A Simplified Red Blood Cell Folate Calculation: Comparison to the Traditional Calculation Using Data from NHANES 2007–2010
Authors: Zhang Mindy , Sternberg Maya R , Pfeiffer Christine M 
Published: November 2023

Red blood cell folate (RBF) concentrationsare considered an accurate indicator of folate body stores and are usuallymeasured to assess the population baseline status or the impact of folateintervention. The traditional calculation of RBF requires 3 components, wholeblood folate (WBF), serum folate (SFOL), and hematocrit (Hct) and is calculatedas [WBF–SFOL(1–Hct/100)]/(Hct/100). In some cases data for SFOL and/or Hct maynot be available, but the hemoglobin (Hb) concentration is generally availablein health and nutrition surveys. Using data for persons 1 y and olderparticipating in NHANES 2007–2010 (n ~ 17000), we investigated whether asimplified calculation generated accurate RBF results. The available dataincluded SFOL and RBF measured by use of microbiologic assay, Hct, Hb, and meancell Hb content (MCHC); population median values for these indicators were 39.8nmol/L, 1070 nmol/L, 40.8%, 140 g/L, and 344 g/L, respectively. We calculatedthe WBF concentration as (RBF*Hct/100)+SFOL(1–Hct/100). We calculated anestimated Hct as Hb/MCHC, using the population median MCHC; the populationmedian estimated Hct was 40.8%. We investigated 5 simplified calculationscenarios: 1) use simple formula by ignoring SFOL (WBF/Hct); 2) use an imputed SFOLconcentration of 40 nmol/L; 3) use an imputed Hct value of 40%; 4) use an estimated Hct value; 5) use both an imputed SFOL value and an estimated Hct value with WBFand Hb being the only measured parameters. We compared geometric mean RBF results from these 5 scenarios with traditionally calculated RBF results for the entire population and demographic subgroups of age, gender and race‐ethnicity, as well as for women of reproductive age (WRA, 15–44 y). Compared to the traditional formula, the simple formula (ignoring SFOL) produced on average 5.6% (4.5–9.6% in subgroups; 5.9% in WRA) higher RBF results. Using an imputed SFOL concentration had on average 0% bias (−1.2% to 2.8% in subgroups; −1.2% in WRA). Using an imputed Hct value had on average 1.9% bias (−9.2% to 7.6% in subgroups; −3.9% in WRA). Using an estimatedHct had on average 0% bias (−3.5% to 3.5% in subgroups; 0% in WRA). Using both an imputed SFOL and an estimated Hct had on average 0% bias (−1.4% to 1.9%| in subgroups). In summary, ignoring the SFOL concentration in the calculation of RBF or using an imputed Hct value bias the RBF results by as much as 10% incertain demographic subgroups. Conversely, using the population median SFOL as an imputed value, or the estimated Hct, or a combination of the 2 parameters resulted in small average biases. This demonstrates the potential of simplifying the RBF calculation to estimate central tendency in a population by only measuring WBF and Hb in each study participant and by using an estimated population median SFOL value derived from a small subsample. However, this approach will not accurately predict an individual RBF value. These initial findings need to be confirmed in other data sets, particularly in settings with low folate status. Furthermore, the impact of the simplified calculation on prevalence estimates using different folate cutoff value has to be assessed.