What are the signs and symptoms of vitamin B12 deficiency in adults, particularly those over 60 or with risk factors such as a vegan diet or history of gastrointestinal disorders?

Signs and Symptoms of Vitamin B12 Deficiency

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—and sometimes without—any blood abnormalities. 1

Neurological Manifestations

The neurological symptoms are particularly important because they can become irreversible if treatment is delayed beyond 3 months, and they may occur even when blood counts appear completely normal. 2, 1

Sensory symptoms:

• Numbness and tingling (paraesthesia) in the hands, feet, and limbs 3, 1, 4
• Loss of proprioception (position sense), vibratory sensation, and touch sensation 1, 4
• These sensory symptoms typically appear before motor dysfunction develops 1, 4

Motor and coordination problems:

• Gait ataxia and balance problems due to impaired proprioception 1, 4
• Difficulty walking and falls, particularly in elderly patients 1
• Muscle weakness, abnormal reflexes, and spasticity as deficiency progresses 1
• In severe cases, subacute combined degeneration of the spinal cord with extensive demyelination can occur 1, 4

Cognitive and psychiatric symptoms:

• Brain fog, difficulty concentrating, and memory problems 1, 4
• Cognitive difficulties and short-term memory loss 1
• Depression and mood changes 5
• Mild disorientation in severe cases 6

Visual symptoms:

• Blurred vision related to optic nerve dysfunction 1
• Visual field loss or optic atrophy in advanced cases 1

Hematological Manifestations

Critical pitfall: One-third of patients with B12 deficiency have NO anemia, so normal blood counts do not exclude deficiency. 1, 4

• Megaloblastic anemia (when present) 1, 4
• Macrocytosis (enlarged red blood cells) on complete blood count 1
• Hypersegmented neutrophils on peripheral blood smear 4
• Anemia that doesn't respond to iron treatment 1, 4

Other Physical Manifestations

• Glossitis (inflamed, sore tongue) 1
• Severe fatigue and weakness 5, 6
• Neuropathic pain 6

High-Risk Populations Requiring Vigilance

Adults over 60 years: 18.1% have metabolic B12 deficiency, increasing to 25% in those over 85 years. 1 These patients frequently have functional deficiency despite "normal" serum B12 levels. 1

Dietary risk factors:

• Vegans and strict vegetarians (no animal products including milk or eggs) 1, 7
• Limited consumption of fortified foods 1
• Food allergies to eggs, milk, or fish 1

Gastrointestinal disorders:

• Atrophic gastritis affecting the gastric body 1
• Celiac disease 1
• Post-bariatric surgery patients (sleeve gastrectomy, Roux-en-Y gastric bypass, duodenal switch) due to reduced intrinsic factor and gastric acid 1
• Crohn's disease with ileal resection >20 cm 1
• History of gastric or small intestine resections 7

Medication-induced deficiency:

• Metformin use >4 months 1, 7
• Proton pump inhibitors or H2 receptor antagonists >12 months 1, 7
• Colchicine, phenobarbital, pregabalin, primidone 1

Autoimmune conditions:

• Thyroid disease, Sjögren syndrome, type 1 diabetes 1

Critical Diagnostic Pitfall

Up to 50% of patients with "normal" serum B12 levels have functional metabolic deficiency when measured by methylmalonic acid (MMA). 1, 4 This means standard B12 testing misses half of all deficiencies. Neurological symptoms can progress to permanent damage even with normal serum B12 levels, so metabolic testing (MMA or holotranscobalamin) should be performed when clinical suspicion is high despite normal total B12. 1, 4

Never administer folic acid before treating B12 deficiency—folic acid can mask the anemia while allowing irreversible neurological damage to progress. 3, 2