Fewer US adults had low or transitional vitamin B12 status based on the novel combined indicator of vitamin B12 status compared with individual, conventional markers, NHANES 1999-2004.

BACKGROUND:Elevated plasma methylmalonic acid (MMA) and/or total homocysteine (tHcy), as well as low serum vitamin B12 and/or holotranscobalamin (holoTC) are indicative of vitamin B12 deficiency. Combined indicators (cB12), which pool some or all 4 markers into an index, may be a more reliable diagnostic tool to overcome inconclusive diagnoses with individual markers. OBJECTIVES:We aimed to describe different cB12 score combinations and estimate the prevalence of low or transitional vitamin B12 status compared with individual markers. DESIGN:Using cross-sectional data for B12, MMA, and tHcy in persons ≥20 y participating in NHANES 1999-2004 (n = 12,335), we examined raw and covariate-adjusted regression models to assess determinants of 3cB12 (all 3 markers) and combinations of 2cB12 (2 markers). RESULTS:3cB12 was significantly associated with B12 (Spearman r = 0.75), MMA (r = -0.70), and tHcy (r = -0.59). The 3cB12 reference interval (2.5th to 97.5th percentile) was -0.538 to 1.60. In covariate-adjusted models, we found no association of 3cB12 with age; adult females and users of B12 supplements had higher, while adults with advanced chronic kidney disease had lower 3cB12 levels regardless of race-Hispanic origin group (self-reported). Only 2.7% of adults had low or transitional vitamin B12 status using the proposed cB12 cutoff of ≤-0.5, while the prevalence of low (or low-normal) status depended on the selected individual marker and its cutoff: 2.2% and 13% for B12 < 148 and 148-222 pmol/L, respectively; 6.0% for MMA exceeding an age-specific cutoff (250-320 nmol/L); and 8.4% for tHcy > 13 µmol/L. The reference intervals for B12, MMA, and tHcy overlapped from the low (<-2.5) to the transitional (-2.5 to -0.5) and to the adequate (>-0.5) cB12 categories. CONCLUSIONS:Vitamin B12 deficiency may be overestimated among US adults when individual, conventional markers are used. When only 2 markers are available, the combination of B12 and MMA provides results comparable to 3cB12.