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Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy)
Huang, Xiao Bao, Huihui Ding, Congcong Li, Junpei Cao, Tianyu Liu, Lishun Wei, Yaping Zhou, Ziyi Zhang, Nan Song, Yun
Huang, Xiao
Bao, Huihui
Ding, Congcong
Li, Junpei
Cao, Tianyu
Liu, Lishun
Wei, Yaping
Zhou, Ziyi
Zhang, Nan
Song, Yun
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Journal article
Date
2024-03-13
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Microbiology, Immunology and Inflammation
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DOI
https://doi.org/10.1007/s00394-024-03344-8
Abstract
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.
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Citation
Huang, X., Bao, H., Ding, C. et al. Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy). Eur J Nutr 63, 1513–1528 (2024). https://doi.org/10.1007/s00394-024-03344-8
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Springer Science and Business Media
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European Journal of Nutrition, Vol. 63, Iss. 5
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