Folate and the Brain: Different Types and Doses

In our previous blog post, we discussed cerebral folate deficiency (CFD), a condition where some children develop folate receptor autoantibodies (FRAs) that block or bind to folate receptors, preventing folate from properly entering brain cells. This can contribute to autistic symptoms and is detectable through the FRAT test.

Understanding Folate

Folate is a broad term that includes all forms of vitamin B9, but the best type depends on individual needs, genetics, and sensitivity to methylation:

Folate from food (leafy greens, legumes, liver) is the most natural and well-tolerated but may not be sufficient for those with high folate needs.
Folic Acid is a synthetic form found in fortified foods and many supplements. Since it must go through multiple conversion steps to become active, it can build up in the body and interfere with natural folate use.
Methylfolate (5-MTHF) is the most active and bioavailable form, but many individuals are sensitive to methyl groups may experience overstimulation, anxiety, or detox reactions.
Folinic Acid is an effective, active form of folate that does not contain methyl groups, making it less likely to cause overstimulation. This is the form we use most often in our practice.

Folate and the Brain

In CFD, folate (any type) has trouble reaching the brain because autoantibodies block or bind to its receptors. To counter this, high-dose folinic acid is used to saturate the blood, increasing the chances of folate getting into the brain. This can be done through supplements or the prescription drug leucovorin. However, testing is recommended, as high doses may not be necessary for everyone and could cause unwanted effects.

Folate and Detoxification

Folate supports detox by aiding methylation, glutathione production, and immune function, helping the body eliminate bacteria, candida, and mould; starting slowly is key to avoiding symptoms like fatigue, headaches, or irritability. Sufficient support from minerals, antioxidants, and antibacterials are important.

DHFR Mutations

Those with DHFR (dihydrofolate reductase) mutations should take lower doses (around 500 mcg) since they process folinic acid more slowly. Too much folinic can build up, leading to side effects like irritability, headaches, or worsening symptoms. The genetic test we offer looks at this gene.

Not Everyone Benefits from High-Dose folate

Not all children have CFD, and flooding the brain with excess folate can lead to symptoms such as irritability, headaches, migraines, or insomnia. While folinic acid is a powerful nutrient for brain health, it’s not a one-size-fits-all solution.

Addressing Root Causes, Including Dairy

If diagnosed with CFD, Dr. Frye, Dr. Rossignol, and Dr. Ben Lynch recommend cutting out dairy first, as it’s a major trigger for folate receptor autoantibodies in the brain. This includes ghee and any supplements containing casein from any animal—except goat or camel.

Elevated homocysteine is another key factor to address, which I’ll cover in a future blog post.

Small Doses, Good Gains

Folinic acid can do amazing things for brain function, and we’ve seen huge gains for our clients at smaller doses. It’s helped with everything from reduced seizures to improved speech, focus, growth, and overall brain function. Many do really well on small to moderate amounts, seeing great progress without the side effects.