Folate and vitamin B-12 biomarkers in NHANES: history of their measurement and use

Abstract

NHANES measured folate and vitamin B-12 status biomarkers, starting with serum folate from NHANES I (1974-1975) through 2010. Subsequent NHANES measured additional biomarkers [eg, red blood cell folate, serum vitamin B-12, total homocysteine (tHcy), methylmalonic acid, serum folic acid, and 5-methyltetrahydrofolic acid]. Examples of the uses of these data are wide ranging and include public policy applications, the derivation of reference intervals, and research. Periodically, the National Center for Health Statistics and its federal partners convene expert panels to review the use of the folate- and vitamin B-12-related biomarkers in NHANES. These panels have evaluated the need for results to be comparable across time and with published data and the use of crossover studies and adjustment equations to ensure comparability. With the recent availability of reference methods and materials for serum folate and tHcy, NHANES has started to use traceability approaches to enhance the accuracy and comparability of its results. A major user concern over the years has been the use of cutoffs to estimate the prevalence of inadequate folate and vitamin B-12 status. Because these cutoffs depend on the measurement procedure, several expert panels suggested approaches for dealing with cutoff challenges. This review summarizes the history and use of folate- and vitamin B-12-related biomarkers beginning with NHANES I (1974-1975) through 2010.

FIGURE 1.

Mountain plots of serum folate (A), red blood cell (RBC) folate (B), and serum vitamin B-12 (C). All 3 panels represent the total population of the United States according to NHANES, which spanned 1988–1994, 1999–2000, 2001–2002, 2003–2004, and 2005–2006. The vertical dotted lines indicate commonly used cutoffs for assessment of low serum and RBC folate and serum vitamin B-12. For serum and RBC folate, 1 ng/mL = 2.266 nmol/L. Panels A and B are updated versions of Figure 1 in reference , and panel is an updated version of Figure 2 in reference to include NHANES data published subsequent to these earlier publications (C Pfeiffer, personal communication, 2011).

FIGURE 2.

Mountain plots of plasma total homocysteine (Hcy) in the total US population (with the exclusion of persons with chronic kidney disease) according to NHANES, which spanned 1991–1994, 1999–2000, 2001–2002, and 2003–2004. This is an updated version of Figure 2 in reference to include NHANES data published subsequent to this earlier publication (C Pfeiffer, personal communication, 2011).

FIGURE 3.

Comparison of median red blood cell (RBC) folate values and spina bifida incidence rates that spanned NHANES 1988–1994, 1999–2000, 2001–2002, 2003–2004, and 2005–2006. For RBC folate, 1 ng/mL = 2.266 nmol/L (C Johnson, personal communication, 2011).