Systematic Review of Observational Studies with Dose-Response Meta-Analysis between Folate Intake and Status Biomarkers in Adults and the Elderly

Abstract

Background: Dietary reference values for folate intake vary widely across Europe. Methods: MEDLINE and Embase through November 2016 were searched for data on the association between folate intake and biomarkers (serum/plasma folate, red blood cell [RBC] folate, plasma homocysteine) from observational studies in healthy adults and elderly. The regression coefficient of biomarkers on intake (beta) was extracted from each study, and the overall and stratified pooled beta and SE (beta) were obtained by random effects meta-analysis on a double log scale. These dose-response estimates may be used to derive folate intake reference values. Results: For every doubling in folate intake, the changes in serum/plasma folate, RBC folate and plasma homocysteine were +22, +21, and -16% respectively. The overall pooled regression coefficients were beta = 0.29 (95% CI 0.21-0.37) for serum/plasma folate (26 estimates from 17 studies), beta = 0.28 (95% CI 0.21-0.36) for RBC (13 estimates from 11 studies), and beta = -0.21 (95% CI -0.31 to -0.11) for plasma homocysteine (10 estimates from 6 studies). Conclusion: These estimates along with those from randomized controlled trials can be used for underpinning dietary recommendations for folate in adults and elderly.