Are vitamin B-12 measurements adequate for evaluating its deficiency in individuals?

Background and Objectives: Measurement of vitamin B-12 deficiency using different methods may cause diagnostic difficulties. In order to rapidly and safely diagnose vitamin B-12 deficiency, it is important to determine the reference ranges of serum B-12 and its related biomarkers such as homocysteine, holotranscobalamine (holoTC) and methylmalonic acid (MMA). This study aimed to determine reference interval (RI)s for serum vitamin B-12 and related markers. Methods and Study Design: Samples were collected from 404 young-to-middle-aged healthy adults aged 18-65 years. Vitamin B-12, homocysteine, holotranscobalamin, folate were analyzed using the Arcitect i2000 device. Plasma MMA was analyzed by LC/MS. RIs were then evaluated accordingly. Results: Vitamin B-12, folate, homocysteine, holotranscobalamin and plasma MMA were 139-619 pg/mL, 3.0-14.7 ng/mL, 5.6-18.4 mu mol/L, 10.7-101 pmol/L, and 0.01-0.8 mu mol/L, respectively. Age group-specific RIs were also generated. Conclusions: This study revealed that the diagnosis of vitamin B-12 deficiency should not only be based on serum vitamin B-12 levels, but also of folate, homocysteine, holotranscobalamin and MMA levels; all which are related to vitamin B-12 metabolism.