Folate status and concentrations of serum folate forms in the US population: National Health and Nutrition Examination Survey 2011-2.
Serum and erythrocyte (RBC) total folate are indicators of folate status. No nationally representative population data exist for folate forms. We measured the serum folate forms (5-methyltetrahydrofolate (5-methylTHF), unmetabolised folic acid (UMFA), non-methyl folate (sum of tetrahydrofolate (THF), 5-formyltetrahydrofolate (5-formylTHF), 5,10-methenyltetrahydrofolate (5,10-methenylTHF)) and MeFox (5-methylTHF oxidation product)) by HPLC-MS/MS and RBC total folate by microbiologic assay in US population ≥ 1 year (n approximately 7500) participating in the National Health and Nutrition Examination Survey 2011-2. Data analysis for serum total folate was conducted including and excluding MeFox. Concentrations (geometric mean; detection rate) of 5-methylTHF (37·5 nmol/l; 100 %), UMFA (1·21 nmol/l; 99·9 %), MeFox (1·53 nmol/l; 98·8 %), and THF (1·01 nmol/l; 85·2 %) were mostly detectable. 5-FormylTHF (3·6 %) and 5,10-methenylTHF (4·4 %) were rarely detected. The biggest contributor to serum total folate was 5-methylTHF (86·7 %); UMFA (4·0 %), non-methyl folate (4·7 %) and MeFox (4·5 %) contributed smaller amounts. Age was positively related to MeFox, but showed a U-shaped pattern for other folates. We generally noted sex and race/ethnic biomarker differences and weak (Spearman's r< 0·4) but significant (P< 0·05) correlations with physiological and lifestyle variables. Fasting, kidney function, smoking and alcohol intake showed negative associations. BMI and body surface area showed positive associations with MeFox but negative associations with other folates. All biomarkers showed significantly higher concentrations with recent folic acid-containing dietary supplement use. These first-time population data for serum folate forms generally show similar associations with demographic, physiological and lifestyle variables as serum total folate. Patterns observed for MeFox may suggest altered folate metabolism dependent on biological characteristics.
National Center for Environmental Health, Centers for Disease Control and Prevention,Atlanta,GA,USA.
Christine M
CM
Pfeiffer
National Center for Environmental Health, Centers for Disease Control and Prevention,Atlanta,GA,USA.
Maya R
MR
Sternberg
National Center for Environmental Health, Centers for Disease Control and Prevention,Atlanta,GA,USA.
Zia
Z
Fazili
National Center for Health Statistics, Centers for Disease Control and Prevention,Hyattsville,MD,USA.
David A
DA
Lacher
National Center for Environmental Health, Centers for Disease Control and Prevention,Atlanta,GA,USA.
Mindy
M
Zhang
National Center for Health Statistics, Centers for Disease Control and Prevention,Hyattsville,MD,USA.
Clifford L
CL
Johnson
National Center for Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention,Atlanta,GA,USA.
Heather C
HC
Hamner
Office of Dietary Supplements, National Institutes of Health,Bethesda,MD,USA.
Regan L
RL
Bailey
Center for Food Safety and Applied Nutrition, Food and Drug Administration,College Park,MD,USA.
Jeanne I
JI
Rader
Center for Food Safety and Applied Nutrition, Food and Drug Administration,College Park,MD,USA.
Sedigheh
S
Yamini
National Center for Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention,Atlanta,GA,USA.
R J
RJ
Berry
Office of Dietary Supplements, National Institutes of Health,Bethesda,MD,USA.
Elizabeth A
EA
Yetley
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D004912:Erythrocytes / Q000737:chemistry; D005006:Ethnicity; D005260:Female; D005492:Folic Acid / Q000097:blood*; D006801:Humans; D007223:Infant; D002955:Leucovorin / Q000097:blood; D008019:Life Style; D008297:Male; D008875:Middle Aged; D009749:Nutrition Surveys; D009752:Nutritional Status; D012016:Reference Values; D012737:Sex Factors; D053719:Tandem Mass Spectrometry; D013763:Tetrahydrofolates / Q000097:blood; D014481:United States / Q000453:epidemiology; D055815:Young Adult
D015415:Biomarkers; D013763:Tetrahydrofolates; C018092:5,10-methenyltetrahydrofolate; D005492:Folic Acid; D002955:Leucovorin; C005984:5-methyltetrahydrofolate
5-Methyltetrahydrofolate; Folate oxidation products; Folate vitamers; Liquid chromatography–MS/MS; National Health and Nutrition Examination Survey; Non-methyl folate; Unmetabolised folic acid