Study examines outcomes of lowering homocysteine levels with folic acid and vitamin B12

June 22, 2010, JAMA and Archives Journals

Patients who had experienced a heart attack and lowered their blood homocysteine levels with folic acid and vitamin B12 supplementation did not have an associated lower risk of heart attack, coronary death or stroke, according to a study in the June 23/30 issue of JAMA. However, the researchers did find that folic acid supplementation did not increase the risk of cancer, which has been speculated.

Blood homocysteine levels are positively associated with , but it is uncertain whether the association is causal, according to background information in the article. A meta-analysis of prospective studies indicated that, after adjustment for known risk factors, a 25 percent lower than usual homocysteine concentration was associated with an 11 percent lower risk of coronary and 19 percent lower risk of stroke. "Daily supplementation with folic acid typically lowers homocysteine levels by about 25 percent, and the addition of vitamin B12 lowers it by a further 7 percent," the authors write. Other research has suggested supplementation with folic acid may offer a protective effect against stroke.

Jane M. Armitage, F.R.C.P., of the University of Oxford, United Kingdom, and colleagues with the Study of the Effectiveness of Additional Reductions In Cholesterol and Homocysteine (SEARCH) trial assessed the effects of lowering homocysteine levels with folic acid plus vitamin B12 in 12,064 survivors of (heart attack) in secondary care hospitals in the United Kingdom between 1998 and 2008. Patients were randomized to receive either 2 mg. folic acid plus 1 mg. vitamin B12 daily or matching placebos. The primary outcomes measured included first major vascular event, defined as major coronary event (coronary death, , or coronary revascularization), fatal or nonfatal stroke, or noncoronary revascularization.

Patients who received the study vitamins reduced homocysteine by an average of 3.8 µmol/L (28 percent). During 6.7 years of follow-up, major vascular events occurred in 1,537 of 6,033 participants (25.5 percent) allocated folic acid plus vitamin B12 vs. 1,493 of 6,031 participants (24.8 percent) allocated placebo. "There was no evidence of any benefit beginning to emerge with more prolonged treatment and follow-up," the authors write.

Receipt of study vitamins also was not associated with a significant effect on any stroke (vitamins, 4.5 percent vs. placebo, 4.4 percent); noncoronary revascularizations (vitamins, 3.0 percent vs. placebo, 2.5 percent); or major coronary events (vitamins, 20.4 percent vs. placebo, 19.6 percent). There were no apparent differences in the numbers of deaths attributed to vascular causes or nonvascular causes.

New primary cancers (excluding non-melanoma skin cancer) were diagnosed in 11.2 percent of the participants allocated folic acid plus vs. 10.6 percent allocated placebo, with this difference not being significant.

"Taken together with the previous homocysteine-lowering trials, the results of SEARCH indicate that folic acid supplementation has no significant adverse effects on cancer or other major health outcomes, even if it also produces no beneficial effects on cardiovascular disease. In addition, these results highlight the importance of focusing on drug treatments (e.g., aspirin, statins, and antihypertensive therapy) and lifestyle changes (in particular, stopping smoking and avoiding excessive weight gain) that are of proven benefit, rather than lowering homocysteine with folic acid-based vitamin supplements, for the prevention of cardiovascular disease," the authors conclude.

More information: JAMA. 2010;303[24]:2486-2494.

Related Stories

Recommended for you

Human 'chimeric' cells restore crucial protein in Duchenne muscular dystrophy

March 16, 2018
Cells made by fusing a normal human muscle cell with a muscle cell from a person with Duchenne muscular dystrophy —a rare but fatal form of muscular dystrophy—were able to significantly improve muscle function when implanted ...

Team develops 3-D tissue model of a developing human heart

March 16, 2018
The heart is the first organ to develop in the womb and the first cause of concern for many parents.

Democratizing science: Researchers make neuroscience experiments easier to share, reproduce

March 16, 2018
Over the past few years, scientists have faced a problem: They often cannot reproduce the results of experiments done by themselves or their peers.

Genetic variant discovery to help asthma sufferers

March 16, 2018
Research from the University of Liverpool, published today in Lancet Respiratory Medicine, identifies a genetic variant that could improve the safety and effectiveness of corticosteroids, drugs that are used to treat a range ...

Researchers say use of artificial intelligence in medicine raises ethical questions

March 15, 2018
In a perspective piece, Stanford researchers discuss the ethical implications of using machine-learning tools in making health care decisions for patients.

Study identifies potential drug for treatment of debilitating inherited neurological disease

March 15, 2018
St. Jude Children's Research Hospital scientists have demonstrated in mouse studies that the neurological disease spinal bulbar muscular atrophy (SBMA) can be successfully treated with drugs. The finding paves the way for ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

1 / 5 (1) Jun 22, 2010
Folic acid is not the form of folate found in green vegetables and virtually every other food. About 11% of us cannot convert folate to the active and natural form folinate or tetrahydrofolate. This commercially available form would likely give the kind of results the authors purport to have been seeking.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.