Abstract
Since 1998, the U.S. has mandated folic acid (FA) fortification of certain grain products to reduce the risk of neural tube defects. Folate intake and red blood cell (RBC) folate concentrations increased substantially post-intervention, although recent studies raise concerns about the level of ongoing benefit. This study investigated blood folate level determinants in healthy young adults, including intake of naturally occurring food folate, synthetic FA, and the interaction of naturally occurring food folate with a common missense variant in the FOLH1 gene thought to affect absorption. Participants (n = 265) completed the Diet History Questionnaire II, RBC folate testing, and were genotyped for the 484T>C FOLH1 variant. Men reported significantly greater intake of all folate sources except for supplemental FA, but RBC folate levels did not significantly differ by sex. Synthetic FA was a stronger predictor of RBC folate than naturally occurring food folate. In the largest racial group, synthetic FA and the interaction of FOLH1 genotype with naturally occurring food folate significantly predicted RBC folate, with the overall model accounting for 13.8% of the variance in RBC folate levels. Blood folate levels rely on a complex interaction of natural and synthetic folate intake as well as FOLH1 genotype.
Highlights
Folate refers to a diverse set of water-soluble vitamers with different oxidation states, one-carbon substitutions, and numbers of conjugated glutamates [1,2] (Table S1)
This cross-sectional study of folate intake patterns in healthy young adults demonstrates the importance of separately considering the contributions of naturally occurring food folate and synthetic folic acid intake to circulating folate levels, especially when viewed in concert with sex and genetic variation in folate absorption
In the second part of our analysis, we examined the relative contributions of naturally occurring food folate, synthetic folate, and a common genetic variant in FOLH1 to circulating folate levels
Summary
Folate refers to a diverse set of water-soluble vitamers with different oxidation states, one-carbon substitutions, and numbers of conjugated glutamates [1,2] (Table S1). Dietary sources of folate include leafy green vegetables, legumes, and fortified grain products. Folate bioavailability depends on dietary intake and on cellular mechanisms mediating absorption and metabolism, as well as genetic polymorphisms of key enzymes or carriers in the folate pathway [3]. Folate hydrolase (FOLH1, known as glutamate carboxypeptidase II, GCP-II) is an enzyme located on the intestinal brush border that must cleave the polyglutamated tail from naturally occurring food folate before it can be absorbed [4,5]. Folate is critical for a variety of cellular pathways [2], including the production of nucleotides and neurotransmitters [1], histone methylation and regulation of gene expression [6], and the methylation of homocysteine to methionine [7].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
