Leucovorin for Autism
All contents of this resource were created for informational purposes only and are not intended to be a substitute for professional advice, diagnosis, or treatment. Always seek the advice of your physician, therapist, or other qualified health providers with any questions or concerns you may have.
Leucovorin is best known for treating cancer patients to protect them against chemotherapy and methotrexate toxicity. However, in autism, Leucovorin is used to treat low folate levels in the brain. This is called “Cerebral Folate Deficiency (CFD)” and it happens when there is low folate (vitamin B9) in the brain but normal folate levels in the blood. You can learn more about Cerebral Folate Deficiency in this TACA article.
You may have seen media coverage on this topic on CBS Evening News, Fox News, and in The New York Post. Interestingly, TACA has been talking about Leucovorin treating autism for over ten years!
This article will cover frequently asked questions about Leucovorin.
What is Leucovorin?
Leucovorin is a prescription high-dose calcium folinic acid. It is vitamin B9, but this is NOT the same as folic acid. *Please note that folic acid is detrimental to those with Cerebral Folate Deficiency because it blocks folate receptors.*
Leucovorin comes in 5mg, 10mg, 15mg, and 25mg tablets, which are much higher dose than over-the-counter supplements. Over-the-counter folinic acid is usually dosed in much smaller micrograms (mcg), and Leucovorin is dosed in higher dose milligrams (mg).
Additionally, since Leucovorin is only available via prescription, its quality is regulated by the FDA.
The tablets can be crushed and added to food for consumption. A bit of applesauce works well.
It can also be compounded into a liquid form, but this will not be covered by insurance.
Why is Leucovorin given?
Individuals with autism may have an autoimmune condition where blocking or binding folate autoantibodies block folate from getting into the brain, resulting in developmental problems and more. That is why a folate blood test doesn’t tell you much. Learn more in this IG Reel from Dr Frye.
Additionally, there may be other reasons why Leucovorin is needed, such as mitochondrial dysfunction or genetics.
Is there research showing dosage for autism?
This meta-analysis, which is a review of numerous research studies, was done in 2021. The typical dose for positive blocking or binding autoantibodies is 0.5 to 2 mg / kg / day, but may go higher depending on individual needs.
For example, if your child weighs 100 lbs, you first convert that to kg. 100 lbs = 45 kg
45 lbs x 0.5mg = 22.5 mg (minimum, starting dose)
45 lbs x 2mg = 90 mg target dose.
Print and bring this research to your doctor.
How do I get access to Leucovorin?
Leucovorin needs to be prescribed. A functional medicine doctor (MD, PA, NP, or DO) who can prescribe medication and is trained in how to treat autism medically, or an open-minded neurologist willing to read the research may be able to help. Always bring studies for the doctor’s perusal when you would like to discuss a medication with your doctor.
Is Leucovorin covered by health insurance?
Yes, it should be. Check your policy and make sure you have met your deductible for the year.
How do I know if my child needs Leucovorin?
The only way to know for certain is to do a lumbar puncture (spinal tap) because that can tell you the level of folate (5MTHF) in the brain. Other than that, the only other possible testing is a blood test called a FRAT (Folate Receptor Autoantibody Test). This looks for blocking or binding autoantibodies in the blood. If the test reveals autoantibodies, this may indicate that the brain is not getting the folate it needs.
The FRAT is a test kit that you have to order and have mailed to you. Once you get it, you fill out the requisition form, and bring to your doctor to sign off on. Then get the blood drawn and sent to the lab. The results are sent to your doctor.
To learn how to read these test results, please read the book called “The Folate Fix by Dr Frye.”
What does this have to do with MTHFR?
Not much. There is no direct link between CFD in autism and MTHFR.
MTHFR is a single nucleotide polymorphism (SNP) that is found in 40-60% of the population. It can make it harder for the body to use folate. However, the treatment for MTHFR is typically a low dose of 5MTHF (methylfolate), methyl B12, and B6. (These are typically the first things prescribed by a functional medicine doctor for autism.)
By contrast, Cerebral Folate Deficiency (CFD) can result in a severe folate deficiency in the brain, and it is caused by autoimmunity, mitochondrial dysfunction, or specific genetic abnormalities.
My kid is negative on a FRAT (Folate Receptor Autoantibody Test). Can they still benefit from Leucovorin and/or 5MTHF?
Possibly. It is possible to have severe Cerebral Folate Deficiency and no folate receptor autoantibodies because of mitochondrial dysfunction or genetics.
What is the difference between Leucovorin and 5MTHF (methylfolate)?
5MTHF (Methylfolate) is a bit different than Leucovorin, which is high-dose folinic acid.
5MTHF is the most bioavailable form of folate, and at least half of Leucovorin is converted to 5MTHF in the gut. However, it is unknown if 5MTHF can treat CFD like Leucovorin because studies have not been done. But we do know that some kids tolerate one over the other, so if Leucovorin doesn’t work, it may be worth exploring 5MTHF.
Are there side effects to Leucovorin?
There may be. It is a B vitamin, and B vitamins are activating. Talk to your doctor about introducing it slowly. Your child may need time to adjust to it.
Work with your doctor if your child is not tolerating it. There are strategies that may help. You may need to lower the dose while your child adjusts, try compounding it, trial 5MTHF instead, or introduce calming supplements.
Are there supplements needed in conjunction with Leucovorin?
Since Leucovorin is B9 and B vitamins give energy, most functional medicine doctors start by introducing a combination of calming supplements before Leucovorin. Examples include magnesium glycinate, Omega 3 Fish oil, Lithium orotate, L-Theanine, GABA, and more.
Additionally, you may need to discuss introducing some mitochondrial supplements that can help push folate into the cell. Examples include prescription LevoCarnitine, B12, Riboflavin, and B6.
Does my child need to be on a special diet while on Leucovorin?
Yes! Your child needs to be dairy-free while on treating Cerebral Folate Deficiency with Leucovorin because dairy blocks folate receptors. If your child is still consuming dairy, they may have a harder time getting folate to the brain.
Conclusion
There have been numerous questions about Leucovorin for autism due to the media coverage. We hope that this information is helpful. For additional information about Cerebral Folate Deficiency, please see the TACA article here.
