Leucovorin and Autism: What Families Should Know About This Possible Complementary Support.

By Maite Rodríguez Márquez, PhD

Introduction

In recent months, the topic of Leucovorin (folinic acid) has gained attention across social media and news outlets. Public discussions spark excitement… but also questions. It’s understandable: when parents hear about something that could help a child communicate better, their hearts fill with hope, and their minds with questions.

Because when it comes to a child’s well-being, hope is always a reflection of love. Hearing about a treatment that could improve a child’s communication touches something deep within us; it reminds us that every parent lives between faith, doubt, and the desire to see their child move forward.

Before continuing, it’s important to make a clarification: folinic acid and folic acid are not the same. Folic acid is the “common” form of vitamin B9, found in supplements and fortified foods. Folinic acid, on the other hand, is an active form of folate that the body can utilize immediately, and some studies have investigated its use in groups of children with autism and language delay [1,2].

Without getting too technical, my intention is to explain what Leucovorin is, what it is not, and when it might be considered, always from the perspective that it is a complement to the therapies your child is already receiving and, above all, that it should be used under medical supervision.

My goal is to provide you with clear information, enabling you to make informed decisions calmly: reliable facts, without false promises, and with realistic hope. This is an evolving topic, and new information is likely to emerge in the coming years, helping us better understand it.

Now let’s take a moment to learn a bit more about the doctor who has dedicated years to studying folinic acid and its possible effects in children with autism. In this article, we will focus solely on his work and the findings of his studies to date.

Later, in another blog, we will continue to expand the conversation as new information becomes available.

Who is Dr. Richard E. Frye?

Dr. Richard E. Frye, MD, PhD, is a pediatric neurologist specializing in neurodevelopmental disorders, brain metabolism, and autism spectrum disorders. He earned his medical degree and PhD in Physiology and Biophysics from Georgetown University and completed his residency in Pediatrics and Child Neurology at hospitals affiliated with Harvard Medical School and Boston University [1].

Dr. Frye previously served as Director of Autism Research at the Arkansas Children’s Hospital Research Institute and as a professor at the University of Arkansas for Medical Sciences (UAMS) [2]. From these institutions, he led clinical studies on how metabolic abnormalities—such as those related to folate metabolism or mitochondrial function-may influence the development of some children within the autism spectrum [3,4].

Dr. Frye is widely recognized for his research on the use of folinic acid (Leucovorin) to improve language and social communication in children with autism, particularly in those who have folate receptor alpha antibodies (FRAA), a condition that can interfere with the absorption of folate in the brain [5,6].

His peer-reviewed publications focus on complementary treatments grounded in scientific evidence, always aiming to balance the hope of families with academic rigor.

2016 Study: Early Signs of Improvement

In 2016, Frye and his team studied 48 children with autism and language delay. Some were given folinic acid (Leucovorin) daily for 12 weeks, while others received a placebo (a pill with no medication) [1].

At the end of the study, the children who received Leucovorin showed greater improvement in verbal communication compared to those in the placebo group. The progress was even more evident in those who had a blood marker related to folate, known as FRAA [1].

The authors concluded that Leucovorin could be a promising complementary option for some children on the spectrum, especially when there are difficulties transporting folate to the brain.

Even so, they recommended interpreting the results with caution, as the study had a small number of participants and a limited duration.

In other words, this study opens a door of hope but does not represent a cure. If considered, its use should always be part of a broader support system: speech and language therapy, occupational therapy, behavioral interventions (such as ABA), family involvement, and guidance from the multidisciplinary IEP team.

2018 Study: Consistent Results

In 2018, Dr. Frye’s team once again studied folinic acid (Leucovorin) in children with autism [2].

The results showed improvements in language, both in speaking and understanding, especially among children with a positive FRAA marker, which indicates difficulty in transporting folate to the brain.

Parents and therapists also reported better attention and increased social interaction.

Although the findings are encouraging, the researchers noted that larger and longer-term studies are still needed to confirm the treatment’s effectiveness and safety.

In summary, Leucovorin can serve as an additional support in some cases, but medical supervision and early intervention remain the cornerstones of child development.

2024 Study: Small Improvements, Big Questions

In 2024, new studies evaluated Leucovorin in children with autism between the ages of 2 and 10, always in combination with language and behavioral therapies [3]. The results showed small but significant improvements in language and social communication.

However, the researchers emphasized that not all children respond in the same way and that this treatment does not replace fundamental therapies. It should be considered only as a complementary option, under professional guidance and with ongoing monitoring.

Experts, such as Robert Hendren, a child psychiatrist and a leading figure in integrative autism treatments, encourage maintaining realistic expectations: viewing Leucovorin as a possibility within neuroscience, rather than as a magical solution [4].

Final Reflection

These recent studies encourage families to stay informed, ask questions, and make decisions with medical guidance, without fear and with realistic hope.

Science advances step by step, just like our children, and each discovery adds an important piece to the puzzle of development. Yet what truly remains powerful is constant love, daily observation, and early intervention.

Being informed is also an act of love.

Every time a family seeks, reads, or asks for guidance, they are building a bridge between science and the heart.

"Accompanying others with knowledge is a form of hope.

And every well-guided hope has the power to transform lives."

-- Dr. Maite Rodríguez, Márquez

References

1.         Georgetown University. Alumni Profiles: Dr. Richard Frye, MD, PhD.

2.         University of Arkansas for Medical Sciences (UAMS). Department of Pediatrics: Faculty Profile – Richard E. Frye, MD, PhD.

3.         Frye, R.E., et al. (2016). Folinic acid improves verbal communication in children with autism and language impairment. Molecular Psychiatry, 23(2), 247–256.

4.         Frye, R.E., Rossignol, D.A. (2020). Metabolic disorders and targeted treatments in autism spectrum disorder: an update. Current Opinion in Pediatrics, 32(6), 726–732.

5.         Linus Pauling Institute. Folate (Vitamin B9). Oregon State University.

6.         Frye, R.E., Rossignol, D.A. (2016). Treatment of mitochondrial dysfunction in autism spectrum disorder. Seminars in Pediatric Neurology, 23(2), 163–175.