TY - JOUR
T1 - Optimal folic acid dosage in lowering homocysteine
T2 - Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy)
AU - Huang, Xiao
AU - Bao, Huihui
AU - Ding, Congcong
AU - Li, Junpei
AU - Cao, Tianyu
AU - Liu, Lishun
AU - Wei, Yaping
AU - Zhou, Ziyi
AU - Zhang, Nan
AU - Song, Yun
AU - Chen, Ping
AU - Jiang, Chongfei
AU - Xie, Liling
AU - Qin, Xianhui
AU - Zhang, Yan
AU - Li, Jianping
AU - Sun, Ningling
AU - Tang, Genfu
AU - Wang, Xiaobin
AU - Wang, Hong
AU - Huo, Yong
AU - Cheng, Xiaoshu
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/8
Y1 - 2024/8
N2 - BACKGROUND: While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes.METHODS: This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment.RESULTS: The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0-1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2-1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering.CONCLUSIONS: This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg.GOV IDENTIFIER: NCT03472508 (Registration Date: March 21, 2018).
AB - BACKGROUND: While folic acid (FA) is widely used to treat elevated total homocysteine (tHcy), promoting vascular health by reducing vascular oxidative stress and modulating endothelial nitric oxide synthase, the optimal daily dose and individual variation by MTHFR C677T genotypes have not been well studied. Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by MTHFR C677T genotypes.METHODS: This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (≥ 10 mmol/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10 mg enalapril maleate, taken daily for 8 weeks of treatment.RESULTS: The intent to treat analysis included 2163 participants. In the overall sample, increasing FA dosage led to steady tHcy reduction within the FA dosing range of 0-1.2 mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2-1.6 mg, indicating a ceiling effect. In contrast, FA doses were positively and linearly associated with serum folate levels without signs of plateau. Among MTHFR genotype subgroups, participants with the TT genotype showed greater efficacy of FA in tHcy lowering.CONCLUSIONS: This randomized trial lent further support to the efficacy of FA in lowering tHcy; more importantly, it provided critically needed evidence to inform optimal FA dosage. We found that the efficacy of FA in lowering tHcy reaches a plateau if the daily dosage exceeds 1.2 mg, and only has a small gain by increasing the dosage from 0.8 to 1.2 mg.GOV IDENTIFIER: NCT03472508 (Registration Date: March 21, 2018).
KW - Folic acid
KW - Homocysteine
KW - MTHFR C677T genotypes
KW - Optimal dosage
KW - Enalapril/administration & dosage
KW - Double-Blind Method
KW - Humans
KW - Middle Aged
KW - Male
KW - Genotype
KW - Dose-Response Relationship, Drug
KW - Hyperhomocysteinemia/drug therapy
KW - Folic Acid/administration & dosage
KW - Methylenetetrahydrofolate Reductase (NADPH2)/genetics
KW - Female
KW - Adult
KW - Homocysteine/blood
KW - Aged
KW - Hypertension/drug therapy
UR - http://www.scopus.com/inward/record.url?scp=85187673892&partnerID=8YFLogxK
U2 - 10.1007/s00394-024-03344-8
DO - 10.1007/s00394-024-03344-8
M3 - Article
C2 - 38478042
AN - SCOPUS:85187673892
SN - 1436-6207
VL - 63
SP - 1513
EP - 1528
JO - European Journal of Nutrition
JF - European Journal of Nutrition
IS - 5
ER -
