cognitive inflexibility.

A study published in Molecular Psychiatry (Frye et al., 2013) found that 75% of children

with autism tested positive for at least one type of FRAA. A protein in dairy cross reacts with FRa, yet another reason for children with autism to be supported with a dairy free diet.

Is Folic Acid Making it Worse?

This is where it gets interesting - and concerning.

Folic acid (the synthetic form in foods and many supplements) can bind to the folate

receptor without activating it, essentially blocking access for the active form, 5-MTHF).

In children with FRAAs (remember, 75%) this worsens folate transport issues.

This is why functional and integrative practitioners often avoid folic acid in children with

autism and instead use methylated folate (5-MTHF) - a form that bypasses common

roadblocks.

The Good News

Several clinical studies have shown that children with autism who receive the right kind of

folate can significantly improve in:

• Speech, language and communication

• Social interaction

• Cognition and learning

• Behaviour and mood

In a randomised controlled trial (Frye et al., 2016), children with autism and FRAAs who

were treated with folinic acid showed marked improvements in verbal communication,

compared to the control group.

What Can Parents Do?

Ask About Genetic Testing

Knowing what genes are impacted by methylation and folate synthesis can be helpful in

treating autism. This is done as a whole panel, not an individual gene (like MTHFR).

Avoid Synthetic Folic Acid in Fortified Food and Supplements

Look for supplements with 5-MTHF or folinic acid instead. Although some children with

autism appear to do well on methylated B vitamins, it is important to remember that the

research is limited in regards to long-term outcomes. Methylation is a huge player in

altering the expression of genes - something that can be passed down through

generations. This is called epigenetics.

Eat Folate-Rich Foods

Choose natural, whole foods that are rich in real folate.

Spinach, kale, silverbeet, broccoli, asparagus, Brussels sprouts, avocados, lentils,

chickpeas, black beans, oranges, strawberries, sunflower seeds, liver.

Tip: Lightly steam greens until they’re bright green (around 90 seconds for broccoli) to

retain maximum folate content.

Ask your Practitioner for Help. Although FRAA testing is not available in Australia at

this point, under guidance by a practitioner and a specific pharmacist, high dose

folinic acid can be used as a trial, then as a treatment if indicated.

Amanda Downsborough, BSc, PGDip, GCert, MSc, ACAAM,

Functional & Nutrigenomic Medicine Practitioner

Brain Kids – www.brainkids.com.au

About the Author

Amanda Downsborough, BSc, PGDip, GCert, MSc, ACAAM, is a Functional and Nutrigenomic Medicine Practitioner specialising in autism and child neurodevelopment. Through her practice, Brain Kids, Amanda combines functional medicine, genetics, and neuroscience to uncover the biochemical and environmental factors affecting children’s health. Her work empowers families with science-based strategies to support brain balance, behaviour, and lifelong wellbeing.

Disclaimer

This information is provided for educational purposes only and is not intended as a

substitute for medical advice, diagnosis, or treatment. Always seek the advice of a

qualified healthcare provider with any questions regarding a medical condition or before

making changes to your or your child’s care plan.