Folate Biomarkers, Folate Intake, and Risk of Death From All Causes, Cardiovascular Disease, and Cancer: A Systematic Review and Dose-Response Meta-Analysis of Prospective Cohort Studies

Existing evidence on the relation between folate intake and biomarkers with mortality risk is controversial. Previous cohort studies were examined regarding folate intake and biomarkers in relation to risk of all-cause, cardiovascular disease- (CVD), and cancer-related mortality through a systematic review and meta-analysis. A systematic search was performed of the PubMed, Scopus, and ISI Web of Science databases up to July 2023. Prospective cohort studies examining the association of folate biomarkers (in serum, plasma, red blood cells) and intake with risk of all-cause, CVD-, and cancer-related mortality were considered. A random-effects model was applied to combine study-specific risk estimates. Dose-response relations were assessed by 1-stage weighted mixed-effects meta-analysis. A total of 25 cohorts with 423 304 participants, 36 558 all-cause, 12 662 CVD-, and 2426 cancer-related deaths were included. No significant association was observed between the highest levels of folate biomarkers and all-cause mortality risk (hazard ratio [HR], 0.91; 95% CI, 0.77-1.06; n = 17; I2 = 89.4%; P