Folate status and concentrations of serum folate forms in the US population: National Health and Nutrition Examination Survey 2011–2

Abstract

Serum and red blood cell (RBC) total folate are indicators of folate status. No nationally representative population data exist for folate forms. We measured serum folate forms [5-methyltetrahydrofolate (5-methylTHF), unmetabolized folic acid (UMFA), non-methyl folate (sum of THF, 5-formylTHF, 5,10-methenylTHF), and MeFox (5-methylTHF oxidation product)] by HPLC-MS/MS and RBC total folate by microbiologic assay in US persons ≥1 year (n ~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 r <0.4) but significant (P <0.05) correlations with physiologic 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, physiologic, and lifestyle variables as serum total folate. Patterns observed for MeFox may suggest altered folate metabolism dependent on biological characteristics.

Serum folate concentrations and all-cause, cardiovascular disease and cancer mortality: A cohort study based on 1999–2010 National Health and Nutrition Examination Survey (NHANES)

“…Another theory is that high folate concentrations could lead to decreased levels of thymidylate and 5-methylenetetrahydrofolate (5-MTHF), thus impairing DNA integrity and affecting protein production [26]. Age and gender differentials in folate concentrations are reported in several studies [27,28]. While there is a possibility age and/or gender could alter the correlations between folate and mortality the possible underlying mechanisms are mainly unexplored and need further investigation.…”

Correspondence of folate dietary intake and biomarker data

“…The microbiological assay was used to estimate RBC folate; serum folate was determined by use of HPLC-tandem mass spectrometry (MS/MS) (14). According to the DRI summary of folate, the cutoffs for assessing the adequacy of folate status are ,7 nmol/L for serum folate and ,305 nmol/L for RBC folate (9).…”

Potential Links between Impaired One-Carbon Metabolism Due to Polymorphisms, Inadequate B-Vitamin Status, and the Development of Alzheimer’s Disease

“…Age itself might further contribute to impaired OCM as there was an age-dependent decrease in THF accompanied by an increase in products of its oxidation, which are biologically inactive [184]. Hcy levels were elevated in both dementia patients and elderly controls when compared to a younger group of neurological patients without dementia [131].…”