U01.01.071 Vitamin B12

Vitamin B12 is an essential water-soluble vitamin that acts as a cofactor for several enzymes involved in critical metabolic pathways. It is required for DNA synthesis, and the production of red blood cells, and is particularly important for maintaining the nervous system.

Key Functions:

Methionine synthase: Transfers methyl groups as methylcobalamin, aiding in the conversion of homocysteine to methionine.
Methylmalonyl-CoA mutase: Plays a role in the metabolism of fatty acids and amino acids, particularly in the conversion of methylmalonyl-CoA to succinyl-CoA.

Sources of Vitamin B12:

Animal products (meat, fish, poultry, eggs, dairy).
Synthesized by microorganisms (not found in plant foods).

Deficiency Causes:

Cause	Example Conditions	Mechanism of Deficiency
Malabsorption	Sprue, enteritis, bacterial overgrowth, alcohol excess	Impaired absorption in the GI tract
Lack of Intrinsic Factor	Pernicious anemia, gastric bypass surgery	Impaired vitamin B12 absorption due to loss of intrinsic factor
Surgical Resection	Crohn’s disease, ileum resection	Loss of the terminal ileum (site of vitamin B12 absorption)
Medications	Metformin	Altered gut flora or impaired absorption
Dietary Insufficiency	Veganism	Lack of B12 in plant-based diet

Symptoms of Deficiency:

Hematologic symptoms: Anemia, macrocytosis.
Neurologic symptoms: Peripheral neuropathy, ataxia, cognitive changes, and possibly irreversible nerve damage.

Diagnostic Tips:

Anti-intrinsic factor antibodies: Diagnostic for pernicious anemia (autoimmune destruction of intrinsic factor).
Folate supplementation: Can mask the hematologic symptoms of B12 deficiency but does not correct the neurologic symptoms.

Points to Remember for USMLE Step 1:

Vitamin B12 deficiency can lead to both hematologic (macrocytic anemia) and neurologic symptoms (peripheral neuropathy).
Pernicious anemia is caused by a lack of intrinsic factor and is associated with anti-intrinsic factor antibodies.
Malabsorption syndromes (e.g., Crohn’s disease) and certain medications (e.g., metformin) can impair vitamin B12 absorption.
Folate supplementation can temporarily alleviate anemia but cannot address the neurologic damage caused by B12 deficiency.
Vitamin B12 is stored in large quantities in the liver (with a reserve pool lasting several years), making deficiency rare unless absorption is severely impaired.

Clinical Note:

In cases of suspected B12 deficiency, neurologic evaluation is critical, as early intervention can prevent irreversible damage to the nervous system.

USMLE Step 1 Review Series

Curriculum