Low B12 most often reflects inadequate intake (vegan or vegetarian diets, chronic alcohol use) or malabsorption.
Malabsorption causes include pernicious anemia (autoimmune loss of intrinsic factor), celiac disease, Crohn’s disease, atrophic gastritis, low stomach acid, prior gastric or ileal surgery, inflammatory bowel disease, and H. pylori or small intestinal bacterial overgrowth.
Common drug causes: long-term metformin, proton pump inhibitors, and H2 blockers.
High B12 is usually caused by B12 supplements or injections, which is generally not a concern since B12 is not considered toxic.
When not intake-related, elevated B12 can accompany liver disease (cirrhosis, hepatitis, hepatocellular carcinoma, or liver metastases), kidney failure, diabetes, myeloproliferative and other hematological disorders (leukemia, polycythemia vera, hypereosinophilic syndrome), and other cancers (colon, pancreas, breast, stomach).
Elevated serum B12 can also coexist with functional B12 deficiency, since the test also measures B12 bound to transport proteins that is not taken up by cells.
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