Wong Chui Mae, Tan Charmain Samantha, Koh Hwan Cui, Gan Xinyi, Hie Szu Liang, Saffari Seyed Ehsan, Yeo Joo Guan, Lam Joyce Ching Mei
Department of Child Development, KK Women's and Children's Hospital, Singapore.
Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Int J Dev Neurosci. 2025 Feb;85(1):e10402. doi: 10.1002/jdn.10402.
The folate cycle has been implicated in the pathophysiology of autism due to its role in the glutathione oxidative stress pathway, amino acid and DNA methylation reactions, and neurotransmitter synthesis pathway. Previous research on folinic acid supplementation in autistic children has suggested potential benefits. The primary aim of this pilot study was to determine the safety, feasibility and efficacy of oral folinic acid in improving communication and behaviour in autistic children. Ten autistic children were recruited into an open-label pre-post treatment within-subjects design study. At T = 0, 12 and 24 weeks, participants underwent safety evaluations, standardized assessments of language, autism symptoms, adaptive skills and global illness severity, and eye-gaze tracking. During the control period (0-12 weeks), participants continued with standard care. In the treatment period (12-24 weeks), participants took oral folinic acid at 2 mg/kg/day. All 10 children (nine boys, one girl; aged 4-8 years), successfully consumed oral folinic acid supplements with no adverse events. There was a reduction in Pervasive Developmental Disorder Behavior Inventory (PDDBI) Autism Composite T-score with treatment (mean [SD] T-score 49.2 [8.89] pre-treatment, 44.6 [6.19] post-treatment, p = 0.103). Although this difference was not statistically significant due to the small sample size, the effect size was medium-large, indicating that, as a group, there were clinically meaningful changes in PDDBI T-scores. There were also trends towards gains in communication scores and overall Clinical Global Impression scores. Folinic acid is a safe and feasible potential treatment for autism, and results from this pilot justify the need for a larger placebo-controlled trial.
由于叶酸循环在谷胱甘肽氧化应激途径、氨基酸和DNA甲基化反应以及神经递质合成途径中发挥作用，它已被认为与自闭症的病理生理学有关。先前关于对自闭症儿童补充亚叶酸的研究表明了其潜在益处。这项初步研究的主要目的是确定口服亚叶酸在改善自闭症儿童沟通和行为方面的安全性、可行性和有效性。十名自闭症儿童被招募到一项开放标签的治疗前后受试者自身对照设计研究中。在第0、12和24周时，参与者接受了安全性评估、语言、自闭症症状、适应技能和整体疾病严重程度的标准化评估以及目光追踪。在对照期（0 - 12周），参与者继续接受标准护理。在治疗期（12 - 24周），参与者每天按2毫克/千克的剂量口服亚叶酸。所有10名儿童（9名男孩，1名女孩；年龄4 - 8岁）均成功服用了口服亚叶酸补充剂，且未出现不良事件。治疗后广泛性发育障碍行为量表（PDDBI）自闭症综合T分数有所降低（治疗前平均[标准差]T分数为49.2[8.89]，治疗后为44.6[6.19]，p = 0.103）。尽管由于样本量小，这种差异没有统计学意义，但效应量为中到大，表明作为一个群体，PDDBI T分数有临床意义的变化。沟通分数和整体临床总体印象分数也有上升趋势。亚叶酸是一种安全可行的自闭症潜在治疗方法，这项初步研究的结果证明有必要进行更大规模的安慰剂对照试验。
