Unmetabolized folic acid is detected in nearly all serum samples from US children, adolescents, and adults.
BACKGROUND
Serum total folate consists mainly of 5-methyltetrahydrofolate (5-methylTHF). Unmetabolized folic acid (UMFA) may occur in persons consuming folic acid-fortified foods or supplements.


OBJECTIVE
We describe serum 5-methylTHF and UMFA concentrations in the US population ≥1 y of age by demographic variables and fasting time, stratified by folic acid-containing dietary supplement use. We also evaluate factors associated with UMFA concentrations >1 nmol/L.


METHODS
Serum samples from the cross-sectional NHANES 2007-2008 were measured for 5-methylTHF (n = 2734) and UMFA (n = 2707) by HPLC-tandem mass spectrometry.


RESULTS
In supplement users compared with nonusers, we found significantly higher geometric mean concentrations of 5-methylTHF (48.4 and 30.7 nmol/L, respectively) and UMFA (1.54 and 0.794 nmol/L, respectively). UMFA concentrations were detectable (>0.3 nmol/L) in >95% of supplement users and nonusers, regardless of demographic or fasting characteristics; concentrations differed significantly by age and fasting time, but not by sex and race-ethnicity, both in supplement users and nonusers. The prevalence of UMFA concentrations >1 nmol/L was 33.2% overall and 21.0% in fasting (≥8 h) adults (≥20 y of age). Using multiple logistic regression analysis, UMFA concentrations >1 nmol/L were associated with being older, non-Hispanic black, nonfasting (<8 h), having smaller body surface area, higher total folic acid intake (diet and supplements), and higher red blood cell folate concentrations. In fasting adults, a decrease in the mean daily alcohol consumption was also associated with increased odds of UMFA concentrations >1 nmol/L.


CONCLUSIONS
UMFA detection was nearly ubiquitous, and concentrations >1 nmol/L were largely but not entirely explained by fasting status and by total folic acid intake from diet and supplements. These new UMFA data in US persons ≥1 y of age provide much-needed information on this vitamer in a fortified population with relatively high use of dietary supplements.
National Center for Environmental Health, CDC, Atlanta, GA; CPfeiffer@cdc.gov.
Christine M
CM
Pfeiffer
National Center for Environmental Health, CDC, Atlanta, GA;
Maya R
MR
Sternberg
National Center for Environmental Health, CDC, Atlanta, GA;
Zia
Z
Fazili
Office of Dietary Supplements, NIH, Bethesda, MD; and.
Elizabeth A
EA
Yetley
National Center for Health Statistics, CDC, Hyattsville, MD.
David A
DA
Lacher
Office of Dietary Supplements, NIH, Bethesda, MD; and.
Regan L
RL
Bailey
National Center for Health Statistics, CDC, Hyattsville, MD.
Clifford L
CL
Johnson
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood*; D005527:Food, Fortified; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009749:Nutrition Surveys; D053719:Tandem Mass Spectrometry; D013763:Tetrahydrofolates / Q000097:blood; D014481:United States; D055815:Young Adult
D015415:Biomarkers; D013763:Tetrahydrofolates; D005492:Folic Acid; C005984:5-methyltetrahydrofolate
5-methyltetrahydrofolate; HPLC–tandem mass spectrometry; NHANES; serum folate; unmetabolized folic acid