From the Guidelines
Elevated vitamin B12 levels require a comprehensive workup to identify the underlying cause, focusing on liver disease, kidney disease, blood disorders, excessive supplementation, and certain medications like metformin. The initial evaluation should include a comprehensive medical history, physical examination, and laboratory tests such as complete blood count, liver function tests, kidney function tests, and serum methylmalonic acid and homocysteine levels 1. Common causes of elevated B12 include liver disease, kidney disease, certain blood disorders like myeloproliferative neoplasms and leukemias, excessive supplementation, and certain medications like metformin. Specific tests to consider include:
- Hepatitis panel if liver disease is suspected
- Bone marrow biopsy if blood disorders are suspected
- Imaging studies like abdominal ultrasound to evaluate liver and kidney structure It's essential to note that elevated B12 levels can sometimes mask an actual B12 deficiency at the tissue level, particularly in liver disease where B12 binding proteins are increased but functional B12 may be low 1. Treatment depends on addressing the underlying cause rather than attempting to lower B12 levels directly. Discontinuing unnecessary B12 supplements is recommended if excessive supplementation is identified as the cause. In patients who have undergone bariatric surgery, routine supplementation with vitamin B12 intramuscular injections is recommended, with a frequency of every 3 months 1. Additionally, if a vitamin B12 deficiency is identified, treatment should be initiated immediately, following guidelines such as those from NICE CKS: Anaemia—B12 and folate deficiency, which recommend administering hydroxocobalamin 1 mg intramuscularly on alternate days until there is no further improvement, then administering hydroxocobalamin 1 mg intramuscularly every 2 months for people with neurological involvement 1.
From the Research
Elevated B12 Workup
- The evaluation of elevated vitamin B12 levels should consider various underlying pathologies, including solid neoplasms, haematological malignancies, and liver and kidney diseases 2.
- In patients with chronic liver disease, plasma levels of vitamin B12 are often high, while plasma folate levels are low 3.
- The ratio between vitamin B12 and folic acid may be useful in the differential diagnosis of the etiology of chronic liver disease 3.
- A codified approach is needed to determine the potential indications of a search for high serum cobalamin and the practical clinical strategy to adopt upon discovery of elevated cobalamin levels 2.
- Functional cobalamin deficiency can occur at any serum level, and an abnormally high serum cobalamin level forms a warning sign requiring exclusion of serious underlying pathologies 2.
Diagnostic Approach
- The diagnostic approach to elevated liver chemistries should include testing for viral hepatitis, nonalcoholic fatty liver disease, alcoholic liver disease, hereditary hemochromatosis, autoimmune hepatitis, Wilson's disease, and alpha-1 antitrypsin deficiency 4.
- For the evaluation of an alkaline phosphatase elevation determined to be of hepatic origin, testing for primary biliary cholangitis and primary sclerosing cholangitis should be undertaken 4.
- A liver biopsy may be considered when serologic testing and imaging fails to elucidate a diagnosis, to stage a condition, or when multiple diagnoses are possible 4.
Laboratory Tests
- Liver function tests, including biochemical parameters (AST, ALT, GGT, and alkaline phosphatase), bilirubin, and albumin levels, as well as coagulation tests, are essential in the diagnosis of liver disease 5, 6.
- The interpretation of liver function tests should always be performed correctly, considering the presence of liver disease and the potential for advanced chronic liver disease or liver fibrosis 6.