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Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials.
JAMA 2006; 296(22):2720-6JAMA

Abstract

CONTEXT

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.

DATA SOURCES

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.

STUDY SELECTION

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.

DATA EXTRACTION

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.

DATA SYNTHESIS

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.

Authors+Show Affiliations

Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, La 70112-2715, USA. lbazzano@tulane.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

17164458

Citation

Bazzano, Lydia A., et al. "Effect of Folic Acid Supplementation On Risk of Cardiovascular Diseases: a Meta-analysis of Randomized Controlled Trials." JAMA, vol. 296, no. 22, 2006, pp. 2720-6.
Bazzano LA, Reynolds K, Holder KN, et al. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA. 2006;296(22):2720-6.
Bazzano, L. A., Reynolds, K., Holder, K. N., & He, J. (2006). Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA, 296(22), pp. 2720-6.
Bazzano LA, et al. Effect of Folic Acid Supplementation On Risk of Cardiovascular Diseases: a Meta-analysis of Randomized Controlled Trials. JAMA. 2006 Dec 13;296(22):2720-6. PubMed PMID: 17164458.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. AU - Bazzano,Lydia A, AU - Reynolds,Kristi, AU - Holder,Kevin N, AU - He,Jiang, PY - 2006/12/14/pubmed PY - 2006/12/19/medline PY - 2006/12/14/entrez SP - 2720 EP - 6 JF - JAMA JO - JAMA VL - 296 IS - 22 N2 - CONTEXT: 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. DATA SOURCES: 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. STUDY SELECTION: 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. DATA EXTRACTION: 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. DATA SYNTHESIS: 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. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/17164458/Effect_of_folic_acid_supplementation_on_risk_of_cardiovascular_diseases:_a_meta_analysis_of_randomized_controlled_trials_ L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.296.22.2720 DB - PRIME DP - Unbound Medicine ER -