National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology, PR China; Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/ National Center of Gerontology, PR China.
Clin Chim Acta. 2022 Dec 1;537:96-104. doi: 10.1016/j.cca.2022.09.019. Epub 2022 Oct 17.
Little known about folates status in folate deficiency patients. This study aims to establish liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay-specific reference intervals (RIs) for serum 5-Methyltetrahydrofolate (5MeTHF), folic acid (FA), 5-Formyltetrahydrofolate (5FoTHF), and total folate (TFOL), and investigate the folates status in FA-supplemented folate deficient patients.
Sera from 120 reference subjects were selected and measured. An LC-MS/MS method for serum 5MeTHF, FA, and 5FoTHF was employed. RIs were derived based on the CLSI C28-A3. Serum folate levels of 38 FA-supplemented folate deficiency patients were analyzed.
RIs (median) for 5MeTHF, FA, 5FoTHF, and TFOL were 3.83-62.33 nmol/L (12.27 nmol/L), 0.30-0.92 nmol/L (0.49 nmol/L), <0.73 nmol/L (0.00 nmol/L), and 4.17-63.47 nmol/L (12.66 nmol/L), respectively. Approximately 53 % (20/38), 74 % (28/38), and 63 % (24/38) of patients presented high levels of 5MeTHF, FA, and TFOL, respectively, which far exceeded the upper reference limit (URL) of the corresponding RIs. A half (18/38) of patients showed simultaneously higher 5MeTHF and FA levels which were beyond the URLs of RIs. Near one-third (11/38) of patients exhibited extremely high FA levels which exceeded the 100-fold URL of RIs. The highest levels can be 539 nmol/L for FA, 364 nmol/L for 5MeTHF, and 686 nmol/L for TFOL.
LC-MS/MS assay-specific RIs were established for folates vitamers without age or gender partitioning. Abnormally high levels of unmetabolized FA and 5MeTHF were observed in quite a few FA-supplemented patients. Considering the adverse risks caused by folates excess, we appeal for a justifiable and individualized FA supplementation. We also recommend establishing LC-MS/MS assay-specific RIs for routine monitoring of folates status.
关于叶酸缺乏患者的叶酸状态知之甚少。本研究旨在建立血清 5-甲基四氢叶酸（5-Methyltetrahydrofolate，5MeTHF）、叶酸（Folic acid，FA）、5-甲酰四氢叶酸（5-Formyltetrahydrofolate，5FoTHF）和总叶酸（Total folate，TFOL）的液相色谱-串联质谱（LC-MS/MS）检测专用参考区间（reference intervals，RIs），并探讨补充 FA 后叶酸缺乏患者的叶酸状态。
选取 120 例参考对象的血清进行检测。采用 LC-MS/MS 方法检测血清 5MeTHF、FA 和 5FoTHF。RIs 基于 CLSI C28-A3 推导。分析 38 例补充 FA 后叶酸缺乏患者的血清叶酸水平。
5MeTHF、FA、5FoTHF 和 TFOL 的 RI（中位数）分别为 3.83-62.33 nmol/L（12.27 nmol/L）、0.30-0.92 nmol/L（0.49 nmol/L）、<0.73 nmol/L（0.00 nmol/L）和 4.17-63.47 nmol/L（12.66 nmol/L）。约 53%（20/38）、74%（28/38）和 63%（24/38）的患者血清 5MeTHF、FA 和 TFOL 水平升高，超过相应 RI 的上限（upper reference limit，URL）。半数（18/38）患者同时出现 5MeTHF 和 FA 水平升高，超出 RI 的 URL。近三分之一（11/38）的患者出现 FA 水平极高，超过 RI 上限的 100 倍。FA 的最高水平可达 539 nmol/L，5MeTHF 为 364 nmol/L，TFOL 为 686 nmol/L。
建立了无年龄和性别分区的叶酸代谢物 LC-MS/MS 检测专用 RIs。在相当数量的补充 FA 患者中观察到未代谢的 FA 和 5MeTHF 水平异常升高。鉴于叶酸过量引起的不良风险，我们呼吁合理且个体化的 FA 补充。我们还建议为常规监测叶酸状态建立 LC-MS/MS 检测专用 RIs。
