Folate Receptor Autoantibodies – Folinic Acid

The connection between folinic acid and folate receptor autoantibodies (FRAAs) lies in the role of folinic acid as a therapeutic agent to bypass the functional folate deficiency caused by these autoantibodies. Let’s examine this in a bit more depth.

• FRAAs are antibodies that mistakenly target the folate receptor alpha (FRα), a protein responsible for transporting folate (vitamin B9) into cells, particularly in the brain and other tissues.
• When FRAAs bind to FRα, they block folate transport, leading to a functional folate deficiency even if blood folate levels are normal. In many instances it is believed that folate transport into the brain will be impaired because of folate receptor autoantibodies.
• This condition is associated with disorders such as cerebral folate deficiency (CFD) and has been linked to neurodevelopmental conditions like autism spectrum disorder (ASD).

• Folinic acid (also called leucovorin or 5-formyltetrahydrofolate) is a biologically active form of folate that does not rely solely on the folate receptor alpha (FRα) for cellular uptake.
• Instead, folinic acid can enter cells via alternative transport mechanisms, such as the reduced folate carrier (RFC) or other folate transporters.
• This makes folinic acid a potential treatment for individuals with FRAAs, as it can bypass the blocked FRα pathway and restore intracellular folate levels.

• Restores Folate Levels: By using folinic acid, cells can receive the folate they need for critical processes like DNA synthesis, methylation, and neurotransmitter production, even in the presence of FRAAs.
• Neurological Benefits: In conditions like CFD or ASD, where FRAAs impair folate transport to the brain, folinic acid can help correct folate deficiency in the central nervous system, potentially improving symptoms such as cognitive dysfunction, motor delays, or behavioral issues.
• Clinical Evidence: Some studies and case reports have shown improvements in symptoms when individuals with FRAAs are treated with folinic acid, particularly in children with CFD or ASD.

• Testing for FRAAs: Before using folinic acid, it is important to confirm the presence of FRAAs through blood tests. This can be done through the FRAT^® test. Not all individuals with neurological or developmental disorders have FRAAs, and folinic acid may not be effective in their absence.
• Dosage and Monitoring: Folinic acid must be administered at appropriate doses, and patients should be monitored for side effects or changes in symptoms. A physician must be consulted to prescribe the FRAT^® test as well as prescribe folinic acid.
• Individual Variability: Responses to folinic acid can vary. Some individuals may show significant improvement, while others may not respond at all. Please consult your medical professional for further information.

• Not a Cure: Folinic acid addresses the functional folate deficiency caused by FRAAs but does not eliminate the autoantibodies themselves.
• Long-Term Safety: The long-term safety of folinic acid, especially in children, is not fully understood. Again, a physician’s oversight is necessary.
• Alternative Treatments: In some cases, other forms of folate (e.g., methylfolate) or dietary changes and restrictions may also be considered to reduce autoantibody production. There is some evidence to suggest that the consumption of animal milk, particularly bovine milk, will increase the titers of folate receptor autoantibodies. ¹

Folinic acid is a promising treatment for individuals with folate receptor autoantibodies (FRAAs) because it can bypass the blocked folate receptor alpha (FRα) and restore intracellular folate levels. This is particularly relevant in conditions like cerebral folate deficiency (CFD) or autism spectrum disorder (ASD) associated with FRAAs. However, its use should be guided by a healthcare professional, with proper testing and monitoring to ensure safety and efficacy.

Recently, this topic was covered by CBS Evening News. Please click on the link to view the broadcast covering this important subject matter.

https://www.cbsnews.com/news/autism-leucovorin-medicine-folic-acid/