这篇综述探讨了过量叶酸(维生素B9)摄入量之间的复杂关系,尤其是它的合成形式,即,叶酸,以及它对健康和疾病的影响。虽然叶酸在单碳循环中起着关键作用,这对DNA合成至关重要,修复,甲基化,人们担心它的过量摄入。文献强调了潜在的有害影响,如癌症发生的风险增加;DNA甲基化的破坏;以及对胚胎发生的影响,妊娠结局,神经发育,和疾病风险。值得注意的是,这些后果超出了直接影响,通过表观遗传重编程可能影响后代。研究了这些效应的分子机制,包括改变的一碳代谢,未代谢叶酸的积累,维生素B12依赖机制,改变的甲基化模式,以及与关键受体和信号通路的相互作用。此外,与天然叶酸相比,叶酸介导的作用和机制的差异被强调。鉴于广泛的叶酸补充剂,必须进一步研究其最佳摄入水平和受过量摄入影响的分子途径,确保全球人口的健康和福祉。
This
review delves into the intricate relationship between excess folate (vitamin B9) intake, especially its synthetic form, namely, folic acid, and its implications on health and disease. While folate plays a pivotal role in the one-carbon cycle, which is essential for DNA synthesis, repair, and methylation, concerns arise about its excessive intake. The literature underscores potential deleterious effects, such as an increased risk of carcinogenesis; disruption in DNA methylation; and impacts on
embryogenesis, pregnancy outcomes, neurodevelopment, and disease risk. Notably, these consequences stretch beyond the immediate effects, potentially influencing future generations through epigenetic reprogramming. The molecular mechanisms underlying these effects were examined, including altered one-carbon metabolism, the accumulation of unmetabolized folic acid, vitamin-B12-dependent mechanisms, altered methylation patterns, and interactions with critical receptors and signaling pathways. Furthermore, differences in the effects and mechanisms mediated by folic acid compared with natural folate are highlighted. Given the widespread folic acid supplementation, it is imperative to further research its optimal intake levels and the molecular pathways impacted by its excessive intake, ensuring the health and well-being of the global population.