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Safety and Efficacy of High-Dose Folinic Acid in Children with Autism: The Impact of Folate Metabolism Gene
Caiyun Zhang1,2, Yanlin Chen3, Fang Hou3
1Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510275, China.
Insights
High-dose folinic acid shows promise for improving social reciprocity in children with autism spectrum disorder (ASD). Efficacy may be linked to specific genetic variations in folate metabolism, with no significant adverse effects observed.
Area of Science:
- Pediatric Neurology
- Nutritional Psychiatry
- Genetics and Personalized Medicine
Background:
- Limited research exists on high-dose folinic acid for Chinese children with autism spectrum disorder (ASD).
- The influence of folate metabolism gene polymorphisms on folinic acid efficacy in ASD is not well understood.
Purpose of the Study:
- To evaluate the safety and efficacy of high-dose folinic acid in Chinese children diagnosed with ASD.
- To investigate the association between folate metabolism gene polymorphisms and the treatment response to folinic acid.
Main Methods:
- A 12-week randomized clinical trial involving 80 children with ASD.
- Intervention group received high-dose folinic acid (2 mg/kg/day); control group did not.
- Efficacy assessed using the Psycho-Educational Profile, Third Edition (PEP-3); genotyping performed for MTHFR, MTR, and MTRR genes.
Main Results:
- The folinic acid group showed significantly greater improvements in social reciprocity compared to the control group.
- Children with MTHFR A1298C or MTRR A66G mutations exhibited enhanced improvements in developmental domains.
- No significant adverse effects were reported during the 12-week intervention period.
Conclusions:
- High-dose folinic acid is a potentially effective intervention for children with ASD, particularly those with specific genetic profiles.
- Efficacy appears linked to folate metabolism gene polymorphisms, suggesting a personalized approach to treatment.
- Folinic acid may improve neurodevelopmental outcomes by addressing folate metabolism abnormalities in ASD.
Abstract:
Background/Objectives: Research on the safety and efficacy of high-dose folinic acid in Chinese children with autism spectrum disorder (ASD) is limited, and the impact of folate metabolism gene polymorphisms on its efficacy remains unclear. This trial aimed to evaluate the safety and efficacy of high-dose folinic acid intervention in Chinese children with ASD and explore the association between folate metabolism gene polymorphisms and efficacy. Methods: A 12-week randomized clinical trial was conducted, including 80 eligible children with ASD, randomly assigned to an intervention group (n = 50) or a control group (n = 30). The intervention group was administered folinic acid (2 mg/kg/day, max 50 mg/day) in two divided doses. Efficacy was measured using the Psycho-Educational Profile, Third Edition (PEP-3) at baseline and 12 weeks by two trained professionals blind to the group assignments. Methylenetetrahydrofolate reductase (MTHFR C677T, MTHFR A1298C), methionine synthase (MTR A2756G), and methionine synthase reductase (MTRR A66G) were genotyped by the gold standard methods in the intervention group. Results: 49 participants in the intervention group and 27 in the control group completed this trial. Both groups showed improvements from baseline to 12 weeks across most outcome measures. The intervention group demonstrated significantly greater improvements in social reciprocity compared to the control group. Children with MTHFR A1298C or MTRR A66G mutations demonstrated greater improvements in various developmental domains than wild type. Folinic acid may be more effective in certain genotype combinations, such as MTHFR C677T and A1298C. No significant adverse effects were observed during the intervention. Conclusions: High-dose folinic acid may be a promising intervention for children with ASD, and its efficacy is associated with folate metabolism gene polymorphisms. High-dose folinic acid intervention may promote better neurodevelopmental outcomes by alleviating folate metabolism abnormalities caused by single or combined mutations in folate metabolism genes.
