Neuroprotection and Neurometabolic Diseases Laboratory (Wyse's Lab), Graduate Program in Biological Sciences: Biochemistry, Department of Biochemistry, Federal University of Rio Grande Do Sul (UFRGS), Rua Ramiro Barcelos, 2600-Anexo, Zip Code 90035003, Porto Alegre, RS, Brazil.
Neurotox Res. 2023 Dec;41(6):730-740. doi: 10.1007/s12640-023-00674-z. Epub 2023 Oct 21.
Autism spectrum disorder (ASD) is characterized by early-appearing social communication deficits, with genetic and environmental factors potentially playing a role in its etiology, which remains largely unknown. During pregnancy, certain deficiencies in critical nutrients are mainly associated with central nervous system impairment. The vitamin B9 (folate) is primarily related to one-carbon and methionine metabolism, participating in methyl donor generation. In addition, supplementation with folic acid (FA) is recommended by the World Health Organization (WHO) in the first three gestational months to prevent neural tube defects. Vitamin B12 is related to folate regeneration, converting it into an active form. Deficiencies in this vitamin have a negative impact on cognitive function and brain development since it is involved in myelin synthesis. Vitamin D is intimately associated with Ca levels, acting in bone development and calcium-dependent signaling. This vitamin is associated with ASD at several levels since it has a relation with ASD genes and oxidative stress environment. This review carries the recent literature about the role of folate, vitamin B12, and vitamin D in ASD. In addition, we discuss the possible impact of nutrient deficiency or hypersupplementation during fetal development. On the other hand, we explore the biases of vitamin supplementation studies such as the loss of participants in retrospective studies, as well as multiple variants that are not considered in the conclusion, like dietary intake or auto-medication during pregnancy. In this regard, we aim to contribute to the discussion about the role of vitamins in ASD currency, but also in pregnancy and fetal development as well. Furthermore, stress during pregnancy can be an ASD predisposition, with cortisol as a regulator. In this view, we propose that cortisol is the bridge of susceptibility between vitamin disorders and ASD prevalence.
自闭症谱系障碍（ASD）的特征是早期出现的社交沟通障碍，遗传和环境因素可能在其发病机制中起作用，但这在很大程度上仍是未知的。在怀孕期间，某些关键营养素的缺乏主要与中枢神经系统损伤有关。维生素 B9（叶酸）主要与一碳和蛋氨酸代谢有关，参与甲基供体的生成。此外，世界卫生组织（WHO）建议在妊娠前三个月补充叶酸（FA），以预防神经管缺陷。维生素 B12 与叶酸的再生有关，将其转化为活性形式。由于它参与髓鞘合成，这种维生素的缺乏会对认知功能和大脑发育产生负面影响。维生素 D 与 Ca 水平密切相关，在骨骼发育和钙依赖性信号传导中发挥作用。这种维生素与 ASD 有几个方面的关联，因为它与 ASD 基因和氧化应激环境有关。这篇综述介绍了叶酸、维生素 B12 和维生素 D 在 ASD 中的作用的最新文献。此外，我们还讨论了胎儿发育过程中营养缺乏或过度补充的可能影响。另一方面，我们探讨了维生素补充研究中的偏见，例如回顾性研究中参与者的流失，以及在结论中未考虑到的多种变体，如饮食摄入或怀孕期间的自我用药。在这方面，我们旨在为讨论维生素在 ASD 中的作用做出贡献，也为妊娠和胎儿发育做出贡献。此外，怀孕期间的压力也可能是 ASD 的易患因素，而皮质醇则是其调节剂。在这种观点下，我们提出皮质醇是维生素紊乱与 ASD 患病率之间易感性的桥梁。
