Causes of Vitamin B12 Deficiency
Vitamin B12 deficiency is primarily caused by inadequate dietary intake, malabsorption syndromes, and medication effects, and should be treated with oral vitamin B12 supplementation at 1500-2000 mcg daily for 3 months in most cases. 1
Common Causes of Vitamin B12 Deficiency
Inadequate Intake
- Vegetarian or vegan diets (no animal products) 1, 2
- Malnutrition 2
- Elderly individuals with poor dietary habits 2, 3
- Pregnancy (increased requirements) 4, 2
Malabsorption Conditions
- Pernicious anemia (autoimmune atrophic gastritis) 1, 4
- Inflammatory bowel disease 1
- Celiac disease/gluten enteropathy 1, 4
- Gastrointestinal surgeries:
- Small bowel bacterial overgrowth 4
- Fish tapeworm infestation 4
- Pancreatic or bowel malignancy 4
- Atrophic gastritis (common in elderly) 3
Medication-Induced
- Metformin use (especially long-term >4 months) 1, 2, 5
- Proton pump inhibitors (>12 months) 5
- Histamine H2 blockers (>12 months) 5
- Most antibiotics (can interfere with B12 absorption) 4
- Colchicine 4
- Para-aminosalicylic acid 4
Other Causes
- Heavy alcohol consumption (>2 weeks) 4, 2
- Advanced age (>75 years) 5, 3
- Increased requirements (pregnancy, thyrotoxicosis, hemolytic anemia, hemorrhage) 4
- Hepatic and renal disease 4, 2
Diagnostic Approach
Initial Testing
- Serum vitamin B12 level (total B12) or active B12 (holotranscobalamin) 1, 6
- <180 ng/L (total B12) or <25 pmol/L (active B12): Confirmed deficiency
- 180-350 ng/L (total B12) or 25-70 pmol/L (active B12): Indeterminate
350 ng/L (total B12) or >70 pmol/L (active B12): Unlikely deficiency
- Complete blood count (to assess for megaloblastic anemia) 1, 5
Confirmatory Testing (for indeterminate results)
Treatment Recommendations
Initial Treatment
- Oral vitamin B12 supplementation at 1500-2000 mcg daily for 3 months is the recommended first-line treatment for most patients 1
- Oral administration is as effective as intramuscular injections for most patients, including those with malabsorption 1
- Sublingual B12 supplementation offers comparable efficacy to intramuscular administration 1
Special Situations
- Severe deficiency or severe neurologic symptoms: Consider intramuscular therapy for more rapid improvement 5
- Pernicious anemia: Patients require lifelong supplementation 1, 4
- Ileal resection >20 cm: Lifelong B12 supplementation is mandatory 1
- Post-bariatric surgery: 1 mg oral vitamin B12 daily indefinitely 5
Monitoring
- Assess response after 3 months by measuring serum B12 levels 1
- Monitor platelet count until normalization 1
- For pernicious anemia: Monitor serum potassium closely during first 48 hours of treatment 4
- Hematocrit and reticulocyte counts should be repeated daily from days 5-7 of therapy until hematocrit normalizes 4
Important Considerations and Pitfalls
Urgent Treatment Needed
- Vitamin B12 deficiency left untreated for >3 months may cause permanent degenerative lesions of the spinal cord 1, 4
- Prompt treatment is required to reverse damage before it becomes irreversible 3
Folic Acid Caution
- Doses of folic acid >0.1 mg/day may mask B12 deficiency by correcting hematologic abnormalities while allowing neurologic damage to progress 4
- Patients should be warned about the danger of taking folic acid in place of vitamin B12 4
High-Risk Populations Requiring Screening
- Adults >75 years 5, 3
- Patients with gastrointestinal surgeries or diseases 5
- Long-term metformin, PPI, or H2 blocker users 5
- Vegans or strict vegetarians 5
- Pregnant women 4, 2
Prevention
- Regular consumption of animal-source foods or fortified cereals 1
- Daily multivitamin containing appropriate amounts of B12 1
- Patients >50 years should consume B12-fortified foods or supplements 5
By understanding the various causes of vitamin B12 deficiency and implementing appropriate diagnostic and treatment strategies, clinicians can prevent the potentially irreversible neurological complications associated with prolonged deficiency.