Chen Ping, Tang Linlin, Song Yun, Wang Binyan, Qin Xianhui, Zhang Nan, Wei Yaping, Xu Xiping, Zhou Ziyi, He Qiangqiang, Liu Lishun, Siddiqi Sultan Mehmood, Huang Xiao, Cheng Xiaoshu, Tang Genfu, Duan Yong, Zhou Houqing, Jiang Jie, Li Sha
College of Pharmacy, Jinan University, Guangzhou, China.
State Key Laboratory of Natural Medicines, Research Center of Biostatistics and Computational Pharmacy, China Pharmaceutical University, Nanjing, China.
Front Nutr. 2023 Sep 14;10:1191610. doi: 10.3389/fnut.2023.1191610. eCollection 2023.
There is growing concern regarding elevated levels of circulating unmetabolized folic acid (UMFA) due to excessive intake of folic acid (FA). However, no randomized clinical trial has been conducted to examine the FA-UMFA dose-response relationship.
This study aimed to investigate the FA-UMFA dose-response relationship in Chinese adults with hypertension and elevated homocysteine (H-type hypertension), a population with clear clinical indication for FA treatment.
The data for this study were derived from a randomized, double-blind, multicenter clinical trial of 8 FA dosages on efficacy of homocysteine (Hcy) lowering. The parent trial had three 3 stages: screening period (2-10 days), run-in period (0-2 weeks, baseline visit), and double-blind treatment period (8 weeks) with follow-up visits at the end of the 2nd, 4th, 6th, and 8th weeks of treatment. Participants were randomly assigned to 8 treatment groups corresponding to FA dosages of 0, 0.4, 0.6, 0.8, 1.2, 1.6, 2.0 mg to 2.4 mg.
This study included 1,567 Chinese adults aged ≥45 years with H-type hypertension. There was a positive but non-linear association between FA supplementation and UMFA levels in the dosage range of 0 mg to 2.4 mg. In the regression analysis, the coefficients for the linear and quadratic terms of FA dosage were both statistically significant ( < 0.001). Notably, the slope for UMFA was greater for FA dosages >0.8 mg (ß = 11.21, 95% CI: 8.97, 13.45) compared to FA dosages ≤0.8 mg (ß = 2.94, 95% CI: 2.59, 3.29). Furthermore, FA dosages higher than 0.8 mg did not confer additional benefits in terms of increasing 5-methyl tetrahydrofolic acid (5-MTHF, active form of folate) or reducing homocysteine (Hcy).
In Chinese adults with H-type hypertension, this study showed a positive, non-linear, dosage-response relationship between FA supplementation ranging from 0 to 2.4 mg and circulating UMFA levels. It revealed that 0.8 mg FA is an optimal dosage in terms of balancing efficacy (increasing 5-MTHF and lowering Hcy) while minimizing undesirable elevation of UMFA.
https://clinicaltrials.gov/ct2/show/NCT03472508?term=NCT03472508&draw=2&rank=1, identifier NCT03472508.
由于叶酸（FA）摄入过量，循环中未代谢叶酸（UMFA）水平升高引发了越来越多的关注。然而，尚未进行随机临床试验来研究FA与UMFA的剂量反应关系。
本研究旨在探讨中国高血压合并高同型半胱氨酸血症成人（H型高血压）中FA与UMFA的剂量反应关系，这是一类有明确FA治疗临床指征的人群。
本研究数据来源于一项关于8种FA剂量降低同型半胱氨酸（Hcy）疗效的随机、双盲、多中心临床试验。母试验有三个阶段：筛查期（2 - 10天）、导入期（0 - 2周，基线访视）和双盲治疗期（8周），在治疗的第2、4、6和8周结束时进行随访。参与者被随机分配到8个治疗组，对应FA剂量分别为0、0.4、0.6、0.8、1.2、1.6、2.0毫克至2.4毫克。
本研究纳入了1567名年龄≥45岁的中国H型高血压成人。在0毫克至2.4毫克的剂量范围内，FA补充与UMFA水平之间存在正相关但非线性关系。在回归分析中，FA剂量的线性和二次项系数均具有统计学意义（<0.001）。值得注意的是，与FA剂量≤0.8毫克（ß = 2.94，95%CI：2.59，3.29）相比，FA剂量>0.8毫克时UMFA的斜率更大（ß = 11.21，95%CI：8.97，13.45）。此外，高于0.8毫克的FA剂量在增加5 - 甲基四氢叶酸（5 - MTHF，叶酸的活性形式）或降低同型半胱氨酸（Hcy）方面没有带来额外益处。
在患有H型高血压的中国成年人中，本研究表明0至2.4毫克范围内的FA补充与循环UMFA水平之间存在正的、非线性的剂量反应关系。研究表明，就平衡疗效（增加5 - MTHF和降低Hcy）同时最小化UMFA的不良升高而言，0.8毫克FA是最佳剂量。
https://clinicaltrials.gov/ct2/show/NCT03472508?term=NCT03472508&draw=2&rank=1，标识符NCT03472508。
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