Comparison of Serum and Red Blood Cell Folate Microbiologic Assays for National Population Surveys

National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA 30341, USA.
Journal of Nutrition (Impact Factor: 3.88). 07/2011; 141(7):1402-9. DOI: 10.3945/jn.111.141515
Source: PubMed


Three laboratories participated with their laboratory-specific microbiologic growth assays (MA) in the NHANES 2007-2008 to assess whether the distributions of serum (n = 2645) and RBC folate (n = 2613) for the same one-third sample of participants were comparable among laboratories. Laboratory (L) 2 produced the highest and L1 the lowest serum and RBC folate geometric means (nmol/L) in the NHANES sample (serum: L1, 39.5; L2, 59.2; L3, 47.7; and RBC: L1, 1120; L2, 1380; L3, 1380). Each laboratory produced different reference intervals for the central 95% of the population. Pearson correlation coefficients were highest between L3 and L1 (serum, r = 0.95; RBC, r = 0.92) and lowest between L2 and L1 (serum, r = 0.81; RBC, r = 0.65). Notable procedural differences among the laboratories were the Lactobacillus rhamnosus microorganism (L1 and L3: chloramphenicol resistant, L2: wild type) and the calibrator [L1: [6S]5-methyltetrahydrofolate (5-methylTHF), L2: [6R,S] 5-formyltetrahydrofolate ([6R,S] 5-formylTHF), L3: folic acid (FA)]. Compared with 5-methylTHF as calibrator, the folate results were 22-32% higher with FA as calibrator and 8% higher with 5-formylTHF as calibrator, regardless of the matrix (n = 30 serum, n = 28 RBC). The use of different calibrators explained most of the differences in results between L3 and L1 but not between L2 and L1. The use of the wild-type L. rhamnosus by L2 appeared to be the main reason for the differences in results between L2 and the other 2 laboratories. These findings indicate how assay variations influence MA folate results and how those variations can affect population data. To ensure data comparability, better assay harmonization is needed.

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    • "The red blood cell folate concentrations presented by Pfeiffer et al 2012 and Branum et al 2013 were generated by a microbiological assay (calibrated with 5' methylTHF) that was normalized to the microbiological assay used in the Folic Acid Dosing Trial and the Daly study (calibrated with folic acid) using the equation: NHANES red blood cell folate (nmol/L)=(Daly and Folic Acid Dosing Trial red blood cell folate (nmol/L)×0.7876)+34.2802 (nmol/L) (personal communication from the data presented in Pfeiffer et al 2011). 33-35 We normalized the pre-fortification folate concentration data to the microbiological assay in the original manuscript 33 ; we then converted them by using the same conversion equation to approximate a match to the Daly et al data. "
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