Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials.
BACKGROUND
Epidemiologic studies have suggested that folate intake decreases risk of cardiovascular diseases. However, the results of randomized controlled trials on dietary supplementation with folic acid to date have been inconsistent.


OBJECTIVE
To evaluate the effects of folic acid supplementation on risk of cardiovascular diseases and all-cause mortality in randomized controlled trials among persons with preexisting cardiovascular or renal disease.


METHODS
Studies were retrieved by searching MEDLINE (January 1966-July 2006) using the Medical Subject Headings cardiovascular disease, coronary disease, coronary thrombosis, myocardial ischemia, coronary stenosis, coronary restenosis, cerebrovascular accident, randomized controlled trial, clinical trials, homofolic acid, and folic acid, and the text words folic acid and folate. Bibliographies of all retrieved articles were also searched, and experts in the field were contacted.


METHODS
From 165 relevant retrieved reports, 12 randomized controlled trials compared folic acid supplementation with either placebo or usual care for a minimum duration of 6 months and with clinical cardiovascular disease events reported as an end point.


METHODS
Data on study design, characteristics of participants, changes in homocysteine levels, and cardiovascular disease outcomes were independently abstracted by 2 investigators using a standardized protocol.


RESULTS
Studies including data from 16 958 participants with preexisting vascular disease were analyzed using a random-effects model. The overall relative risks (95% confidence intervals) of outcomes for patients treated with folic acid supplementation compared with controls were 0.95 (0.88-1.03) for cardiovascular diseases, 1.04 (0.92-1.17) for coronary heart disease, 0.86 (0.71-1.04) for stroke, and 0.96 (0.88-1.04) for all-cause mortality. The relative risk was consistent among participants with preexisting cardiovascular or renal disease.


CONCLUSIONS
Folic acid supplementation has not been shown to reduce risk of cardiovascular diseases or all-cause mortality among participants with prior history of vascular disease. Several ongoing trials with large sample sizes might provide a definitive answer to this important clinical and public health question.
Bazzano
Lydia A
LA
Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, La 70112-2715, USA. lbazzano@tulane.edu
Reynolds
Kristi
K
Holder
Kevin N
KN
He
Jiang
J
D002318:Cardiovascular Diseases / Q000453:epidemiology*; D019587:Dietary Supplements; D005492:Folic Acid / Q000008:administration & dosage*; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D014803:Vitamin B Complex / Q000008:administration & dosage*
D014803:Vitamin B Complex; D005492:Folic Acid