Folate and risk of coronary heart disease: A meta-analysis of prospective studies

doi:10.1016/j.numecd.2011.04.011

Nutrition, Metabolism and Cardiovascular Diseases

Volume 22, Issue 10, October 2012, Pages 890-899

https://doi.org/10.1016/j.numecd.2011.04.011 Get rights and content

Abstract

Background and aims

Epidemiologic studies are inconsistent regarding the association between folate and coronary heart disease (CHD) risk. The aim was to perform a meta-analysis to determine whether an association exists between folate and total CHD endpoints in prospective studies.

Methods and results

We searched the PUBMED and EMBASE databases for studies conducted from 1966 through August 2010. Data were independently abstracted by 2 investigators using a standardized protocol. Study-specific risk estimates were combined by using a random effects model.

A total of 14 studies were included in the meta-analysis: 7 studies on dietary folate intake and 8 studies on blood folate levels. For dietary intake, the summary relative risk (RR) indicated a significant association between the highest folate intake and reduced risk of CHD (summary RR: 0.69; 95% CI: 0.60, 0.80). Furthermore, an increase in folate intake of 200 ug/day was associated with a 12% decrease in the risk of developing CHD (summary RR: 0.88; 95% CI: 0.82, 0.94). For blood folate levels, we also found a borderline inverse association of highest blood folate levels on CHD risk (summary RR: 0.74; 95% CI: 0.53, 1.02); our dose-response analysis indicated that an increment in blood folate levels of 5 mmol/l was associated with an 8% decrease in the risk of developing CHD (summary RR: 0.92; 95% CI: 0.84, 1.00).

Conclusion

This meta-analysis suggests that dietary folate intake and blood folate level are inversely associated with CHD risk.

Introduction

Folate is the generic term for the water-soluble B-complex vitamin, which functions as an essential coenzyme in 1-carbon transfer reactions in the metabolism of amino acids and nucleic acids [1]. During the past few years, studies have demonstrated that folic acid supplementation during the periconceptional period reduces the risk of neural tube defects (NTDs) [2], [3]. For this reason, the US and Canadian governments implemented mandatory folic acid fortification of all enriched cereal grain products to improve folate status in 1998 and thereby reduced the birth prevalence of NTDs successfully [4], [5]. Since then, more and more epidemiologic studies and randomized controlled trials (RCTs) have provided compelling evidence that folate has been associated with public health benefits in the United States and worldwide.

Coronary heart disease (CHD) is still the most common cause of death globally; an estimated 7.2 million people died of the disease in 2004 [6]. To date, many epidemiologic studies have been conducted to investigate the association between folate and the risk of CHD. However, the results of those observational studies remain inconsistent and have not yet been quantitatively summarized. Hence, we chose to conduct a meta-analysis to combine the results from the available prospective studies, to evaluate whether dietary intake or blood levels of folate is associated with CHD risk.

Section snippets

Search strategy

We performed a literature search of the PUBMED and EMBASE databases that included the years 1966 through August 2010. We used search terms “folate,” “folic acid” combined with “coronary artery disease,” “coronary heart disease,” “myocardial infarction,” “ischemic heart disease,” “CAD,” and “CHD” in the full-text option, without language restrictions. The titles and abstracts were scanned to exclude any studies that were clearly irrelevant. We read the full texts of the remaining articles to

Literature search

As shown in Appendix 1 Supplementary Material, our literature search identified 22 potentially relevant studies concerning folate and CHD risk [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27], [28], [29], [30], [31], [32], [33], [34], [35], [36]. Two articles [15], [16] were excluded because they did not include sufficient information. Five studies [17], [18], [19], [20], [21] were excluded because the endpoint was cardiovascular disease containing stroke events. One

Discussion

The present meta-analysis evaluated the association between folate and CHD risk based on 14 prospective results published from 1996 to 2010. The results suggest that highest dietary folate intake was statistically significantly associated with 31% decreased risk of CHD, and an increase of folate intake of 200 ug/day was related to a 12% decrease in CHD risk.

We also found a borderline inverse association of highest blood folate levels on CHD risk. It seemed that the study by Giles et al. [31]

Conflict of interest

None declared.

Acknowledgements

This work was supported by a grant from the National Natural Science Foundation of China (No. 30871078).

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¹: Drs Ze-Mu Wang, Bo Zhou and Zhen-Lin Nie contributed equally to this work.

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Folate and risk of coronary heart disease: A meta-analysis of prospective studies

Abstract

Background and aims

Methods and results

Conclusion

Introduction

Section snippets

Search strategy

Literature search

Discussion

Conflict of interest

Acknowledgements

Am J Clin Nutr

Lancet

Control Clin Trials

Am J Clin Nutr

J Nutr

Ann Epidemiol

Atherosclerosis

Am J Clin Nutr

Mayo Clin Proc

Life Sci

Am J Clin Nutr

Arch Cardiovasc Dis

Folic acid supplementation for the prevention of neural tube defects: an update of the evidence for the U.S. preventive services task force

Ann Intern Med

Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects

JAMA

Reduction in neural-tube defects after folic acid fortification in Canada

N Engl J Med

Green tea consumption and prevention of coronary artery disease

Circ J

Methods for trend estimation from summarized dose-response data, with applications to meta-analysis

Am J Epidemiol

Generalized least squares for trend estimation of summarized dose-response data

Stata J

Quantifying heterogeneity in a meta-analysis

Stat Med

The power of statistical tests in meta-analysis

Psychol Methods

Bias in meta-analysis detected by a simple, graphical test

BMJ

Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of observational studies in epidemiology (MOOSE) group

JAMA

The association of vitamin b 12 and folate blood levels with mortality and cardiovascular morbidity incidence in the old old: the Bronx aging study

Am J Ther

Both vitamin B6 and total homocysteine plasma levels predict long-term atherothrombotic events in healthy subjects

Eur Heart J

Serum folate and chronic disease risk: findings from a cohort of United States adults

Int J Epidemiol