Causes of Falsely Elevated Vitamin B12 Levels
Falsely elevated vitamin B12 levels can occur in myeloproliferative disorders, liver diseases, renal failure, and due to immune complex formation, despite actual vitamin B12 deficiency being present. 1, 2
Myeloproliferative Disorders
- Myeloproliferative disorders commonly show elevated serum vitamin B12 levels despite functional vitamin B12 deficiency 1
- Up to 69% of patients with myeloproliferative disorders may have actual vitamin B12 deficiency despite high serum vitamin B12 levels 1
- The elevation is caused by increased levels of transcobalamin (TC) I or III, which are vitamin B12 binding proteins in serum 3
- Different myeloproliferative disorders show varying degrees of elevation and types of transcobalamin involved 3
Other Medical Conditions Associated with Falsely Elevated B12
- Liver diseases including cirrhosis and acute-phase hepatitis 4
- Renal failure 4
- Alcohol use disorder with or without liver involvement 4
- Solid tumors of the lung, liver, esophagus, pancreas, and colorectum 4
- Hematological malignancies such as leukemia and bone marrow dysplasia 4
- Hypereosinophilic syndromes 5
- Disseminated neoplasia 5
Immune Complex Formation
- IgG-IgM-vitamin B12 immune complexes can cause extraordinarily increased vitamin B12 concentrations 5
- These immune complexes can occur in patients without typical underlying conditions associated with elevated B12 5
Clinical Implications
- Normal or elevated serum vitamin B12 levels can mask true underlying vitamin B12 deficiency 2
- In one study, 27.27% of patients with myeloproliferative disorders had occult vitamin B12 deficiency despite normal to elevated vitamin B12 levels 2
- This can lead to missed diagnosis and treatment of vitamin B12 deficiency, potentially causing significant neurological and hematological complications 2
Better Testing Methods
- Methylmalonic acid (MMA) is a sensitive marker for actual vitamin B12 deficiency and should be used when false elevation is suspected 2
- Holotranscobalamin (holoTC) levels ≤40.6 pmol/L have 75% sensitivity and 80% specificity for detecting true B12 deficiency in patients with myeloproliferative disorders 1
- Homocysteine levels >14 μmol/L have 70% sensitivity and 68% specificity for detecting true B12 deficiency 1
- In patients with suspected false elevation, holotranscobalamin may be the best initial test to accompany MMA and homocysteine levels 1
Clinical Approach to Suspected False Elevation
- When elevated B12 levels are found, consider underlying myeloproliferative disorders, liver disease, or renal failure 4
- For patients with myeloproliferative disorders and normal/high B12 levels, order methylmalonic acid testing to detect occult deficiency 2
- Consider testing holotranscobalamin and homocysteine levels as additional markers of functional B12 status 1
- Early detection of vitamin B12 deficiency using these alternative markers can prevent significant neurologic and hematologic complications 2