The Application of Holotranscobalamin and Methylmalonic Acid in Hospital Patients and Total Vitamin B12 in Primary Care Patients to Assess Low Vitamin B12 Status

Background: Low vitamin B12 (B12) status is common in patient populations. The timely detection and correction of low B12 prevents megaloblastic anaemia and neurological impairment. However, prompt diagnosis is recognised as problematic especially when status is estimated using total B12 abundance in serum as the sole laboratory indicator. Emerging evidence indicates that holotranscobalamin (holoTC), the active fraction of B12, is a more reliable marker. Functional markers of B12 utilisation e.g. elevations in serum methylmalonic acid (MMA) concentration, can complement the assessment of B12 status. Methods: We assessed the prevalence of low vitamin B12 status using two different approaches. HoloTC was used for 9073 patients attending Guy's & St. Thomas' Hospital (‘internal patients') supported by MMA if holoTC was between 25-70 pmol/L. The prevalence of low B12 status (serum B12 < 138 pmol/L) was also evaluated in 17875 primary care patients (‘external patients'). Markers associated with low vitamin B12 status were also investigated. Results: The prevalence of low B12 status in internal and external patients was 14% (5.7% had a holoTC < 25 pmol/L and 8.3% had an elevated MMA) and 4.4% respectively. There was no difference in the prevalence of low serum folate between the two groups of patients. HoloTC and MMA correlated with markers associated with B12 deficiency as well as factors independent of B12 status. Conclusions: Using the two different approaches the prevalence of low B12 status in internal patients was higher than for external patients. The incidence of elevated MMA in the small group of external patients was also high; suggesting that the application of total B12 alone may not identify all patients with low vitamin B12 status, and that MMA is a useful marker in confirming B12 status.