On the Shelf
Mickie Cathers
Folate is critical for healthy cell growth and plays an especially important role preventing congenital disorders such as spina bifida and neural tube defects. Recently, folate has been in the spotlight for its potential effect on autism spectrum disorder, prompting questions from patients.
Background
Folate, also known as vitamin B9, is critical for genetic material production and healthy cell growth. It plays an especially vital role during infancy, rapid growth phases, and pregnancy. A diet that includes folate is crucial for maintaining overall health. Beyond producing genetic material, and supporting healthy cell growth and division, folate is also important for preventing congenital disorders such as spina bifida and neural tube defects. Folate is also used to prevent methotrexate toxicity in noncancer-related conditions, aid in treating anemia, and may reduce autism risk with early pregnancy supplementation.
Natural folate, found in foods, has a bioavailability of about 50%, requiring conversion in the gut for absorption. Folic acid, folate’s synthetic form, is more easily absorbed and found in fortified foods and vitamins.
Is there a benefit?
The United States began mandatory folic acid fortification of enriched cereal grain products in 1998, and since then, about 1,300 babies are born each year without neural tube defects who would have otherwise developed them without folic acid supplementation, according to CDC.
While the initiative has had positive impacts, some groups remain at higher risk for pregnancies affected by neural tube defects. Research shows Hispanic/Latina women still have lower folate levels, and in 2016, FDA allowed voluntary fortification of corn masa flour to address this.
National surveys show a decline in daily multivitamin use among women aged 18 to 44 years. Specifically, the decline is seen among women aged 25 to 44 years and among Hispanic/Latina and non-Hispanic white women, while use among other groups remain unchanged.
Folate’s potential role in reducing autism risk
When it comes to prevention of birth defects, there is a long history of evidence-based science to support folate supplementation.
While the literature is not quite as robust regarding prevention of autism spectrum disorder (ASD), there are several studies on this topic, including reviews.
A meta-analysis and meta-regression published March 20, 2021, in the Journal of Autism and Developmental Disorders revealed the results of the association between maternal folic acid supplementation and the risk of ASD in children. After extracting and reviewing 10 out of 2,788 articles, Liu and colleagues found that maternal folic acid supplements administered during the prenatal period were associated with 43% lower odds of ASD in offspring compared to subjects without maternal folic acid supplement exposure. The authors concluded that maternal consumption of at least 400 μg/day of folic acid from dietary sources and supplements during or before pregnancy may provide a protective effect on reducing the risk of ASD in offspring.
Dosage and availability
Folate is found naturally in dark green leafy vegetables, fruits, nuts, seafood, eggs, meats, and beans. Sources of folic acid include fortified, enriched foods such as flours, breads, pastas, rice, and breakfast cereals. Folate supplements come in two primary forms: folic acid and methylfolate (5-MTHF). 5-MTHF is the active form and is more easily absorbed, especially by those with MTHFR (methylenetetrahydrofolate reductase) gene variants.
The recommended adult daily intake of folate in the United States is 400 μg. Understanding the difference between natural and fortified sources of folate can impact health choices and enhance nutritional intake, especially for those with restrictions or increased needs.
What to tell patients
Patients may be confused about folate, folic acid, and folinic acid and will come to their trusted pharmacists for clarity. Advise them on the differences and recommendations as well as how to read labels carefully and ensure their vitamins contain folic acid. Caution patients that while folate is essential, too-high folate levels do carry risks such as masking vitamin B12 deficiency, contributing to cancer risks, causing allergic reactions, or interacting with specific anti-seizure medications including phenytoin, carbamazepine, and valproate. ■
FDA approves prescription-only leucovorin to treat autism symptoms
Folinic acid is a prescription-only form of folate used primarily in managing specific medical conditions and counteracting drug toxicity. Unlike folic acid, folinic acid is already active and rapidly absorbed when taken orally, making it effective in treating or preventing adverse effects from medications. Leucovorin is commonly used to counteract methotrexate toxicity and treat conditions such as megaloblastic anemia and advanced colorectal cancer.
On September 22, 2025, FDA approved folinic acid, known as leucovorin, for patients with cerebral folate deficiency (CFD), a neurological condition affecting folate transport to the brain. CFD is linked to developmental delays and autistic features such as challenges with social communication, sensory processing, and repetitive behaviors, as well as seizures and problems with movement and coordination. Leucovorin bypasses the blocked folate receptor, providing an alternative transport method to restore folate levels in the brain.
Studies indicate 60% to 75% of children with autism spectrum disorder might have antibodies blocking folate transport, leading to reduced levels in cerebrospinal fluid. Children with autism treated with folinic acid in these studies have shown improvements in language, communication, and social interaction. Further large-scale studies are needed to confirm these findings and explore the broader benefits of folinic acid supplementation. ■