James S Jill, Melnyk Stepan, Fuchs George, Reid Tyra, Jernigan Stefanie, Pavliv Oleksandra, Hubanks Amanda, Gaylor David W
Department of Pediatrics and Biostatistics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock, AR 72202, USA.
Am J Clin Nutr. 2009 Jan;89(1):425-30. doi: 10.3945/ajcn.2008.26615. Epub 2008 Dec 3.
Metabolic abnormalities and targeted treatment trials have been reported for several neurobehavioral disorders but are relatively understudied in autism.
The objective of this study was to determine whether or not treatment with the metabolic precursors, methylcobalamin and folinic acid, would improve plasma concentrations of transmethylation/transsulfuration metabolites and glutathione redox status in autistic children.
In an open-label trial, 40 autistic children were treated with 75 microg/kg methylcobalamin (2 times/wk) and 400 microg folinic acid (2 times/d) for 3 mo. Metabolites in the transmethylation/transsulfuration pathway were measured before and after treatment and compared with values measured in age-matched control children.
The results indicated that pretreatment metabolite concentrations in autistic children were significantly different from values in the control children. The 3-mo intervention resulted in significant increases in cysteine, cysteinylglycine, and glutathione concentrations (P < 0.001). The oxidized disulfide form of glutathione was decreased and the glutathione redox ratio increased after treatment (P < 0.008). Although mean metabolite concentrations were improved significantly after intervention, they remained below those in unaffected control children.
The significant improvements observed in transmethylation metabolites and glutathione redox status after treatment suggest that targeted nutritional intervention with methylcobalamin and folinic acid may be of clinical benefit in some children who have autism. This trial was registered at (clinicaltrials.gov) as NCT00692315.
已有关于几种神经行为障碍的代谢异常及靶向治疗试验的报道,但在自闭症方面的研究相对较少。
本研究的目的是确定使用代谢前体甲钴胺和亚叶酸治疗是否会改善自闭症儿童血浆中甲基化/转硫代谢物的浓度及谷胱甘肽氧化还原状态。
在一项开放标签试验中,40名自闭症儿童接受75微克/千克甲钴胺(每周2次)和400微克亚叶酸(每日2次)治疗3个月。在治疗前后测量甲基化/转硫途径中的代谢物,并与年龄匹配的对照儿童所测值进行比较。
结果表明,自闭症儿童治疗前的代谢物浓度与对照儿童的值有显著差异。3个月的干预导致半胱氨酸、半胱氨酰甘氨酸和谷胱甘肽浓度显著增加(P<0.001)。治疗后谷胱甘肽的氧化二硫形式减少,谷胱甘肽氧化还原比增加(P<0.008)。虽然干预后平均代谢物浓度有显著改善,但仍低于未受影响的对照儿童。
治疗后甲基化代谢物和谷胱甘肽氧化还原状态的显著改善表明,对一些自闭症儿童进行甲钴胺和亚叶酸的靶向营养干预可能具有临床益处。该试验在(clinicaltrials.gov)注册,注册号为NCT00692315。