Trials That Matter: Should We Routinely Measure Homocysteine Levels and “Treat” Mild Hyperhomocysteinemia?
Authors: Irwin H. Rosenberg, Cynthia D. Mulrow
Journal: Annals of Internal Medicine (2006)

Editorials1 August 2006Trials That Matter: Should We Routinely Measure Homocysteine Levels and “Treat” Mild Hyperhomocysteinemia?Irwin H. Rosenberg, MD and Cynthia D. Mulrow, MD, MSc, Deputy EditorIrwin H. Rosenberg, MDFrom U.S. Department of Agriculture Jean Mayer Human Nutrition Research Center on Aging, Boston, MA 02111, and American College of Physicians, Philadelphia, PA 19106.Search for more papers by this author and Cynthia D. Mulrow, MD, MSc, Deputy EditorFrom U.S. Department of Agriculture Jean Mayer Human Nutrition Research Center on Aging, Boston, MA 02111, and American College of Physicians, Philadelphia, PA 19106.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-145-3-200608010-00011 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Several observational studies involving healthy populations in the 1990s showed positive associations between elevated homocysteine level and increased risk for ischemic heart disease and stroke (1). Several small trials conducted in western populations in the early and mid-1990s suggested that “daily supplementation with both 0.5-5 mg folic acid and about 0.5 mg vitamin B-12 would be expected to reduce blood homocysteine concentrations by about a quarter to a third (for example, from about 12 µmol/l to 8-9 µmol/l)” (2). In 1998, the U.S. Food and Drug Administration mandated fortification of enriched cereal grain flour products with 140 µg of folic ...References1. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA. 2002;288:2015-22. [PMID: 12387654] CrossrefMedlineGoogle Scholar2. Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomised trials. Homocysteine Lowering Trialists' Collaboration. BMJ. 1998;316:894-8. [PMID: 9569395] CrossrefMedlineGoogle Scholar3. Food standards: amendment of standards of identity for enriched grain products to require addition of folic acid. Federal Register. 1996;61:8781-97. Google Scholar4. Bostom AG, Selhub J, Jacques PF, Rosenberg IH. Power Shortage: clinical trials testing the “homocysteine hypothesis” against a background of folic acid-fortified cereal grain flour. Ann Intern Med. 2001;135:133-7. [PMID: 11453713] LinkGoogle Scholar5. Yang Q, Botto LD, Erickson JD, Berry RJ, Sambell C, Johansen H, et al. Improvement in stroke mortality in Canada and the United States, 1990 to 2002. Circulation. 2006;113:1335-43. [PMID: 16534029] CrossrefMedlineGoogle Scholar6. Toole JF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC, Howard VJ, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized, controlled trial. JAMA. 2004;291:565-75. [PMID: 14762035] CrossrefMedlineGoogle Scholar7. Lonn E, Yusuf S, Arnold MJ, Sheridan P, Pogue J, Micks M, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354:1567-77. [PMID: 16531613] CrossrefMedlineGoogle Scholar8. Bønaa KH, Njølstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006;354:1578-88. [PMID: 16531614] CrossrefMedlineGoogle Scholar9. Loscalzo J. Homocysteine trials—clear outcomes for complex reasons [Editorial]. N Engl J Med. 2006;354:1629-32. [PMID: 16531615] CrossrefMedlineGoogle Scholar10. Malinow MR, Bostom AG, Krauss RM. Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation. 1999;99:178-82. [PMID: 9884399] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAuthors: Irwin H. Rosenberg, MD; Cynthia D. Mulrow, MD, MSc, Deputy EditorAffiliations: From U.S. Department of Agriculture Jean Mayer Human Nutrition Research Center on Aging, Boston, MA 02111, and American College of Physicians, Philadelphia, PA 19106.Disclosures: Grants received: I.H. Rosenberg (National Institutes of Health).Corresponding Author: Cynthia D. Mulrow, MD, MSc, American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106.Current Author Addresses: Dr. Rosenberg: U.S. Department of Agriculture Jean Mayer Human Nutrition Research Center on Aging, 711 Washington Street, Boston, MA 02111.Dr. Mulrow: American College of Physicians, 190 N. Independence Mall West, Philadelphia, PA 19106. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoCorrection: Trials That Matter: Should We Routinely Measure Homocysteine Levels and “Treat” Mild Hyperhomocysteinemia? Metrics Cited byHomocysteine lowering and cardiovascular disease risk: Lost in translationThrombophilia and pregnancy complications: cause or association?Pregnancy Failure and Heritable ThrombophiliaCorrection: Trials That Matter: Should We Routinely Measure Homocysteine Levels and “Treat” Mild Hyperhomocysteinemia?Inherited thrombophilia and early pregnancy 1 August 2006Volume 145, Issue 3Page: 226-227KeywordsAttentionBlood plasmaCardiovascular disease riskCardiovascular therapyFolic acidMyocardial infarctionPopulation statisticsRelative riskStrokeVascular diseases ePublished: 1 August 2006 Issue Published: 1 August 2006 Copyright & PermissionsCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...