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

Vitamin B12 Deficiency: Symptoms and Clinical Manifestations

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 frequently appearing before any blood abnormalities develop. 1, 2

Neurological Symptoms (Often the First to Appear)

Peripheral Nervous System:

• Peripheral neuropathy manifesting as pins and needles or numbness (paresthesia), typically starting in the distal extremities and potentially progressing to the trunk 1, 2
• Sensory loss affecting proprioception, vibratory sensation, tactile sensation, and pain perception—with proprioceptive and vibratory loss being particularly prominent 2
• Impaired nerve conduction velocity directly affecting peripheral motor function 2

Central Nervous System and Spinal Cord:

• Subacute combined degeneration of the spinal cord—the most serious neurological complication characterized by extensive demyelination in the spinal cord and brain white matter, which can become irreversible if untreated 2, 3
• Gait ataxia and balance problems due to impaired proprioception linked to sensory ataxia, leading to increased falls 1, 2
• Impaired mobility with patients unable to sit or walk without support in severe cases 2
• Spasticity and abnormal reflexes including both diminished and hyperactive tendon jerks 2

Cognitive and Psychiatric:

• Cognitive difficulties including difficulty concentrating, short-term memory loss, and "brain fog" 2, 4
• Depression 4

Visual:

• Blurred vision related to optic nerve dysfunction, optic atrophy, and visual field loss 1, 2

Motor:

• Muscle weakness affecting various muscle groups 2

Hematological Symptoms

• Anemia symptoms including fatigue, particularly anemia that doesn't respond to iron treatment 1, 4
• Abnormal blood count findings including macrocytosis (enlarged red blood cells), though megaloblastic anemia may be absent in one-third of cases 1, 5

Gastrointestinal and Mucosal Symptoms

• Glossitis (inflammation of the tongue) 1, 2

Critical Clinical Pitfalls

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, 2, 5

• Neurological symptoms often appear before hematological changes and represent the initial presentation in most cases, appearing before anemia develops 2, 5
• Untreated vitamin B12 deficiency can cause irreversible neurological damage, including subacute combined degeneration of the spinal cord, which may progress despite normal serum B12 levels 1, 3
• Vitamin B12 deficiency that is allowed to progress for longer than 3 months may produce permanent degenerative lesions of the spinal cord 3

High-Risk Populations Requiring Vigilance

• Vegan or vegetarian diets with limited consumption of fortified foods 1, 3
• Post-bariatric surgery patients (sleeve gastrectomy, Roux-en-Y gastric bypass, duodenal switch) due to reduced intrinsic factor and gastric acid 1, 5
• Patients with more than 20 cm distal ileum resection in Crohn's disease 1
• Elderly patients (age ≥60 years, with 25% of those ≥85 years having deficiency) 5
• Medication users: metformin (especially >4 months), proton pump inhibitors or H2 receptor antagonists (especially >12 months), colchicine, phenobarbital, pregabalin, primidone 1, 5, 4, 6
• Medical conditions: atrophic gastritis, celiac disease, autoimmune conditions (thyroid disease, Sjögren syndrome, type 1 diabetes) 1, 5
• Pregnancy and breastfeeding (increased requirements) 1, 3

Treatment Options

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 1
• Oral vitamin B12 (1000-2000 mcg daily) is as effective as intramuscular administration for most patients and costs less 5, 7, 4, 6

For patients WITH neurological involvement:

• Hydroxocobalamin 1 mg intramuscularly on alternate days until no further improvement, then hydroxocobalamin 1 mg intramuscularly every 2 months 1
• Intramuscular administration should be strongly considered in patients with severe deficiency or severe neurologic manifestations as it leads to more rapid improvement 5, 4, 6

Special Populations:

• Patients with more than 20 cm ileal resection require 1000 mcg intramuscularly monthly for life 1
• Post-bariatric surgery patients should receive 1 mg of oral vitamin B12 per day indefinitely 6
• Patients with pernicious anemia require monthly injections of vitamin B12 for the remainder of their lives 3

Critical Treatment Considerations

It is essential to 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

• Doses of folic acid greater than 0.1 mg per day may result in hematologic remission in patients with vitamin B12 deficiency, but neurologic manifestations will not be prevented with folic acid, and if not treated with vitamin B12, irreversible damage will result 3
• Treatment should continue until levels normalize, then maintenance therapy 5
• During initial treatment of pernicious anemia, serum potassium must be observed closely the first 48 hours and potassium replaced if necessary 3