建立 LC-MS/MS 测定法特定的血清叶酸参考区间及其在评估补充叶酸的叶酸缺乏症患者中的应用：呼吁进行合适和个体化的补充。
The establishment of LC-MS/MS assays-specific reference intervals for serum folates and its application in evaluating FA-supplemented folate deficiency patients: Appeals for a suitable and individualized supplementation.
机构信息
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.
出版信息
Clin Chim Acta. 2022 Dec 1;537:96-104. doi: 10.1016/j.cca.2022.09.019. Epub 2022 Oct 17.
BACKGROUND
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.
METHODS
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.
RESULTS
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.
CONCLUSIONS
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.
背景
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。
方法
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。
结果
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。
结论
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。
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