What are the symptoms and treatment of vitamin B12 deficiency?

Symptoms of Vitamin B12 Deficiency

Vitamin B12 deficiency presents with a broad spectrum of hematological, neurological, psychiatric, and gastrointestinal symptoms that can occur independently or in combination, with neurological symptoms often appearing before hematological changes. 1

Hematological Manifestations

• Megaloblastic anemia with macrocytosis (enlarged red blood cells) is a classic finding, though it may be absent in one-third of cases 1, 2
• Hypersegmented neutrophils appear on blood smear due to impaired DNA synthesis affecting rapidly dividing bone marrow cells 3
• Pancytopenia (low counts of all blood cell types) can occur in severe cases 4
• Symptoms of anemia that don't respond to iron treatment, particularly during pregnancy or breastfeeding 1

Neurological Symptoms

• Peripheral neuropathy with pins and needles or numbness (paresthesia) in hands and feet 1
• Subacute combined degeneration of the spinal cord causing balance problems, gait disturbances, and impaired proprioception leading to falls 1, 5
• Blurred vision related to optic nerve dysfunction 1
• Cognitive difficulties, concentration problems, and memory issues 6
• These neurological symptoms can become irreversible if untreated and may occur even before anemia develops 1, 5

Other Clinical Features

• Glossitis (inflammation and soreness of the tongue) 1, 6
• Mild transient diarrhea 5
• Fatigue and weakness 6
• Unexplained sensory and/or motor symptoms 7

Critical Clinical Pitfall

A major diagnostic pitfall is that normal serum B12 levels do not exclude functional B12 deficiency—up to 50% of patients with "normal" serum B12 have metabolic deficiency when measured by methylmalonic acid (MMA). 1, 6 This means you cannot rely solely on standard B12 testing to rule out deficiency, especially when clinical symptoms are present.

Treatment Approach

For Patients WITH Neurological Involvement

• Hydroxocobalamin 1 mg intramuscularly on alternate days until there is no further improvement, then hydroxocobalamin 1 mg intramuscularly every 2 months for life 7, 1
• Seek urgent specialist advice from a neurologist and hematologist when unexplained sensory, motor, or gait symptoms are present 7

For Patients WITHOUT Neurological Involvement

• Hydroxocobalamin 1 mg intramuscularly three times a week for 2 weeks, followed by maintenance treatment with 1 mg intramuscularly every 2-3 months for life 7, 1
• Oral vitamin B12 (1,000-2,000 mcg daily) is as effective as intramuscular administration for most patients without severe neurological symptoms and costs less 6, 2

Critical Treatment Warning

It is essential to treat vitamin B12 deficiency immediately BEFORE initiating folic acid supplementation, as folic acid may mask the anemia but allow progression of subacute combined degeneration of the spinal cord, causing irreversible neurological damage. 7, 1, 5

High-Risk Populations Requiring Vigilance

• Post-bariatric surgery patients (sleeve gastrectomy, Roux-en-Y gastric bypass, duodenal switch) due to reduced intrinsic factor and gastric acid 1
• Vegans and strict vegetarians with limited dietary B12 intake 1, 2
• Adults older than 75 years (25% of those ≥85 years have B12 deficiency) 6
• Patients on metformin for more than 4 months 1, 2
• Patients on proton pump inhibitors or H2 receptor antagonists for more than 12 months 1, 2
• Patients with atrophic gastritis, celiac disease, or inflammatory bowel disease 1
• Patients with ileal resection greater than 20 cm (require 1,000 mcg intramuscularly monthly for life) 1

Diagnostic Considerations

• Check complete blood count for megaloblastic anemia and macrocytosis 1, 5
• Measure serum B12 as initial screening, but recognize its limitations 1, 8
• Consider measuring methylmalonic acid (MMA) or active B12 (holotranscobalamin) when B12 levels are indeterminate or clinical suspicion remains high despite normal B12 1, 6, 9
• Monitor serum potassium closely during the first 48 hours of treatment and replace if necessary 5
• Check hematocrit and reticulocyte counts daily from days 5-7 of therapy, then frequently until hematocrit normalizes 5