Vitamin B12 (Cyanocobalamin, Cobalamin)


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Subject: Vitamin B12 (Cyanocobalamin, Cobalamin)

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  • Vitamin B12 is essential in DNA synthesis, hematopoiesis, and CNS integrity. Its absorption depends on the presence of intrinsic factor (IF) and may be due to lack of IF secretion by gastric mucosa (e.g., gastrectomy, gastric atrophy) or intestinal malabsorption (e.g., ileal resection, small intestinal diseases). Vitamin B12 deficiency frequently causes macrocytic anemia, glossitis, peripheral neuropathy, weakness, hyperreflexia, ataxia, loss of proprioception, poor coordination, and affective behavioral changes. These manifestations may occur in any combination; many patients have the neurologic defects without macrocytic anemia. PA is a macrocytic anemia caused by B12 deficiency that is due to a lack of IF secretion by gastric mucosa. Serum methylmalonic acid (MMA) and homocysteine levels are also elevated in vitamin B12 deficiency states. A significant increase in RBC MCV may be an important indicator of vitamin B12 deficiency.

  • Normal range: 180–914 pg/mL.

    • Indeterminate range: 145–180 pg/mL

    • Deficient range: <145 pg/mL


  • Investigation of macrocytic anemia

  • Workup of deficiencies seen in megaloblastic anemias

  • Assistance in the diagnosis of CNS disorders

  • Evaluation of alcoholism

  • Evaluation of malabsorption syndromes


Increased In

  • Chronic granulocytic leukemia

  • COPD

  • Chronic renal failure

  • Diabetes

  • Leukocytosis

  • Liver cell damage (hepatitis, cirrhosis)

  • Obesity

  • Polycythemia vera

  • Protein malnutrition

  • Severe CHF

  • Some carcinomas

Decreased In

  • Abnormalities of cobalamin transport or metabolism

  • Bacterial overgrowth

  • Crohn disease

  • Dietary deficiency (e.g., in vegetarians)

  • Diphyllobothrium (fish tapeworm) infestation

  • Gastric or small intestine surgery

  • Hypochlorhydria

  • Inflammatory bowel disease

  • Intestinal malabsorption

  • Intrinsic factor deficiency

  • Late pregnancy

  • PA


  • Serum samples should be protected from light at room temperature (15–30°C) for no longer than 1 hour. If the assay will not be completed within 2 hours, samples should be frozen and be protected from light exposure.

  • Drugs such as chloral hydrate increase vitamin B12 levels. On the other hand, alcohol, aminosalicylic acid, anticonvulsants, ascorbic acid, cholestyramine, cimetidine, colchicine, metformin, neomycin, oral contraceptives, ranitidine, and triamterene decrease vitamin B12 levels.

  • Many other conditions are known to cause an increase (vitamin C, vitamin A, estrogens, hepatocellular injury, myeloproliferative disorders, uremia) or decrease (pregnancy, smoking, hemodialysis, multiple myeloma) serum B12 levels.

  • The evaluation of macrocytic anemia requires measurement of both vitamin B12 and folate levels; ideally, they should be measured simultaneously.

  • Specimen collection soon after blood transfusion can falsely increase vitamin B12 levels.

  • Patients taking vitamin B12 supplementation may have misleading results.

  • A normal serum concentration of B12 does not rule out tissue deficiency of vitamin B12. The most sensitive test for B12 deficiency at the cellular level is the assay for MMA. If clinical symptoms suggest deficiency, measurement of MMA and homocysteine should be considered, even if serum B12 concentrations are normal.