Homocysteine consensus

Authors: Ján Lietava 1;  Pavel Blažíček 2;  Martin Čaprnda 1;  Katarína Rašlová 3;  Jana Tisoňová 4;  Branislav Vohnout 3,5,6
Authors‘ workplace: I. interná klinika LF UK a UNB, Nemocnica Staré Mesto, Bratislava 1;  Ústav chémie, klinickej biochémie a laboratórnej medicíny LF SZU v Bratislave 2;  Koordinačné centrum pre familiárne hyperlipoproteinémie, SZU v Bratislave 3;  Ústav farmakológie a klinickej farmakológie LF UK, Bratislava 4;  Ústav výživy, FOaZOŠ SZU v Bratislave 5;  Ústav epidemiológie LF UK v Bratislave 6
Published in: AtheroRev 2020; 5(1): 8-15
Category: Guidelines


Homocysteine consensus reflects current knowledge that homocysteine is rather a risk marker then a factor and treatment of hyperhomocysteinemia does not reduce cardiovascular morbidity and mortality. Panel of experts state this position to approach cardiovascular prevention and treatment in praxis.

A. General therapeutic intervention is not generally indicated based on current EBM data.

B. General screening of homocysteine is not clinically beneficial in both general population and in patients with cardiovascular disease.

  • Preventive administration of B group vitamins to reduce plasma homocysteine level in general population is not supported based on current EBM data. Population screening is not indicated – class III, level A.
  • Therapeutic administration of B group vitamins to reduce plasma homocysteine level in patients in secondary or tertiary prevention is not supported based on current EBM data. Population screening is not indicated – class III, level A.
  • There are no sufficient data on effect of measuring homocysteine on decision to start treating hypertension or dyslipidemias. Population screening is not indicated, only individual patients´ examination – class IIb, level A.


screening – cardiovascular prevention – homocysteine – vitamins group B

  1. Lietava J, Dukát A, Blažíček P et al. Návrh na homocysteínový konsenzus. Cardiol 2003; 12(3): K/C 42–46.
  2. 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(11): 1392–1403.Dostupné z DOI: <http://dx.doi.org/10.1515/CCLM.2003.214>.
  3. Refsum H, Smith AD, Ueland PM et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 2004; 50(1): 3–32. Dostupné z DOI: <http://dx.doi.org/10.1373/clinchem.2003.021634>.
  4. Stehouwer CD, van Guldener C. Does homocysteine cause hypertension? Clin Chem Lab Med 2003; 41(11): 1408–1411. Dostupné z DOI: <http://dx.doi.org/10.1515/CCLM.2003.216>.
  5. Chamberlain K. Homocysteine and cardiovascular disease: a review of current recommendations for screening and treatment. J Am Acad Nurse Pract 2005; 17(3): 90–95. Dostupné z DOI: <http://dx.doi.org/10.111/j.1041–2972.2005.0016.x>.
  6. Mosca L, Banka CL, Benjamin EJ et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update. J Am Coll Cardiol. 2007; 49(11): 1230–1250. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2007.02.020>.
  7. Teramoto T, Sasaki J, Ishibashi S et al. Cardiovascular disease risk factors other than dyslipidemia. Executive summary of the Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan – 2012 version.. J Atheroscler Thromb 2013; 20(10): 733–742. Dostupné z DOI: <http://dx.doi.org/10.5551/jat.17368>.
  8. Guilliams TG. Homocysteine – a risk factor for vascular diseases: Guidelines for the clinical practice. JANA 2004; 7(1): 11–21.
  9. 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(13): 1049–1057. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.1995.03530130055028>.
  10. Gerritsen T, Waisman HA. Homocystinuria, an error in the metabolism of methionine. Pediatrics 1964; 33: 413–20.
  11. Carson NA, Neill D. Metabolic abnormalities detected in a survey of mentally backward individuals in Northern Ireland. Arch Dis Child 1962; 37: 505–513. Dostupné z DOI: <http://dx.doi.org/10.1136/adc.37.195.505>.
  12. Ueland P, Refsum H. Plasma homocysteine, a risk factor for vascular disease: plasma levels in health, disease, and drug therapy. J Lab Clin Med 1989; 114(5): 473–501.
  13. Ueland P, Refsum H. Plasma homocysteine, a risk factor for premature vascular disease. Plasma levels in healthy persons; during pathologic conditions and drug therapy. Nord Med 1989; 104(11) :293–298.
  14. Bolander-Gouaille C. Focus on Homocysteine and the Vitamins Involved in its metabolism: Involved in Its Metabolism: Springer Science & Business Media: 2002. ISBN 978–2-8178–0845–1.
  15. Armitage J, Bowman L, Wallendszus K et al. [Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group]. Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial. Lancet 2010; 376(9753): 1658–1669. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(10)60310–8>.
  16. Kaul S, Zadeh AA, Shah PK. Homocysteine hypothesis for atherothrombotic cardiovascular disease: not validated. J Am Coll Cardiol 2006; 48(5): 914–923. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2006.04.086>.
  17. Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet 1999; 354(9176): 407–413. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(98)11058–9>.
  18. Voutilainen S, Lakka T, Porkkala-Sarataho E et al. Low serum folate concentrations are associated with an excess incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study. Eur J Clin Nutr 2000; 54(5): 424–428. Dostupné z DOI: <http://dx.doi.org/10.1038/sj.ejcn.1600991>.
  19. Voutilainen S, Lakka T, Hämelahti P et al. Plasma total homocysteine concentration and the risk of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Studytpdel. J Intern Med 2000; 248(3): 217–222. Dostupné z DOI: <http://dx.doi.org/10.1046/j.1365–2796.2000.00741.x>.
  20. Gašparovič J, Rašlová K, Bašistová Z et al. Effect of C677T methylenetetrahydrofolate reductase gene polymorphism on plasma homocysteine levels in ethnic groups. Physiol Res 2004; 53(2): 215–218.
  21. Rašlová K, Smolková B, Vohnout B et al. Risk factors for atherosclerosis in survivors of myocardial infarction and their spouses: comparison to controls without personal and family history of atherosclerosis. Metabolism 2001; 50(1): 24–29. Dostupné z DOI: <http://dx.doi.org/10.1053/meta.2001.19499>.
  22. Lietava J, Dukát A, Kotrec M et al. Relationship of absolute risk of atherosclerosis to hyperhomocysteinemia in Slovak males after myocardial infarction. Atherosclerosis 2000; 151(1):107. Dostupné z DOI: <https://doi.org/10.1016/S0021–9150(00)80484–0>.
  23. Lietava J, Dukat A, Fodor G. Homocysteine Slovakia study: study design and occurrence of hyperhomocysteinaemia and other risk factors. Bratisl Lek Listy 2012; 113(2): 80–86.
  24. Smulders YM, Blom HJ. The homocysteine controversy. J Inherit Metab Dis 2011; 34(1): 93–99. Dostupné z DOI: <http://dx.doi.org/10.1007/s10545–010–9151–1>.
  25. Voutilainen S, Virtanen JK, Rissanen TH et al. Serum folate and homocysteine and the incidence of acute coronary events: the Kuopio Ischaemic Heart Disease Risk Factor Study. Am J Clin Nutr 2004; 80(2): 317–323. Dostupné z DOI: <http://dx.doi.org/10.1093/ajcn/80.2.317>.
  26. Martí‐Carvajal AJ, Sola I, Lathyris D et al. Homocysteine‐lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev 2017; 8: CD006612. Dostupné z DOI: <http://dx.doi.org/10.1002/14651858.CD006612.pub5>.
  27. Helfand M, Buckley DI, Freeman M et al. Emerging risk factors for coronary heart disease: a summary of systematic reviews conducted for the US Preventive Services Task Force. Ann Intern Med 2009; 151(7): 496–507.
  28. Teramoto T, Sasaki J, Ishibashi S et al. Executive summary of the Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan—2012 version. J Atheroscler Thromb 2014; 21(4): 291–295. Dostupné z DOI: <http://dx.doi.org/10.5551/jat.19711>.
  29. Veeranna V, Zalawadiya SK, Niraj A et al. Homocysteine and reclassification of cardiovascular disease risk. J Am Coll Cardiol 2011; 58(10): 1025–1033. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jacc.2011.05.028>.
  30. Paynter NP, Cook NR. Adding tests to risk based guidelines: evaluating improvements in prediction for an intermediate risk group. BMJ 2016; 354: i4450. Dostupné z DOI: <http://dx.doi.org/10.1136/bmj.i4450>.
  31. 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(8): 973–979. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.288.8.973>.
  32. Holmes MV, Newcombe P, Hubacek JA et al. Effect modification by population dietary folate on the association between MTHFR genotype, homocysteine, and stroke risk: a meta-analysis of genetic studies and randomised trials. Lancet 2011; 378(9791): 584–594. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(11)60872–6>.
  33. Clarke R, Bennett DA, Parish S et al. Homocysteine and coronary heart disease: meta-analysis of MTHFR case-control studies, avoiding publication bias. PLoS Med 2012; 9(2): e1001177. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pmed.1001177>.
  34. Vincent KR, Braith RW, Bottiglieri T et al. Homocysteine and lipoprotein levels following resistance training in older adults. Prev Cardiol 2003 Fall; 6(4): 197–203. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1520–037x.2003.01723.x>.
  35. Pizzorno J. Homocysteine: Friend or Foe? Integr Med (Encinitas) 2014; 13(4): 8–14.
  36. Kumar A, Palfrey HA, Pathak R et al. The metabolism and significance of homocysteine in nutrition and health. Nutr Metab (Lond) 2017; 14: 78. Dostupné z DOI: <http://10.1186/s12986–017–0233-z>.
  37. Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J 2015; 14: 6. Dostupné z DOI: <http://dx.doi.org/10.1186/1475–2891–14–6>.
  38. Broxmeyer L. Heart disease: the greatestrisk‘factor of them all. Med Hypotheses 2004; 62(5): 773–779. Dostupné z DOI: <http://dx.doi.org/10.1016/j.mehy.2003.12.018>.
  39. Dias V, Bamforth F, Forward L et al. Evaluation and intermethod comparison of the Bio-Rad high-performance liquid chromatographic method for plasma total homocysteine. Clin Chem 1998; 44(10): 2199–201.
  40. Pfeiffer CM, Huff DL, Smith SJ et al. Comparison of plasma total homocysteine measurements in 14 laboratories: an international study. Clin Chem 1999; 45(8 Pt 1): 1261–1268.
  41. Flicker L, Vasikaran SD, Thomas J et al. Efficacy of B vitamins in lowering homocysteine in older men: maximal effects for those with B12 deficiency and hyperhomocysteinemia. Stroke 2006; 37(2): 547–549. Dostupné z DOI: <http://dx.doi.org/10.1161/01.STR.0000198815.07315.68>.
  42. Nicoll R, Howard J, Henein M. A review of the effect of diet on cardiovascular calcification. Int J Mol Sci 2015; 16(4):8861–8883. Dostupné z DOI: <http://dx.doi.org/10.3390/ijms16048861>.
  43. Herrmann M, Schorr H, Obeid R et al. Homocysteine increases during endurance exercise. Clin Chem Lab Med 2003; 41(11): 1518–1524. Dostupné z DOI: <http://dx.doi.org/10.1515/CCLM.2003.233>.
  44. Deminice R, Ribeiro DF, Frajacomo FT. The effects of acute exercise and exercise training on plasma homocysteine: A meta-analysis. PloS One 2016; 11(3): e0151653. Dostupné z DOI: <http://dx.doi.org/10.1371/journal.pone.0151653>.
  45. Pettigrew LC, Bang H, Chambless LE et al. [Vitamin Intervention for Stroke Prevention Investigators.]. Assessment of pre-and post-methionine load homocysteine for prediction of recurrent stroke and coronary artery disease in the Vitamin Intervention for Stroke Prevention Trial. Atherosclerosis 2008; 200(2): 345–349. Dostupné z DOI: <http://dx.doi.org/10.1016/j.atherosclerosis.2007.11.014>.
  46. 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(5): 565–575. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.291.5.565>.
  47. Bønaa KH, Njølstad I, Ueland PM et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med 2006; 354(15): 1578–1588. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa055227>.
  48. Lonn E, Yusuf S, Arnold MJ et al. [Heart Outcomes Prevention Evaluation (HOPE) 2 Investigators]. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med 2006; 354(15): 1567–1577. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa060900>.
  49. Albert CM, Cook NR, Gaziano JM 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(17): 2027–2036. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.299.17.2027>.
  50. [VITATOPS Trial Study Group]. B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial. Lancet Neurol 2010; 9(9): 855–865. Dostupné z DOI: <http://dx.doi.org/10.1016/S1474–4422(10)70187–3>.
  51. Wang X, Qin X, Demirtas H et al. Efficacy of folic acid supplementation in stroke prevention: a meta-analysis. Lancet 2007; 369(9576): 1876–1882. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(07)60854-X>.
Angiology Diabetology Internal medicine Cardiology General practitioner for adults
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.


Don‘t have an account?  Create new account