Homocysteine in Health and Disease

Editorials7 September 1999Homocysteine in Health and DiseaseIan Graham, FRCPI, FCCPIan Graham, FRCPI, FCCPRoyal College of Surgeons in Ireland and Trinity College; Dublin, Ireland (Graham)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-131-5-199909070-00010 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Is an elevated plasma homocysteine level bad for you? Homocystinuria, the consequence of a severely elevated plasma homocysteine level of genetic origin, was first described in 1962 (1, 2). Patients with homocystinuria frequently experience thromboembolic events. Thirty years ago, McCully (3) noted that several different metabolic defects were characterized by two common factors: homocystinuria and premature thromboembolic disease. This implied that the elevated plasma levels of homocysteine, rather than any other metabolite, was the cause. With this information, McCully and Wilson evolved the homocysteine theory of arteriosclerosis (4), from which it has been suggested that a moderately elevated plasma homocysteine ...References1. Carson NA, Neill DW. Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland. Arch Dis Child. 1962;37:505-13. CrossrefMedlineGoogle Scholar2. Gerritsen T, Vaughan JG, Waisman HA. The identification of homocysteine in the urine. Biochem Biophys Res Commun. 1962;9:493-6. CrossrefMedlineGoogle Scholar3 McCully KS. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol. 1969;56:111-28. MedlineGoogle Scholar4. McCully KS, Wilson RB. Homocysteine theory of arteriosclerosis. Atherosclerosis. 1975;22:215-27. CrossrefMedlineGoogle Scholar5. Refsum H, Ueland PM, Nygård O, Vollset SE. Homocysteine and cardiovascular disease. Annu Rev Med. 1998;49:31-62. CrossrefMedlineGoogle Scholar6. Wilcken DE. Novel risk factors for vascular disease: the homocysteine hypothesis of cardiovascular disease. J Cardiovasc Risk. 1998;5:217-21. CrossrefMedlineGoogle Scholar7. Boushey C, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA. 1995;274:1049-57. CrossrefMedlineGoogle Scholar8. Danesh J, Lewington S. Plasma homocysteine and coronary heart disease: systematic review of published epidemiological studies. J Cardiovasc Risk. 1998;5:229-32. CrossrefMedlineGoogle Scholar9. Kark JD, Selhub J, Adler B, Gofin J, Abramson JH, Friedman G, et al . Nonfasting plasma total homocysteine level and mortality in middle-aged and elderly men and women in Jerusalem. Ann Intern Med. 1999;131:321-30. LinkGoogle Scholar10. Bostom AG, Silbershatz H, Rosenberg IH, Selhub J, D'Agostino RB, Wolf PA, et al . Nonfasting plasma total homocysteine levels and all-cause and cardiovascular disease mortality in elderly Framingham men and women. Arch Intern Med. 1999;159:1077-80. CrossrefMedlineGoogle Scholar11. Eikelboom JW, Lonn E, Genest J, Hankey G, Yusuf S. Homocyst(e)ine and cardiovascular disease: a critical review of the epidemiologic evidence. Ann Intern Med. 1999;131:363-75. LinkGoogle Scholar12. Graham IM, Daly LE, Refsum IM, Robinson K, Brattström LE, Ueland PM, et al . Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project. JAMA. 1997;277:1775-81. CrossrefMedlineGoogle Scholar13. Selhub J, Jacques PF, Rosenberg IH, Rogers G, Bowman BA, Gunter EW, et al . Serum total homocysteine concentrations in the Third National Health and Nutrition Examination Survey (1991–1994): population reference ranges and contribution of vitamin status to high serum concentrations. Ann Intern Med. 1999;131:331-9. LinkGoogle Scholar14. Meleady RA, Graham IM. Homocysteine and vascular disease: nature or nurture? J Cardiovasc Risk. 1998;5:233-7. CrossrefMedlineGoogle Scholar15. Clarke R, Collins R. Can dietary supplements with folic acid or vitamin B6 reduce cardiovascular risk? Design of clinical trials to test the homocysteine hypothesis of vascular disease. J Cardiovasc Risk. 1998;5:249-55. CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: Royal College of Surgeons in Ireland and Trinity College; Dublin, Ireland (Graham)Corresponding Author: Ian Graham, FRCPI, FCCP, The Charlemont Clinic, Charlemont Mall, Dublin 2, Ireland. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoNonfasting Plasma Total Homocysteine Level and Mortality in Middle-Aged and Elderly Men and Women in Jerusalem Jeremy D. Kark , Jacob Selhub , Bella Adler , Jaime Gofin , Joseph H. Abramson , Gideon Friedman , and Irwin H. Rosenberg Serum Total Homocysteine Concentrations in the Third National Health and Nutrition Examination Survey (1991–1994): Population Reference Ranges and Contribution of Vitamin Status to High Serum Concentrations Jacob Selhub , Paul F. Jacques , Irwin H. Rosenberg , Gail Rogers , Barbara A. Bowman , Elaine W. Gunter , Jacqueline D. Wright , and Clifford L. Johnson Homocyst(e)ine and Cardiovascular Disease: A Critical Review of the Epidemiologic Evidence John W. 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