He Qiangqiang, Li Jianping
Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, Guangdong Province, China.
Shenzhen Evergreen Medical Institute, Shenzhen 518057, Guangdong Province, China.
J Transl Int Med. 2023 Jul 5;11(2):128-137. doi: 10.2478/jtim-2023-0087. eCollection 2023 Jul.
Folate is a crucial nutrient that supports physiological functions. Low folate levels is a risk factor for several diseases, including cardiovascular diseases and neural tube defects. The most used folate supplement is folic acid, a synthetic oxidative form, and folic acid grain fortification is a success story of public health. However, the metabolic conversion of folic acid to bioactive tetrahydrofolate requires several enzymes and cofactors. Therefore, these factors influence its bioavailability and efficacy. In contrast, 5-methyltetrahydrofolate is used directly and participates in one-carbon metabolism, and the use of 5-methyltetrahydrofolate as an alternative folate supplement has increased. The metabolism of 5-methyltetrahydrofolate is primarily dependent on the transmembrane transporter, reduced folate carrier (), and the gene variant is a functional polymorphism that affects folate status indexes. Recent studies demonstrated that the expression of and cystathionine β-synthase, another enzyme required for homocysteine clearance, increases significantly by supplementation with calcitriol (vitamin D3), suggesting that calcitriol intake promotes the bioavailability of folate and has synergistic effects in homocysteine clearance. The advancements in biomedical and cohort studies and clinical trials have enhanced our understanding of the critical roles of folate and the regulation of one-carbon metabolism. We anticipate that the field of folate supplementation is poised to evolve from one size for all to personalized, precision, poly-paths (3Ps), which is a critical measure to meet individual needs, maximize health benefits, and minimize side effects.
叶酸是一种支持生理功能的关键营养素。低叶酸水平是包括心血管疾病和神经管缺陷在内的多种疾病的危险因素。最常用的叶酸补充剂是叶酸，一种合成的氧化形式，叶酸强化谷物是公共卫生领域的一个成功案例。然而，叶酸代谢转化为具有生物活性的四氢叶酸需要多种酶和辅助因子。因此，这些因素会影响其生物利用度和功效。相比之下，5-甲基四氢叶酸可直接使用并参与一碳代谢，并且将5-甲基四氢叶酸用作替代叶酸补充剂的情况有所增加。5-甲基四氢叶酸的代谢主要依赖于跨膜转运蛋白——还原型叶酸载体（RFC），而RFC基因变体是一种影响叶酸状态指标的功能性多态性。最近的研究表明，补充骨化三醇（维生素D3）可显著增加RFC和另一种同型半胱氨酸清除所需的酶——胱硫醚β-合酶的表达，这表明摄入骨化三醇可促进叶酸的生物利用度，并在同型半胱氨酸清除中具有协同作用。生物医学、队列研究和临床试验的进展增强了我们对叶酸的关键作用以及一碳代谢调节的理解。我们预计，叶酸补充领域将从一刀切模式发展为个性化、精准化、多途径（3P）模式，这是满足个体需求、最大化健康益处并最小化副作用的关键措施。
