What are the symptoms and treatment options for Vitamin B12 deficiency?

Vitamin B12 Deficiency Symptoms

Vitamin B12 deficiency presents with a broad spectrum of hematological, neurological, psychiatric, and gastrointestinal manifestations that can occur independently or in combination, with neurological symptoms often appearing before hematological changes—and critically, normal serum B12 levels do not exclude functional deficiency. 1

Neurological Symptoms

The neurological manifestations are often the most concerning and can become irreversible if treatment is delayed:

• Peripheral neuropathy with pins and needles or numbness (paraesthesia), particularly in the extremities and trunk, is a hallmark symptom that can occur even with normal serum B12 levels 1, 2
• Sensory loss affecting proprioceptive, vibratory, tactile, and nociceptive sensation typically appears before motor dysfunction 1, 2
• Balance problems and falls due to impaired proprioception and sensory ataxia are common presentations 1, 2
• Gait ataxia can represent early-stage deficiency 2
• Muscle weakness, abnormal reflexes, and spasticity occur as the deficiency progresses 1
• Subacute combined degeneration of the spinal cord with extensive demyelination in the CNS represents severe deficiency and can become permanent if treatment is delayed 1, 2, 3
• Blurred vision related to optic nerve dysfunction 1

Cognitive and Psychiatric Symptoms

• Brain fog, cognitive difficulties, and concentration problems are frequently reported 2, 4
• Memory issues 2
• Depression 4
• Fatigue (often severe) 4, 5
• Mild disorientation in more advanced cases 5

Hematological Manifestations

A critical pitfall: anemia may be absent in one-third of cases, so normal blood counts do not exclude B12 deficiency. 2

• Macrocytic anemia (enlarged red blood cells) 1, 2
• Anemia unresponsive to iron treatment, especially during pregnancy or breastfeeding 1, 2
• Hypersegmented neutrophils due to impaired DNA synthesis 2
• Abnormal blood count findings including macrocytosis, especially in patients with restricted diets 1

Other Physical Symptoms

• Glossitis (inflammation of the tongue) 1, 2
• Neuropathic pain 5

Critical Clinical Considerations

Up to 50% of patients with "normal" serum B12 levels have metabolic deficiency when measured by methylmalonic acid (MMA), making standard B12 testing unreliable for excluding deficiency. 1, 2 This is particularly important because:

• Neurological symptoms often present before hematological changes 2, 3
• Neurological damage can become irreversible if treatment is delayed beyond 3 months 3
• Subacute combined degeneration can progress despite normal serum B12 levels 1

High-Risk Populations Requiring Vigilance

You should maintain high clinical suspicion in these groups:

• Dietary factors: Vegans, strict vegetarians, or those with limited consumption of fortified foods 1, 3
• Gastrointestinal conditions: Atrophic gastritis, celiac disease, inflammatory bowel disease, Crohn's disease with >20 cm ileal resection 1, 3
• Post-surgical patients: Gastric or small bowel resections, bariatric surgery (sleeve gastrectomy, Roux-en-Y gastric bypass, duodenal switch) 1, 3, 6
• Autoimmune conditions: Thyroid disease, Sjögren syndrome, type 1 diabetes 1
• Medication use: Metformin (especially >4 months), proton pump inhibitors or H2 receptor antagonists (especially >12 months), colchicine, phenobarbital, pregabalin, primidone 1, 6, 4
• Age: Adults >75 years, with 18.1% of those >80 years having metabolic deficiency 7
• Pregnancy and lactation: Increased requirements during these periods 3

Treatment Approach

For patients without neurological involvement: Hydroxocobalamin 1 mg intramuscularly three times weekly for 2 weeks, followed by maintenance treatment with 1 mg intramuscularly every 2-3 months for life 1

For patients with neurological involvement: Hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement, then 1 mg intramuscularly every 2 months 1

Oral therapy alternative: High-dose oral vitamin B12 (1,000-2,000 mcg daily) is as effective as intramuscular administration for most patients and costs less, though intramuscular therapy leads to more rapid improvement and should be considered with severe deficiency or severe neurologic symptoms 7, 6, 4

Critical warning: Treat vitamin B12 deficiency immediately before initiating folic acid supplementation to avoid masking the deficiency and precipitating subacute combined degeneration of the spinal cord 1, 3