Wiens Darrell, DeSoto M Catherine
Department of Biology, University of Northern Iowa, Cedar Falls, IA 50614, USA.
Department of Psychology, University of Northern Iowa, Cedar Falls, IA 50614, USA.
Brain Sci. 2017 Nov 10;7(11):149. doi: 10.3390/brainsci7110149.
Folate is required for metabolic processes and neural development. Insuring its adequate levels for pregnant women through supplementation of grain-based foods with synthetic folic acid (FA) in order to prevent neural tube defects has been an ongoing public health initiative. However, because women are advised to take multivitamins containing FA before and throughout pregnancy, the supplementation together with natural dietary folates has led to a demographic with high and rising serum levels of unmetabolized FA. This raises concerns about the detrimental effects of high serum synthetic FA, including a rise in risk for autism spectrum disorder (ASD). Some recent studies have reported a protective effect of FA fortification against ASD, but others have concluded there is an increased risk for ASD and other negative neurocognitive development outcomes. These issues are accompanied by further health questions concerning high, unmetabolized FA levels in serum. In this review, we outline the reasons excess FA supplementation is a concern and review the history and effects of supplementation. We then examine the effects of FA on neuronal development from tissue culture experiments, review recent advances in understanding of metabolic functional blocks in causing ASD and treatment for these with alternative forms such as folinic acid, and finally summarize the conflicting epidemiological findings regarding ASD. Based on the evidence evaluated, we conclude that caution regarding over supplementing is warranted.
叶酸是代谢过程和神经发育所必需的。通过在谷类食品中添加合成叶酸（FA）来确保孕妇体内叶酸水平充足，以预防神经管缺陷，这是一项持续进行的公共卫生举措。然而，由于建议女性在怀孕前及整个孕期服用含FA的多种维生素，这种补充加上天然膳食中的叶酸，导致了未代谢FA血清水平高且不断上升的人群。这引发了人们对高血清合成FA有害影响的担忧，包括自闭症谱系障碍（ASD）风险增加。最近一些研究报告了FA强化对ASD有保护作用，但其他研究得出结论认为ASD及其他负面神经认知发育结果的风险增加。这些问题还伴随着关于血清中高未代谢FA水平的进一步健康问题。在本综述中，我们概述了过量补充FA令人担忧的原因，并回顾了补充的历史和影响。然后我们从组织培养实验研究FA对神经元发育的影响，回顾在理解导致ASD的代谢功能障碍及其用亚叶酸等替代形式治疗方面的最新进展，最后总结关于ASD的相互矛盾的流行病学研究结果。基于所评估的证据，我们得出结论，有必要谨慎对待过度补充。
