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Therefore, this study aimed to explore the efficacy of eight different FA dosages on tHcy lowering in the overall sample and by <jats:italic>MTHFR C677T<\/jats:italic> genotypes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This multicentered, randomized, double-blind, controlled clinical trial included 2697 eligible hypertensive adults with elevated tHcy (\u2265\u200910\u00a0mmol\/L) and without history of stroke and cardiovascular disease. Participants were randomized into eight dose groups of FA combined with 10\u00a0mg enalapril maleate, taken daily for 8\u00a0weeks of treatment.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>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\u20131.2\u00a0mg. However, a plateau in tHcy lowering was observed in FA dose range of 1.2\u20131.6\u00a0mg, 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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>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\u00a0mg, and only has a small gain by increasing the dosage from 0.8 to 1.2\u00a0mg.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>ClinicalTrials.gov Identifier<\/jats:title>\n                <jats:p>NCT03472508 (Registration Date: March 21, 2018).<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00394-024-03344-8","type":"journal-article","created":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T08:32:07Z","timestamp":1710318727000},"page":"1513-1528","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Optimal folic acid dosage in lowering homocysteine: Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy)"],"prefix":"10.1007","volume":"63","clinical-trial-number":[{"clinical-trial-number":"nct03472508","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0686-6318","authenticated-orcid":false,"given":"Xiao","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huihui","family":"Bao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congcong","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junpei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyu","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lishun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaping","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chongfei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liling","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianhui","family":"Qin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ningling","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genfu","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaobin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Huo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoshu","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Precision Folic Acid Trial to lower homocysteine (PFAT-Hcy) Trial Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,13]]},"reference":[{"key":"3344_CR1","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s10194-016-0652-7","volume":"17","author":"S Menon","year":"2016","unstructured":"Menon S, Nasir B, Avgan N et al (2016) The effect of 1 mg folic acid supplementation on clinical outcomes in female migraine with aura patients. 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Dr. Xiaoshu Cheng reports grant from the Jiangxi Science and Technology Innovation Platform Project (20165BCD41005). All other authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}