{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T16:52:26Z","timestamp":1789404746283,"version":"build-2803163510"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background and Purpose\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Although plasma total homocysteine (tHcy) levels are associated with cardiovascular disease, it remains unclear whether homocysteine is a cause or a marker of atherosclerotic vascular disease. We determined whether reduction of tHcy levels with B vitamin supplementation reduces subclinical atherosclerosis progression.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    In this double-blind clinical trial, 506 participants 40 to 89 years of age with an initial tHcy &gt;8.5 \u03bcmol\/L without diabetes and cardiovascular disease were randomized to high-dose B vitamin supplementation (5 mg folic acid+0.4 mg vitamin B\n                    <jats:sub>12<\/jats:sub>\n                    +50 mg vitamin B\n                    <jats:sub>6<\/jats:sub>\n                    ) or matching placebo for 3.1 years. Subclinical atherosclerosis progression across 3 vascular beds was assessed using high-resolution B-mode ultrasonography to measure carotid artery intima media thickness (primary outcome) and multidetector spiral CT to measure aortic and coronary artery calcium (secondary outcome).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Although the overall carotid artery intima media thickness progression rate was lower with B vitamin supplementation than with placebo, statistically significant between-group differences were not found (\n                    <jats:italic>P<\/jats:italic>\n                    =0.31). However, among subjects with baseline tHcy \u22659.1 \u03bcmol\/L, those randomized to B vitamin supplementation had a statistically significant lower average rate of carotid artery intima media thickness progression compared with placebo (\n                    <jats:italic>P<\/jats:italic>\n                    =0.02); among subjects with a baseline tHcy &lt;9.1 \u03bcmol\/L, there was no significant treatment effect (probability value for treatment interaction=0.02). B vitamin supplementation had no effect on progression of aortic or coronary artery calcification overall or within subgroups.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusion\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    High-dose B vitamin supplementation significantly reduces progression of early-stage subclinical atherosclerosis (carotid artery intima media thickness) in well-nourished healthy B vitamin \u201creplete\u201d individuals at low risk for cardiovascular disease with a fasting tHcy \u22659.1 \u03bcmol\/L.\n                  <\/jats:p>","DOI":"10.1161\/strokeaha.108.526798","type":"journal-article","created":{"date-parts":[[2008,12,31]],"date-time":"2008-12-31T20:44:40Z","timestamp":1230756280000},"page":"730-736","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":107,"title":["High-Dose B Vitamin Supplementation and Progression of Subclinical Atherosclerosis"],"prefix":"10.1161","volume":"40","author":[{"given":"Howard N.","family":"Hodis","sequence":"first","affiliation":[{"name":"From the Atherosclerosis Research Unit (H.N.H., W.J.M., L.D., S.P.A., C.-r.L., C.-h.L., J.H., R.H.S.), the Department of Preventive Medicine (H.N.H., W.J.M., L.D., S.P.A.), the Department of Medicine (H.N.H., C.-r.L., C.-h.L.), and the Department of Radiology (A.G.W.), University of Southern California, Keck School of Medicine, Los Angeles, Calif; the Department of Molecular Pharmacology and Toxicology (H.N.H., J.H.), University of Southern California, School of Pharmacy, Los Angeles, Calif; Kaiser..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy J.","family":"Mack","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (H.N.H., W.J.M., L.D., S.P.A., C.-r.L., C.-h.L., J.H., R.H.S.), the Department of Preventive Medicine (H.N.H., W.J.M., L.D., S.P.A.), the Department of Medicine (H.N.H., C.-r.L., C.-h.L.), and the Department of Radiology (A.G.W.), University of Southern California, Keck School of Medicine, Los Angeles, Calif; the Department of Molecular Pharmacology and Toxicology (H.N.H., J.H.), University of Southern California, School of Pharmacy, Los Angeles, Calif; Kaiser..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie","family":"Dustin","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (H.N.H., W.J.M., L.D., S.P.A., C.-r.L., C.-h.L., J.H., R.H.S.), the Department of Preventive Medicine (H.N.H., W.J.M., L.D., S.P.A.), the Department of Medicine (H.N.H., C.-r.L., C.-h.L.), and the Department of Radiology (A.G.W.), University of Southern California, Keck School of Medicine, Los Angeles, Calif; the Department of Molecular Pharmacology and Toxicology (H.N.H., J.H.), University of Southern California, School of Pharmacy, Los Angeles, Calif; Kaiser..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Mahrer","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (H.N.H., W.J.M., L.D., S.P.A., C.-r.L., C.-h.L., J.H., R.H.S.), the Department of Preventive Medicine (H.N.H., W.J.M., L.D., S.P.A.), the Department of Medicine (H.N.H., C.-r.L., C.-h.L.), and the Department of Radiology (A.G.W.), University of Southern California, Keck School of Medicine, Los Angeles, Calif; the Department of Molecular Pharmacology and Toxicology (H.N.H., J.H.), University of Southern California, School of Pharmacy, Los Angeles, Calif; Kaiser..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley P.","family":"Azen","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (H.N.H., W.J.M., L.D., S.P.A., C.-r.L., C.-h.L., J.H., R.H.S.), the Department of Preventive Medicine (H.N.H., W.J.M., L.D., S.P.A.), the Department of Medicine (H.N.H., C.-r.L., C.-h.L.), and the Department of Radiology (A.G.W.), University of Southern California, Keck School of Medicine, Los Angeles, Calif; the Department of Molecular Pharmacology and Toxicology (H.N.H., J.H.), University of Southern California, School of Pharmacy, Los Angeles, Calif; Kaiser..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Detrano","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (H.N.H., W.J.M., L.D., S.P.A., C.-r.L., C.-h.L., J.H., R.H.S.), the Department of Preventive Medicine (H.N.H., W.J.M., L.D., S.P.A.), the Department of Medicine (H.N.H., C.-r.L., C.-h.L.), and the Department of Radiology (A.G.W.), University of Southern California, Keck School of Medicine, Los Angeles, Calif; the Department of Molecular Pharmacology and Toxicology (H.N.H., J.H.), University of Southern California, School of Pharmacy, Los Angeles, Calif; Kaiser..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Selhub","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (H.N.H., W.J.M., L.D., S.P.A., C.-r.L., C.-h.L., J.H., R.H.S.), the Department of Preventive Medicine (H.N.H., W.J.M., L.D., S.P.A.), the Department of Medicine (H.N.H., C.-r.L., C.-h.L.), and the Department of Radiology (A.G.W.), University of Southern California, Keck School of Medicine, Los Angeles, Calif; the Department of Molecular Pharmacology and Toxicology (H.N.H., J.H.), University of Southern California, School of Pharmacy, Los Angeles, Calif; Kaiser..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petar","family":"Alaupovic","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (H.N.H., W.J.M., L.D., S.P.A., C.-r.L., C.-h.L., J.H., R.H.S.), the Department of Preventive Medicine (H.N.H., W.J.M., L.D., S.P.A.), the Department of Medicine (H.N.H., C.-r.L., C.-h.L.), and the Department of Radiology (A.G.W.), University of Southern California, Keck School of Medicine, Los Angeles, Calif; the Department of Molecular Pharmacology and Toxicology (H.N.H., J.H.), University of Southern California, School of Pharmacy, Los Angeles, Calif; Kaiser..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-ran","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (H.N.H., W.J.M., L.D., S.P.A., C.-r.L., C.-h.L., J.H., R.H.S.), the Department of Preventive Medicine (H.N.H., W.J.M., L.D., S.P.A.), the Department of Medicine (H.N.H., C.-r.L., C.-h.L.), and the Department of Radiology (A.G.W.), University of Southern California, Keck School of Medicine, Los Angeles, Calif; the Department of Molecular Pharmacology and Toxicology (H.N.H., J.H.), University of Southern California, School of Pharmacy, Los Angeles, Calif; Kaiser..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ci-hua","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (H.N.H., W.J.M., L.D., S.P.A., C.-r.L., C.-h.L., J.H., R.H.S.), the Department of Preventive Medicine (H.N.H., W.J.M., L.D., S.P.A.), the Department of Medicine (H.N.H., C.-r.L., C.-h.L.), and the Department of Radiology (A.G.W.), University of Southern California, Keck School of Medicine, Los Angeles, Calif; the Department of Molecular Pharmacology and Toxicology (H.N.H., J.H.), University of Southern California, School of Pharmacy, Los Angeles, Calif; Kaiser..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Hwang","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (H.N.H., W.J.M., L.D., S.P.A., C.-r.L., C.-h.L., J.H., R.H.S.), the Department of Preventive Medicine (H.N.H., W.J.M., L.D., S.P.A.), the Department of Medicine (H.N.H., C.-r.L., C.-h.L.), and the Department of Radiology (A.G.W.), University of Southern California, Keck School of Medicine, Los Angeles, Calif; the Department of Molecular Pharmacology and Toxicology (H.N.H., J.H.), University of Southern California, School of Pharmacy, Los Angeles, Calif; Kaiser..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison G.","family":"Wilcox","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (H.N.H., W.J.M., L.D., S.P.A., C.-r.L., C.-h.L., J.H., R.H.S.), the Department of Preventive Medicine (H.N.H., W.J.M., L.D., S.P.A.), the Department of Medicine (H.N.H., C.-r.L., C.-h.L.), and the Department of Radiology (A.G.W.), University of Southern California, Keck School of Medicine, Los Angeles, Calif; the Department of Molecular Pharmacology and Toxicology (H.N.H., J.H.), University of Southern California, School of Pharmacy, Los Angeles, Calif; Kaiser..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert H.","family":"Selzer","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit (H.N.H., W.J.M., L.D., S.P.A., C.-r.L., C.-h.L., J.H., R.H.S.), the Department of Preventive Medicine (H.N.H., W.J.M., L.D., S.P.A.), the Department of Medicine (H.N.H., C.-r.L., C.-h.L.), and the Department of Radiology (A.G.W.), University of Southern California, Keck School of Medicine, Los Angeles, Calif; 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