What exactly is leucovorin, the newly approved medication by the FDA for autism treatment?
This week, the Trump administration made headlines by announcing that the FDA has given the green light to leucovorin, a generic medication, as a potential treatment for autism. This revelation took many health professionals by surprise, as it deviates from the FDA's standard, thorough approval process, which is typically lengthy and meticulous.
Leucovorin, which is also referred to as folinic acid, is a derivative of vitamin B. It is primarily utilized to mitigate the adverse effects of methotrexate, a widely used chemotherapy agent. In a statement, FDA Commissioner Martin Makary indicated that this drug would now be available for patients suffering from cerebral folate deficiency (CFD), a condition that can sometimes be linked to autism spectrum disorders.
While a handful of studies have suggested that leucovorin may lead to some improvements in children diagnosed with autism, many researchers and advocates in the autism community believe that this announcement is premature and that further investigation is essential.
"The current research on high-dose leucovorin is still in its early stages," explains Danielle Hall, the director of health equity at the Autism Society of America. She cautions that making premature claims about its effectiveness could foster "false hope" and create a misunderstanding that leucovorin could serve as a "cure" for autism.
So, what should you know about leucovorin?
Leucovorin is described as being "very similar to folic acid," according to Dr. David Mandell, a professor of psychiatry at the University of Pennsylvania Perelman School of Medicine. The key distinction is that leucovorin has been modified to facilitate its passage through the blood-brain barrier, particularly for individuals who struggle to metabolize folic acid.
Folic acid is a synthetic variant of folate, or vitamin B, which is crucial for the body’s production of red blood cells and is vital for "healthy cell growth and function," as noted by the Mayo Clinic. Folate is naturally present in various foods, including leafy greens, beans, nuts, and fruits like oranges and bananas.
Folic acid is especially critical for those who are newly pregnant or may become pregnant.
"Insufficient folate during fetal development can lead to brain abnormalities," warns Dr. Edward Quadros, a professor specializing in folate absorption at SUNY Downstate.
Specifically, a lack of folate can result in severe birth defects of the brain and spine, known as neural tube defects (NTDs). To mitigate this risk, the CDC recommends that individuals who might become pregnant take 400mg of folic acid daily.
The side effects associated with leucovorin are generally minimal, according to Mandell, and typically involve gastrointestinal discomfort. A review published in 2021 in the Journal of Personalized Medicine found that while side effects in individuals with autism spectrum disorder and CFD were mostly mild, some reported issues such as aggression, agitation, headaches, insomnia, and increased tantrums.
What is the connection between folate deficiency and autism?
The relationship is not entirely understood.
Dr. Matthew Lerner, an associate professor and director of the Life Course Outcomes research program at the AJ Drexel Autism Institute, states, "The percentage of autistic individuals with folate deficiencies is still being studied," but he emphasizes that it is "certainly not the majority."
The FDA's association of CFD with autism has raised eyebrows among some experts.
Mandell points out that the FDA's announcement suggests that leucovorin can assist children with CFD, and because "these children exhibit some autism-like symptoms, we should consider it as a treatment for autism," he explains.
"That’s quite a convoluted reasoning," he adds.
Dr. Elliott Gavin Keenan, a post-doctoral fellow at the AJ Drexel Autism Institute, notes that the general public often perceives autism as a singular diagnosis. However, he clarifies that autism can arise from a multitude of factors, including genetic influences and significant maternal stress during pregnancy. "It’s truly a spectrum of various disorders, each likely requiring different treatment approaches."
Has leucovorin been previously utilized in autism treatment?
Not in an official capacity. However, for at least the past decade, there has been interest in the off-label use of leucovorin for treating autism.
The Facebook group "Leucovorin for Autism" boasts over 45,000 members, and discussions about the drug have been ongoing in subreddits like r/Autism_Parenting. One user shared in 2023, "My two sons both take leucovorin. For one, it works wonders; for the other, it’s just okay."
Keenan recalls his own experience with leucovorin for autism and bipolar disorder back in 2018. "I didn’t notice a significant improvement," he admits, nor did he experience any adverse effects. "It just passed through my system," he says, leading him to discontinue the medication after a few months.
While autism researchers do not dismiss the possibility that leucovorin could be beneficial for some individuals with autism, they stress that extensive research is necessary to determine which populations might gain the most from it.
"To take the potential of leucovorin seriously, we need rigorous, double-blind, placebo-controlled, and transparent trials," insists Lerner.
How does the FDA typically approve medications?
In his announcement regarding the FDA's approval of leucovorin, Makary stated that the agency arrived at this decision following "a systematic analysis of literature published between 2009-2024." This approach appears to diverge significantly from the FDA's traditional drug approval methods.
Lerner notes, "There have been numerous attempts to have other medications approved for autism, which have taken years and involved extensive, rigorous studies. In most cases, those medications were not approved."
According to the FDA’s own website, the drug approval process is intricate and time-consuming, often requiring years of clinical trials, thorough research evaluations, and inspections of manufacturing facilities.
Keenan acknowledges that while the FDA's standard approval process is "costly and flawed," it is essential for ensuring public safety.
The announcement regarding leucovorin was particularly surprising because, unlike typical FDA approvals, it did not provide dosage recommendations or safety guidelines for the drug's use. Lerner argues that without this crucial information, the guidance essentially amounts to, "Here’s a medication; perhaps you should give it a try."
"I can’t recall another instance where a drug received approval without any accompanying guidelines," Lerner states. "That’s generally not how we approach healthcare in this country or in the modern world."
But here's where it gets controversial: Is the FDA's decision a step forward in autism treatment, or does it risk misleading families searching for solutions? What do you think? Are you in favor of this new approach, or do you believe it could lead to more confusion and false hope? Share your thoughts in the comments!
