Manifestations and Treatment of Folate, B12, and Thiamine Deficiencies
Deficiencies of folate, vitamin B12, and thiamine present with distinct clinical manifestations and require specific treatment approaches based on the severity and underlying cause of the deficiency.
Vitamin B12 (Cobalamin) Deficiency
Clinical Manifestations
- Hematologic manifestations: Megaloblastic anemia with oval macrocytes, moderate leukopenia, thrombocytopenia, and few reticulocytes 1, 2
- Neurological manifestations:
- Psychiatric manifestations:
- Other manifestations:
- Alterations to vision and smell
- Urinary incontinence
- Fatigue
- Pale appearance 4
Diagnosis
- Serum vitamin B12 levels (total B12)
- Active B12 (serum holotranscobalamin)
- Methylmalonic acid (MMA) testing for confirmation of indeterminate results
- Total homocysteine 6
Treatment
- Parenteral therapy: 1000-2000 μg daily intramuscularly initially, then 1000 μg monthly for life for pernicious anemia 6, 7
- Oral therapy: 1000-1500 μg daily (cyanocobalamin or mecobalamin) for those with intact absorption 6
- Initial treatment regimen for pernicious anemia:
- 100 mcg daily for 6-7 days (IM or deep subcutaneous)
- If clinical improvement occurs, give same amount on alternate days for seven doses
- Then every 3-4 days for 2-3 weeks
- Maintenance: 100 mcg monthly for life 7
- Important caution: Vitamin B12 deficiency left untreated for >3 months may produce permanent degenerative lesions of the spinal cord 7
Folate Deficiency
Clinical Manifestations
- Hematologic manifestations: Megaloblastic anemia (identical to B12 deficiency) 1, 2
- Neurological manifestations:
- Cognitive impairment
- Peripheral neuropathy (less common)
- Subacute combined degeneration (less common) 5
- Psychiatric manifestations:
- Dementia
- Depression 5
Diagnosis
- Serum folate levels
- Red blood cell folate levels
- Total homocysteine 6
Treatment
- Oral folic acid supplementation
- Important caution: High-dose folic acid (>0.1 mg/day) may mask B12 deficiency by correcting the anemia while allowing neurological damage to progress 7, 8, 5
- Special attention required for pregnant women or those planning to conceive due to risk of neural tube defects 3
Thiamine Deficiency
Clinical Manifestations
- Neurological manifestations:
- Wernicke-Korsakoff encephalopathy
- Mental changes (apathy, decreased short-term memory, confusion, irritability)
- Cognitive deficits
- Optic neuropathy
- Central pontine myelinolysis 3
- Cardiovascular manifestations (wet beriberi):
- Metabolic manifestations:
- Metabolic acidosis
- Dry beriberi 3
Diagnosis
- Thiamine diphosphate (ThDP) in erythrocytes
- Lactate, pyruvate, alpha-ketoglutarate, and glyoxylate concentrations 3
Treatment
Based on clinical situation 3:
- Mild deficiency (outpatients): 10 mg/day thiamine for a week, followed by 3-5 mg daily for at least 6 weeks
- High suspicion or proven deficiency: 200 mg, 3 times a day, IV
- Encephalopathy of uncertain etiology: 500 mg, 3 times a day, IV
- Maintenance dose in proven deficiency: 50-100 mg/day, orally
- Important caution: Glucose should not be given before thiamine repletion due to risk of worsening thiamine deficiency 3
Special Considerations
Risk Factors for Deficiencies
- B12 and folate: Malabsorption, poor dietary intake (especially vegans/vegetarians), bariatric surgery, Crohn's disease with ileal involvement, pregnancy/lactation 6
- Thiamine: Rapid weight loss, decreased consumption, persistent vomiting, chronic alcohol consumption, malignancies, bariatric surgery, heart failure, critical illness 3
Monitoring
- For B12: Reassess levels after 1-3 months of supplementation, then annually for maintenance therapy 6
- For thiamine: Monitor response to supplementation trial to confirm diagnosis 3
- For all deficiencies: Early diagnosis and prompt treatment are essential to prevent irreversible neurological damage 3, 6