Signs of Vitamin B12 Deficiency and Treatment
Vitamin B12 deficiency should be promptly identified and treated to prevent permanent degenerative lesions of the spinal cord, which can occur if deficiency progresses for longer than 3 months. 1, 2
Clinical Manifestations of B12 Deficiency
Hematologic Signs
- Megaloblastic anemia
- Abnormal complete blood count (CBC) with macrocytosis
- Elevated mean corpuscular volume (MCV)
- Hypersegmented neutrophils
Neurological Signs
- Paresthesias (tingling/numbness) in hands and feet
- Progressive peripheral neuropathy
- Ataxia (impaired coordination)
- Decreased vibratory and position sense
- Muscle weakness
- Spasticity
- Abnormal reflexes
Neuropsychiatric Manifestations
- Cognitive impairment
- Memory loss
- Irritability
- Depression
- Psychosis in severe cases
Gastrointestinal Symptoms
- Glossitis (smooth, red, painful tongue)
- Anorexia
- Weight loss
- Diarrhea
Diagnosis of B12 Deficiency
Initial Testing
- Serum total B12 (cobalamin) or active B12 (holotranscobalamin) should be measured first 1
- Interpretation thresholds:
- Confirmed deficiency: Total B12 <180 ng/L or active B12 <25 pmol/L
- Indeterminate: Total B12 180-350 ng/L or active B12 25-70 pmol/L
- Unlikely deficiency: Total B12 >350 ng/L or active B12 >70 pmol/L
Additional Testing for Indeterminate Results
- Serum methylmalonic acid (MMA) - elevated in B12 deficiency
- Homocysteine levels - elevated in B12 deficiency
- Complete blood count
- Folate levels 1
Treatment of B12 Deficiency
Initial Treatment Options
For most patients, oral administration of high-dose vitamin B12 (1500-2000 mcg daily) is as effective as intramuscular administration, even in patients with malabsorption issues. 1, 3
Oral Supplementation
- Dosage: 1500-2000 mcg daily for 3 months 1
- Effective even in malabsorption due to 1-2% passive absorption 1, 3
- Better patient compliance and cost-effectiveness 1
Intramuscular (IM) Administration
- Recommended for:
- Patients with severe deficiency
- Severe neurological symptoms
- When rapid correction is needed 3
- Initial loading dose followed by maintenance therapy
- According to guidelines, many patients with malabsorption can be managed with 1000 μg IM hydroxocobalamin once every two months after initial loading 4
Special Considerations
- Patients with pernicious anemia require lifelong treatment 2
- Monitor serum potassium closely during the first 48 hours of treatment 2
- Patients who have had bariatric surgery should receive 1 mg oral vitamin B12 daily indefinitely 3
- Sublingual B12 supplementation offers comparable efficacy to IM administration 1
Monitoring Response to Treatment
- Assess serum B12 levels after 3 months of treatment 1
- Monitor hematocrit and reticulocyte counts daily from the fifth to seventh days of therapy until hematocrit normalizes 2
- Monitor platelet count until normalization 1
- If reticulocytes have not increased after treatment or reticulocyte counts do not continue at least twice normal as long as the hematocrit is less than 35%, reevaluate diagnosis or treatment 2
Prevention in High-Risk Groups
- Regular consumption of animal-source foods and fortified breakfast cereals 1
- Adults over 50 years and vegans/vegetarians should consume B12-fortified foods or take supplements 3
- Consider daily multivitamin containing appropriate amounts of both folate and B12 1
- Monitor B12 levels in patients taking metformin, especially those with other risk factors 1
Important Cautions
- Folic acid supplementation can mask B12 deficiency by correcting the anemia but allowing neurological damage to progress 2
- Doses of folic acid greater than 0.1 mg per day may result in hematologic remission in patients with B12 deficiency while neurologic manifestations continue to progress 2
- Treatment should not be delayed once B12 deficiency is diagnosed, as permanent neurological damage can occur 1, 2