Department of Psychiatry and Behavioral Sciences, University of California, Davis Medical Center, Sacramento, CA, USA.
J Altern Complement Med. 2010 May;16(5):555-60. doi: 10.1089/acm.2009.0177.
The study objectives were to determine whether methyl B12 treatment improves behavioral measures in children with autism and whether improvement is associated with increased plasma concentrations of glutathione (GSH) and an increased redox ratio of reduced glutathione to oxidized glutathione (GSH/GSSG), both of which have been previously identified to be low in children with autism.
This was a 12-week, double-blind, placebo-controlled, cross-over clinical trial of injectable methyl B12. Following this 12-week study, subjects were given the option of entering a 6-month open-label trial of methyl B12.
SETTINGS/LOCATION: All procedures took place at the UC Davis M.I.N.D. Institute.
Subjects were 3 to 8 years old with autism.
All subjects received 6 weeks of placebo and 6 weeks of methyl B12 at a dose of 64.5 mcg/kg every three days administered subcutaneously into the buttocks.
Blood for GSH analysis and behavioral assessments were obtained at baseline, week 6, and week 12.
Thirty (30) subjects completed the 12-week, double-blind study and 22 subjects completed the 6-month extension study. No statistically significant mean differences in behavior tests or in glutathione status were identified between active and placebo groups. Nine (9) subjects (30%) demonstrated clinically significant improvement on the Clinical Global Impression Scale and at least two additional behavioral measures. More notably, these responders exhibited significantly increased plasma concentrations of GSH and GSH/GSSG.
Comparison of the overall means between groups suggests that methyl B12 is ineffective in treating behavioral symptoms of autism. However, detailed data analysis suggests that methyl B12 may alleviate symptoms of autism in a subgroup of children, possibly by reducing oxidative stress. An increase in glutathione redox status (GSH/GSSG) may provide a biomarker for treatment response to methyl B12. Additional research is needed to delineate a subgroup of potential responders and ascertain a biomarker for response to methyl B12.
本研究旨在确定甲基 B12 治疗是否能改善自闭症儿童的行为表现，以及改善是否与血浆谷胱甘肽（GSH）浓度升高和还原型谷胱甘肽与氧化型谷胱甘肽的还原氧化比（GSH/GSSG）升高有关，先前的研究已经表明自闭症儿童的这两者水平均较低。
这是一项为期 12 周的、双盲、安慰剂对照、交叉临床试验，研究对象为接受肌内注射甲基 B12 的儿童。在这项 12 周的研究之后，研究对象可以选择参加为期 6 个月的开放性甲基 B12 试验。
所有程序均在加州大学戴维斯分校 M.I.N.D. 研究所进行。
受试者为 3 至 8 岁自闭症儿童。
所有受试者均接受 6 周的安慰剂和 6 周的甲基 B12 治疗，剂量为 64.5mcg/kg，每 3 天经皮注射入臀部。
30 名（30 名）受试者完成了为期 12 周的双盲研究，22 名受试者完成了为期 6 个月的扩展研究。在行为测试或谷胱甘肽状态方面，活性组和安慰剂组之间未发现具有统计学意义的均值差异。9 名（9 名）受试者（30%）在临床总体印象量表和至少另外两项行为测量上表现出明显的临床改善。更值得注意的是，这些应答者的血浆 GSH 和 GSH/GSSG 浓度显著升高。
组间总体均值比较表明，甲基 B12 治疗自闭症的行为症状无效。然而，详细数据分析表明，甲基 B12 可能通过降低氧化应激减轻一部分儿童自闭症的症状。谷胱甘肽氧化还原状态（GSH/GSSG）的增加可能为甲基 B12 治疗反应提供生物标志物。需要进一步的研究来确定潜在应答者亚组，并确定对甲基 B12 治疗反应的生物标志物。
