{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T01:33:23Z","timestamp":1792892003665,"version":"4.5.0"},"reference-count":68,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2016,8,8]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Results from observational and genetic epidemiological studies suggest that lower serum homocysteine levels are associated with lower incidence of cardiovascular disease (CVD). Numerous randomized controlled trials have investigated the efficacy of lowering homocysteine with folic acid supplementation for CVD risk, but conflicting results have been reported.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Three bibliographic databases (Medline, Embase, and the Cochrane Database of Systematic Reviews) were searched from database inception until December 1, 2015. Of the 1933 references reviewed for eligibility, 30 randomized controlled trials involving 82\u00a0334 participants were included in the final analysis. The pooled relative risks of folic acid supplementation compared with controls were 0.90 (95% CI 0.84\u20130.96;\n              <jats:italic>P<\/jats:italic>\n              =0.002) for stroke, 1.04 (95% CI 0.99\u20131.09;\n              <jats:italic>P<\/jats:italic>\n              =0.16) for coronary heart disease, and 0.96 (95% CI 0.92\u20130.99;\n              <jats:italic>P<\/jats:italic>\n              =0.02) for overall CVD. The intervention effects for both stroke and combined CVD were more pronounced among participants with lower plasma folate levels at baseline (both\n              <jats:italic>P<\/jats:italic>\n              &lt;0.02 for interaction). In stratified analyses, a greater beneficial effect for overall CVD was seen in trials among participants without preexisting CVD (\n              <jats:italic>P<\/jats:italic>\n              =0.006 for interaction) or in trials with larger reduction in homocysteine levels (\n              <jats:italic>P<\/jats:italic>\n              =0.009 for interaction).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Our meta\u2010analysis indicated a 10% lower risk of stroke and a 4% lower risk of overall CVD with folic acid supplementation. A greater benefit for CVD was observed among participants with lower plasma folate levels and without preexisting CVD and in studies with larger decreases in homocysteine levels. Folic acid supplementation had no significant effect on risk of coronary heart disease.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.116.003768","type":"journal-article","created":{"date-parts":[[2016,8,16]],"date-time":"2016-08-16T00:33:41Z","timestamp":1471307621000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":234,"title":["Folic Acid Supplementation and the Risk of Cardiovascular Diseases: A Meta\u2010Analysis of Randomized Controlled Trials"],"prefix":"10.1161","volume":"5","author":[{"given":"Yanping","family":"Li","sequence":"first","affiliation":[{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianyi","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA"},{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tauland","family":"Muka","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna","family":"Troup","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank B.","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA"},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA"},{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","first-page":"111","article-title":"Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis","volume":"56","author":"McCully KS","year":"1969","unstructured":"McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. 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