Cochrane for Clinicians

Putting Evidence into Practice

Effectiveness of B-Complex Vitamins for Prevention of Cardiovascular Events


Am Fam Physician. 2010 Apr 1;81(7):850.

Clinical Question

Are B-complex vitamins (i.e., vitamins B12, B9, and B6) effective in primary or secondary prevention of myocardial infarction (MI) or stroke?

Evidence-Based Answer

Eight randomized clinical trials that included 24,210 patients did not show a reduction in MI, stroke, or all-cause mortality with B-complex vitamin therapy. (Strength of Recommendation = A, based on consistent and good quality patient-oriented evidence)

Practice Pointers

A high level of circulating total homocysteine is associated with an increased risk of cardiovascular disease. Levels of homocysteine in the blood are influenced by serum levels of vitamins B12, B9, and B6. For example, folic acid (B9) supplementation reduces circulating total homocysteine levels. Therefore, supplementation with B-complex vitamins is plausible as a primary or secondary prevention measure. However, this Cochrane review confirms that supplementation with B-complex vitamins is not an effective strategy for reducing cardiovascular events.

Patients were followed for one to 7.3 years. Results of eight randomized controlled trials were consistent despite different risk factors for cardiovascular disease, baseline total homocysteine levels, access to foods fortified with folic acid, dose of vitamin, and duration of treatment.

Although they acknowledge the lack of evidence, the American Heart Association and American Stroke Association recommend that all persons meet current dietary guidelines for foods rich in folate and vitamins B6 and B12.1,2 They recommend that, given their safety and low cost, supplementation with folic acid and B vitamins may be useful in patients with elevated homocysteine levels.1 For patients who have had an ischemic stroke or transient ischemic attack with hyper-homocysteinemia (i.e., homocysteine levels greater than 1.35 mg per L [10 μmol per L]), they recommend standard vitamin preparations, yet acknowledge that there is no evidence that the vitamins will reduce the occurrence of stroke.2

The authors of this review point out that the United States is the only country with mandatory fortification of foods with folic acid. The justification for this was to modify risk of neural tube defects. Fortification reduced the prevalence of low folic acid levels and either did not change or reduced homocysteine levels. However, it did not influence death from cardiovascular causes, MI, or stroke. On the other hand, high folic acid levels can mask vitamin B12 deficiency. Therefore, the effects of mandatory folic acid fortification deserve further evaluation.

Author disclosure: Nothing to disclose.


Martí-Carvajal AJ, Solà I, Lathyris D, Salanti G. Homocysteine lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2009;(4):CD006612.


1. Goldstein LB, Adams R, Alberts MJ, et al. Primary prevention of ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council: cosponsored by the Atherosclerotic Perhipheral Vascular Disease Interdisciplinary Working Group; Cardiovascular Nursing Council; Clinical Cardiology Council; Nutrition, Physical Activity, and Metabolism Council; and the Quality of Care and Outcomes Research Interdisciplinary Working Group [published correction appears in Circulation. 2006;114(22):e617]. Circulation. 2006;113(24):e873–923.

2. Adams RJ, Albers G, Alberts MJ, et al., for the American Heart Association, American Stroke Association. Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Stroke. 2008;39(5):1647–1652.



Copyright © 2010 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions

More in AFP

Editor's Collections

Related Content

More in Pubmed


Jan 2022

Access the latest issue of American Family Physician

Read the Issue

Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article