Vitamin B12 Deficiency
- Vitamin deficiency related to inadequate intake or absorption of cobalamin (vitamin B12)
- Cobalamin is critical for central nervous system myelination, red blood cell (RBC) production, and DNA synthesis.
- Deficiency can cause megaloblastic anemia, bone marrow dysfunction, and diverse and potentially irreversible neuropsychiatric changes.
- Neuropsychiatric disorders are due to demyelination of cervical, thoracic dorsal, and lateral spinal cords; demyelination of white matter; and demyelination of cranial and peripheral nerves.
- Elevated MMA and homocysteine levels may be early markers of vitamin B12 deficiency (1).
Normal vitamin B12 absorption
- Vitamin B12 is a water-soluble vitamin present in animal-source foods and foods fortified with vitamin B12.
- Dietary vitamin B12 (cobalamin) bound to food is cleaved by acids in stomach and bound to haptocorrin (commonly known as R-factor).
- Duodenal proteases cleave vitamin B12 from haptocorrin.
- In duodenum, vitamin B12 uptake depends on binding to intrinsic factor (IF) secreted by gastric parietal cells.
- Vitamin B12-IF complex is absorbed by terminal ileum into portal circulation.
- Body’s vitamin B12 stored in liver: 50–90%
- Vitamin B12 secreted into bile from liver recycled via enterohepatic circulation
- Delay 5 to 10 years from onset of vitamin B12 deficiency to clinical symptoms due to hepatic stores and enterohepatic circulation
- Typical Western diet: 5 to 30 mg/day; however, only 1 to 5 mg/day is effectively absorbed.
- Recommend 2.4 mg/day for adults and 2.6 mg/day during pregnancy and 2.8 mg/day during lactation (most prenatal vitamins contain vitamin B12).
- Endemic area: Northern Europe, including Scandinavia; more common in those of African ancestry
- Increasing recognition in breastfed-only infant populations with vitamin B12deficient mothers
- Prevalence 5–20% in developed countries
- Prevalence in those <60 years old is 6%, and in those >60 years old, it is 20%.
Etiology and Pathophysiology
- Decreased oral intake
- Vegetarians and vegans: Vitamin B12 is found in animal source foods.
- Decreased IF
- Pernicious anemia (PA): can be associated with autoantibodies directed against gastric parietal cells and/or IF
- Chronic atrophic gastritis: autoimmune attack on gastric parietal cells causing autoimmune gastritis and leading to decreased IF production
- Gastrectomy: removal of entire or part of stomach
- Decreased absorption
- Crohn disease: Terminal ileal inflammation decreases body’s ability to absorb vitamin B12.
- Chronic alcoholism: decreases body’s ability to absorb vitamin B12
- Gluten hypersensitivity (celiac disease) intestinal villi atrophy and subsequent malabsorption
- Ileal resection
- Pancreatic insufficiency: Pancreatic proteases are required to cleave the vitamin B12haptocorrin bond to allow vitamin B12 to bind to IF.
- Helicobacter pylori infection: impairs release of vitamin B12 from bound proteins
- Proton pump inhibitors (PPIs), H2 antagonists, and antacids decrease gastric acidity, inhibiting vitamin B12 release from dietary protein; metformin
- Metformin usage can cause calcium-dependent membrane inhibition, interfering with vitamin B12IF absorption.
- Hereditary (rare)
- Food-cobalamin malabsorption syndrome
- 60–70% of cases; primary cause in elderly
- Pathophysiology: inability to release cobalamin from food or binding protein, especially if in the setting of hypochlorhydria
- Seen in atrophic gastritis, long-term ingestion of antacids and biguanides, possible relationship to H. pylori infection
- 15–30% of all cases; most frequent cause of severe disease; neurologic disorders are common presenting complaints.
- Common in elderly, as high as 20%, with mild atrophic gastritis, hypochlorhydria, and impaired release of dietary vitamin B12
- Antigastric parietal cell antibodies: sensitivity >90%, specificity 50%; use for screening test
- Insufficient dietary intake: 2% of cases; vegans or long-standing vegetarians
- Infants born to vitamin B12deficient mothers may develop it if breastfed exclusively.
- Intestinal causes:
- 1% of cases; prevalence depends on risk factors, such as surgical conditions.
- Gastrectomy: due to decreased production of IF
- Gastric bypass: appears 1 to 9 years after surgery, prevalence 12–33%
- Ileal resection or disease
- Fish tapeworm
- Severe pancreatic insufficiency
- Undetermined etiology
- Food-cobalamin malabsorption syndrome
Imerslund-Gräsbeck disease (juvenile megaloblastic anemia) caused by mutations in the amnionless (AMN) or cubilin (CUBN) genes with autosomal recessive pattern of inheritance; inadequate ileal uptake of vitamin B12-IF complex and vitamin B12 renal protein reabsorption
Commonly Associated Conditions
- Gastric abnormalities: PA, gastritis, gastrectomy/bariatric surgery
- Small bowel disease: malabsorption syndrome, ileal resection, IBD, celiac disease
- Pancreatitis: pancreatic insufficiency
- Diet: breastfed infant in vitamin B12 deficient mother, strict vegan diet
- Medications: neomycin, metformin, PPI, histamine 2 receptor antagonists, nitrous oxide (N2O) abuse
There's more to see -- the rest of this topic is available only to subscribers.