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

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.