Drugs & Aging

, Volume 23, Issue 6, pp 491–502 | Cite as

Homocysteine Lowering with Folic Acid and Vitamin B Supplements

Effects on Cardiovascular Disease in Older Adults
Review Article


Cardiovascular disease (CVD) is the leading cause of death in older men and women and contributes significantly to morbidity in later life. Folic acid and other vitamin B deficiencies and elevated total plasma homocysteine levels are associated with increased cardiovascular risk in geriatric patients, but recent studies have questioned the importance of these risk factors in older people. Data on the effects of homocysteine-lowering therapy (e.g. folic acid and vitamin B supplements) on surrogate CVD endpoints, such as atherosclerotic progression, endothelial function, inflammation and hypercoagulation, are conflicting. Findings from randomised clinical trials using clinical CVD outcomes show that folic acid and vitamin B supplements may not provide cardiovascular protection. Furthermore, these findings raise questions about whether the combination of folic acid and B vitamins may actually be harmful. Other large randomised clinical trials are underway to help clarify the role of folic acid and vitamin B supplements in CVD prevention in older people. Data to date do not support use of homocysteine-lowering therapies in either middle-aged or older adults.



The author was supported in part through the Beeson Career Development Award (1K23 AG026752–01), a grant jointly funded by the National Institute on Aging, the John A. Hartford Foundation, Atlantic Philanthropies and the Starr Foundation. The author has no conflicts of interest relevant to the contents of this review.


  1. 1.
    Thom T, Haase N, Rosamond W, et al. Heart disease and stroke statistics–2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee [published erratum appears in Circulation 2006; 113 (14): e696]. Circulation 2006; 113(6): e85–151PubMedCrossRefGoogle Scholar
  2. 2.
    Stein JH, Carlsson CM, Papcke-Benson K, et al. The effects of lipid-lowering and antioxidant vitamin therapies on flow-mediated vasodilation of the brachial artery in older adults with hypercholesterolemia. J Am Coll Cardiol 2001; 38: 1806–13PubMedCrossRefGoogle Scholar
  3. 3.
    Carlsson CM, Pharo LM, Aeschlimann SE, et al. Effects of multivitamins and low-dose folic acid supplements on flow-mediated vasodilation and plasma homocysteine levels in older adults. Am Heart J 2004; 148: E11PubMedCrossRefGoogle Scholar
  4. 4.
    Homocysteine Studies Collaboration. Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis. JAMA 2002; 288: 2015–22CrossRefGoogle Scholar
  5. 5.
    Bots ML, Launer LJ, Lindemans J, et al. Homocysteine and short-term risk of myocardial infarction and stroke in the elderly: the Rotterdam Study. Arch Intern Med 1999; 159: 38–44PubMedCrossRefGoogle Scholar
  6. 6.
    Whincup PH, Refsum H, Perry IJ, et al. Serum total homocysteine and coronary heart disease: prospective study in middle aged men. Heart 1999; 82: 448–54PubMedGoogle Scholar
  7. 7.
    Arnesen E, Refsum H, Bonaa KH, et al. Serum total homocysteine and coronary heart disease. Int J Epidemiol 1995; 24: 704–9PubMedCrossRefGoogle Scholar
  8. 8.
    Stehouwer CD, Weijenberg MP, van den Berg M, et al. Serum homocysteine and risk of coronary heart disease and cerebrovascular disease in elderly men: a 10-year follow-up. Arterioscler Thromb Vasc Biol 1998; 18: 1895–901PubMedCrossRefGoogle Scholar
  9. 9.
    Ubbink JB, Fehily AM, Pickering J, et al. Homocysteine and ischaemic heart disease in the Caerphilly cohort. Atherosclerosis 1998; 140: 349–56PubMedCrossRefGoogle Scholar
  10. 10.
    Wald NJ, Watt HC, Law MR, et al. Homocysteine and ischemic heart disease: results of a prospective study with implications regarding prevention. Arch Intern Med 1998; 158: 862–7PubMedCrossRefGoogle Scholar
  11. 11.
    Aronow WS, Ahn C, Schoenfeld MR. Association between plasma homocysteine and extracranial carotid arterial disease in older persons. Am J Cardiol 1997; 79: 1432–3PubMedCrossRefGoogle Scholar
  12. 12.
    Aronow WS, Ahn C, Gutstein H. Increased plasma homocysteine is an independent predictor of new atherothrombotic brain infarction in older persons. Am J Cardiol 2000; 86: 585–6, A10PubMedCrossRefGoogle Scholar
  13. 13.
    Aronow WS, Ahn C. Increased plasma homocysteine is an independent predictor of new coronary events in older persons. Am J Cardiol 2000; 86: 346–7PubMedCrossRefGoogle Scholar
  14. 14.
    Aronow WS, Ahn C. Association between plasma homocysteine and peripheral arterial disease in older persons. Coron Artery Dis 1998; 9: 49–50PubMedCrossRefGoogle Scholar
  15. 15.
    Moat SJ, Lang D, McDowell IF, et al. Folate, homocysteine, endothelial function and cardiovascular disease. J Nutr Biochem 2004; 15: 64–79PubMedCrossRefGoogle Scholar
  16. 16.
    Mattson MP, Kruman II, Duan W. Folic acid and homocysteine in age-related disease. Ageing Res Rev 2002; 1: 95–111PubMedCrossRefGoogle Scholar
  17. 17.
    Lucock M. Is folic acid the ultimate functional food component for disease prevention? BMJ 2004; 328: 211–4PubMedCrossRefGoogle Scholar
  18. 18.
    Lucock MD, Wild J, Smithells RW, et al. In vivo characterization of the absorption and biotransformation of pteroylmonoglutamic acid in man: a model for future studies. Biochem Med Metab Biol 1989; 42: 30–42PubMedCrossRefGoogle Scholar
  19. 19.
    Kelly P, McPartlin J, Goggins M, et al. Unmetabolized folic acid in serum: acute studies in subjects consuming fortified food and supplements. Am J Clin Nutr 1997; 65: 1790–5PubMedGoogle Scholar
  20. 20.
    Dierkes J, Westphal S. Effect of drugs on homocysteine concentrations. Semin Vasc Med 2005; 5: 124–39PubMedCrossRefGoogle Scholar
  21. 21.
    Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet 1999 Jul 31; 354(9176): 407–13PubMedCrossRefGoogle Scholar
  22. 22.
    Quinn K, Basu TK. Folate and vitamin B12 status of the elderly. Eur J Clin Nutr 1996; 50: 340–2PubMedGoogle Scholar
  23. 23.
    Russell RM, Krasinski SD, Samloff IM, et al. Folic acid malabsorption in atrophic gastritis: possible compensation by bacterial folate synthesis. Gastroenterology 1986; 91: 1476–82PubMedGoogle Scholar
  24. 24.
    Krasinski SD, Russell RM, Samloff IM, et al. Fundic atrophic gastritis in an elderly population: effect on hemoglobin and several serum nutritional indicators. J Am Geriatr Soc 1986; 34: 800–6PubMedGoogle Scholar
  25. 25.
    Selhub J. Folate, vitamin B12 and vitamin B6 and one carbon metabolism. J Nutr Health Aging 2002; 6: 39–42PubMedGoogle Scholar
  26. 26.
    Bostom AG, Silbershatz H, Rosenberg IH, 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: 1077–80PubMedCrossRefGoogle Scholar
  27. 27.
    Selhub J, Jacques PF, Wilson PW, et al. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 1993; 270: 2693–8PubMedCrossRefGoogle Scholar
  28. 28.
    Saw SM, Yuan JM, Ong CN, et al. Genetic, dietary, and other lifestyle determinants of plasma homocysteine concentrations in middle-aged and older Chinese men and women in Singapore. Am J Clin Nutr 2001; 73: 232–9PubMedGoogle Scholar
  29. 29.
    Zamboni M, Di Francesco V, Zoico E, et al. Homocysteine and life-style in the elderly. Aging (Milan) 2001; 13: 437–42Google Scholar
  30. 30.
    Hernanz A, Fernandez-Vivancos E, Montiel C, et al. Changes in the intracellular homocysteine and glutathione content associated with aging. Life Sci 2000; 67: 1317–24PubMedCrossRefGoogle Scholar
  31. 31.
    Kullo IJ, Ballantyne CM. Conditional risk factors for atherosclerosis. Mayo Clin Proc 2005; 80: 219–30PubMedCrossRefGoogle Scholar
  32. 32.
    Ortega RM, Jimenez A, Andres P, et al. Homocysteine levels in elderly Spanish people: influence of pyridoxine, vitamin B12 and folic acid intakes. J Nutr Health Aging 2002; 6: 69–71PubMedGoogle Scholar
  33. 33.
    Mudd SH, Skovby F, Levy HL, et al. The natural history of homocystinuria due to cystathionine beta-synthase deficiency. Am J Hum Genet 1985; 37: 1–31PubMedGoogle Scholar
  34. 34.
    Wang J, Dudman NP, Wilcken DE, et al. Homocysteine catabolism: levels of 3 enzymes in cultured human vascular endothelium and their relevance to vascular disease. Atherosclerosis 1992; 97: 97–106PubMedCrossRefGoogle Scholar
  35. 35.
    Dekou V, Whincup P, Papacosta O, et al. The effect of the C677T and A1298C polymorphisms in the methylenetetrahydrofolate reductase gene on homocysteine levels in elderly men and women from the British regional heart study. Atherosclerosis 2001; 154: 659–66PubMedCrossRefGoogle Scholar
  36. 36.
    Russo GT, Friso S, Jacques PF, et al. Age and gender affect the relation between methylenetetrahydrofolate reductase C677T genotype and fasting plasma homocysteine concentrations in the Framingham Offspring Study Cohort. J Nutr 2003; 133: 3416–21PubMedGoogle Scholar
  37. 37.
    Jacques PF, Selhub J, Bostom AG, et al. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N Engl J Med 1999; 340: 1449–54PubMedCrossRefGoogle Scholar
  38. 38.
    Bostom AG, Selhub J, Jacques PF, et al. Power shortage: clinical trials testing the “homocysteine hypothesis” against a background of folic acid-fortified cereal grain flour. Ann Intern Med 2001; 135: 133–7PubMedGoogle Scholar
  39. 39.
    Carlsson CM, Stein JH. Clinical trials testing the homocysteine hypothesis. Ann Intern Med 2002; 137: 295–6PubMedGoogle Scholar
  40. 40.
    Wilson KM, Lentz SR. Mechanisms of the atherogenic effects of elevated homocysteine in experimental models. Semin Vasc Med 2005; 5: 163–71PubMedCrossRefGoogle Scholar
  41. 41.
    Tsai JC, Perrella MA, Yoshizumi M, et al. Promotion of vascular smooth muscle cell growth by homocysteine: a link to atherosclerosis. Proc Natl Acad Sci U S A 1994; 91: 6369–73PubMedCrossRefGoogle Scholar
  42. 42.
    Tawakol A, Omland T, Gerhard M, et al. Hyperhomocyst(e)inemia is associated with impaired endothelium-dependent vasodilation in humans. Circulation 1997; 95: 1119–21PubMedCrossRefGoogle Scholar
  43. 43.
    Smulders YM, Stehouwer CD. Folate metabolism and cardiovascular disease. Semin Vasc Med 2005; 5: 87–97PubMedCrossRefGoogle Scholar
  44. 44.
    Chen Z, Karaplis AC, Ackerman SL, et al. Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition. Hum Mol Genet 2001; 10: 433–43PubMedCrossRefGoogle Scholar
  45. 45.
    Woo KS, Chook P, Lolin YI, et al. Hyperhomocyst(e)inemia is a risk factor for arterial endothelial dysfunction in humans. Circulation 1997; 96: 2542–4PubMedCrossRefGoogle Scholar
  46. 46.
    Gori AM, Corsi AM, Fedi S, et al. A proinflammatory state is associated with hyperhomocysteinemia in the elderly. Am J Clin Nutr 2005; 82: 335–41PubMedGoogle Scholar
  47. 47.
    Woo CW, Siow YL, Pierce GN, et al. Hyperhomocysteinemia induces hepatic cholesterol biosynthesis and lipid accumulation via activation of transcription factors. Am J Physiol Endocrinol Metab 2005; 288: E1002–10PubMedCrossRefGoogle Scholar
  48. 48.
    Aguilar B, Rojas JC, Collados MT. Metabolism of homocysteine and its relationship with cardiovascular disease. J Thromb Thrombolysis 2004; 18: 75–87PubMedCrossRefGoogle Scholar
  49. 49.
    Hiltunen MO, Turunen MP, Hakkinen TP, et al. DNA hypomethylation and methyltransferase expression in atherosclerotic lesions. Vasc Med 2002; 7: 5–11PubMedCrossRefGoogle Scholar
  50. 50.
    Laukkanen MO, Mannermaa S, Hiltunen MO, et al. Local hypomethylation in atherosclerosis found in rabbit ec-sod gene. Arterioscler Thromb Vasc Biol 1999; 19: 2171–8PubMedCrossRefGoogle Scholar
  51. 51.
    Zairis MN, Ambrose JA, Manousakis SJ, et al. The impact of plasma levels of C-reactive protein, lipoprotein (a) and homocysteine on the long-term prognosis after successful coronary stenting: the Global Evaluation of New Events and Restenosis after Stent Implantation study. J Am Coll Cardiol 2002; 40: 1375–82PubMedCrossRefGoogle Scholar
  52. 52.
    Hodish I, Matetzky S, Sela BA, et al. Effect of elevated homocysteine levels on clinical restenosis following percutaneous coronary intervention. Cardiology 2002; 97: 214–7PubMedCrossRefGoogle Scholar
  53. 53.
    Durga J, Verhoef P, Bots ML, et al. Homocysteine and carotid intima-media thickness: a critical appraisal of the evidence. Atherosclerosis 2004; 176: 1–19PubMedCrossRefGoogle Scholar
  54. 54.
    Chao CL, Kuo TL, Lee YT. Effects of methionine-induced hyperhomocysteinemia on endothelium-dependent vasodilation and oxidative status in healthy adults. Circulation 2000; 101: 485–90PubMedCrossRefGoogle Scholar
  55. 55.
    Chen P, Poddar R, Tipa EV, et al. Homocysteine metabolism in cardiovascular cells and tissues: implications for hyperhomocysteinemia and cardiovascular disease. Adv Enzyme Regul 1999; 39: 93–109PubMedCrossRefGoogle Scholar
  56. 56.
    James SJ, Melnyk S, Pogribna M, et al. Elevation in S-adenosylhomocysteine and DNA hypomethylation: potential epigenetic mechanism for homocysteine-related pathology. J Nutr 2002; 132 (8 Suppl.): 2361S–6SPubMedGoogle Scholar
  57. 57.
    Chambers JC, McGregor A, Jean-Marie J, et al. Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia: an effect reversible with vitamin C therapy. Circulation 1999; 99: 1156–60PubMedCrossRefGoogle Scholar
  58. 58.
    Shai I, Stampfer MJ, Ma J, et al. Homocysteine as a risk factor for coronary heart disease and its association with inflammatory biomarkers, lipids and dietary factors. Atherosclerosis 2004; 177: 375–81PubMedCrossRefGoogle Scholar
  59. 59.
    Stanger O, Herrmann W, Pietrzik K, et al. DACH-LIGA homocystein (German, Austrian and Swiss Homocysteine Society): consensus paper on the rational clinical use of homocysteine, folic acid and B-vitamins in cardiovascular and thrombotic diseases: guidelines and recommendations. Clin Chem Lab Med 2003; 41: 1392–403PubMedGoogle Scholar
  60. 60.
    Jacques PF, Bostom AG, Wilson PW, et al. Determinants of plasma total homocysteine concentration in the Framingham Offspring cohort. Am J Clin Nutr 2001; 73: 613–21PubMedGoogle Scholar
  61. 61.
    Kario K, Duell PB, Matsuo T, et al. High plasma homocyst(e)ine levels in elderly Japanese patients are associated with increased cardiovascular disease risk independently from markers of coagulation activation and endothelial cell damage. Atherosclerosis 2001; 157: 441–9PubMedCrossRefGoogle Scholar
  62. 62.
    Vasan RS, Beiser A, D’Agostino RB, et al. Plasma homocysteine and risk for congestive heart failure in adults without prior myocardial infarction. JAMA 2003; 289: 1251–7PubMedCrossRefGoogle Scholar
  63. 63.
    Matetzky S, Freimark D, Ben-Ami S, et al. Association of elevated homocysteine levels with a higher risk of recurrent coronary events and mortality in patients with acute myocardial infarction. Arch Intern Med 2003; 163: 1933–7PubMedCrossRefGoogle Scholar
  64. 64.
    Boushey CJ, Beresford SA, Omenn GS, et al. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease: probable benefits of increasing folic acid intakes. JAMA 1995; 274: 1049–57PubMedCrossRefGoogle Scholar
  65. 65.
    Sacco RL, Anand K, Lee HS, et al. Homocysteine and the risk of ischemic stroke in a triethnic cohort: the NOrthern MAnhattan Study. Stroke 2004; 35: 2263–9PubMedCrossRefGoogle Scholar
  66. 66.
    Klerk M, Verhoef P, Clarke R, et al. MTHFR 677C→T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 2002; 288: 2023–31PubMedCrossRefGoogle Scholar
  67. 67.
    McKay DL, Perrone G, Rasmussen H, et al. Multivitamin/mineral supplementation improves plasma B-vitamin status and homocysteine concentration in healthy older adults consuming a folate-fortified diet. J Nutr 2000; 130: 3090–6PubMedGoogle Scholar
  68. 68.
    McKinley MC, McNulty H, McPartlin J, et al. Low-dose vitamin B6 effectively lowers fasting plasma homocysteine in healthy elderly persons who are folate and riboflavin replete. Am J Clin Nutr 2001; 73: 759–64PubMedGoogle Scholar
  69. 69.
    Rydlewicz A, Simpson JA, Taylor RJ, et al. The effect of folic acid supplementation on plasma homocysteine in an elderly population. QJM 2002; 95: 27–35PubMedCrossRefGoogle Scholar
  70. 70.
    Henning BF, Tepel M, Riezler R, et al. Long-term effects of vitamin B12, folate, and vitamin B6 supplements in elderly people with normal serum vitamin B12 concentrations. Gerontology 2001; 47: 30–5PubMedCrossRefGoogle Scholar
  71. 71.
    Homocysteine Lowering Trialists’ Collaboration. Dose-dependent effects of folic acid on blood concentrations of homocysteine: a meta-analysis of the randomized trials. Am J Clin Nutr 2005; 82: 806–12Google Scholar
  72. 72.
    Till U, Rohl P, Jentsch A, et al. Decrease of carotid intima-media thickness in patients at risk to cerebral ischemia after supplementation with folic acid, vitamins B6 and B12. Atherosclerosis 2005; 181: 131–5PubMedCrossRefGoogle Scholar
  73. 73.
    Schnyder G, Roffi M, Pin R, et al. Decreased rate of coronary restenosis after lowering of plasma homocysteine levels. N Engl J Med 2001; 345: 1593–600PubMedCrossRefGoogle Scholar
  74. 74.
    Lange H, Suryapranata H, De Luca G, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004; 350: 2673–81PubMedCrossRefGoogle Scholar
  75. 75.
    Woo KS, Chook P, Lolin YI, et al. Folic acid improves arterial endothelial function in adults with hyperhomocystinemia. J Am Coll Cardiol 1999; 34: 2002–6PubMedCrossRefGoogle Scholar
  76. 76.
    Bellamy MF, McDowell IF, Ramsey MW, et al. Oral folate enhances endothelial function in hyperhomocysteinaemic subjects. Eur J Clin Invest 1999; 29: 659–62PubMedCrossRefGoogle Scholar
  77. 77.
    Title LM, Cummings PM, Giddens K, et al. Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease. J Am Coll Cardiol 2000; 36: 758–65PubMedCrossRefGoogle Scholar
  78. 78.
    Chambers JC, Ueland PM, Obeid OA, et al. Improved vascular endothelial function after oral B vitamins: an effect mediated through reduced concentrations of free plasma homocysteine. Circulation 2000; 102: 2479–83PubMedCrossRefGoogle Scholar
  79. 79.
    Doshi SN, Naka KK, Payne N, et al. Flow-mediated dilatation following wrist and upper arm occlusion in humans: the contribution of nitric oxide. Clin Sci (Lond) 2001; 101: 629–35CrossRefGoogle Scholar
  80. 80.
    Woo KS, Chook P, Chan LL, et al. Long-term improvement in homocysteine levels and arterial endothelial function after 1-year folic acid supplementation. Am J Med 2002; 112: 535–9PubMedCrossRefGoogle Scholar
  81. 81.
    Verhaar MC, Stroes E, Rabelink TJ. Folates and cardiovascular disease. Arterioscler Thromb Vasc Biol 2002; 22: 6–13PubMedCrossRefGoogle Scholar
  82. 82.
    Neunteufl T, Heher S, Katzenschlager R, et al. Late prognostic value of flow-mediated dilation in the brachial artery of patients with chest pain. Am J Cardiol 2000; 86: 207–10PubMedCrossRefGoogle Scholar
  83. 83.
    van Dijk RA, Rauwerda JA, Steyn M, et al. Long-term homocysteine-lowering treatment with folic acid plus pyridoxine is associated with decreased blood pressure but not with improved brachial artery endothelium-dependent vasodilation or carotid artery stiffness: a 2-year, randomized, placebo-controlled trial. Arterioscler Thromb Vasc Biol 2001; 21: 2072–9PubMedCrossRefGoogle Scholar
  84. 84.
    Dusitanond P, Eikelboom JW, Hankey GJ, et al. Homocysteine-lowering treatment with folic acid, cobalamin, and pyridoxine does not reduce blood markers of inflammation, endothelial dysfunction, or hypercoagulability in patients with previous transient ischemic attack or stroke: a randomized substudy of the VITATOPS Trial. Stroke 2005; 36: 144–6PubMedCrossRefGoogle Scholar
  85. 85.
    Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 2003; 349: 523–34PubMedCrossRefGoogle Scholar
  86. 86.
    Baker F, Picton D, Blackwood S, et al. Blinded comparison of folic acid and placebo in patients with ischemic heart disease: an outcome trial [abstract]. Circulation 2002; 106Suppl. II: II–741Google Scholar
  87. 87.
    Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006; 354: 1567–77PubMedCrossRefGoogle Scholar
  88. 88.
    Bonaa KH, Njolstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006; 354: 1578–88PubMedCrossRefGoogle Scholar
  89. 89.
    B-Vitamin Treatment Trialists’ Collaboration. Homocysteine-lowering trials for prevention of cardiovascular events: a review of the design and power of the large randomized trials. Am Heart J 2006; 151: 282–7CrossRefGoogle Scholar
  90. 90.
    Schnyder G, Roffi M, Flammer Y, et al. Effect of homocysteine-lowering therapy with folic acid, vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart Study: a randomized controlled trial. JAMA 2002; 288: 973–9PubMedCrossRefGoogle Scholar
  91. 91.
    Toole JF, Malinow MR, Chambless LE, 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: 565–75PubMedCrossRefGoogle Scholar
  92. 92.
    Hankey GJ, Eikelboom JW, Loh K, et al. Is there really a power shortage in clinical trials testing the “homocysteine hypothesis”? [letter]. Arterioscler Thromb Vasc Biol 2004; 24: E147PubMedCrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Department of Medicine, Section of Geriatrics and GerontologyUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  2. 2.Department of Veterans Affairs (VA) Geriatric ResearchEducation and Clinical Center (GRECC)MadisonUSA

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