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Homocysteine Reduction References

Disease Prevention and Treatment, 5th edition

The references on this page correspond with the print version of Disease Prevention and Treatment, 5th edition. Since we continuously update the protocols online in response to new scientific developments, readers are encouraged to review the latest versions of the protocols.

  1. Albert CM, Cook NR, et al. Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial. JAMA. 2008;299:2027-2036.
  2. Méndez-González J, Rodríguez-Millán E, et al. [Vitamin treatments that lower homocysteine concentration: can they decrease cerebrovascular disease in primary prevention?]. Rev Neurol. 2010;50:235-244.
  3. Guo H, Chi J, et al. Influence of folic acid on plasma homocysteine levels & arterial endothelial function in patients with unstable angina. Indian J Med Res. 2009;129:279-284.
  4. Nygård O, Vollset SE, et al. Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study. JAMA. 1995;274: 1526-1533.
  5. Jacobsen DW. Homocysteine and vitamins in cardiovascular disease. Clin Chem. 1998;44:1833-1843.
  6. Verhoef P, van Vliet T, et al. A high-protein diet increases postprandial but not fasting plasma total homocysteine concentrations: a dietary controlled, crossover trial in healthy volunteers. Am J Clin Nutr. 2005;82:553-558.
  7. Selhub J. Homocysteine metabolism. Annu Rev Nutr. 1999 (a);19:217-246.
  8. Selhub J, Jacques PF, 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 (b);131:331-339.
  9. Must A, Jacques PF, et al. Serum total homocysteine concentrations in children and adolescents: results from the third National Health and Nutrition Examination Survey (NHANES III). J Nutr. 2003;133:2643-2649.
  10. Jacques PF, Rosenberg IH, et al. Serum total homocysteine concentrations in adolescent and adult Americans: results from the third National Health and Nutrition Examination Survey. Am J Clin Nutr. 1999;69:482-489.
  11. Ganji V, Kafai MR. Population reference values for plasma total homocysteine concentrations in US adults after the fortification of cereals with folic acid. Am J Clin Nutr. 2006;84:989-994.
  12. Ruscin JM, Page RL 2nd, et al. Vitamin B-12 deficiency associated with histamine (2)–receptor antagonists and a proton-pump inhibitor. Ann Pharmacother. 2002;36:812-816.
  13. Wulffelé MG, Kooy A, et al. Effects of short-term treatment with metformin on serum concentrations of homocysteine, folate and vitamin B12 in type 2 diabetes mellitus: a randomized, placebo-controlled trial. J Intern Med. 2003;254:455-463.
  14. Targher G, Bertolini L, et al. Cigarette smoking and plasma total homocysteine levels in young adults with type 1 diabetes. Diabetes Care. 2000;23:524-528.
  15. Temple ME, Luzier AB, et al. Homocysteine as a risk factor for atherosclerosis. Ann Pharmacother. 2000;34:57-65.
  16. Sakuta H, Suzuki T. Alcohol consumption and plasma homocysteine. Alcohol. 2005;372:73-77.
  17. Broxmeyer L. Heart disease: the greatest 'risk' factor of them all. Med Hypotheses. 2004;62:773-779.
  18. Elias MF, Sullivan LM, et al. Homocysteine and cognitive performance in the Framingham offspring study: age is important. Am J Epidemiol. 2005;162:644-653.
  19. Zeng X, Dai J, et al. Homocysteine mediated expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human monocytes. Circ Res. 2003;93:311-320.
  20. Mann JF, Sheridan P, et al. Homocysteine lowering with folic acid and B vitamins in people with chronic kidney disease—results of the renal Hope-2 study. Nephrol Dial Transplant. 2008;23:645-653.
  21. Carlsen SM, Jacobsen G, et al. In pregnant women who smoke, caffeine consumption is associated with an increased level of homocysteine. Acta Obstet Gynecol Scand. 2005;84:1049-1054.
  22. Guzelmeric K, Alkan N, et al. Chronic inflammation and elevated homocysteine levels are associated with increased body mass index in women with polycystic ovary syndrome. Gynecol Endocrinol. 2007;23:505-510.
  23. McNulty H, Pentieva K, et al. Homocysteine, B-vitamins and CVD. Proc Nutr Soc. 2008;67:232-237.
  24. Robinson K, Mayer EL, et al. Hyperhomocysteinemia and low pyridoxal phosphate: common and independent reversible risk factors for coronary artery disease. Circulation. 1995; 92:2825-2830.
  25. McLean RR, Jacques PF, et al. Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med. 2004;350:2042-2049.
  26. Botto LD, Yang Q. 5,10-Methylenetetrahydrofolate reductase gene variants and congenital anomalies: a HuGE review. Am J Epidemiol. 2000;151:862-877.
  27. Willems FF, Boers GH, et al. Pharmacokinetic study on the utilization of 5-methyltetrahydrofolate and folic acid in patients with coronary artery disease. Br J Pharmacol. 2004;141:825-830.
  28. Weir DG, Scott JM. Brain function in the elderly: role of vitamin B12 and folate. Br Med Bull. 1999;55:669-682.
  29. Venn BJ, Green TJ, et al. Increases in blood folate indices are similar in women of childbearing age supplemented with [6S]-5-methyltetrahydrofolate and folic acid. J Nutr. 2002;132:3353-3355.
  30. Seshadri S, Beiser A, et al. Plasma homocysteine as a risk factor for dementia and Alzheimer’s disease. N Engl J Med. 2002 Feb 14;346(7):476-83.
  31. Gallai V, Caso V, et al. Mild hyperhomocyst(e)inemia: a possible risk factor for cervical artery dissection. Stroke. 2001;32:714-718.
  32. Papatheodorou L, Weiss N. Vascular oxidant stress and inflammation in hyperhomocysteinemia. Antioxid Redox Signal. 2007;9:1941-1958.
  33. Hofmann MA, Lalla E, et al. Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model. J Clin Invest. 2001;107:675-683.
  34. Osanai T, Fujiwara N, et al. Novel pro-atherogenic molecule coupling factor 6 is elevated in patients with stroke: a possible linkage to homocysteine. Ann Med. 2010;42:79-86.
  35. Cooke GE, Eaton GM, et al. Plasma atherogenic markers in congestive heart failure and posttransplant (heart) patients. J Am Coll Cardiol. 2000;36:509-516.
  36. Chen P, Poddar R, et al. Homocysteine metabolism in cardiovascular cells and tissues: implications for hyperhomocysteinemia and cardiovascular disease. Adv Enzyme Reg. 1999;39:93-109.
  37. Loscalzo J. The oxidant stress of hyperhomocyst(e)inemia. J Clin Invest. 1996;98:5-7.
  38. Miller A, Mujumdar V, et al. Reversal of endocardial endothelial dysfunction by folic acid in homocysteinemic hypertensive rats. Am J Hypertens. 2002;15:157-163.
  39. Blacher J, Demuth K, et al. Association between plasma homocysteine concentrations and cardiac hypertrophy in end-stage renal disease. J Nephrol. 1999;12:248-255.
  40. Vasan RS, Beiser A, et al. Plasma homocysteine and risk for congestive heart failure in adults without prior myocardial infarction. JAMA. 2003;289:1251-1257.
  41. Kurth T, Ridker PM, et al. Migraine and biomarkers of cardiovascular disease in women. Cephalalgia. 2008;28:49-56.
  42. Moschiano F, D'Amico D, et al. Homocysteine plasma levels in patients with migraine with aura. Neurol Sci. 2008;29 Suppl 1:S173-S175.
  43. Hamed SA. The vascular risk associations with migraine: relation to migraine susceptibility and progression. Atherosclerosis. 2009;205:15-22.
  44. Lea R, Colson N, et al. The effects of vitamin supplementation and MTHFR (C677T) genotype on homocysteine-lowering and migraine disability. Pharmacogenet Genomics. 2009;19:422-428.
  45. Oterino A, Toriello M, et al. The relationship between homocysteine and genes of folate-related enzymes in migraine patients. Headache. 2010;50:99-168.
  46. Rochtchina E, Wang JJ, et al. Elevated serum homocysteine, low serum vitamin B12, folate, and age-related macular degeneration: the Blue Mountains Eye Study. Am J Ophthalmol. 2007;143:344-346.
  47. Christen WG, Glynn RJ, et al. Folic acid, pyridoxine, and cyanocobalamin combination treatment and age-related macular degeneration in women: the Women's Antioxidant and Folic Acid Cardiovascular Study. Arch Intern Med. 2009;169:335-341.
  48. Durga J, Verhoef P, et al. Effects of folic acid supplementation on hearing in older adults: a randomized, controlled trial. Ann Intern Med. 2007;146:1-9.
  49. Gok U, Halifeoglu I, et al. Comparative analysis of serum homocysteine, folic acid and Vitamin B12 levels in patients with noise-induced hearing loss. Auris Nasus Larynx. 2004;31:19-22.
  50. Toole JF, Malinow MR, 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;291:565-575.
  51. Saposnik G, Ray JG, et al, Heart Outcomes Prevention Evaluation 2 Investigators. Homocysteine-lowering therapy and stroke risk, severity, and disability: additional findings from the HOPE 2 trial. Stroke. 2009;40:1365-1372.
  52. Bønaa KH. NORVIT: Randomized trial of homocysteine-lowering with B-vitamins for secondary prevention of cardiovascular disease after acute myocardial infarction. Program and Abstracts from the European Society of Cardiology Congress 2005; September 3-7, 2005; Stockholm, Sweden. Hot Line II.
  53. Albert C. A randomized trial of folic acid and B-vitamins in the secondary prevention of cardiovascular events in women: Results from the Women's Antioxidant and Folic Acid Cardiovascular Study (WAFACS). American Heart Association 2006 Scientific Sessions; November 13, 2006; Chicago, IL. PS.03.Late-Breaking Clinical Trials I.
  54. Ebbing M, Bleie Ø, et al. Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial. JAMA. 2008;300:795-804.
  55. Bazzano LA, Reynolds K, et al. Effect of folic acid supplementation on risk of cardiovascular diseases: A meta-analysis of randomized controlled trials. JAMA. 2006;296:2720-2726.
  56. Bostom AG, Selhub J, 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: 133-137.
  57. Clarke R. Homocysteine-lowering trials for prevention of heart disease and stroke. Semin Vasc Med. 2005;5:215-222.
  58. Ueland PM, Clarke R. Homocysteine and cardiovascular risk: considering the evidence in the context of study design, folate fortification, and statistical power. Clin Chem. 2007;53:807-809.
  59. Namazi MH, Motamedi MR, et al. Efficacy of folic acid therapy for prevention of in-stent restenosis: a randomized clinical trial. Arch Iran Med. 2006;9:108-110.
  60. Lange H, Suryapranata H, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med. 2004;350(26):2673-2681.
  61. Schnyder G, Roffi M, 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;288:973-979.
  62. Wang X, Qin X, et al. Efficacy of folic acid supplementation in stroke prevention: A meta-analysis. Lancet. 2007;369:1876 –1882.
  63. Khandanpour N, Armon MP, et al. Randomized clinical trial of folate supplementation in patients with peripheral arterial disease. Br J Surg. 2009;96:990-998.
  64. Shidfar F, Homayounfar R, et al. Effect of folate supplementation on serum homocysteine and plasma total antioxidant capacity in hypercholesterolemic adults under lovastatin treatment: a double-blind randomized controlled clinical trial. Arch Med Res. 2009;40:380-386.
  65. Xu T, Zhang XW, et al. Treatment of hyperhomocysteinemia and endothelial dysfunction in renal transplant recipients with B vitamins in the Chinese population. J Urol. 2008;179:1190-1194.
  66. Alvares Delfino VD, de Andrade Vianna AC, et al. Folic acid therapy reduces plasma homocysteine levels and improves plasma antioxidant capacity in hemodialysis patients. Nutrition. 2007;23:242-247.
  67. Akoglu B, Schrott M, et al. The folic acid metabolite L-5-methyltetrahydrofolate effectively reduces total serum homocysteine level in orthotopic liver transplant recipients: a double-blind placebo-controlled study. Eur J Clin Nutr. 2008;62:796-801.
  68. Ntaios G, Savopoulos C, et al. The effect of folic acid supplementation on carotid intima-media thickness in patients with cardiovascular risk: A randomized, placebo-controlled trial. Int J Cardiol. 2010;143:16-19.
  69. Held C, Sumner G, et al. Correlations between plasma homocysteine and folate concentrations and carotid atherosclerosis in high-risk individuals: baseline data from the Homocysteine and Atherosclerosis Reduction Trial (HART). Vasc Med. 2008;13:245-253.
  70. Zoccali C, Mallamaci F, et al. It is important to lower homocysteine in dialysis patients. Semin Dial. 2007; 20:530-533.
  71. Nolin TD, Ouseph R, et al. Multiple-Dose Pharmacokinetics and Pharmacodynamics of N-Acetylcysteine in Patients with End-Stage Renal Disease. Clin J Am Soc Nephrol. 2010; 5:1588-94.
  72. Yilmaz H, Sahin S, et al. Effects of folic acid and N-acetylcysteine on plasma homocysteine levels and endothelial function in patients with coronary artery disease. Acta Cardiol. 2007;62:579-85.
  73. Wiklund O, Fager G, et al. N-acetylcysteine treatment lowers plasma homocysteine but not serum lipoprotein(a) levels. Atherosclerosis. 1996;119:99-106.
  74. Roes EM, Raijmakers MT, et al. Effects of oral N-acetylcysteine on plasma homocysteine and whole blood glutathione levels in healthy, non-pregnant women. Clin Chem Lab Med. 2002;40:496-498.
  75. Huang T, Wahlqvist ML, et al. Docosahexaenoic acid decreases plasma homocysteine via regulating enzyme activity and mRNA expression involved in methionine metabolism. Nutrition. 2010;26:112-119.
  76. Pooya Sh, Jalali MD, et al. The efficacy of omega-3 fatty acid supplementation on plasma homocysteine and malondialdehyde levels of type 2 diabetic patients. Nutr Metab Cardiovasc Dis. 2010;20:326-331.
  77. Zulli A, Lau E, et al. High dietary taurine reduces apoptosis and atherosclerosis in the left main coronary artery: association with reduced CCAAT/enhancer binding protein homologous protein and total plasma homocysteine but not lipidemia. Hypertension. 2009;53:1017-1022.
  78. Zulli A, Lau E, Wijaya BP, et al. High dietary taurine reduces apoptosis and atherosclerosis in the left main coronary artery: association with reduced CCAAT/enhancer binding protein homologous protein and total plasma homocysteine but not lipidemia. Hypertension. 2009;53(6):1017-22.
  79. Ahn CS. Effect of taurine supplementation on plasma homocysteine levels of the middle-aged Korean women. Adv Exp Med Biol. 2009;643:415-422.
  80. Lv S, Fan R, et al. Betaine supplementation attenuates atherosclerotic lesion in apolipoprotein E-deficient mice. Eur J Nutr. 2009;48:205-212.
  81. Cho E, Zeisel SH, et al. Dietary choline and betaine assessed by food-frequency questionnaire in relation to plasma total homocysteine concentration in the Framingham Offspring Study. Am J Clin Nutr. 2006;83:905–911.
  82. da Costa KA, Gaffney CE, et al. Choline deficiency in mice and humans is associated with increased plasma homocysteine concentration after a methionine load. Am J Clin Nutr. 2005;81:440-444.
  83. Schwab U, Törrönen A, et al. Betaine supplementation decreases plasma homocysteine concentrations but does not affect body weight, body composition, or resting energy expenditure in human subjects. Am J Clin Nutr. 2002;76:961-967.
  84. Devlin TM. Textbook of Biochemistry with Clinical Correlations . 5th ed. New York , NY : Wiley-Liss; 2001.
  85. Loehrer FM, Schwab R, et al. Influence of oral S-adenosylmethionine on plasma 5-methyltetrahydrofolate, S-adenosylhomocysteine, homocysteine and methionine in healthy humans. J Pharmacol Exper Ther. 1997;282:845-850.
  86. Brosnan JT, Brosnan ME. The sulfur-containing amino acids: an overview. J Nutr. 2006; 136:1636S-1640S.
  87. Stead LM, Brosnan JT, et al. Is it time to reevaluate methyl balance in humans? Am J Clin Nutr. 2006;83:5-10.
  88. Brosnan JT, Jacobs RL, et al. Methylation demand: a key determinant of homocysteine metabolism. Acta Biochim Pol. 2004;51:405-413.
  89. Hustad S, Ueland PM, et al. Riboflavin as a determinant of plasma total homocysteine: effect modification by the methylenetetrahydrofolate reductase C677T polymorphism. Clin Chem. 2000;46:1065-1071.
  90. McNulty H, Dowey le RC, et al. Riboflavin lowers homocysteine in individuals homozygous for the MTHFR 677C->T polymorphism. Circulation. 2006;113:74-80.
  91. Tavares NR, Moreira PA,et al. Riboflavin supplementation and biomarkers of cardiovascular disease in the elderly. J Nutr Health Aging. 2009;13:441-446.
  92. Smith AD, Smith SM, et al. Homocysteine-Lowering by B Vitamins Slows the Rate of Accelerated Brain Atrophy in Mild Cognitive Impairment: A Randomized Controlled Trial. PLoS ONE 2010; 5(9): e12244. doi:10.1371/journal.pone.0012244
  93. Plassman BL, Langa KM, et al. Prevalence of cognitive impairment without dementia in the United States. Ann Intern Med. 2008;148:427-434
  94. McKillop DJ, Pentieva K, et. al. The effect of different cooking methods on folate retention in various foods that are amongst the major contributors to folate intake in the UK diet. British J Nutr. 2002;88:681–688.
  95. Levitt M, Nixon PF, et al. Transport characteristics of folates in cerebrospinal fluid; a study utilizing doubly labeled 5-methyltetrahydrofolate and 5- formyltetrahydrofolate. J Clin Invest. 1971;50:1301-1308.
  96. Schwammenthal Y, Tanne D. Homocysteine, B-vitamin supplementation, and stroke prevention: from observational to interventional trials. Lancet Neurol. 2004;3:493-495.
  97. Zettner A, Boss GR, et al. A long-term study of the absorption of large oral doses of folic acid. Ann Clin Lab Sci. 1981;11:516-524.
  98. Schuster O, Weimann HJ, et al. Pharmacokinetics and relative bioavailability of iron and folic acid in healthy volunteers. Arzneimittelforschung.1993;43:761-766.
  99. Wright AJ, Dainty JR, et al. Folic acid metabolism in human subjects revisited: potential implications for proposed mandatory folic acid fortification in the UK. Br J Nutr. 2007;98:667-675.
  100. Wierzbicki AS. Homocysteine and cardiovascular disease: a review of the evidence. Diab Vasc Dis Res. 2007;4:143-150.
  101. Verhoef P, Pasman WJ, et al. Contribution of caffeine to the homocysteine-raising effect of coffee: a randomized controlled trial in humans. Am J Clin Nutr. 2002;76:1244-1248.
  102. Tonstad F, Refsum H, et al. The C677T mutation in the methylenetetrahydrofolate reductase gene predisposes to hyperhomocysteinemia in children with familial hypercholesterolemia treated with cholestyramine. J Pediatr. 1998;132: 365-368.
  103. Seshadri, N., Robinson, K. Homocysteine and coronary risk, Curr Cardiol Rep 1999; 1, 91-98.
  104. Foucher C, Brugère L, et al. Fenofibrate, homocysteine, and renal function. Curr Vasc Pharmacol. 2010;8:589-603.
  105. Lee SH, Kim MJ, et al. Hyperhomocysteinemia due to levodopa treatment as a risk factor for osteoporosis in patients with Parkinson’s disease. Calcif Tissue Int. 2010;86:132-141.
  106. Desouza C, Keepler M, et al. Drugs affecting homocysteine metabolism: impact on cardiovascular risk. Drugs. 2002;62:605-616.
  107. Myles PS, Chan MT, et al. Effect of nitrous oxide anesthesia on plasma homocysteine and endothelial function. Anesthesiology. 2008;109:657-663.
  108. Li KM, Rivory LP, et al. Pemetrexed pharmacokinetics and pharmacodynamics in a phase I/II study of doublet chemotherapy with vinorelbine: implications for further optimisation of pemetrexed schedules. Br J Cancer. 2007;97:1071-1076.
  109. Mintzer S, Skidmore CT, et al. Effects of antiepileptic drugs on lipids, homocysteine, and C-reactive protein. Ann Neurol. 2009;65:448-456.
  110. Das KC, Herbert V. Vitamin B12--folate interrelations. Clin Haematol. 1976;5:697-745.
  111. Haagsma CJ, Blom HJ, et al. Influence of sulphasalazine, methotrexate, and the combination of both on plasma homocysteine concentrations in patients with rheumatoid arthritis. Ann Rheum Dis. 1999;58:79-84.
  112. Ali A, Mehra MR, et al. Modulatory impact of cardiac rehabilitation on hyperhomocysteinemia in patients with coronary artery disease and "normal" lipid levels. Am J Cardiol. 1998;82:1543-5.
  113. Lever M, George PM, et al. Fibrates may cause an abnormal urinary betaine loss which is associated with elevations in plasma homocysteine. Cardiovasc Drugs Ther. 2009;23:395-401.
  114. Jahangir E, Vita JA, et al. The effect of L-arginine and creatine on vascular function and homocysteine metabolism. Vasc Med. 2009;14:239-248.