Folinic Acid for Autism: Does It Help Kids?

randomized-controlled-trial PMID: 39243316

Quick Summary: A recent study found that giving children with autism folinic acid (a form of Vitamin B-) helped reduce their autism symptoms. The children taking folinic acid showed improvements in behavior and autism severity compared to those who didn't.

What The Research Found

Researchers studied children with autism and found that taking folinic acid, along with their regular therapies, led to noticeable improvements. Children taking folinic acid showed:

Fewer Autism Symptoms: Their autism symptoms, as measured by a standard scale, decreased more than those who didn't take the supplement.

Better Behavior: Parents reported fewer behavioral problems in children taking folinic acid.

The study also found that children with certain antibodies (anti-folate receptor autoantibodies) seemed to benefit even more from the folinic acid.

Study Details

Who was studied: 80 children with autism, aged 2 to 10 years old.

How long: The study lasted for 24 weeks (about 6 months).

What they took: Half the children took folinic acid (a type of Vitamin B-) by mouth, and the other half took a placebo (a "dummy" pill). Both groups continued their regular autism therapies, like ABA and sensory integration therapy.

What This Means For You

This research suggests that folinic acid could be a helpful addition to autism treatment for some children.

Talk to Your Doctor: If you have a child with autism, discuss this study with their doctor. They can help you understand if folinic acid might be an option and if any tests are needed.

Consider the Benefits: The study showed improvements in autism symptoms and behavior.

Important Note: This study used a specific dose of folinic acid. Never give your child any supplement without talking to a doctor first.

Study Limitations

It's important to keep these things in mind:

Short Study: The study was only 6 months long, so we don't know the long-term effects.

More Research Needed: More studies are needed to confirm these findings and see if they apply to all children with autism.

Not a Cure: Folinic acid is not a cure for autism, but it may help manage some symptoms.

Single Location: The study was conducted in a single location, so the results might not be the same for everyone.

Key Findings

This 24-week randomized controlled trial found that oral folinic acid supplementation (2 mg/kg/day, max 50 mg/day) significantly improved autism symptom severity in children aged 2–10 years compared to placebo. The folinic acid group showed a greater reduction in Childhood Autism Rating Scale (CARS) scores (3.6 ± 0.8 vs. 2.4 ± 0.7, p < 0.001) and behavioral problems via Child Behavior Checklist (CBCL) total (19.7 ± 9.5 vs. 12.6 ± 8.4, p < 0.001) and internalizing scores (15.4 ± 7.8 vs. 8.5 ± 5.7, p < 0.001). Benefits were amplified in children with high-titer anti-folate receptor autoantibodies, where symptom improvement was significantly greater than in those without (p = 0.03). No adverse effects were reported.

Study Design

The study was a double-blind, placebo-controlled randomized trial (RCT) conducted in India, registered under CTRI/2021/07/034901. It enrolled 80 children (40 per group) with autism spectrum disorder (ASD), aged 2–10 years. Participants received either folinic acid or placebo alongside standard care (applied behavior analysis and sensory integration therapy). Follow-up assessments occurred at 24 weeks, with 39 (folinic acid) and 38 (placebo) completers.

Dosage & Administration

Folinic acid was administered orally at 2 mg/kg/day, capped at 50 mg/day, for 24 weeks. The placebo group received identical-appearing inert tablets. Both groups continued standard behavioral therapies throughout the trial.

Results & Efficacy

Primary Outcome: CARS score reduction was significantly greater in the folinic acid group (mean difference: 1.2 points, p < 0.001).
Secondary Outcomes:
CBCL total score improvement: 19.7 ± 9.5 (folinic acid) vs. 12.6 ± 8.4 (placebo), p < 0.001.
CBCL internalizing score improvement: 15.4 ± 7.8 vs. 8.5 ± 5.7, p < 0.001.
Autoantibody Subgroup: Among high-titer autoantibody carriers (32/40 in folinic acid, 33/40 in placebo), folinic acid showed enhanced efficacy (p = 0.03). Autoantibody status did not affect placebo outcomes (p = 0.11).
Safety: No adverse events reported in either group.

Limitations

Short Duration: 24 weeks may be insufficient to assess long-term efficacy or safety.
Autoantibody Measurement: Anti-folate receptor autoantibody levels were not a primary randomization criterion, potentially introducing subgroup imbalance.
Single-Center Design: Results may lack generalizability across populations.
Mechanistic Gaps: The biological mechanism linking folinic acid to symptom improvement remains unexplored.
Sample Size: Relatively small (n=80), limiting statistical power for rare subgroups.

Clinical Relevance

Folinic acid supplementation appears safe and effective as an adjunct to behavioral therapies for reducing ASD symptom severity in children aged 2–10. Clinicians may consider screening for anti-folate receptor autoantibodies to identify patients likely to benefit most. The 2 mg/kg/day dosage (max 50 mg/day) provides a practical guideline for supplementation. However, larger, multi-center trials are needed to confirm these findings and explore long-term outcomes.

Source: RCT on PubMed (2024)