{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T17:48:25Z","timestamp":1793468905876,"version":"4.5.0"},"reference-count":50,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2018,6,5]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The aim of this study was to determine whether reducing plasma homocysteine concentrations with long\u2010term, combined treatment with folic acid, vitamin B\n              <jats:sub>6<\/jats:sub>\n              , and vitamin B\n              <jats:sub>12<\/jats:sub>\n              alters plasma biomarkers of inflammation and endothelial dysfunction in women at increased risk of cardiovascular disease.\n            <\/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              We conducted a blood substudy of 300 treatment\u2010adherent participants (150 in the active treatment group, 150 in the placebo group) in the WAFACS (Women's Antioxidant and Folic Acid Cardiovascular Study), a randomized, double\u2010blind, placebo\u2010controlled trial testing a daily combination of folic acid (2.5\u00a0mg), vitamin B\n              <jats:sub>6<\/jats:sub>\n              (50\u00a0mg), vitamin B\n              <jats:sub>12<\/jats:sub>\n              (1\u00a0mg), or matching placebo, in cardiovascular disease prevention among women at increased risk of cardiovascular disease. Plasma concentration of 3 biomarkers of inflammation (C\u2010reactive protein, interleukin\u20106, and fibrinogen) and a biomarker of endothelial dysfunction (intercellular adhesion molecule 1) were measured at baseline and at the end of treatment and follow\u2010up. After 7.3\u00a0years of combined treatment with folic acid, vitamin B\n              <jats:sub>6<\/jats:sub>\n              , and vitamin B\n              <jats:sub>12<\/jats:sub>\n              , homocysteine concentrations were reduced by 18% in the active treatment group as compared with the placebo group (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001). However, there was no difference between treatment groups in change in blood concentration from baseline to follow\u2010up for C\u2010reactive protein (\n              <jats:italic>P<\/jats:italic>\n              =0.77), interleukin\u20106 (\n              <jats:italic>P<\/jats:italic>\n              =0.91), intercellular adhesion molecule 1 (\n              <jats:italic>P<\/jats:italic>\n              =0.38), or fibrinogen (\n              <jats:italic>P<\/jats:italic>\n              =0.68).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              These findings indicate that long\u2010term, combined treatment with folic acid, vitamin B\n              <jats:sub>6<\/jats:sub>\n              , and vitamin B\n              <jats:sub>12<\/jats:sub>\n              lowers homocysteine concentrations, but does not alter major biomarkers of vascular inflammation, consistent with the lack of clinical cardiovascular disease benefit in the trial.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Clinical Trial Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              <jats:styled-content style=\"fixed-case\">URL<\/jats:styled-content>\n              :\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifier:\n              <jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>\n              00000541.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.117.008517","type":"journal-article","created":{"date-parts":[[2018,5,18]],"date-time":"2018-05-18T09:15:18Z","timestamp":1526634918000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":35,"title":["Effect of Combined Treatment With Folic Acid, Vitamin B\n            <sub>6<\/sub>\n            , and Vitamin B\n            <sub>12<\/sub>\n            on Plasma Biomarkers of Inflammation and Endothelial Dysfunction in Women"],"prefix":"10.1161","volume":"7","author":[{"given":"William G.","family":"Christen","sequence":"first","affiliation":[{"name":"Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy R.","family":"Cook","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Boston, MA"},{"name":"Department of Epidemiology, Harvard School of Public Health, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Van Denburgh","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine","family":"Zaharris","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine M.","family":"Albert","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Boston, MA"},{"name":"Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JoAnn E.","family":"Manson","sequence":"additional","affiliation":[{"name":"Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital Harvard Medical School, Boston, MA"},{"name":"Department of Epidemiology, Harvard School of Public Health, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1997.03540460039030"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1191\/1358863x02vm428ra"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.288.16.2015"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199804093381507"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.299.17.2027"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinternmed.2010.348"},{"key":"e_1_3_4_8_2","first-page":"CD006612","article-title":"Homocysteine\u2010lowering interventions for preventing cardiovascular events","volume":"1","author":"Marti\u2010Carvajal AJ","year":"2015","unstructured":"Marti\u2010Carvajal AJ, Sola I, Lathyris D. 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