Serum folic acid concentrations in the U.S. population after the introduction of folic acid fortification

Abstract

Knowing what the serum folic acid (FA) concentrations in the U.S. population post‐fortification are is of great interest because FA might have a dual modulatory effect in carcinogenesis and circulating levels of FA in serum have been associated with reduced natural killer cell cytotoxicity in postmenopausal women. As part of a method comparison study, we analyzed 232 serum samples from NHANES 1999‐2004 (convenience set) for folate species by LC‐MS/MS. The distribution of FA concentrations was right‐skewed, with ~30% and 5% of the samples having levels >10 and >100 nmol/L, respectively. Median FA concentrations (nmol/L) were dependent on the length of fasting (29.0 at ≤3 h; 1.72 at 4‐6 h; 0.98 at 7‐12 h; 0.83 at >12 h), the use of FA‐containing supplements during the past month (4.90 for users; 0.63 for non‐users), and the use of a dietary supplement since starting the fasting for the blood draw (14.8 for users; 1.0 for non‐users). Fifteen percent of the FA variability was explained by these variables in a regression model. Subjects who fasted >3h and used no supplement during the past month or during fasting, had a baseline FA concentration of 3.11 nmol/L. For =3h fasting, use of a supplement during the past month, or use of a supplement during fasting, 21.5, 16.8, and 16.0 nmol/L FA needs to be added, respectively. To better interpret "free" FA serum levels, it is important to understand its determinants.