Abstract

Abstract Objectives High blood methylmalonic acid (MMA) and homocysteine (tHcy) and low serum B-12 and holotranscobalamin (holoTC) concentrations indicate vitamin B-12 deficiency. The diagnosis is often contradictory when using any test independently. A mathematical model including all 4 biomarkers, named combined indicator of vitamin B-12 status (cB12), has been proposed. Our goal was to describe cB12 in US adults and estimate the prevalence of low or transitional vitamin B-12 status compared to conventional single biomarkers. Methods We assessed cB12 in persons ≥20 y participating in NHANES from 1999 to 2004 from 3 biomarkers: serum vitamin B-12, MMA, and plasma tHcy. Results The following groups had significantly lower cB12: persons ≥70 y compared with younger age groups, males compared with females, non-Hispanic whites compared with non-Hispanic blacks and Mexican Americans, and non-users of vitamin B-12 containing supplements compared with users. Shorter fasting times and impaired renal function also resulted in lower cB12. There was a strong significant association of cB12 with serum vitamin B-12 (Spearman r = 0.75), MMA (r = −0.70), and tHcy concentrations (r = −0.59). The prevalence of vitamin B-12 deficiency varied with the biomarker and cutoff used: 2.2% and 13% for serum vitamin B-12 < 148 and 148 − 222 pmol/L, respectively; 6.0% for MMA exceeding an age-specific cutoff between 250 and 320 nmol/L; and 8.4% for tHcy > 13 μmol/L. Using the proposed cB12 cutoff of < −0.5, 2.7% of adults had “low or transitional vitamin B-12 status”. Conclusions Based on the new combined indicator using 3 biomarkers a larger portion of US adults had adequate vitamin B-12 status (97%) compared to conventional single biomarkers (between 85% and 94%), likely indicating the higher specificity of cB12. It is unclear whether the availability of holoTC data would change these findings. Funding Sources This work was supported by direct appropriations from US Congress.

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