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维生素D与自闭症,有什么新进展?

Vitamin D and autism, what's new?

作者信息

Cannell John Jacob

机构信息

Vitamin D Council Inc., 1411 Marsh Street, Suite 203, San Luis Obispo, CA, 93401, USA.

出版信息

Rev Endocr Metab Disord. 2017 Jun;18(2):183-193. doi: 10.1007/s11154-017-9409-0.

Abstract

An increasing amount of evidence points to the possibility that gestational and early childhood vitamin D deficiency [25(OH)D < 40 ng/ml] cause some cases of autism. Vitamin D is metabolized into a seco-steroid hormone that regulates about 3% of the 26,000 genes in the coding human genome. It is also a neurosteroid that is active in brain development, having effects on cellular proliferation, differentiation, calcium signaling, neurotrophic and neuroprotective actions; it also appears to have an effect on neurotransmission and synaptic plasticity. Children who are, or who are destined to become, autistic have lower 25(OH)D levels at 3 months of gestation, at birth and at age 8 compared to their unaffected siblings. Two open label trials found high dose vitamin D improves the core symptoms of autism in about 75% of autistic children. A few of the improvements were remarkable. The vitamin D doses used in these children were 300 IU/KG/day up to a maximum of 5000 IU/day (highest final 25(OH)D level reached was 45 ng/ml). The other study used 150,000 IU/month IM as well as 400 IU/day [highest final 25(OH)D level was 52 ng/ml]. These two open label trials were recently confirmed with a randomized controlled trial (RCT) using 300 IU/kg/day with a maximum of 5000 IU/day and resulted in effects similar to the two open label studies. In terms of prevention, a recent small study showed vitamin D supplementation during pregnancy (5000 IU/day) and during infancy and early childhood (1000 IU/day) significantly reduced the expected incidence of autism in mothers who already had one autistic child from 20% to 5%. Vitamin D is safe; for example, over the last 15 years, Poison Control reports there have been approximately 15,000 cases of vitamin D overdose. However only three of these 15,000 people developed clinical toxicity and no one died. Given those facts, practitioners might consider treating autism with 300 IU/kg/day, and seek to prevent autism by supplementing pregnant and lactating women (5000 IU/day) and infants and young children (150 IU/kg/day) checking 25(OH)D levels every 3 months. These doses will increase 25(OH)D blood levels to those recommended by the Endocrine Society. As the American Academy of Pediatrics recommends vitamin D supplementation during infancy and childhood, pediatricians and family practitioners should evaluate the current evidence on autism and vitamin D and act accordingly.

摘要

越来越多的证据表明,孕期和幼儿期维生素D缺乏(25羟维生素D<40纳克/毫升)可能导致某些自闭症病例。维生素D可代谢为一种甾体激素,它能调节人类编码基因组中26000个基因中的约3%。它也是一种在大脑发育中起作用的神经甾体,对细胞增殖、分化、钙信号传导、神经营养和神经保护作用有影响;它似乎还对神经传递和突触可塑性有作用。与未患自闭症的兄弟姐妹相比,患自闭症或注定会患自闭症的儿童在妊娠3个月、出生时和8岁时的25羟维生素D水平较低。两项开放标签试验发现,高剂量维生素D可改善约75%自闭症儿童的核心症状。其中一些改善非常显著。这些儿童使用的维生素D剂量为300国际单位/千克/天,最高可达5000国际单位/天(最终达到的最高25羟维生素D水平为45纳克/毫升)。另一项研究使用每月150000国际单位的肌肉注射以及每天400国际单位(最终最高25羟维生素D水平为52纳克/毫升)。这两项开放标签试验最近通过一项随机对照试验(RCT)得到证实,该试验使用300国际单位/千克/天,最高可达5000国际单位/天,结果与两项开放标签研究相似。在预防方面,最近一项小型研究表明,孕期(5000国际单位/天)以及婴儿期和幼儿期(1000国际单位/天)补充维生素D可将已有一个自闭症孩子的母亲所生子女自闭症的预期发病率从20%显著降低至5%。维生素D是安全的;例如,在过去15年中,毒物控制中心报告大约有15000例维生素D过量病例。然而,在这15000人中只有3人出现临床毒性,无人死亡。鉴于这些事实,医生可以考虑用300国际单位/千克/天的剂量治疗自闭症,并通过给孕妇和哺乳期妇女(5000国际单位/天)以及婴幼儿(150国际单位/千克/天)补充维生素D来预防自闭症,每3个月检查一次25羟维生素D水平。这些剂量将使25羟维生素D血液水平升至内分泌学会推荐的水平。由于美国儿科学会建议在婴儿期和儿童期补充维生素D,儿科医生和家庭医生应评估目前关于自闭症和维生素D的证据并据此采取行动。

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