Impact of Mandatory Folic Acid Fortification on Population Folate Levels: A Systematic Review and Meta-Analysis Open Access

Parker, Jessica (Spring 2024)

Permanent URL: https://etd.library.emory.edu/concern/etds/4f16c434h?locale=en
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Abstract

Background

Folate is an essential nutrient for optimum health outcomes. Many countries (n=70) have mandated the fortification of wheat flour, maize flour or rice (i.e., grains) with folic acid (a synthetic form of folate). This study assesses the effectiveness of such fortification on serum/plasma folate and red blood cell (RBC) folate levels.

Methods

We systematically reviewed and meta-analyzed studies from countries with mandatory grain fortification with folic acid that reported primary pre- and post-fortification data on folate status outcomes. We searched PubMed and Embase and conducted a second search with an Emory University librarian. Meta-analyses were conducted using random effects models, with results stratified by age and gender, country income level, fortification duration, and study bias risk.

Results

We screened 4,311 studies, identifying 188 full-text articles for data extraction, 22 of which reported folate status outcomes. About 86% of studies were conducted in high-income countries (HICs), while 14% were in low- or middle-income countries (LMICs). Meta-analyses revealed that mandatory fortification increased serum/plasma and RBC folate levels, albeit with considerable heterogeneity across studies (I²=99%), indicating that the fortification impact differed significantly across populations or settings. The MDM (95% CI) across all serum/plasma studies was 15.0 nmol/L (9.4-20.5), with variations observed by strata; 17.0 nmol/L (8.5-25.5) among females of reproductive age, 9.8 nmol/L (3.3-16.3) in LMICs, and 15.9 nmol/L (9.5-22.3) in HICs. RBC folate levels similarly increased across all strata, with an overall MDM of 329.4 nmol/L (95% CI 243.9-414.9). The effect for both serum/plasma and RBC folate levels increased with the duration of fortification. 

Discussion

This review addresses the current gap in the understanding of the effectiveness of folic acid fortification and corroborates previous research suggesting that mandatory folic acid fortification improves population folate levels. These findings highlight the importance of continued monitoring and evaluation of global fortification programs and legislation. This advances progress toward addressing micronutrient malnutrition and reducing neural tube defects, particularly among vulnerable populations.

Table of Contents

Table of Contents

ABSTRACT……………………………………………………..…………….......….………….....1

INTRODUCTION………………………………………………………………......………….…..2

METHODS……………………………………………………………………….......………….....5

Data sources and search strategy…………………………………………......………….……5

Eligibility criteria……………………………………………………….…....….………...….....6

Selection process……………………………………………………..……....….…………....…7

Data extraction and management…………………………………………....….……………7

Risk of bias………………………………………………..………………....…….…………......8

Data synthesis and analysis……………………………………………….…..…….…….....10

RESULTS…………………………………………………………………………….....…....……11

Study characteristics……………………………………………………….…….......…….….11

Results of meta-analyses for serum/plasma folate………………………….....……..…13

Results of meta-analyses for red blood cell folate…………………………....………….20

DISCUSSION………………………………………………………………………………...……26

REFERENCES…………………………………………………………………………….....…...32

APPENDIX…………………………………………………………………………………...……42

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