The American Journal of Medicine
Volume 116, Issue 3 , Pages 158-164 , 1 February 2004

Effect of folic acid fortification of food on homocysteine-related mortality

  • Jeffrey L Anderson, MD

      Affiliations

    • Corresponding Author InformationRequests for reprints should be addressed to Jeffrey L. Anderson, MD, Cardiovascular Department, LDS Hospital, 8th Avenue and C Street, Salt Lake City, Utah 84143, USA
    • Cardiovascular Department, LDS Hospital, and University of Utah, Salt Lake City, Utah, USA
    • ,
  • Kurt R Jensen, MS

      Affiliations

    • Cardiovascular Department, LDS Hospital, and University of Utah, Salt Lake City, Utah, USA
    • ,
  • John F Carlquist, PhD

      Affiliations

    • Cardiovascular Department, LDS Hospital, and University of Utah, Salt Lake City, Utah, USA
    • ,
  • Tami L Bair

      Affiliations

    • Cardiovascular Department, LDS Hospital, and University of Utah, Salt Lake City, Utah, USA
    • ,
  • Benjamin D Horne, MStat, MPH

      Affiliations

    • Cardiovascular Department, LDS Hospital, and University of Utah, Salt Lake City, Utah, USA
    • ,
  • Joseph B Muhlestein, MD

      Affiliations

    • Cardiovascular Department, LDS Hospital, and University of Utah, Salt Lake City, Utah, USA

References 

  1. Finkelstein JD. The metabolism of homocysteine (pathways and regulation). Eur J Pediatr. 1998;154(suppl 2):S40–S44
  2. Eikelboom JW, Lonn E, Genest JJ, Hankey G, Yusuf S. Homocyst(e)ine and cardiovascular disease (a critical review of the epidemiologic evidence). Ann Intern Med. 1999;131:363–375
  3. Bellamy MF, McDowell IFW, Ramsey MW, et al.  Hyperhomocysteinemia after an oral methionine load acutely impairs endothelial function in healthy adults. Circulation. 1998;98:1848–1852
  4. Nappo F, DeRosa N, Marfella R, et al.  Impairment of endothelial functions by acute hyperhomocysteinemia and reversal by antioxidant vitamins. JAMA. 1999;281:2113–2118
  5. Graham I. Homocysteine in health and disease. [editorial] Ann Intern Med. 1999;131:387–388
  6. Boushey CJ, Beresford SA, Omenn GS, Motuldy AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease (probable benefits of increasing folic acid intakes). JAMA. 1995;274:1049–1057
  7. Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med. 1997;337:230–236
  8. Anderson JL, Muhlestein JB, Horne BJ, et al.  Plasma homocysteine predicts mortality independently of traditional risk factors and C-reactive protein in patients with angiographically-defined coronary artery disease. Circulation. 2000;102:1227–1232
  9. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease (evidence on causality from a meta-analysis). BMJ. 2002;325:1202–1209
  10. Homocysteine Lowering Trialists' Collaborative Group . Lowering blood homocysteine with folic acid based supplements (meta-analysis of randomised trials). BMJ. 1998;316:894–898
  11. Foulke J. Folic Acid to Fortify U.S. Food Products to Prevent Birth Defects. [press release] Washington, D.C: U.S. Food and Drug Administration; 1996;
  12. Anderson JL, Horne BD, Carlquist JF, et al.  Effect of implementation of folic acid fortification of food on homocysteine concentrations in subjects with coronary artery disease. Am J Cardiol. 2002;90:536–539
  13. Taylor GS, Muhlestein JB, Wagner GS, Bair TL, Li P, Anderson JL. Implementation of a computerized cardiovascular information system in a private hospital setting. Am Heart J. 1998;136:792–803
  14. Ubbink JB, Vermaak WJ, van der Merwe A, Becker PJ. Vitamin B-12, vitamin B-6, and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr. 1993;57:47–53
  15. Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA. 1993;270:2693–2698
  16. Malinow MR, Duell PB, Hess DL, et al.  Reduction of plasma homocysteine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. N Engl J Med. 1998;338:1009–1015
  17. Lawrence JM, Petitti DB, Watkins M, Umekubo MA. Trends in serum folate after food fortification. [research letter] Lancet. 1999;354:915–916
  18. Komoromy-Hiller G, Nuttall KL. Folic acid fortification. [letter] Lancet. 1999;354:2167–2168
  19. Chasan-Taber L, Selhub J, Rosenberg IH, et al.  A prospective study of folate and vitamin B6 and risk of myocardial infarction in US physicians. J Am Coll Nutr. 1996;15:136–143
  20. Den Heijer M, Brouwer IA, Bos GM, et al.  Vitamin supplementation reduces blood homocysteine levels (a controlled trial in patients with venous thrombosis and healthy volunteers). Arterioscler Thromb Vasc Biol. 1998;18:356–361
  21. Jacques PF, Selhub J, Bostom AG, Wilson PW, Rosenberg IH. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med. 1999;340:1449–1454
  22. Stubbs PJ, Al-Obaidi MK, Conroy RM, Collinson PO, Graham IM, Noble MIM. Effect of plasma homocysteine concentration on early and late events in patients with acute coronary syndromes. Circulation. 2000;102:605–610
  23. Schnyder G, Flammer Y, Roffi M, Pin R, Hess OM. Plasma homocysteine levels and late outcome after coronary angioplasty. J Am Coll Cardiol. 2002;40:1769–1776
  24. Hoogeveen EK, Kostense PJ, Jakobs C, et al.  Hyperhomocysteinemia increases risk of death, especially in type 2 diabetes. Circulation. 2000;101:1506–1511
  25. Cleophas TJ, Hornstra M, van Hoogstraten B, van der Meulen J. Homocysteine, a risk factor for coronary artery disease or not? A meta-analysis. Am J Cardiol. 2000;86:1005–1009
  26. The Homocysteine Studies Collaboration . Homocysteine and risk of ischemic heart disease and stroke. A meta-analysis. JAMA. 2002;288:2015–2022
  27. Klerk M, Verhoef P, Clarke R, et al.  MTHFR 677C–T polymorphism and risk of coronary heart disease. A meta-analysis. JAMA. 2002;288:2023–2031
  28. Virdis A, Ghiadoni L, Cardinal H, et al.  Mechanisms responsible for endothelial dysfunction induced by fasting hyperhomocystinemia in normotensive subjects and patients with essential hypertension. J Am Coll Cardiol. 2001;38:1106–1115
  29. Doshi SN, McDowell IFW, Moat SJ, et al.  Folic acid improves endothelial function in coronary artery disease via mechanisms largely independent of homocysteine lowering. Circulation. 2002;105:22–26
  30. 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;5:249–255

☆ This study was supported by a grant from the Deseret Foundation, Salt Lake City, Utah, and an in-kind grant from Abbott Diagnostics, Abbott Park, Illinois.

PII: S0002-9343(03)00690-9

doi: 10.1016/j.amjmed.2003.10.024

The American Journal of Medicine
Volume 116, Issue 3 , Pages 158-164 , 1 February 2004

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