Age and ethnicity influence serum holotranscobalamin (‘Active’ B12) and methylmalonic acid concentrations, two markers of vitamin B12 status assessment
Year: 2026
Type: article
Abstract: Background Serum vitamin B 12 and holotranscobalamin (holoTC) are biomarkers of vitamin B 12 status, often used with confirmatory tests such as methylmalonic acid (MMA). Serum B 12 concentrations vary by age and ethnicity, but the impact of these factors on holoTC is unclear. Methods HoloTC was measured in 61,193 samples from an ethnically-diverse hospital population in London (Jan 2022–Oct 2023). HoloTC <25, 25–70 and >70 pmol/L were classified as deficient, indeterminate and replete, respectively. MMA was measured in 12,233 patients with holoTC 25–70 pmol/L. Results HoloTC concentrations differed significantly by ethnicity. Ethnic differences were minimal in children but became apparent in adulthood, with Black patients showing the highest holoTC concentrations, Asians intermediate, and White the lowest ( p < 0.001). Overall, 1.7% of patients were holoTC deficient and 25.3% indeterminate. Among patients with holoTC 25–70 pmol/L, elevated MMA occurred in 32.7% of White, 14.8% of Black and 34.1% of Asian patients ( p < 0.001) using age-specific MMA cut-offs ( > 280 nmol/L for ≤65 years; >360 nmol/L for >65 years). Using a higher MMA cut-off ( > 750 nmol/L), prevalence fell to 4.0%, 1.2%, and 4.7%, respectively. The overall prevalence of vitamin B 12 deficiency in the entire cohort was 7.8% or 2.4%, depending on the MMA threshold. Compared with White patients, Black patients were 34.6% less likely to have elevated MMA. Conclusions HoloTC and MMA concentrations vary significantly by age and ethnicity. Black adults exhibited higher holoTC and lower MMA concentrations, suggesting better B 12 status or differences in metabolism. Age- and ethnicity-specific reference ranges for holoTC and MMA should be considered.
Institutions: King's College London, University of Surrey
Language: English
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,590
OpenAlex ID: W7223475263