From the Guidelines
Elevated vitamin B12 levels in the blood can be caused by several conditions, including liver disease, certain blood disorders, kidney disease, and certain types of cancer, as well as excessive supplementation and genetic disorders affecting B12 transport proteins. The most common causes of elevated vitamin B12 levels include liver disease (such as cirrhosis, hepatitis, or liver cancer), certain blood disorders (like myeloproliferative disorders, polycythemia vera, or chronic myelogenous leukemia), kidney disease, and certain types of cancer (particularly liver, colon, and blood cancers) 1. Excessive supplementation with vitamin B12 can also lead to elevated levels, though this is less common as B12 is water-soluble and excess amounts are typically excreted in urine. Some medications can interfere with B12 metabolism or testing, including metformin and oral contraceptives. Genetic disorders affecting B12 transport proteins, such as transcobalamin II deficiency, can also cause elevated serum B12 levels despite cellular deficiency.
When evaluating the causes of elevated vitamin B12 levels, it is essential to consider the clinical context and investigate the underlying cause rather than simply attributing it to excess intake, as it may be a marker of serious underlying disease 1. The elevation itself is generally not harmful, but the underlying condition causing it may require treatment. In some cases, elevated vitamin B12 levels may be associated with other immune-mediated diseases, such as pernicious anemia, which can lead to B12 deficiency despite elevated serum levels. However, available case-control studies have not identified any significant differences in B12 levels in patients with alopecia areata compared to controls 1.
Key points to consider when evaluating elevated vitamin B12 levels include:
- Investigating the underlying cause of elevated B12 levels
- Considering the clinical context and potential associations with other diseases
- Evaluating the role of medications and genetic disorders in B12 metabolism
- Recognizing that elevated B12 levels may be a marker of serious underlying disease
- Providing appropriate treatment for the underlying condition causing elevated B12 levels.
From the Research
Causes of B12 Elevation
- Solid neoplasia (primary or metastatic) and acute or chronic hematological diseases are related to high serum levels of vitamin B12 2
- Liver disorders, such as chronic liver disease, can cause falsely elevated vitamin B12 levels due to increased excretion of vitamin B12 into the serum from the liver 3, 4, 5
- Monoclonal gammapathy of undetermined significance, renal failure, and inflammatory or autoimmune diseases can also contribute to elevated vitamin B12 levels 2
- Excess intake of vitamin B12 and transient hematological disorders (neutrophilia and secondary eosinophilia) are less frequent causes of hypervitaminosis B12 2
- Elevated vitamin B12 levels have been associated with a higher risk of cancer, with risk ratios ranging from 1.88 to 5.9 6
Disease Severity and Prognosis
- Vitamin B12 levels can be used as a severity and prognostic marker in chronic liver disease, with higher levels indicating more severe disease and poorer prognosis 3, 5
- The vitamin B12/folate ratio may be useful in the differential diagnosis of the etiology of chronic liver disease 4
- Elevated B12 levels are associated with increased severity of liver disease and 3-month mortality rate in patients with acute-on-chronic liver failure 5