Homocysteine lowering interventions for preventing cardiovascular events

Cochrane Database Syst Rev. 2009 Oct 7:(4):CD006612. doi: 10.1002/14651858.CD006612.pub2.


Background: Cardiovascular disease such as coronary artery disease, stroke and congestive heart failure, is a leading cause of death worldwide. A postulated risk factor is elevated circulating total homocysteine (tHcy) levels which is influenced mainly by blood levels of cyanocobalamin (vitamin B12), folic acid (vitamin B9) and pyridoxine (vitamin B6). There is uncertainty regarding the strength of association between tHcy and the risk of cardiovascular disease.

Objectives: To assess the clinical effectiveness of homocysteine-lowering interventions (HLI) in people with or without pre-existing cardiovascular disease.

Search strategy: We searched The Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (issue 3 2008), MEDLINE (1950 to August 2008), EMBASE (1988 to August 2008), and LILACS (1982 to September 2, 2008). We also searched in Allied and Complementary Medicine (AMED; 1985 to August 2008), ISI Web of Science (1993 to August 2008), and the Cochrane Stroke Group Specialised Register (April 2007). We hand searched pertinent journals and the reference lists of included papers. We also contacted researchers in the field. There was no language restriction in the search.

Selection criteria: We included randomised clinical trials (RCTs) assessing the effects of HLI for preventing cardiovascular events with a follow-up period of 1 year or longer. We considered myocardial infarction and stroke as the primary outcomes. We excluded studies in patients with end-stage renal disease.

Data collection and analysis: We independently performed study selection, risk of bias assessment and data extraction. We estimated relative risks (RR) for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model to synthesise the findings.

Main results: We included eight RCTs involving 24,210 participants with a low risk of bias in general terms. HLI did not reduce the risk of non-fatal or fatal myocardial infarction, stroke, or death by any cause (pooled RR 1.03, 95% CI 0.94 to 1.13, I(2) = 0%; pooled RR 0.89, 95% CI 0.73 to 1.08, I(2) = 15%); and pooled RR 1.00 (95% CI 0.92 to 1.09, I(2): 0%), respectively.

Authors' conclusions: Results from available published trials suggest that there is no evidence to support the use of HLI to prevent cardiovascular events.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Angina Pectoris / prevention & control
  • Cardiovascular Diseases / prevention & control*
  • Humans
  • Hyperhomocysteinemia / therapy*
  • Myocardial Infarction / prevention & control
  • Randomized Controlled Trials as Topic
  • Stroke / prevention & control
  • Vitamin B Complex / therapeutic use*


  • Vitamin B Complex