Background: Adult vitamin B12 (B12) deficiency may present itself with nonspecific mainly neurological symptoms, and thus plasma biomarkers are often judged to be of major importance in the further diagnostic process. Four biomarkers are of special relevance: total B12, holotranscobalamin (the part of B12 bound to the active transport protein, transcobalamin, also named holoTC or active B12) and the 2 so-called metabolic markers that accumulate if B12 is lacking, methylmalonic acid (MMA) and homocysteine.
Objective: This article briefly reviews the inherent limitation of biomarkers, discusses its use in establishing the diagnosis and cause of B12 deficiency, and when following or discontinuing treatment with B12.
Methods: The review is based on published papers, but also on knowledge gained from working within the area.
Conclusion: It is concluded that a combination of a B12 and a metabolic marker, for example, total B12 and MMA, may prove most useful in daily practice. An unexpectedly high level of total B12 is most often of no clinical importance, though sometimes related to the presence of underlying cancer. Measurement of total B12 is of limited value in patients on treatment with pharmacological doses of B12 but may be helpful if B12 treatment is discontinued.
Keywords: B12 deficiency; diagnostic strategy; holotranscobalamin; homocysteine; methylmalonic acid; review; vitamin B12.
Plain language titleVitamin B12-Related Blood TestsPlain language summaryBlood-testing is considered an important part of the diagnostic procedure in patients suspected to suffer from B12 deficiency. A deficiency is supported by a low level of plasma B12, and confirmed by a high level of methylmalonic acid, judged according to age and kidney function. Alternatively, a high level of homocysteine may support the diagnosis. Treatment of B12 deficiency is mainly guided by improvement of symptoms, with a very limited need for further blood testing. If B12-treatment is discontinued, B12 status should be judged every 6 months for approximately 2 years to detect a possible reoccurrence of a deficient state. An unexpected high level of plasma B12 is most often of no clinical implication.