Impact of Mandatory Grain Fortification With Folic Acid on Population Folate Concentrations and the Risk of Folate Deficiency and Insufficiency: A Systematic Review and Meta-Analysis.

BACKGROUND

Wheat flour, maize flour, and rice (i.e., grain) fortification with folic acid is an important folate dietary source globally. There are no systematic reviews or meta-analyses evaluating the effect of mandatory grain fortification on folate insufficiency (using serum/plasma folate and red blood cell [RBC] folate), or folate deficiency using RBC folate.

OBJECTIVES

This study aimed to assess the effectiveness of mandatory grain fortification with folic acid on serum/plasma folate and RBC folate concentrations and the risk of folate deficiency and insufficiency based on these biomarkers.

METHODS

We searched PubMed and Embase with assistance from a professional library informationist. We selected studies from countries with mandatory grain fortification that include folic acid in standards if they reported primary pre- and post-fortification data on folate status outcomes. We ran meta-analyses in R using random effects models with results expressed as meta-differences of means (MDMs) or meta-prevalence ratios (mPRs) for continuous and binary outcomes, respectively. All meta-estimates were accompanied by 95% confidence intervals (CIs).

RESULTS

We screened 4311 documents, identifying 30 articles that reported folate status outcomes (22 reported mean serum/plasma or RBC folate, 17 reported prevalence of folate deficiency or insufficiency). About 19% of studies were conducted in low- or middle-income countries. Mandatory fortification improved folate status, albeit with considerable heterogeneity across studies (I2>73%). For serum/plasma folate concentrations, the MDM across all studies was 15.0 nmol/L (95% CI: 9.4, 20.5). For serum/plasma folate insufficiency and deficiency, the mPR estimates were 0.17 (95% CI: 0.08, 0.37) and 0.08 (95% CI: 0.03, 0.23), respectively. For RBC folate concentrations, the MDM was 329.4 nmol/L (95% CI: 243.9-414.9). For RBC folate insufficiency and deficiency, mPRs were 0.16 (95% CI: 0.08-0.30) and 0.05 (95% CI: 0.01-0.46), respectively.

CONCLUSIONS

Mandatory grain fortification with folic acid increases blood folate concentrations and decreases the risk of folate insufficiency and folate deficiency.