The application and interpretation of laboratory biomarkers for the evaluation of vitamin B12 status

Vitamin B₁₂ (cobalamin; B₁₂) is an essential micronutrient, but deficiency is common. The prompt diagnosis and treatment of B₁₂ deficiency protects against megaloblastic anaemia, neuropathy and neuropsychiatric changes. Biomarkers of B₁₂ status include the measurement of serum B₁₂ (also known as total B₁₂ or serum cobalamin), holotranscobalamin (holoTC or 'active B12'), methylmalonic acid (MMA) and total plasma homocysteine (Hcy). There is no 'gold standard' test for deficiency and the sensitivity and specificity of each biomarker for the evaluation of B₁₂ status is affected by analytical and biological factors that may confer a high degree of diagnostic uncertainty. Limited access to technical and clinical expertise can lead to an over-reliance on the serum B₁₂ test, which is readily available and highly automated. In some cases, the sequential use of different B₁₂ status biomarkers or the calculation of a composite B₁₂ status score, derived from a panel of B₁₂ biomarkers and adjusted for folate status and age, can be used to detect deficient states that may otherwise be overlooked when using a single biomarker approach. This review summarizes the utility of B₁₂-related biomarkers and describes approaches to their application and interpretation.