"We found no evidence that homocysteine-lowering interventions, in the form of supplements of vitamin B₆ (pyridoxine), B₉ (folic acid), or B₁₂ (cyanocobalamin), given alone or in combination at any dosage, compared with placebo or standard care, prevents myocardial infarction [MI] or stroke or reduces total mortality in participants at risk of or with established cardiovascular disease," they report.

AJ Martí-Carvajal wrote that, "The review was necessary despite the fact that trial after trial has failed to show a benefit of homocysteine-lowering therapy. Healthcare providers, consumers, researchers, and policy makers are inundated with unmanageable amounts of information, and it is unlikely they will all have the time to properly interpret this evidence and incorporate it into healthcare decisions."

The new research provides "scientific proof ... that folic acid, vitamin B₁₂, and vitamin B₆ do not work to prevent cardiovascular disease," he said, adding that his message to people would be: "Save your money." Doctors should advise their patients of this message and instead encourage them to quit smoking, exercise more, and monitor blood pressure, glucose, and lipids to reduce the risk of cardiovascular events, he stressed.

The new review includes data from eight randomized clinical trials -- CHAOS, FOLARDA, GOES, HOPE-2, NORVIT, VISP, WAFACS, and WENBIT -- assessing the effects of homocysteine lowering for preventing cardiovascular events with a follow-up period of one year or longer, in a total of 24,210 participants. MI and stroke were the primary outcomes.

Homocysteine lowering did not reduce the risk of nonfatal or fatal MI (pooled relative risk 1.03), stroke (RR 0.89; 95% CI 0.72–1.09), or death from any cause (RR 1.00).

The researchers note that the participants in the eight trials differed somewhat in cardiovascular-risk levels, baseline homocysteine levels, access to foods fortified with folic acid, dosages of vitamin, and control groups, with treatment periods varying from two to seven years. Nevertheless, they say, the data "are very consistent."

Use of vitamin-B supplementation to lower homocysteine "is not justified, unless new evidence from large high-quality trials alters this conclusion," they say.

Another trial, SEARCH, also found no evidence that lowering homocysteine using folic acid and vitamin B₁₂ has any effect on vascular events compared with placebo in more than 12,000 heart-attack survivors, according to a presentation at the 2008 AHA meeting. However, as this trial has not yet been published, it was not included in the review by Martí-Carvajal et al.

1. Martí-Carvajal AJ, Sola I, Lathyris D, et al. Homocysteine lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev 2009; 4:CD006612. Cochrane Database
2. Syst Rev 2009; 4:CD006612. Homocysteine lowering interventions for preventing cardiovascular events [podcast]. Available here.

Published October 7, 2009, in the Cochrane Database of Systematic Reviews.